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。     

Hepatocellular carcinoma： Therapy and prevention

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these scientific advances and the implementation of measures for the early detection of HCC in patients at risk, patient survival has not improved during the last three decades. This is due to the advanced stage of the disease at the time of clinical presentation and limited therapeutic options. The therapeutic options fall into five main categories: surgical interventions including tumor resection and liver transplantation, percutaneous interventions including ethanol injection and radiofrequency thermal ablation, transarterial interventions including embolization and chemoembolization, radiation therapy and drugs as well as gene and immune therapies. These therapeutic strategies have been evaluated in part in randomized controlled clinical trials that are the basis for therapeutic recommendations. Though surgery, percutaneous and transarterial interventions are effective in patients with limited disease (1-3 lesions, <5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis more than 80% patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care. In order to reduce the morbidity and mortality of HCC, early diagnosis and the development of novel systemic therapies for advanced disease, including drugs, gene and immune therapies as well as primary HCC prevention are of paramount importance. Furthermore, secondary HCC prevention after successful therapeutic interventions needs to be improved in order to make an impact on the survival of patients with HCC. New technologies, including gene expression profiling and proteomic analyses, should allow to further elucidate the molecular events underlying HCC development and to identify novel diagnostic markers as well as therapeutic and preventive targets.     

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.     

Surgical management of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the second most common cause of death from cancer worldwide. Standard potentially curative treatments are either resection or transplantation. The aim of this paper is to provide an overview of the surgical management of HCC, as well as highlight current issues in hepatic resection and transplantation. In summary, due to the relationship between HCC and chronic liver disease, the management of HCC depends both on tumourrelated and hepatic function-related considerations. As such, HCC is currently managed largely through nonsurgical means as the criteria, in relation to the above considerations, for surgical management is still largelyrestrictive. For early stage tumours, both resection and transplantation offer fairly good survival outcomes(5 years overall survival of around 50%). Selection therefore would depend on the level of hepatic function derangement, organ availability and local expertise. Patients with intermediate stage cancers have limited options, with resection being the only potential for cure. Otherwise, locoregional therapy with transarterial chemoembolization or radiofrequency ablation are viable options. Current issues in resection and transplantation are also briefly discussed such as laparoscopic resection, ablation vs resection, anatomical vs non-anatomical resection, transplantation vs resection, living donor liver transplantation and salvage liver transplantation.     

Local injection therapy for hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world and ranks the third most common cause of cancer-related death. Surgical resection, liver transplantation and percutaneous ablation are generally considered the only curative treatment for early stage HCC. Besides the limitations of insufficient organ donors and a long waiting time for liver transplantation, however, resection is applied only to patients with good hepatic reserve and localized tumors, with a resectability of 30%. DATA SOURCES: Local ablation therapy, which is minimally invasive but contributes to the significant improvement of survival in patients with unresectable tumor, hasbeen widely used in treating small HCC. Among the techniques of local therapy, percutaneous ethanol injection (PEI) with a complete response in 80% of HCCs less than 3 cm has been accepted as an alternative to surgery in patients with small HCC. Moreover, percutaneous hepatic quantified ethanol injection (PHQEI) or PEI according to the standard criteria has been confirmed to benefit patients with HCC, especially when quantified ethanol is given at a short interval (QESI, the interval was 2-3 days). RESULT: Several limitations related to local percutaneous methods may result in incomplete therapeutic effect in case of larger HCC nodules (>3 cm). CONCLUSION: The combined use of different methods according to the clinical status of patients or tumors may be essential to the effective treatment of HCC.     

Evidence-based diagnosis and locoregional therapy for hepatocellular carcinoma

Early identification of hepatocellular carcinoma (HCC) is crucial to improving the results of therapy and for patients to be eligible for liver transplantation. Recent advances in noninvasive imaging technology include various techniques of harmonic ultrasound, new ultrasound contrast agents, multislice helical computed tomography and rapid high-quality magnetic resonance. The imaging diagnosis relies on the hallmark of arterial hypervascularity with portal venous washout. Since the use of better radiological techniques has improved the accuracy of noninvasive diagnosis, the role of liver biopsy in the diagnosis of HCC has declined. With recent advances in genomics and proteomics, a great number of potential markers have been identified and developed as new candidate markers for HCC. Locoregional therapies currently constitute the best options for early nonsurgical treatment of HCC. Percutaneous ethanol injection shows similar results to resection surgery for single tumors less than 3 cm in diameter. Radiofrequency ablation is superior to percutaneous ethanol injection in terms of local recurrence. Transarterial chemoembolization is currently the most common approach for the management of HCC without curative options since it improves patient survival, but the optimal embolizing agent, length of interval between sessions and whether the chemotherapeutic agent has any effect have not yet been determined. Combining transarterial chemoembolization with antiangiogenic agents, as well as with other techniques, such as radiofrequency ablation, may improve the results. Injection of radioisotopes such as yttrium-90, via the hepatic artery, may be particularly useful in patients with portal vein thrombosis. Comparisons with other transarterial techniques are needed.     

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。     

Progress in systemic therapy of advanced hepatocellular carcinoma

Primary liver cancer, mainly consisting of hepatocellular carcinoma (HCC), is one of common malignancies worldwide, and prevalent among the Chinese population. A diagnosis of early stage HCC has proven to be very difficult because of its insidious feature in onset and development. At the time of diagnosis, most HCC cases are locally advanced and/or distant metastatic, which results in difficulty to be treated and poor prognosis. For advanced HCC, systemic therapy is frequently adopted as an important palliative method. In recent years, clinical studies and observations have often reported about systemic anti-cancer therapy of advanced HCC, including molecular target therapy, systemic chemotherapy and immunotherapy. In this article, we review these treatment modalities to provide a reference for clinicians.     

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.     

Treatment of hepatocellular carcinoma at the dawn of the third millennium: liver transplantation and its alternatives

Hepatocellular carcinoma is one of the most frequent tumors worldwide, and its frequency is increasing. The management of hepatocellular carcinoma has changed in recent years, this because screening allows to discover tumors at an earlier stage, and because of effective treatments are available, such as liver transplantation, liver resection, percutaneous ablation and transarterial chemoembolization. Each one of these treatments has its own advantages and drawbacks, and range of application according to the stage of the tumor and of the underlying liver disease. This review summarizes the recent progress in the management of HCC and the practice in our unit.     

Lokal-ablative Therapie

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world. Its incidence is also increasing in Western countries. Apart from surgical procedures (resection, liver transplantation), percutaneous local ablative (ethanol injection, radiofrequency thermal ablation, as well as radiation therapy) and transarterial local ablative interventions are effective non-surgical therapeutic options based, in part, on randomized controlled trials. In our review, we summarize the different local ablative strategies for patients with HCC.     

Localized hepatocellular carcinoma: Therapeutic options

Hepatocellular carcinoma (HCC) is among the most common malignancies worldwide. Recent surveillance programs have allowed early detection and diagnosis, but overall survival of patients with HCC remains poor. This article provides a definition for localized HCC and summarizes the array of treatments that have emerged and the salient literature and findings for each. Among the treatments reviewed here are surgical resection, orthotopic liver transplantation, and local ablative therapies such as cryosurgery, percutaneous ethanol injection therapy, and transarterial chemoembolization.     

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.     

Management of small hepatocellular carcinoma

In the last years the incidence of hepatocellular carcinoma (HCC) is rising in cirrhotic patients worldwide. Due the importance of early and definite diagnosis of HCC, any nodular lesion detected in patients with chronic liver disease should be considered as suspicious for HCC. The screening and surveillance programs in patients with liver diseases have increased the number of small HCC detected at an early stage, when the therapeutic options available are able to provide benefit. The introduction of new imaging techniques has improved the accuracy of characterizing these nodules. According to the EASL recommendations, contrast-enhanced computed tomography (CT), contrast enhanced ultrasound (US) and magnetic resonance (MR) with different MR-contrast agents are currently used to characterize liver lesions. Imaging guided biopsy is recommended for small nodules or in lesions without typical features (arterial hypervascularization) in at least two imaging techniques. Frequently the differential diagnosis of small nodules is complicated by discordant vascularity and recent studies have also demonstrated the presence of small hypovascular HCC at perfusional US and helical CT. At present, different treatment options can be offered to patients with diagnosis of small HCC at an early stage; percutaneous techniques, surgical resection and liver transplantation can provide benefit in properly selected patients. This review describes some critical points regarding the detection, diagnosis and therapeutic management of small nodules of HCC in cirrhotic patients.     

肝癌微创介入治疗进展

原发性肝癌的治疗方法一直是许多学者研究的重点,近年来尽管新兴治疗方法层出不穷,但由于病变多发生于进展期肝病或肝硬化的基础上,因此目前原发性肝癌仍然是一种难治性恶性肿瘤。在治疗方面,外科手术切除及肝移植虽是根治性治疗方法,但由于移植相关问题的复杂性及原发性肝癌本身的隐匿性,使得上述两种治疗方法并不能适用于大多数患者。近些年,随着设备和技术水平的提高,原发性肝癌的微创介入治疗得到了越来越多的重视,其中应用最为广泛的就是肝动脉化疗栓塞术(TACE)和组织消融术(TA)。该文主要讨论上述两种介入疗法联合应用治疗原发性肝癌的有效性、可行性,以及近年来介入治疗在原发性肝癌治疗领域的研究进展。     

Clinical characteristics, staging and treatment of patients with hepatocellular carcinoma in clinical practice. Prospective study of 136 patients

Hepatocellular carcinoma (HCC) is the most frequent cause of mortality in patients with liver cirrhosis. There are no prospective series from a single tertiary hospital in Spain.

Material and Methods

We performed a prospective study of patients with HCC in our center. Clinical and epidemiological characteristics, diagnostic method, staging according to the Barcelona Clinic Liver Cancer (BCLC) system and treatment were analyzed.

Results

A total of 136 patients were included (80.9% men). The mean age was 66.62±11.68 years and 91.2% were cirrhotic. Hepatitis C virus (HCV) was the leading cause of liver disease (38.97%). The suspected diagnosis was established by a surveillance program in 63.2%. Noninvasive American Association criteria for the Study of Liver Diseases (AASLD) were the main diagnostic method (73.5%). According to the BCLC, 58.1% were in the early stage (0-A), 21.3% in stage B, 12.5% in stage C and 8.1% in stage D. Early stage patients had followed a surveillance program more frequently than those with non-early stages (79.75% versus 44.35%, p <0.001). Potentially curative initial treatment was used in 45.58%, the most common treatment being percutaneous ethanol injection (23.13%).

Conclusions

Most patients with HCC in our hospital have cirrhosis, the most frequent cause being HCV. HCC surveillance in at-risk patients could increase diagnosis of HCC at an early stage. We achieved an early diagnosis in more than half of cases. The most common initial treatment was percutaneous therapy.     

Management of hepatocellular carcinoma with portal vein tumor thrombosis: Review and update at 2016

Portal vein tumor thrombosis(PVTT) is a common phenomenon in hepatocellular carcinoma(HCC). Compared to HCC without PVTT, HCC with PVTT is characterized by an aggressive disease course, worse hepatic function, a higher chance of complications related to portal hypertension and poorer tolerance to treatment. Conventionally, HCC with PVTT is grouped together with metastatic HCC during the planning of its management, and most patients are offered palliative treatment with sorafenib or other systemic agents. As a result, most data on the management of HCC with PVTT comes from subgroup analyses or retrospective series. In the past few years, there have been several updates on management of HCC with PVTT. First, it is evident that HCC with PVTT consists of heterogeneous subgroups with different prognoses. Different classifications have been proposed to stage the degree of portal vein invasion/thrombosis, suggesting that different treatment modalities may be individualized to patients with different risks. Second, more studies indicate that more aggressive treatment, including surgical resection or locoregional treatment, may benefit select HCC patients with PVTT. In this review, we aim to discussthe recent conceptual changes and summarize the data on the management of HCC with PVTT.     

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.     

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.     

Current concepts in hepatic resection for hepatocellular carcinoma in cirrhotic patients

Hepatocellular carcinoma (HCC) is one of the most frequent neoplasms worldwide and in most cases it is associated with liver cirrhosis. Liver resection is considered the most potentially curative therapy for HCC patients when liver transplantation is not an option or is not immediately accessible. This review is aimed at investigating the current concepts that drive the surgical choice in the treatment of HCC in cirrhotic patients; Eastern and Western perspectives are highlighted. An extensive literature review of the last two decades was performed, on topics covering various aspects of hepatic resection. Early post-operative and long-term outcome measures adopted were firstly analyzed in an attempt to define an optimal standardization useful for research comparison. The need to avoid the development of post-hepatectomy liver failure represents the “conditio sine qua non” of surgical choice and the role of the current tools available for the assessment of liver function reserve were investigated. Results of hepatic resection in relationship with tumor burden were compared with those of available competing strategies, namely, radiofrequency ablation for early stages, and trans-arterial chemoembolization for intermediate and advanced stages. Finally, the choice for anatomical versus non-anatomical, as well as the role of laparoscopic approach, was overviewed. The literature review suggests that partial hepatectomy for HCC should be considered in the context of multi-disciplinary evaluation of cirrhotic patients. Scientific research on HCC has moved, in recent years, from surgical therapy toward non-surgical approaches and most of the literature regarding topics debated in the present review is represented by observational studies, whereas very few well-designed randomized controlled trials are currently available; thus, no robust recommendations can be derived.