Neoadjuvant and adjuvant treatment strategies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many patients present with advanced disease and with underlying chronic liver disease and/or cirrhosis, limiting the proportion of patients who are surgical candidates. In addition, the development of recurrent or de novo cancers following surgical resection is common. These issues have led investigators to evaluate the benefit of neoadjuvant and adjuvant treatment strategies aimed at improving resectability rates and decreasing recurrence rates. While high-level evidence to guide treatment decision making is lacking, recent advances in locoregional and systemic therapies, including antiviral treatment and immunotherapy, raise the prospect of novel approaches that may improve the outcomes of patients with HCC. In this review, we evaluate the evidence for various neoadjuvant and adjuvant therapies and discuss opportunities for future clinical and translational research.     

Salvage locoregional therapies for recurrent hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the second most common cause of cancerrelated death worldwide. Despite the advent of screening efforts and algorithms to stratify patients into appropriate treatment strategies, recurrence rates remain high. In contrast to first-line treatment for HCC, which relies on several factors, including clinical staging, tumor burden, and liver function, there is no consensus or general treatment recommendations for recurrent HCC(R-HCC). Locoregional therapies include a s...     

Evaluating the current surgical strategies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Despite careful surveillance programs and the development of antiviral therapy for hepatitis virus infection, the occurrence rate of HCC remains high. Liver resection and liver transplantation are mainstay curative treatments. Most patients with HCC have impaired liver function, and surgical treatment is always accompanied by the risk of decompensation of the remnant liver, especially when the volume of the remnant liver is too small and the liver function too low to meet metabolic demands. The mortality of liver resection has dramatically decreased over the last three decades from 20% to less than 5% due to the accumulation of knowledge of liver anatomy, perioperative management and preoperative assessment of liver function. Here we provide an overview of the multidisciplinary treatments and current standard treatment strategies for HCC, to explore the possibility of expanding surgical treatments beyond the current standards.     

Colorectal liver metastases:An update on multidisciplinary approach

Liver metastasis is the commonest form of distant metastasis in colorectal cancer.Selection criteria for surgery and liver-directed therapies have recently been extended.However,resectability remains poorly defined.Tumour biology is increasingly recognized as an important prognostic factor;hence molecular profiling has a growing role in risk stratification and management planning.Surgical resection is the only treatment modality for curative intent.The most appropriate surgical approach is yet to be established.The primary cancer and the hepatic metastasis can be removed simultaneously or in a two-step approach;these two strategies have comparable long-term outcomes.For patients with a limited future liver remnant,portal vein embolization,combined ablation and resection,and associating liver partition and portal vein ligation for staged hepatectomy have been advocated,and each has their pros and cons.The role of neoadjuvant and adjuvant chemotherapy is still debated.Targeted biological agents and loco-regional therapies(thermal ablation,intra-arterial chemo-or radio-embolization,and stereotactic radiotherapy) further improve the already favourable results.The recent debate about offering liver transplantation to highly selected patients needs validation from large clinical trials.Evidencebased protocols are missing,and therefore optimal management of hepatic metastasis should be personalized and determined by a multi-disciplinary team.     

The current role of neoadjuvant/adjuvant/chemoprevention therapy in partial hepatectomy for hepatocellular carcinoma:a systematic review

BACKGROUND:Following curative treatment for hepato-cellular carcinoma(HCC),50%-90% of postoperative death is due to recurrent disease.Intra-hepatic recurrence is frequently the only site of recurrence.Thus,any neoadjuvant or adjuvant therapy,which can decrease or delay the incidence of intra-hepatic recurrence,or any cancer chemoprevention which can prevent a new HCC from developing in the liver remnant,will improve the results of liver resection.This article systematically reviewed the current evidence of ...     

肝细胞癌降期转化的治疗策略

手术是肝细胞癌(HCC)最重要的根治性手段,但初诊时能获得手术切除的HCC患者不足30%。如何将不能切除转化为可根治性切除成为提高HCC生存率的重要方面,也是近年来的研究热点。目前,综合运用经肝动脉插管治疗、放射治疗、靶向治疗等方法让HCC实现降期,或者通过门静脉栓塞、联合肝脏隔断和门静脉结扎使残余肝体积快速增大,均可实现转化成功从而获得根治性切除的机会。但是,如何优化多种治疗模式,规范复杂性肝癌患者的多学科诊疗路径,提高手术切除的效率和安全性,仍需要进一步深入探讨和研究。     

Recent advances in recurrent hepatocellular carcinoma therapy

Hepatocellular carcinoma(HCC) is the most prevalent form of primary liver cancer, accounting for 75%-85% of cases. Although treatments are given to cure early-stage HCC, up to 50%-70% of individuals may experience a relapse of the illness in the liver after 5 years. Research on the fundamental treatment modalities for recurrent HCC is moving significantly further. The precise selection of individuals for therapy strategies with established survival advantages is crucial to ensuring better outcom...     

Neoadjuvant and Adjuvant Therapy in Intrahepatic Cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and causes major economic and health burdens throughout the world. Although the incidence of ICC is relatively low, an upward trend has been seen over the past few decades. Owing to the lack of specific manifestations and tools for early diagnosis, most ICC patients have relatively advanced disease at diagnosis. Thus, neoadjuvant therapy is necessary to evaluate tumor biology and downstage these patients so that appropriate candidates can be selected for radical liver resection. However, even after radical resection, the recurrence rate is relatively high and is a main cause leading to death after surgery, which makes adjuvant therapy necessary. Because of its low incidence, studies in both neoadjuvant and adjuvant settings of ICC are lagging compared with other types of malignancy. While standard neoadjuvant and adjuvant regimens are not available in the current guidelines due to a lack of high-level evidence, some progress has been achieved in recent years. In this review, the available literature on advances in neoadjuvant and adjuvant strategies in ICC are evaluated, and possible challenges and opportunities for clinical and translational investigations in the near future are discussed.     

Resection of hepatitis B virus-related hepatocellular carcinoma: Evolving strategies and emerging therapies to improve outcome

The incidence of hepatocellular carcinoma (HCC) is increasing worldwide, largely due to hepatitis B virus (HBV), hepatitis C virus and liver cirrhosis. Chronic HBV infection is estimated to cause 55%-60% of the cases of HCC worldwide and over 70% in Asian countries. Liver resection is currently the mainstay of treatment due to the low surgical mortality, a wider treatment indication, and simplicity of post-treatment follow-up. There is an ever-increasing demand on surgeons to perform curative liver resection in HCC, with the hope of avoiding tumor recurrences. Hepatitis B-related-HCC has distinct clinicopathological features, which should be considered when treating the disease. The author presents a review of the recently evolving strategies and emerging therapies to improve HCC postresectional outcomes and focus on perioperative measures to improve patient outcome, with particular reference to the current status of adjuvant therapies in HCC patients after liver resection.     

Future perspectives for hepatocellular carcinoma

BACKGROUND: Five facets of hepatocellular carcinoma (HCC) are identified that impact on future directions in the management of the disease: epidemiology, prevention, screening, diagnosis and therapy. Recent papers on HCC have been reviewed, and predictions have been made on developments in HCC over the next decade. DISCUSSION: It is predicted that hepatitis B-related HCC will decrease with vaccination, while hepatitis C-related HCC will become an increasing problem. Antiviral treatment and chemopreventive agents will prevent HCC development. Whole-population screening will not be an option, but screening is justified for individuals who can pay for it. There will be more emphasis on the use of tumour markers. Transabdominal ultrasound and triphasic spiral computed tomography will remain important radiological imaging techniques. The results of liver resection will not improve unless neoadjuvant/adjuvant therapy is proven to be effective. More patients with initially unresectable HCC will be down-staged to become resectable with improvements in local, regional and systemic therapies. Liver transplantation will be increasingly used. Local ablative therapy will improve the quality of survival but will have no impact on overall survival compared with surgical resection. The author hopes to review the accuracy of these predictions in 2013.     

Locoregional surgical and interventional therapies for advanced colorectal cancer liver metastases: expert consensus statements

Selection of the optimal surgical and interventional therapies for advanced colorectal cancer liver metastases (CRLM) requires multidisciplinary discussion of treatment strategies early in the trajectory of the individual patient''s care. This paper reports on expert consensus on locoregional and interventional therapies for the treatment of advanced CRLM. Resection remains the reference treatment for patients with bilateral CRLM and synchronous presentation of primary and metastatic cancer. Patients with oligonodular bilateral CRLM may be candidates for one-stage multiple segmentectomies; two-stage resection with or without portal vein embolization may allow complete resection in patients with more advanced disease. After downsizing with preoperative systemic and/or regional therapy, curative-intent hepatectomy requires resection of all initial and currently known sites of disease; debulking procedures are not recommended. Many patients with synchronous primary disease and CRLM can safely undergo simultaneous resection of all disease. Staged resections should be considered for patients in whom the volume of the future liver remnant is anticipated to be marginal or inadequate, who have significant medical comorbid condition(s), or in whom extensive resections are required for the primary cancer and/or CRLM. Priority for liver-first or primary-first resection should depend on primary tumour-related symptoms or concern for the progression of marginally resectable CRLM during treatment of the primary disease. Chemotherapy delivered by hepatic arterial infusion represents a valid option in patients with liver-only disease, although it is best delivered in experienced centres. Ablation strategies are not recommended as first-line treatments for resectable CRLM alone or in combination with resection because of high local failure rates and limitations related to tumour size, multiplicity and intrahepatic location.     

Hepatectomy for hepatocellular carcinoma in the era of liver transplantation

The aim of management of hepatocellular carcinoma (HCC) is to improve the prognosis of the patients by radical resection and preserve remnant liver function. Although liver transplantation is associated with a lower tumor recurrence rate, this benefit is counteracted by long-term complications. Therefore, hepatectomy could be the first choice of treatment in selected patients with HCC. However, the higher frequency of tumor recurrence and the lower rate of resectability after hepatectomy for HCC led to an unsatisfactory prognosis. New strategies are required to improve the long-term outcome of HCC after hepatectomy. In this paper, we introduce some strategies to increase the low rate of resectability and reduce the high rate of tumor recurrence. Some aggressive treatments for tumor recurrence to extend long-term survival are also involved. We believe that hepatectomy combined with other therapies, such as portal vein embolization, transarterial chemoembolization, radioembolization, antiviral treatment, radiofrequency ablation and salvage transplantation, is a promising treatment modality for HCC and may improve survival greatly.     

Immunotherapy for hepatocellular carcinoma:Current and future

Hepatocellular carcinoma(HCC) arises on the background of chronic liver disease. Despite the development of effective anti-viral therapeutics HCC is continuing to rise, in part driven by the epidemic of non-alcoholic fatty liver disease. Many patients present with advanced disease out with the criteria for transplant, resection or even locoregional therapy. Currently available therapeutics for HCC are effective in a small minority of individuals. However,there has been a major global interest in immunotherapies for cancer and although HCC has lagged behind other cancers, great opportunities now exist for treating HCC with newer and more sophisticated agents. Whilst checkpoint inhibitors are at the forefront of this revolution, other therapeutics such as inhibitory cytokine blockade, oncolytic viruses, adoptive cellular therapies and vaccines are emerging. Broadly these may be categorized as either boosting existing immune response or stimulating de novo immune response. Although some of these agents have shown promising results as monotherapy in early phase trials it may well be that their future role will be as combination therapy,either in combination with one another or in combination with treatment modalities such as locoregional therapy. Together these agents are likely to generate new and exciting opportunities for treating HCC, which are summarized in this review.     

Neoadjuvant treatment strategies for intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma(ICC) is the second most common primary liver malignancy and is increasing in incidence. Long-term outcomes are optimized when patients undergo margin-negative resection followed by adjuvant chemotherapy. Unfortunately, a significant proportion of patients present with locally advanced, unresectable disease. Furthermore, recurrence rates are high even among patients who undergo surgical resection. The delivery of systemic and/or liver-directed therapies prior to surgery may increase the proportion of patients who are eligible for surgery and reduce recurrence rates by prioritizing early systemic therapy for this aggressive cancer. Nevertheless, the available evidence for neoadjuvant therapy in ICC is currently limited yet recent advances in liver directed therapies, chemotherapy regimens, and targeted therapies have generated increasing interest its role. In this article, we review the rationale for, current evidence for, and ongoing research efforts in the use of neoadjuvant therapy for ICC.     

从NCCN指南更新看靶向药物在结直肠癌肝转移新辅助治疗中的地位

手术切除是结直肠癌肝转移（CRLM）唯一有治愈可能的治疗方式,但有约70%的CRLM患者会在肝切除后出现复发。新辅助化疗是降低术后复发率并延长患者生存期的有效手段,靶向药物问世后更是以其高有效率而被广泛应用于新辅助治疗中。但是由于目前缺乏靶向药物在新辅助治疗中应用的临床证据,2017年新版NCCN指南将新辅助化疗联合靶向治疗的推荐修改为仅推荐新辅助单纯化疗。如何客观地看待NCCN指南推荐意见的变化对于指导临床实践具有重要意义。因此,本文将重点探讨靶向药物在新辅助治疗中的作用和地位。     

From diagnosis to treatment of hepatocellular carcinoma: An epidemic problem for both developed and developing world

Hepatocellular carcinoma(HCC) is the most frequent primary liver malignancy and the third cause of cancer-related death in the Western Countries. The well-established causes of HCC are chronic liver infections such as hepatitis B virus or chronic hepatitis C virus, nonalcoholic fatty liver disease, consumption of aflatoxins and tobacco smocking. Clinical presentation varies widely; patients can be asymptomatic while symptomatology extends from right upper abdominal quadrant paint and weight loss to obstructive jaundice and lethargy. Imaging is the first key and one of the most important aspects at all stages of diagnosis, therapy and follow-up of patients with HCC. The Barcelona Clinic Liver Cancer Staging System remains the most widely classification system used for HCC management guidelines. Up until now, HCC remains a challenge to early diagnose, and treat effectively; treating management is focused on hepatic resection, orthotopic liver transplantation, ablative therapies, chemoembolization and systemic therapies with cytotocix drugs, and targeted agents. This review article describes the current evidence on epidemiology, symptomatology, diagnosis and treatment of hepatocellular carcinoma.     

Combined interventional therapies of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, responsible for an estimated one million deaths annually. It has a poor prognosis due to its rapid infiltrating growth and complicating liver cirrhosis. Surgical resection, liver transplantation and cryosurgery are considered the best curative options, achieving a high rate of complete response, especially in patients with small HCC and good residual liver function. In nonsurgery, regional interventional therapies have led to a major breakthrough in the management of unresectable HCC, which include transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), microwave coagulation therapy (MCT), laser-induced thermotherapy (LITT), etc. As a result of the technical development of locoregional approaches for HCC during the recent decades, the range of combined interventional therapies has been continuously extended. Most combined multimodal interventional therapies reveal their enormous advantages as compared with any single therapeutic regimen alone, and play more important roles in treating unresectable HCC.     

Treatment of locally advanced rectal cancer: Controversies and questions

Rectal cancers extending through the rectal wall, or involving locoregional lymph nodes (T3/4 or N1/2), have been more difficult to cure. The confines of the bony pelvis and the necessity of preserving the autonomic nerves makes surgical extirpation challenging, which accounts for the high rates of local and distant relapse in this setting. Combined multimodality treatment for rectal cancer stage Ⅱ and Ⅲ was recommended from National Institute of Health consensus. Neoadjuvant chemoradiation using fluoropyrimidine-based regimen prior to surgical resection has emerged as the standard of care in the United States. Optimal time of surgery after neoadjuvant treatment remained unclear and prospective randomized controlled trial is ongoing. Traditionally, 6-8 wk waiting period was commonly used. The accuracy of studies attempting to determine tumor complete response remains problematic. Currently, surgery remains the standard of care for rectal cancer patients following neoadjuvant chemoradiation, where-as observational management is still investigational. In this article, we outline trends and controversies associated with optimal pre-treatment staging, neoadjuvant therapies, surgery, and adjuvant therapy.     

Multi-modality treatment of colorectal liver metastases

Liver metastases synchronously or metachronously occur in approximately 50% of colorectal cancer patients. Multimodality comprehensive treatment is the best therapeutic strategy for these patients. However, the optimal pattern of multimodality therapy is still controversial, and it raises several significant concerns. Liver resection is the most important treatment for colorectal liver metastases. The definition of resectability has shifted to focus on the completion of R0 resection and normal liver function maintenance. The role of neoadjuvant and adjuvant chemotherapy still needs to be clarified. The management of either progression or complete remission during neoadjuvant chemotherapy is challenging. The optimal sequencing of surgery and chemotherapy in synchronous colorectal liver metastases patients is still unclear. Conversional chemotherapy, portal vein embolization, two-stage resection, and tumor ablation are effective approaches to improve resectability for initially unresectable patients. Several technical issues and concerns related to these methods need to be further explored. For patients with definitely unresectable liver disease, the necessity of resecting the primary tumor is still debatable, and evaluating and predicting the efficacy of targeted therapy deserve further investigation. This review discusses different patterns and important concerns of multidisciplinary treatment of colorectal liver metastases.     

Advances in non-surgical management of primary liver cancer

Hepatocellular carcinoma(HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. There have been great improvements in the diagnosis and treatment of HCC in recent years, but the problems, including difficult diagnosis at early stage, quick progression, and poor prognosis remain unsolved. Surgical resection is the mainstay of the treatment for HCC. However, 70%-80% of HCC patients are diagnosed at an advanced stage when most are ineligible for potentially curative therapies such as surgical resection and liver transplantation. In recent years, non-surgical management for unrespectable HCC, such as percutaneous ethanol injection, percutaneous microwave coagulation therapy, percutaneous radiofrequency ablation, transcatheter arterial chemoembolization, radiotherapy, chemotherapy, biotherapy, and hormonal therapy have been developed. These therapeutic options, either alone or in combination, have been shown to control tumor growth, prolong survival time, and improve quality of life to some extent. This review covers the current status and progress of non-surgical management for HCC.