Recent advances in multidisciplinary management of hepatocellular carcinoma

The incidence of hepatocellular carcinoma(HCC) is increasing, and it is currently the second leading cause of cancer-related death worldwide. Potentially curative treatment options for HCC include resection, transplantation, and percutaneous ablation, whereas palliative treatments include trans-arterial chemoembolization(TACE), radioembolization, and systemic treatments. Due to the diversity of available treatment options and patients’ presentations, a multidisciplinaryteam should decide clinical management of HCC, according to tumor characteristics and stage of liver disease. Potentially curative treatments are suitable for very-early- and early-stage HCC. However, the vast majority of HCC patients are diagnosed in later stages, where the tumor characteristics or progress of liver disease prevent curative interventions. For patients with intermediate-stage HCC, TACE and radioembolization improve survival and are being evaluated in addition to potentially curative therapies or with systemic targeted therapy. There is currently no effective systemic chemotherapy, immunologic, or hormonal therapy for HCC, and sorafenib is the only approved moleculartargeted treatment for advanced HCC. Other targeted agents are under investigation; trials comparing new agents in combination with sorafenib are ongoing. Combinations of systemic targeted therapies with local treatments are being evaluated for further improvements in HCC patient outcomes. This article provides an updated and comprehensive overview of the current standards and trends in the treatment of HCC.     

Hepatocellular carcinoma: From diagnosis to treatment

Hepatocellular carcinoma(HCC) is the sixth most prevalent malignancy worldwide and is a rising cause of cancer related mortality. Risk factors for HCC are well documented and effective surveillance and early diagnosis allow for curative therapies. The majority of HCC appears to be caused by cirrhosis from chronic hepatitis B and hepatitis C virus. Preventive strategies include vaccination programs and anti-viral treatments.Surveillance with ultrasonography detects early stage disease and improves survival rates. Many treatment options exist for individuals with HCC and are determined by stage of presentation. Liver transplantation is offered to patients who are within the Milan criteria and are not candidates for hepatic resection. In patients with advanced stage disease, sorafenib shows some survival benefit.     

Treatment of hepatocellular carcinoma: Steps forward but still a long way to go

Hepatocellular carcinoma(HCC) is the fifth most common malignancy and the third cause of tumor associated deaths worldwide. HCC incidence rates are increasing in many parts of the world including developing and developed countries. Potentially curative treatments for HCC are resection and liver transplantation, but these are only suitable for patients with small tumors, meeting strict pre-defined criteria, or well-compensated liver disease. Early diagnosis of HCCcan be achieved by surveillance of at-risk populations. For patients with non-resectable disease treatments modalities include loco-ablative and systemic therapies. In this review we focus on treatment options in HCC and their allocation. Although significant research is in progress, to this date, the results are unsatisfactory with limited long-term survival. In the fight against this deadly disease, there is still a long way to go.     

Role of hepatectomy for recurrent or initially unresectable hepatocellular carcinoma

As a result of donor shortage and high postoperative morbidity and mortality after liver transplantation,hepatectomy is the most widely applicable and reliable option for curative treatment of hepatocellular carcinoma(HCC).Because intrahepatic tumor recurrence is frequent after loco-regional therapy,repeated treatments are advocated provided background liver function is maintained.Among treatments including local ablation and transarterial chemoembolization,hepatectomy provides the best long-term outcomes,but studies comparing hepatectomy with other nonsurgical treatments require careful review for selection bias.In patients with initially unresectable HCC,transarterial chemo-or radio-embolization,and/or systemic chemotherapy can down-stage the tumor and conversion to resectable HCC is achieved in approximately 20%of patients.However,complete response is rare,and salvage hepatectomy is essential to help prolong patients’survival.To counter the short recurrence-free survival,excellent overall survival is obtained by combining and repeating different treatments.It is important to recognize hepatectomy as a complement,rather than a contraindication,to other nonsurgical treatments in a mul-tidisciplinary approach for patients with HCC,including recurrent or unresectable tumors.     

Immunotherapy for recurrent hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is presented frequently in late stages that are not amenable for curative treatment. Even for patients who can undergo resection for curative treatment of HCC, up to 50% recur. For patients who were not exposed to systemic therapy prior to recurrence, recurrence frequently cannot be subjected to curative therapy or local treatments. Such patients have several options of immunotherapy(IO). This includes programmed cell death protein 1(PD-1) and cytotoxic T-lymphocyte...     

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.     

非手术治疗原发性肝癌研究进展

肝细胞癌（HCC）是世界范围内第五大常见肿瘤,为肿瘤相关死亡的第三大常见原因。由于HCC 早期症状隐匿,大多数患者在确诊时已是中晚期,失去了接受治愈性治疗的机会。目前,HCC的非手术治疗方法很多,包括介入栓塞化疗、消融、放射治疗、化疗和分子靶向治疗等。现有治疗方法的单独或组合应用已被证明能够控制肿瘤生长,延长生存时间,提高生活质量。     

Progress in the treatment of pulmonary metastases after liver transplantation for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and is the third leading cause of cancer-related death. Liver transplantation (LT) has become a curative treatment for patients with HCC. However, recurrence and metastasis after LT are the main factors reducing long-term survival in patients, and the lung is the most common site of metastasis after LT for HCC, although metastasis to liver, para-aortic lymph nodes and renal periphery are observed. Thus, the treatment of pulmonary metastases after LT for HCC has become a hot research topic, the successful treatment of pulmonary metastases can significantly prolong the survival of LT patients. Although single conventional treatment (chemotherapy, surgery and external beam radiation therapy), immunosuppression, image-guided minimally invasive therapy (radiofrequency ablation, microwave ablation, cryoablation, and brachytherapy) and molecular targeted drugs have had a significant effect, patients do not have durable remission and the long-term survival rate is disappointing. Therefore, improving existing treatments and identifying a more effective combination therapy are important research issues in the prevention and treatment of pulmonary metastases after LT for HCC. The paper reviewed single conventional treatments, new treatments, and combination therapy, to provide a basis for the best treatment of these patients.     

Treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and is the third highest cause of cancer-related mortality. HCC usually develops in patients with chronic liver disease, particularly in those who also have cirrhosis. The possibility of curative treatment depends on both the stage of tumor and liver function. Effective treatments for HCC include percutaneous ablation, surgical resection, and liver transplantation. Both percutaneous ablation and surgical resection provide a high rate of complete responses and are assumed to improve survival that should exceed 50% at 5 years. Liver transplantation results in a better survival rate, and is not contraindicated by advanced liver dysfunction. However, its application is limited by the scarcity of donor organs. Treatments for advanced HCC include transarterial chemoembolization and chemotherapy. Although short-term prognosis of HCC patients has improved recently due to advances in early diagnosis and treatment, long-term prognosis is as yet far from satisfactory due to frequent recurrence. Prevention of recurrence of HCC remains one of the most challenging tasks in current hepatology.     

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.     

Targeted systemic therapies for hepatocellular carcinoma: clinical perspectives, challenges and implications

Hepatocellular carcinoma(HCC) is a lethal disease in most patients,due to its aggressive course and a lack of effective systemic therapies for advanced disease.Surgical resection and liver transplantation remain the only curative options for a small subset of patients.Few patients with HCC are diagnosed early enough to be eligible for curative treatment.Angiogenesis inhibition is a natural therapeutic target for all solid tumors,but particularly for the highly vascularized HCC tumors.With the approval of the targeted agent sorafenib,there are now additional options for patients with HCC.Although sorafenib does produce some improvement in survival in HCC patients,the responses are not durable.In addition,there are significant dermatologic,gastrointestinal,and metabolic toxicities,and,as importantly,there is still limited knowledge of its usefulness in special subpopulations with HCC.Other angiogenesis inhibitors are in development to treat HCC both in the first-line setting and for use following sorafenib failure;the furthest in development is brivanib,a dual fibroblast growth factor pathway and vascular endothelial growth factor receptor inhibitor.Additional agents with antiangiogenic properties also in phase Ⅱ and Ⅲ development for the treatment of patients with HCC include bevacizumab,ramucirumab,ABT-869,everolimus and ARQ 197.     

Epidemiology and management of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a major world health problem because of the high incidence and case fatality rate. In most patients, the diagnosis of HCC is made at an advanced stage, which limits the application of curative treatments. Most HCCs develop in patients with underlying chronic liver disease. Chronic viral hepatitis B and C are the major causes of liver cirrhosis and HCC. Recent improvements in treatment of viral hepatitis and in methods for surveillance and therapy for HCC have contributed to better survival of patients with HCC. This article reviews the epidemiology, cause, prevention, clinical manifestations, surveillance, diagnosis, and treatment approach for HCC.     

肝细胞癌非手术治疗的现状和进展

在过去的20多年中,肝细胞癌（hepatocellular carcinoma,HCC）的诊断和治疗有了显著提高,但仍具有早期诊断难、发展快、恶性程度高、预后差的临床特点。手术切除一直被认为是可能治愈HCC的惟一方法。但70％～80％的患者确诊HCC时已为中晚期,无手术切除时机。对不能手术切除的HCC患者,近年发展的非手术治疗技术可延缓甚至控制肿瘤生长,延长生存期,提高生活质量。本文对HCC非手术治疗现状和进展进行综述。     

Management of hepatocellular carcinoma with portal vein thrombosis

Management of hepatocellular carcinoma(HCC) with portal vein thrombosis(PVT) is complex andrequires an understanding of multiple therapeutic options. PVT is present in 10%-40% of HCC at the time of diagnosis, and is an adverse prognostic factor. Management options are limited, as transplantation is generally contraindicated, and surgical resection is only rarely performed in select centers. Systemic medical therapy with sorafenib has been shown to modestly prolong survival. Transarterial chemoembolization has been performed in select cases but has shown a high incidence of complications. Emerging data on treatment of PVT with Y-90 radioembolization suggest that this modality is well-tolerated and associated with favorable overall survival. Current society guidelines do not yet specifically recommend radioembolization for patients with PVT, but this may change with the development of newer staging systems and treatment algorithms. In this comprehensive literature review, we present current and available management options with the relative advantages, disadvantages and contraindications of these treatment options with summarized data on overall survival.     

Interferon therapy for hepatitis C virus (HCV)-related advanced chronic hepatitis after treatment of recurrent hepatocellular carcinoma: a successful case

A complete response was obtained by interferon (IFN) therapy for hepatitis C virus (HCV)-related advanced chronic hepatitis after curative treatment of initial and recurrent hepatocellular carcinoma (HCC). The patient is alive 73 months after diagnosis of initial HCC and is in a tumor-free state 53 months after diagnosis of the last HCC. This case suggest that it is possible to suppress recurrence and to prolong the life of patients with HCV-related advanced chronic hepatitis, if a complete response is obtained by means of IFN therapy after the curative treatment of the recurrent HCC.     

Früherkennung des hepatozellulären Karzinoms

Screening for hepatocellular carcinoma (HCC) in risk groups increases the percentage of small HCCs which are potentially eligible for curative treatment options. The present method of choice is 6 monthly ultrasound examinations of the liver. All suspect lesions greater than 1 cm in diameter should undergo further investigation by contrast-enhanced imaging techniques including ultrasound, CT and MRI, if the patient potentially qualifies for a (curative) treatment. In lesions greater than 2 cm one contrast-enhanced technique is sufficient to make the diagnosis of HCC. Lesions 1–2 cm in diameter should be diagnosed by two techniques showing a HCC-specific vascular profile. Any atypical imaging pattern should trigger a diagnostic evaluation by (guided) biopsy of the suspect lesion. If imaging and biopsy remain inconclusive the follow-up may be intensified and early re-biopsy can be considered. Very small lesions <1 cm require a close 3-monthly ultrasound examination for up to 2 years if stable or regressive, in the case of a progressive disease course further specific HCC diagnosis should be initiated as outlined.     

The progression of hepatitis B- and C-infections to chronic liver disease and hepatocellular carcinoma: presentation, diagnosis, screening, prevention, and treatment of hepatocellular carcinoma

Much information has been gained in the diagnosis and treatment of HCC during the last 15 years. Ever improving imaging technology has made nonhistologic diagnostic criteria possible, albeit controversial. Liver transplantation, resection, and RFA are considered curative options. Yet,HCC incidence is steadily rising because of limited progress on disease prevention. Accurate and cost-effective screening is necessary. Presently, only 10% to 15% of HCC patients present with a curative stage of disease. Because the field of HCC is rapidly changing, patients with HCC should be referred to liver centers with a full array of services, from surgical to oncologic. The prognosis for HCC patients will surely improve with a multidisciplinary approach to care and further clinical research. Better screening and prevention of recurrence should eventually improve survival. It is hoped that antiviral treatment studies will lower the risk of HCC, and that these changes will occur soon enough to help the many patients at risk for or diagnosed with HCC over the next several years.     

Diagnostic and therapeutic management of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is an increasing health problem, representing the second cause of cancerrelated mortality worldwide. The major risk factorfor HCC is cirrhosis. In developing countries, viral hepatitis represent the major risk factor, whereas in developed countries, the epidemic of obesity, diabetes and nonalcoholic steatohepatitis contribute to the observed increase in HCC incidence. Cirrhotic patients are recommended to undergo HCC surveillance by abdominal ultrasounds at 6-mo intervals. The current diagnostic algorithms for HCC rely on typical radiological hallmarks in dynamic contrast-enhanced imaging, while the use of α-fetoprotein as an independent tool for HCC surveillance is not recommended by current guidelines due to its low sensitivity and specificity. Early diagnosis is crucial for curative treatments. Surgical resection, radiofrequency ablation and liver transplantation are considered the cornerstones of curative therapy, while for patients with more advanced HCC recommended options include sorafenib and trans-arterial chemoembolization. A multidisciplinary team, consisting of hepatologists, surgeons, radiologists, oncologists and pathologists, is fundamental for a correct management. In this paper, we review the diagnostic and therapeutic management of HCC, with a focus on the most recent evidences and recommendations from guidelines.     

Efficacy of iron chelator deferoxamine for hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma patients refractory to current treatments

The prognosis of advanced hepatocellular carcinoma (HCC) remains poor. For patients with advanced HCC, the multikinase inhibitor sorafenib is recommended as the current standard of care. In contrast, hepatic arterial infusion chemotherapy (HAIC) is one of the recommended treatments in Japan. However, in Japan, the use of sorafenib versus hepatic arterial infusion chemotherapy for first-line treatment remains unclear, because there have been no randomized controlled trials comparing HAIC with sorafenib. HAIC can substantially prolong survival in patients with complete and partial response, while non-responders may be suitable candidates for sorafenib therapy. Nonetheless, HAIC non-responders with deteriorated liver function currently have no treatment options. We have shown the efficacy of an alternative therapy, the iron chelator deferoxamine, for advanced HCC patients with deteriorated liver function. Iron chelators may have future therapeutic possibilities in this patient population.     

Biomarkers for hepatocellular cancer

Hepatocellular carcinoma(HCC) is the third leading cause of cancer-related deaths worldwide. If diagnosed early, curative treatment options such as surgical resection, loco-regional therapies, and liver transplantation are available to patients, increasing their chances of survival and improving their quality of life. Unfortunately, most patients are diagnosed with late stage HCC where only palliative treatment is available. Therefore, biomarkers which could detect HCC early with a high degree of sensitivity and specificity, may play a crucial role in the diagnosis and management of the disease. This review will aim to provide an overview of the different biomarkers of HCC comprising those used in the diagnosis of HCC in at risk populations, as well as others with potential for prognosis, risk predisposition and prediction of response to therapeutic intervention.