LIVER TUMORS EPIDEMIOLOGY, DIAGNOSIS, PREVENTION AND TREATMENT potx

LIVER TUMORS - EPIDEMIOLOGY, DIAGNOSIS, PREVENTION AND TREATMENT Edited by Helen Reeves, Derek M. Manas and Rajiv Lochan Liver Tumors - Epidemiology, Diagnosis, Prevention and Treatment http://dx.doi.org/10.5772/56514 Edited by Helen Reeves, Derek M. Manas and Rajiv Lochan Contributors Radu Ion Badea, Simona Ioanitescu, Radu Badea, Mariana Mihaila, Laurentiu Micu, Tetsuya Nakatsura, Yu Sawada, Kazuya Ofuji, Mayuko Sakai, Alejandro Serrablo, Luis Tejedor, Jose M. Ramia-Ángel, Hueseyin Bektas, Arndt Vogel, Nora Schweitzer, Charing Ching Ning Chong Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2013 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. 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Publishing Process Manager Ana Pantar Technical Editor InTech DTP team Cover InTech Design team First published April, 2013 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com Liver Tumors - Epidemiology, Diagnosis, Prevention and Treatment, Edited by Helen Reeves, Derek M. Manas and Rajiv Lochan p. cm. ISBN 978-953-51-1070-5 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface VII Chapter 1 Epidemiology and Risk Factors 1 Nora Schweitzer and Arndt Vogel Chapter 2 Contrast-Enhanced Ultrasonography (CEUS) of Liver Masses — Principles, Clinical Applications, Drawbacks 13 R. Badea and Simona Ioaniţescu Chapter 3 Role of Anti-Viral Therapy on Hepatitis B Virus (HBV)-Related Hepatocellular Carcinoma (HCC) 39 Charing Ching Ning Chong, Grace Lai Hung Wong, Vincent Wai Sun Wong, Kit Fai Lee, Paul Bo San Lai and Henry Lik Yuen Chan Chapter 4 Immunotherapy for Hepatocellular Carcinoma: Current Status and Future Perspectives 59 Yu Sawada, Kazuya Ofuji, Mayuko Sakai and Tetsuya Nakatsura Chapter 5 Primary Liver Tumours – Presentation, Diagnosis and Surgical Treatment 91 H. Bektas, H. Schrem, M. Kleine, A. Tamac, F.W.R. Vondran, S. Uzunyayla and J. Klempnauer Chapter 6 Post-Therapeutic Follow-Up and Early Detection of Recurrence in Hepatocellular Carcinoma 117 Simona Ioaniţescu, L. Micu, Mariana Mihăilă and R. Badea Chapter 7 Liver Metastases — Surgical Treatment 137 Alejandro Serrablo, Luis Tejedor and Jose-Manuel Ramia Preface Tumours of the liver are frequently benign incidental findings. If malignant, however, the prognosis for those affected is often poor. Malignancies include those which have metasta‐ sized to the liver from elsewhere, reflecting advanced stage cancers where cure is rarely pos‐ sible. Similarly, primary liver cancer frequently complicates chronic liver disease, which further limits therapeutic options even for disease presenting at a relatively early stage. In fact, primary liver cancer remains one of the few types of cancer where annual mortality figures and incidence are both similar and increasing, reflecting a relative lack of progress in either prevention of the disease or its treatment. Despite these dismal data, there are signs that change is imminent. Surgery remains the goal for treatment of metastatic or primary liver tumours, and advances in surgical techniques as well as tumour ‘downstaging’ offer potential cure to small but ever increasing numbers of individuals. Successful treatment of viral hepatitis has been rewarded in some parts of the globe with falling incidence of pri‐ mary cancers, while novel means of prevention are also emerging. Imaging modalities have also advanced over the last two to three decades, facilitating surveillance programmes and earlier stage detection of tumours. Medical therapies have markedly improved survival of patients with liver metastases and while the impact of medical therapies for primary liver cancers remains relatively disappointing, small but highly significant advances have been made. In this book, an overview of different liver tumours is presented, focusing particular‐ ly on recent developments. As well as an update on epidemiology and risk factors for pri‐ mary liver cancer, the role of contrast enhanced ultrasound is reviewed, as are the very important roles of anti-viral therapy and the exciting potential of immunotherapy. Manage‐ ment of both primary and metastatic cancers from a surgical perspective is comprehensively covered, including guidance for post therapeutic follow-up. This book serves as an accurate up to date guide for a common and increasing clinical problem. The book will be relevant for all researchers and practitioners involved in the care of patients with liver tumours. Editor: Helen Reeves Newcastle University, UK Co-editors: Derek M. Manas Institute of Transplantation, Newcastle upon Tyne, NHS Hospital Trust, UK Rajiv Lochan Freeman Hospital, Newcastle upon Tyne, UK Chapter 1 Epidemiology and Risk Factors Nora Schweitzer and Arndt Vogel Additional information is available at the end of the chapter http://dx.doi.org/10.5772/55908 1. Introduction 1.1. Epidemiology Worldwide, hepatocellular carcinoma (HCC) is is the fifth most common cancer in men and the seventh in women (Figure 1). Because of impaired treatment options and late diagnosis in many cases, mortality is almost as high as the incidence rate (mortality: incidence rate 0.93). Worldwide, it is the third most frequent cause of tumour-related deaths. In the year 2008, 748,300 new HCCs and 695,900 deaths have been registered (http://www.iarc.fr/). Almost 85% of all cases occur in the developing countries (Figure 1). Regions with a high incidence are Eastern and South-Eastern Asia and Middle and Western Africa. More than a half of all new HCC are diagnosed in China, resulting in an incidence of 35.2/ 100000 inhabitants. While North America, Australia and Northern Europe belong to the low-incidence areas, the incidence is significantly higher in Southern Europe (10.5 per 100,000) (Figure 2). The HCC incidence increases with age [1-3]. Only in regions with high hepatitis B virus (HBV) infection rate, e.g. China, are patients younger at diagnosis, presenting at 55-59 years of age. In contrast, in Japan, where chronic hepatitis C virus (HCV) infection is the most important risk factor for HCC, the peak age is between 70 and 79 years. In Europe and North America most patients are between 60 and 65 years old at diagnosis [4]. In most countries, HCC represents 80% - 90% of all primary liver tumours. An exception is the Khon Kaen region of Thailand, which is known for its high incidence rates of 88/100,000 for men and 35.4/100,000 for women. In this area, the main tumour entity is cholangiocellular carcinoma caused by endemic infestation with liver flukes [5]. Worldwide, the incidence of HCCs is increasing. In Europe and USA, a peak is expected in 2020. In particular, frequent HCV infections during the 50 th and the 60 th are made responsible for that fact. During the last two decades, the mortality rates have increased in some European © 2013 Schweitzer and Vogel; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Countries (e.g. Germany, Austria) and in the US, where the mortality has risen by 40% from 1994 to 2004 [6]. On the other hand, some countries, e.g. France and Italy, have shown a strong increase of mortality-rates in the mid-nineties and a decline thereafter [7]. In almost all populations, more men than women are affected. Men/women ratios of 2:1 to 4:1 in high-risk areas are registered. Certainly, the fact that men are more often exposed to risk factors partly accounts for the higher incidence for men. However, as gender differences can be reproduced in mouse experiments, hormonal changes are likely to influence hepatocarci‐ nogenesis as well. One possible mechanism is that androgens enhance DNA damage and oxidative stress during hepatocarcinogenesis [8]. Furthermore, the inhibition of interleukin-6 production in Kupffer cells by estrogens may be relevant in gender-specific hepatocarcino‐ genesis [9]. Recently, it was shown that the transcription factor foxa1/2 protects female mice from HCC while promoting HCC in male mice [10]. All these results indicate that there exist gender specific mechanisms in hepatocarcinogenesis and that the higher incidence of HCC in men is not restricted to the exposure to risk factors. Figure 1. Cancer Incidence and Mortality Worldwide, Both Sexes Liver Tumors - Epidemiology, Diagnosis, Prevention and Treatment 2 [...]...Epidemiology and Risk Factors http://dx.doi.org/10.5772/55908 Figure 2 Incidence and Mortality of HCC Worldwide (per 100,000) 3 4 Liver Tumors - Epidemiology, Diagnosis, Prevention and Treatment 2 Risk factors In more than 70% of all cases, HCC develops in patients with advanced liver cirrhosis In 90%, the responsible risk factor is known The main risk factors for liver cirrhosis and HCC strongly... with no capsule It may be frequently associated with other benign tumors like cysts or adenomas Hemangiomas are usually asymptomatic (in very rare cases, when extremely large they may cause a distension of the liver capsule and thrombocytopenia) and have a slow, self-limiting 17 18 Liver Tumors - Epidemiology, Diagnosis, Prevention and Treatment development In most cases there is just one lesion, but... hypervascular metastases or HCC is difficult and thus a correlation with other imaging techniques is mandatory [27] 20 Liver Tumors - Epidemiology, Diagnosis, Prevention and Treatment (a) (b) ) (c) Figure 3 a “Atypical” liver hemangioma This is the case of a female patient undergoing chemotherapy for breast cancer There is increased echogenicity of the liver suggesting therapy induced dystrophy In... associated with alcoholic liver disease Nat Genet, (2010) , 21-23 [43] Sookoian, S, & Pirola, C J Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological se‐ verity of nonalcoholic fatty liver disease Hepatology, (2011) , 1883-1894 11 12 Liver Tumors - Epidemiology, Diagnosis, Prevention and Treatment [44] Valenti,... presence of arterio‐ venous communications is characteristic for the neoplastic circulation and in CEUS is ex‐ pressed by the “wash-out” process This phenomenon begins at the end of the arterial phase 15 16 Liver Tumors - Epidemiology, Diagnosis, Prevention and Treatment and/ or during the venous phase, is persistent and is characteristic for neoplastic processes in 90 % of cases [20] There are studies that... inactive and displays its full effect only after ingestion by activation to aflatoxin B1-8,9-epoxide The electrophil epoxide binds 7 8 Liver Tumors - Epidemiology, Diagnosis, Prevention and Treatment covalently to DNA bases and thereby becomes mutagenic Epidemiologic investigations revealed frequent mutations in the tumour suppressor p53 in these patients Simultaneous exposition of aflatoxins and HBV... Organisation For, and C Treatment Of, EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma J Hepatol, (2012) , 908-943 [12] Chang, M H, et al Universal hepatitis B vaccination in Taiwan and the incidence of hepa‐ tocellular carcinoma in children Taiwan Childhood Hepatoma Study Group N Engl J Med, (1997) , 1855-1859 9 10 Liver Tumors - Epidemiology, Diagnosis, Prevention and Treatment. .. unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited 14 Liver Tumors - Epidemiology, Diagnosis, Prevention and Treatment presented on a grey scale, with each shade of grey representing a density (in fact, an acoustic impedance) “Grey scale” ultrasonography is a dynamic examination that allows the overall evaluation of the liver, with measurements of... DNA and the Development of HCC (from Hashem B El-Serag, Gastroenterol‐ ogy 2012, adapted from Chen CJ JAMA 2006 [17] 4 Hepatitis C infection Similar to hepatitis B, patients with hepatitis C are at higher risk to develop HCC Worldwide, over 180 million people are infected [2% of the global population) and about 30% of HCC are HCV-related 5 6 Liver Tumors - Epidemiology, Diagnosis, Prevention and Treatment. .. frequent in women and its development may be linked with the use of oral contraceptives [28] There is no risk of malignant transformation or spontaneous rupture The lesion may be unique or there can be multiple lesions The grey scale ultrasono‐ graphic aspect is that of a solid lesion with no capsule of its own (figure 5) 21 22 Liver Tumors - Epidemiology, Diagnosis, Prevention and Treatment Figure . LIVER TUMORS - EPIDEMIOLOGY, DIAGNOSIS, PREVENTION AND TREATMENT Edited by Helen Reeves, Derek M. Manas and Rajiv Lochan Liver Tumors - Epidemiology, Diagnosis,. Sexes Liver Tumors - Epidemiology, Diagnosis, Prevention and Treatment 2 Figure 2. Incidence and Mortality of HCC Worldwide (per 100,000) Epidemiology and