Ablative strategies for recurrent hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the most common primary liver cancer and is the fifth leading cause of cancer death worldwide and the third leading cause of all diseases worldwide. Liver transplantation, surgical resection and ablation are the three main curative treatments for HCC. Liver transplantation is the optimal treatment option for HCC, but its usage is limited by the shortage of liver sources.Surgical resection is considered the first choice for early-stage HCC, but it does not apply t...     

Current management of patients with hepatocellular carcinoma

The current management therapies for hepatocellular carcinoma(HCC) patients are discussed in this review. Despite the development of new therapies, HCC remains a "difficult to treat" cancer because HCC typically occurs in advanced liver disease or hepatic cirrhosis. The progression of multistep and multicentric HCC hampers the prevention of the recurrence of HCC. Many HCC patients are treated with surgical resection and radiofrequency ablation(RFA), although these modalities should be considered in only selected cases with a certain HCC number and size. Although there is a shortage of grafts, liver transplantation has the highest survival rates for HCC. Several modalities are salvage treatments; however, intensive care in combination with other modalities or in combination with surgical resection or RFA might offer a better prognosis. Sorafenib is useful for patients with advanced HCC. In the near future, HCC treatment will include stronger molecular targeted drugs, which will have greater potency and fewer adverse events. Further studies will be ongoing.     

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.     

Hepatozelluläres Karzinom

Hepatocellular carcinoma (HCC) constitutes one of the most frequent cancers worldwide and in 80-90% develops as a consequence of liver cirrhosis. The prognosis of patients with HCC is not only dependent on the tumor stage, but also on the liver function. Patients with early HCC without extrahepatic metastasis can be successfully treated by liver transplantation, tumor resection or percutaneous tumor ablation (e.g. ethanol injection or radiofrequency ablation). Meta-analyses have shown that transarterial chemoembolization (TACE) appears to be an effective treatment for more advanced tumors, at least for a subgroup of patients with good liver function. However, in approximately 50% of HCC patients these treatment options are not applicable or not effective, because they suffer from advanced tumors and/or impaired liver function. Recently a randomized placebo controlled phase III study showed that the multikinase inhibitor sorafenib significantly improves survival of patients with advanced HCC and good liver function (child A). As a consequence of this study sorafenib is now available for effective systemic treatment of patients with advanced HCC.     

Prevention of intrahepatic hepatocarcinoma recurrence in patients with viral cirrhosis: two potential options

Mortality due to hepatocellular carcinoma (HCC) is still high, because of its development in liver with impaired function due to underlying cirrhosis, of its chemoresistance and of its high rate of recurrence. Liver transplantation is considered the most efficacious treatment for patients with HCC. However, the low availability of organs limits the offer of this option to all candidates. Furthermore, liver transplantation is not lacking in risk of tumour recurrence. Other curative options include surgical resection and ablation using percutaneous techniques. Such approaches give similar and satisfactory survival rates, providing that patient selection is optimal in terms of tumour size and liver function. Since even in the presence of a radical therapeutic result this cancer maintains a high tendency for local recurrence, it is very important to explore the adjuvant ways to increase the disease-free survival in patients surgically treated. Treatment with interferon a and intrahepatic injection of (131)-Iodine labelled lipiodol ((131)I-Lipiodol) are instead showing encouraging results. This review presents a concise update on this issue.     

Targeting the insulin-like growth factor pathway in hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the third leading cause of cancer-related deaths worldwide. Only 30%-40% of the patients with HCC are eligible for curative treatments, which include surgical resection as the first option, liver transplantation and percutaneous ablation. Unfortunately, there is a high frequency of tumor recurrence after surgical resection and most HCC seem resistant to conventional chemotherapy and radiotherapy. Sorafenib, a multi-tyrosine kinase inhibitor, is the only chemotherapeutic option for patients with advanced hepatocellular carcinoma. Patients treated with Sorafenib have a significant increase in overall survival of about three months. Therefore, there is an urgent need to develop alternative treatments. Due to its role in cell growth and development, the insulin-like growth factor system is commonly deregulated in many cancers. Indeed, the insulin-like growth factor(IGF) axis has recently emerged as a potential target for hepatocellular carcinoma treatment. To this aim, several inhibitors of the pathway have been developed suchas monoclonal antibodies, small molecules, antisense oligonucleotides or small interfering RNAs. However recent studies suggest that, unlike most tumors, HCC development requires increased signaling through insulin growth factor Ⅱ rather than insulin growth factor Ⅰ. This may have great implications in the future treatment of HCC. This review summarizes the role of the IGF axis in liver carcinogenesis and the current status of the strategies designed to target the IGF-Ⅰ signaling pathway for hepatocellular carcinoma treatment.     

Treatment of hepatocellular carcinoma

Hepatocellular carcinoma is one of the most common cancers worldwide. The incidence of this disease is also increasing in the Western world. Typically, HCC is diagnosed when patients have already reached an advanced stage of the disease and the prognosis is poor. Potentially curative treatment options include surgical resection or liver transplantation and can be offered to patients with adequate liver function and tumour stage. Other non-surgical treatment options such as radiofrequency ablation, cryoablation, ethanol or acetic acid injection, transarteriel chemoembolisation radiation therapy and systemic chemotherapy can be offered either alone or in combination to selected groups of patients. These treatments can improve (tumour-free) survival and in a few cases even cure the patient.     

Differenzialtherapie von Lebertumoren

Focal nodular hyperplasia is a polyclonal hyperplasia of liver cells as a result of locally enhanced blood flow because of vessel malformations. Only symptomatic FNH is an indication for resection or enucleation. In contrast to FNH growth of adenoma is dependent on sexual hormones. Solitary HNFα-inactivated and inflammatory adenomas larger than 5 cm should be removed because of risk of tumor rupture or bleeding, while β-catenin mutated adenomas should be surgically removed at any stage because of risk of malignant transformation. The prognosis of patients with HCC is dependent on the tumor stage, but also on the liver function. Resection is the treatment of choice for HCC in patients without liver cirrhosis. Patients with liver cirrhosis and early HCC without extrahepatic metastasis can be successfully treated by liver transplantation. If transplantation is not possible these tumors should be removed by local percutaneous ablation. Transarterial chemoembolization is an effective treatment for more advanced HCC in patients with good liver function. Studies showed that the multikinase inhibitor sorafenib significantly improves survival of patients with advanced or metastatic HCC in child A cirrhosis. The only curative option for patients with intrahepatic cholangiocarcinomas is surgical resection. Patients with unresectable cholangiocarcinomas should be treated with a chemotherapy consisting of Gemcitabine-Cisplatin-combination.     

Early detection of liver cancer: Diagnosis and management

Hepatocellular carcinoma (HCC) is the fifth most common cause of cancer deaths worldwide, and the incidence is rising. Despite a wide array of treatment options, fewer than half of candidates for potentially curative treatments receive them. The diagnosis and management of HCC require a multidisciplinary approach involving various clinical specialties. The foundation of diagnosis is high-quality imaging, with MRI being the test of choice. Some patients also require guided biopsy when MRI is equivocal. Treatment options depend upon the tumor stage and the degree of underlying synthetic dysfunction. Potentially curative treatments include surgical resection and transplantation. Other treatments that prolong survival include percutaneous ablation and transarterial chemoembolization. A new oral agent, sorafenib, was recently shown to prolong survival in patients with advanced HCC. By increasing surveillance and treatment of HCC, outcomes for these patients may be improved.     

Outcome of patients with hepatocellular carcinoma referred to a tertiary centre with availability of multiple treatment options including cadaveric liver transplantation.

Hepatocellular carcinoma (HCC) is a primary cancer of the liver with an established causal link to viral hepatitis and other forms of chronic liver disease. Aims: The aim of this study was to analyse the determinants of outcome in patients with HCC referred to a tertiary centre for management. Method: Two hundred and thirty-five prospective patients with HCC and minimum 12-month follow-up were studied. Results: The cohort was heterogeneous, with 52% Caucasian, 40% Asian and 5% of Middle-Eastern origin. Independent predictors of outcome included tumour size and number, the presence of ascites or portal vein thrombosis, alpha-foetoprotein >50 U/L and an impaired performance status. Treatment was determined on an individual case basis by a multidisciplinary tumour team. Surgical resection was primary treatment in 43 patients, liver transplantation in 40 patients, local ablation (percutaneous radiofrequency ablation or alcohol injection) in 33 patients, transarterial chemoembolisation in 33 patients, chemotherapy or other systemic therapy in 30 patients and no treatment in 56 patients. After adjustment for significant covariates, both liver transplantation (P<0.001) and surgical resection (P=0.029) had a significant effect on patient survival compared with no treatment, but local ablation (P=0.410) and chemoembolisation (P=0.831) did not. Liver transplantation resulted in superior overall and, in particular, disease-free survival compared with surgical resection (disease-free survival 84 vs 15% at 5 years). Conclusion: In conclusion, both surgical resection and liver transplantation significantly improve the survival of patients with HCC, but improvements need to be made to the delivery of loco-regional therapy to enhance its effectiveness.     

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.     

Role of radiofrequency ablation in the treatment of small hepatocellular carcinoma

Radiofrequency ablation (RFA), one of the most advanced loco-regional ablative therapeutic methods, is widely utilized in the treatment of hepatocellular carcinoma (HCC). Because of its minimal invasiveness and high efficacy, RFA has been regarded as a curative therapy as alternative to surgical resection and liver transplantation. It brings new hope and a new treatment pattern for small HCC. In this article, we summarize the important role of RFA in the treatment of small HCC according to our clinical experience over six years. The prognosis of small HCC after RFA is comparable to that of surgical resection but with higher safety, less complications, wider applicability, and good long-term survival. RFA will play a more and more important role in the clinical treatment of small HCC.     

Transarterial chemoembolization for hepatocellular carcinoma: A review of techniques

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases worldwide. While curative therapies, including resection, liver transplantation, and percutaneous ablation (percutaneous ethanol injection and radiofrequency ablation), are applicable for only a portion of the HCC population, transcatheter arterial chemoembolization (TACE) has been recognized as an effective palliative treatment option for patients with advanced HCC. TACE is also used even for single HCCs in which it is difficult to perform surgical resection or locoregional treatment due to systemic co-morbidities or anatomical problems. TACE has become widely adopted in the treatment of HCC. By using computed tomography-angiography, TACE is capable of performing diagnosis and treatment at the same time. Furthermore, TACE plays an important role in the multidisciplinary treatment for HCC when combined with other treatment. In this review, we first discuss the history of TACE, and then review the previous findings about techniques of achieving a locoregional treatment effect (liver infarction treatment, e.g., ultra-selective TACE, balloon-occluded TACE), and the use of TACE as a drug delivery system for anti-cancer agents (palliative, e.g., platinum complex agents, drug-eluting beads) for multiple lesions.     

Practical management of hepatocellular carcinoma.

Primary hepatocellular carcinoma (HCC) is one of the ten commonest tumours in the world and occurs mainly in patients with cirrhosis. To date, in Western countries, curative treatment options include partial liver resection or liver transplantation in selected patients with small tumours. Unfortunately, most patients are detected with non-resectable or non-transplantable HCC due to disease extension, hepatic dysfunction or comorbid factors. These patients may benefit from local ablative therapy, such as percutaneous ethanol injection or radiofrequency ablation, with curative intent in patients with small tumours. In advanced HCC chemoembolization has a high response rate, but there is no clear evidence of a survival benefit. In this review we discuss practical considerations in the treatment of HCC and propose an algorithm for the selection of different treatment modalities.     

Endoscopic ultrasound and fine needle aspiration for the diagnosis of hepatocellular carcinoma

Liver cancer is one of the most frequent solid cancers. The major risk factor associated with the development of hepatocellular carcinoma (HCC) is cirrhosis caused by hepatitis B, hepatitis C virus or chronic alcohol consumption. The overall prognosis of patients with HCC is very poor and this is mainly due to the advanced stages of cancer at presentation and also because of underlying cirrhosis. When HCC is diagnosed at early stages, prognosis is better with five-year disease free survival of around 50% with resection, or local ablative treatments such as radio-frequency ablation or percutaneous ethanol injection, and 70-80% with liver transplantation. Therefore, systematic screening of all the high-risk patients is the key to an early diagnosis of small HCC and the use of an appropriate treatment modality. The currently available tools for the screening, surveillance and diagnosis of HCC in the presence of cirrhosis remain sub-optimal. The advancements made in the past 10 years, however, have made HCC a potentially curable disease in a highly selected group of patients. This review will briefly discuss the current guidelines for surveillance and diagnosis of HCC in high-risk subjects and then review the potential role of endoscopic ultrasound and fine needle aspiration for the diagnosis of small HCC.     

肝癌肝移植

肝移植和肝切除是目前肝癌的2种主要治疗方法。早期肝癌合并晚期肝病患者肝移植后疗效评估最佳;但是对于肝功能代偿尚可、不伴门静脉高压的早期肝癌患者来说,最佳的治疗方案仍存在争议。大量的研究证明肝移植后无病生存率更高,但是尚不清楚长期生存率如何。通过改进手术技术和实行补救性肝移植的方法可明显改善肝切除后患者生存率,且避免了可因切除治愈的患者因等待移植时间过长而失去机会。     

Treatment for hepatocellular carcinoma in Japan over the last three decades: Our experience and published work review

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer‐related mortality worldwide. In the last few decades, there has been a marked increase in therapeutic options for HCC and epidemiological characteristics at HCC diagnosis have also significantly changed. With these changes and advances in medical technology and surveillance program for detecting earlier stage HCC, survival in patients with HCC has significantly improved. Especially, patients with liver cirrhosis are at high risk of HCC development, and regular surveillance could enable early detection of HCC and curative therapy, with potentially improved clinical outcome. However, unfortunately, only 20% of HCC patients are amenable to curative therapy (liver transplantation, surgical resection or ablative therapies). Locoregional therapies such as radiofrequency ablation, percutaneous ethanol injection, microwave coagulation therapy and transcatheter arterial chemoembolization play a key role in the management of unresectable HCC. Currently, molecular‐targeted agents such as sorafenib have emerged as a promising therapy for advanced HCC. The choice of the treatment modality depends on the size of the tumor, tumor location, anatomical considerations, number of tumors present and liver function. Furthermore, new promising therapies such as gene therapy and immunotherapy for HCC have emerged. Approaches to the HCC diagnosis and adequate management for patients with HCC are improving survival. Herein, we review changes of epidemiological characteristics, prognosis and therapies for HCC and refer to current knowledge for this malignancy based on our experience of approximately 4000 HCC cases over the last three decades.     

Liver transplantation for hepatocellular carcinoma

Hepatocellular carcinoma can only be cured by physical removal or destruction of the tumor before it has spread. This can be accomplished by the ablation of the tumor, surgical resection of the tumor-bearing liver, or by liver transplantation. Ablation and resection can only be performed in patients who will be left with sufficient liver volume to sustain normal hepatic function. Unfortunately, the same disease that caused the HCC also limits the amount of parenchymal loss that can be tolerated by the patient. Liver transplantation is an appealing treatment option because it has the potential to cure patient of both the cancer and the predisposinig liver disease. Excellent survival rates are possible in patients with early HCC who receive a transplant, but dismal results are seen when patients with advanced tumors are transplanted.Wide criteria for transplant allow for more patients to be cured of HCC, but this comes at the expense of a greater overall recurrence rate. The acceptable recurrence rate is not a concrete number, but this is a function of donor organ availability. A 50% cure rate is viewed as an excellent outcome for many accepted cancer operations; however, in the case of transplant for HCC, this would represent a poor use of the scarce donor resource when the same liver offers a 70% 5-year survival rate to a non-HCC patient. These issues and methods retarding tumor progression while on the transplant waiting list are reviewed herein.     

Strategy for improving survival and reducing recurrence of HCV-related hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the sixth most common cancer and the third leading cause of cancerrelated death in the world.With advances in imaging diagnostics,accompanied by better understanding of high-risk patients,HCC is now frequently detected at an early stage;however,the prognosis remains poor.The recurrence rate after treatment of HCC is higher than that associated with cancers of other organs.This may be because of the high incidence of intrahepatic distant recurrence and multicentric recurrence,especially with hepatitis C virus(HCV)-related hepatocellular carcinoma.The Barcelona Clinic Liver Cancer(BCLC)classification has recently emerged as the standard classification system for the clinical management of patients with HCC.According to the BCLC staging system,curative therapies(resection,transplantation,transcatheter arterial chemoembolization,percutaneous ethanol injection therapy,percutaneous microwave coagulation therapy and percutaneous radiofrequency ablation)can improve survival in HCC patients diagnosed at an early stage and offer a potential long-term cure.However,treatment strategies for recurrent disease are not mentioned in the BCLC classsification.The strategy for recurrence may differ according to the recurrence pattern,i.e.,intrahepatic distant recurrence vs multicentricrecurrence.In this article,we review recurrent HCC and the therapeutic strategies for reducing recurrent HCC,especially HCV-related HCC.     

Hepatozelluläres Karzinom

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world. The major etiologic risk factors include toxins (alcohol, aflatoxin B(1)), hepatitis B and C virus infection as well as various inherited metabolic disorders. The prognosis of HCC patients is generally very poor with a 5-year survival rate of less than 5%. The diagnosis is based on biochemical and imaging tests as well as histology. Therapeutic strategies include surgery (resection or liver transplantation) and non-surgical interventions, such as percutaneous ethanol injection or radiofrequency thermal ablation as well as transarterial embolization or chemoembolization. Radio- or chemotherapy are mostly ineffective. Therefore, the development and evaluation of novel HCC treatment strategies as well as the implementation of existing and the development of new measures to prevent HCC are of utmost importance. The better understanding of the clinical and molecular pathogenesis of HCC should lead to improved diagnostic, therapeutic and preventive strategies with the aim to reduce the incidence of HCC, one of the most devastating malignancies worldwide.