Preface

Chapter 5 **The Diagnostic and Prognostic Potential of MicroRNAs for**

**Section 3 Treatment Modalities for Hepatocellular Carcinoma 129**

Chapter 6 **Oncogenic Secretory Clusterin: A Promising Therapeutic Target**

Chapter 7 **Minimally Invasive Therapies for Hepatocellular Carcinoma:**

Min Yao, Wenjie Zheng, Li Wang, Miao Fang, Dengfu Yao and

**Mechanisms of Local Control and Systemic Immunologic**

Sarwat Fatima, Nikki Pui-Yue Lee, Hiu Yee Kwan and Zhao Xiang

Andrew W. Ritchey, Joshua D. Kuban and Rahul A. Sheth

Chapter 8 **Emerging Targeted Therapies for Treatment of Hepatocellular**

Xi-Dai Long, Wei-Zhong Tang, Jun Lu, Xiao-Ying Huang, Jin-Guang Yao, Tian-Qi Zhang, Xing-Zhizi Wang, Qun-Ying Su, Chun-Ying Luo, Xue-Ming Wu, Chao Wang, Li-Xia Zeng, Qiang Xia and Yun Ma

**Hepatocellular Carcinoma 103**

**for Hepatocellular Carcinoma 131**

Zhizheng Dong

**VI** Contents

**Response 149**

Bian

**Carcinoma (HCC) 173**

The field of cancer research is one of the most dynamic ones in today's medical world. From screening and early diagnosis to deciphering novel molecular pathways and innovative sur‐ gical solutions, the ongoing battle against malignancies seems to progress to new grounds. Since this "silent killer" became acknowledged as one of the leading causes of death world‐ wide, the landscape continuously changes. The incidence of some tumors has been on the rise, while mortality decreased in other cases. All this is due to new risk factors attributed to modern society on one hand, and more diagnostic capabilities leading to early detection coupled with more effective therapeutic options, on the other hand.

In this ever-changing context, hepatocellular carcinoma (HCC) is a very interesting culprit. One of the few malignancies with an almost omnipresent association with previous patholo‐ gy of the same organ, HCC was long thought to provide little surprises. However, since di‐ etary habits and heavy industrialization led to new types of liver injury, what was once thought of as the only certain "at risk" population is now far more diverse. Endemic areas slowly but surely shift, along with modern efficient treatment options for viral hepatitis and the rise of obesity and metabolic disorders – that quietly place other population groups in top positions as HCC candidates.

Current guidelines suffered incremental changes over the last years, as imaging took the leading role in diagnosis, with the advent of contrast agents that can accurately characterize liver lesions. Recent acknowledgment of non-invasive, minimum risk investigations such as contrast-enhanced ultrasound already means better diagnostic options in a variety of novel settings, and for even more categories of patients compared to just a few years ago. As mod‐ ern imaging methods become more available at decreased costs – thus being available in even smaller medical centers, the expertise of clinicians on all continents gradually increases, lead‐ ing to more cases of early HCC diagnosed (and, thus, candidates for curative surgery).

Oncological treatment for HCC has been the subject of long academic debates in recent years. With limited options available, due to a small number of targetable cellular and mo‐ lecular pathways, it seemed a lost battle; however, recent research proves the contrary. In recent years we have witnessed surprising breakthroughs, new lines of therapy, perhaps even a shift in paradigm in regards to invasive loco-regional treatment options. More effi‐ cient targeted drug-delivery methods, coupled with minimally invasive trans-arterial cathe‐ ter-based solutions, may offer a broader array of options for intermediate stages and otherwise untreatable HCCs. Surgery has become more refined, more nuanced in its thera‐ peutic options and goals. Novel techniques, based on minimally invasive set-ups, offer in‐ creased survivability at a lower time and anatomic cost for the patient.

With all these prospects in mind, we feel that this book project comes at the right time – when we are on the "high-tide" of HCC management, having authors that present recent breakthroughs, as well as re-establishing core-concepts and revising the basic concepts of this malignancy. We hope that everyone can find something of interest in this current vol‐ ume – the goal was to bring together as many views and perspectives as possible, in a coher‐ ent, easy to follow, format.

We would like to extend our immense gratitude towards our mentors, close and distant collab‐ orators that offered their invaluable contribution to our daily practice and academic efforts. Also, we would like to thank the authors, their collaborators, as well as the editorial team that made this project possible. A final – and most important – "thank you" goes to our families who give us the motivation to go forward and always offer their unconditional support.

### **Costin Teodor Streba, Cristin Constantin Vere and Ion Rogoveanu**

University of Medicine and Pharmacy of Craiova, Romania

**Section 1**

**Introduction**

**Section 1**
