肝细胞癌防治热点与策略

对肝细胞癌（HCC）的防治已成为人类一大挑战。近年来,在HCC的临床和基础肿瘤细胞生物学研究方面均有较大进展,出现了一批可提供高级别循证医学证据的临床试验结果,也为HCC的防治带来新的关注热点。临床实践中仍然存在不规范治疗和费效比低等严重问题。本文论及HCC防治的热点,旨在指导医生遵守循证医学证据,采用个体化、优化治疗策略,使HCC患者临床治疗最大获益。     

Treatment strategies for hepatocellular carcinoma in Japan

The main methods of treatment for hepatocellular carcinoma (HCC) in Japan are hepatic resection, radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE). Meticulous follow up is then undertaken to check for recurrence, which is treated using repeated RFA or TACE. Hepatic arterial infusion chemotherapy has been introduced as treatment for advanced HCC, and the molecular‐targeted drug sorafenib is also now available. Rigorous medical care using these treatment methods and early diagnosis mean that the prognosis for HCC in Japan is the best in the world. This paper reviews the treatment strategies for HCC in Japan.     

肝细胞癌细胞免疫治疗的研究进展

肝细胞癌(HCC)的治疗目前主要采用以手术为主、配合局部放疗和化疗的综合治疗措施,但多数患者经综合治疗后也容易复发,缺乏有效的治疗药物和手段,总体治疗效果并不理想。越来越多的证据表明,肝癌的发生、发展、转移和复发与机体免疫系统有密切的关系。因此,免疫治疗特别是细胞免疫治疗可以调节机体免疫功能,诱导特异性肿瘤免疫,达到治疗肝癌、减少肝癌复发和转移的目的,已成为肝癌综合治疗的重要组成部分。对细胞免疫治疗在HCC中的临床前研究和临床试验取得的成果进行综述,并讨论当前存在的问题。     

肝细胞癌的分子靶向治疗

分子靶向治疗是近10年来肿瘤治疗领域的重大突破,在肺癌、恶性胃肠间质细胞瘤、恶性淋巴瘤、肠癌、乳腺癌等肿瘤的治疗中已获得很大的成功,尤其HCC的分子靶向治疗在小分子靶向治疗上取得了令人瞩目的新进展,特别是多靶点药物索拉非尼在HCC的靶向治疗中取得的成功,使HCC分子靶向全身治疗有了新的标准。     

多结节肝细胞癌的基础研究及治疗策略

近年来,随着肝细胞癌基础和临床研究的不断深入,肝细胞癌异质性、生物学特性、分子分型和个体化治疗等正逐渐成为现代临床肝癌治疗学的基本指导思想。多结节肝细胞癌作为肝癌大体标本的一种表现形式,无论从分子学起源,还是指导其诊治的临床分型指南,均有了新的进展,同时也出现了新的争议。综述了多结节肝细胞癌的基础研究及临床进展,希望对肝细胞癌的临床防治提供参考,有助于患者生存获益。     

Treatment of non-resectable hepatocellular carcinoma with autologous tumor-pulsed dendritic cells

BACKGROUND: The response of hepatocellular carcinoma (HCC) to therapy is often disappointing and new modalities of treatment are clearly needed. Active immunotherapy based on the injection of autologous dendritic cells (DC) co-cultured ex vivo with tumor antigens has been used in pilot studies in various malignancies such as melanoma and lymphoma with encouraging results. METHODS: In the present paper, the preparation and exposure of patient DC to autologous HCC antigens and re-injection in an attempt to elicit antitumor immune responses are described. RESULTS: Therapy was given to two patients, one with hepatitis C and one with hepatitis B, who had large, multiple HCC and for whom no other therapy was available. No significant side-effects were observed. The clinical course was unchanged in one patient, who died a few months later. The other patient, whose initial prognosis was considered poor, is still alive and well more than 3 years later with evidence of slowing of tumor growth based on organ imaging. CONCLUSIONS: It is concluded that HCC may be a malignancy worthy of DC trials and sufficient details in the present paper are given for the protocol to be copied or modified.     

肝细胞癌免疫治疗的现状与挑战

免疫疗法是目前肿瘤治疗的一种新方法,应用前景广阔,在治疗相关毒性和疗效方面较传统疗法均具有明显优势。免疫检查点抑制、克服肿瘤免疫逃逸和重建抗肿瘤免疫机制是肿瘤免疫治疗的关键。在肝细胞癌中,免疫治疗尚处于初级阶段,免疫治疗单独或联合其他治疗方法可能有利于控制肿瘤进展,但总体疗效仍然有限。本文结合免疫治疗在肿瘤中的研究和应用进展,分析了肝细胞癌免疫治疗研究现状以及面临的挑战。     

Laparoscopic hepatectomy: new approach for hepatocellular carcinoma

This article presents the rationale for the laparoscopic approach to liver surgery, showing the technique of fully endoscopic and endoscopic‐assisted formal and wedge hepatic resections. The early results are comparable to those of conventional surgery, with the benefits derived from minimal access surgery. Laparoscopic liver resections are technically feasible, with an acceptable morbidity and mortality rate, but extensive experience in conventional liver surgery, advanced laparoscopic surgery, and the availability of all requested technologies are indispensable prerequisites.     

Screening for hepatocellular carcinoma

This article reviews methodological issues around screening for hepatocellular carcinoma, and discusses selection of the at-risk group, which screening test to use, and how frequently it should be applied. Screening of patients at risk for hepatocellular carcinoma should be undertaken using ultrasonography applied at six-month intervals. Patients at risk include all those with cirrhosis, and certain non-cirrhotic patients withchronic hepatitis B. In this population, screening has been shown to reduce disease-specific mortality. Although data do not exist for other populations, screening is nonetheless advised because small cancers can be cured with appreciable frequency.     

Management of ruptured hepatocellular carcinoma:Implications for therapy

AIM:To assess the treatment and tumor-related variables associated with outcome after treatment of spontaneously ruptured hepatocellular carcinoma (HCC).METHODS: Patients with ruptured HCC were identif ied. The complications, mortality and survival were assessed. The relationship between tumor size and the severity of hemoperitoneum and between tumor size and grade were examined.RESULTS: From January 1993 to January 2008, 556 patients with HCC with or without cirrhosis were evaluated; of which, 16 (2.87%) p...     

Fibrolamellar hepatocellular carcinoma

Fibrolamellar hepatocellular carcinoma is an uncommon malignancy seen in young adults without underlying liver disease. Physical signs are minimal and laboratory values are noncontributory. Diagnosis is suggested by clinical history, supported by radiographic studies, and confirmed by histologic examination. Individuals with fibrolamellar carcinoma generally have a greater survival than those with hepatocellular carcinoma. Although most patients with fibrolamellar carcinoma undergo curative surgery, two of the three patients we report had inoperable tumors.     

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.     

Imaging of hepatocellular carcinoma

Recent improvements in the treatment of hepatocellular carcinoma (HCC) have resulted in a need to identify the disease at an early stage. The wide range of imaging techniques available reflects the difficulty in demonstrating small HCC, particularly in the cirrhotic liver. This article reviews the current imaging techniques available for the diagnosis of HCC.     

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。     

Surgery for hepatocellular carcinoma

Today there is an array of therapeutic modalities available for the patients with hepatocellular carcinoma (HCC). However, surgery, be it resection or transplantation, offers the only hope of long-term disease-free survival. Unfortunately, because the majority of HCC in Asia is associated with cirrhosis, surgical resection is restricted to only a small proportion of these patients. However, in selected candidates resection may offer a 5-year survival of up to 70%. With the clinical application of adult-to-adult living donor liver transplantation, an increasing number of patients with small HCC and decompensating cirrhosis are undergoing transplantation.     

Molecular pathogenesis of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death worldwide. Hepatocarcinogenesis is a multistep process evolving from normal through chronic hepatitis/cirrhosis and dysplastic nodules to HCC. With advances in molecular methods, there is a growing understanding of the molecular mechanisms in hepatocarcinogenesis. Hepatocarcinogenesis is strongly linked to increases in allelic losses, chromosomal changes, gene mutations, epigenetic alterations and alterations in molecular cellular pathways. Some of these alterations are accompanied by a stepwise increase in the different pathological disease stages in hepatocarcinogenesis. Overall, a detailed understanding of the underlying molecular mechanisms involved in the progression of HCC is of fundamental importance to the development of effective prevention and treatment regimes for HCC.