不同分期对新健脾理气方治疗肝癌预后价值的比较研究
摘要
背景：
原发性肝癌是全世界高发病率中的第5大癌症,是高致死率中的第2大癌症。世界范围内,高发地区主要集中在东亚及非洲,该地区的病因主要是感染乙型肝炎病毒(HBV)及暴露于黄曲霉毒素B1环境；相反在北美、欧洲及日本,其病因主要是感染HCV病毒及酗酒。中国是HBV感染高发区,全世界约75%的乙肝患者集中在中国,而最终约30%的慢性HBV感染病人最终会发展为肝硬化。肝硬化是肝癌的易患因素,约有1/3的肝硬化患者最终将发生肝癌。
目前现代医学对原发性肝癌有多种方法治疗,并取得了一定成效；使用那种治疗方法治疗要根据肝癌的种类、大小、分期和病人的健康状况等因子来作决定。其中病人的肝癌分期尤其重要。所以应有一个适合的肝癌分期,才能作出最适合的治疗方法,又能初步评估患者的预后。但目前肝癌有多种分期方法或评分系统。从1971年的Kampala分期到目前NCCN/AJCC的TNM分期,共有十余种分期系统及各种生物预后分子标志物。由于世界各地原发性肝癌病因的流行病学资料不同,肝脏合并病变各异,诊断水平及治疗水平也不一样,出现了许多不同的肝癌分期方法,至今尚未形成一个公认的、最好的分期方法。
在中国,90%以上的肝癌患者曾接受中医药治疗。近年来,中医药在晚期肝癌的作用也越来越受重视,中医药在改善症状、延长生存期及提高生活质量等方面有一定作用,但目前缺乏中医药治疗恶性肿瘤的疗效评价标准及预后评价系统。目前常用的各种分期或生物标记物能否反映中医药治疗中晚期肝癌的疗效是许多学者思考的问题。健脾理气法是肝癌最主要的治疗方法,其在广东省中医院广泛应用,取得一定的效果。本研究拟采用不同的分期方法对新健脾理气方治疗肝癌的预后价值进行比较研究,以期探索适合评价中医药治疗肝癌的分期方法。
目的：
评估原发性肝癌不同分期方法或评分系统(包括中国肝癌分期、Okuda分期、CLIP评分、French分期及BCLC分期)对新健脾理气方治疗肝癌的预后价值,探索适合评价中医药治疗肝癌的分期方法或评分系统。
方法：
本研究分两部份。首先通过检索国内外文献,分析不同分期的优点及不足,筛选出能用于评估中医药治疗预后的分期或评分系统。最后采用回顾性的研究方法,以2007年5月至2009年12月在广东省中医院就诊接受新健脾理气方治疗的151例原发性肝癌患者为研究对象。所有患者按照筛选出来的各种分期方法或评分系统进行再分期。生存率计算采用Kaplan-Meier方法,用时序检验(log-rank test)进行生存率的单因素比较,用比例风险模型进行多因素分析,采用AIC值评价模型预后价值的贡献大小。用线性趋势卡方检验、似然比卡方检验、Harrell's c-指数(concordant index, c-指数)评估各分期系统的同质性、单调性、判别力,用AIC (Akaike Information Criterion, AIC)寻找最佳的预后模型。
结果：
通过检索国内外文献发现,各种分期或评分系统均有其优点及缺点。目前常用的TEM分期包括血管侵犯,有无血管侵犯主要通过手术切除确认,通过影像学来确认是否有血管侵犯并不准确。Izumi改良分期、简化的TNM分期、第六版UICC/AJCC的TNM分期、日本TNM分期法、日本JIS积分法、香港中文大学预后系数评分系统均包括TNM分期,其用于非手术治疗患者的真确性有待商榷；中国肝癌分期、Okuda分期、CLIP评分、French分期及BCLC分期不含血管侵犯,能通过影像学及临床因素来确定分期,适合用于非手术患者,可用于评估中医药治疗疗效的预后。
采用回顾性的研究方法,比较不同分期或评分系统(中国肝癌分期、Okuda分期、CLIP评分、French分期及BCLC分期)对接受新健脾理气方治疗的原发性肝癌患者预后的价值。本研究共纳入151例原发性肝癌患者,其中男性127例(84.1%),女性24例(15.9%),年龄为27-81岁,中位年龄为56岁。单因素分析中,就诊症状、腹水、总胆红素水平、白蛋白水平、AFP水平、门脉癌栓、病灶比例、中医证型、肝功能分级、Okuda分期、CLIP分期评分、French分期、BCLC评分、中国肝癌分期对预后的影响有统计学显著意义。多因素分析示白蛋白分级、腹水分级、肝硬化、病灶比例、腹腔淋巴结转移及AFP分级对预后有统计学差异。
随后采用线性趋势卡方检验、似然比卡方检验、Harrell's c-指数评估各分期系统的同质性、单调性、判别力发现,CLIP评分的同质性、单调性优于其他分期。采用AIC值评价模型预后价值的贡献大小发现,由Okuda分期、CLIP评分构成的模型AIC值最低,说明其是最有效的模型。CLIP评分的同质性、单调性优于其他分期(包括Okuda分期等),因此CLIP评分具有较好的预后价值。综合不同分期的同质性、单调性及模型预后价值结果,CLIP评分对预后价值的贡献大于其他分期。
结论：
1.单因素分析发现就诊症状、腹水、总胆红素水平、白蛋白水平、AFP水平、门脉癌栓及病灶比例等因素对新健脾理气方治疗肝癌预后有影响。
2.多因素分析提示肝硬化、病灶比例、腹腔淋巴结转移、腹水分级、白蛋白分级及AFP水平对新健脾理气方治疗肝癌预后的影响有统计学差异。
3.预后风险模型评估,结果发现Okuda分期及CLIP评分的预后模型较佳。CLIP评分的同质性、单调性优于其他分期(包括Okuda分期等),因此CLIP评分具有较好的预后价值,比Okuda分期、French分期、BCLC评分、中国肝癌分期分层更好,具有对中医药治疗中晚期肝癌更高的预后判别力,而且简便易行,值得进一步借鉴与研究。
Background:
Out of the all incidents of cancer, primary liver cancer is the fifth most common type of cancer one can develop, and, including every variation, is the second most common cause of death in the world. High-risk areas within the world are mainly concentrated in East Asia and Africa. In these regions, the main cause of liver cancer is exposure to the hepatitis B virus (HBV) infection and/or to aflatoxin B1environment. The etiology of this type of cancer in North America, Japan and Europe, however, is mostly due to the HCV (Hepatitis C) virus and alcoholism. China in particular has a high incidence of HBV infection, making up approximately75%of all Hepatitis B carriers in the world. Eventually, about30%of chronic HBV infected patients will develop cirrhosis. Cirrhosis increases the risk of liver cancer; about one-third of the patients with this disease will eventually develop Hepatocellular Carcinoma.
Modern medicine utilizes a variety of methods in the treatment of primary liver cancer and has achieved some success; these treatments involve prescribing remedies depending on the type, size or stage and also the patient's health status to make a decision. The stage of the patient's liver cancer is essential as well. To improve treatment, there should be a streamlined/standardized liver cancer staging method not only to choose the most appropriate treatment, but also a preliminary assessment of the patient's prognosis. Nowadays, the primary liver cancer had a variety of staging or scoring system. Installments from1971Kampala to the current NCCN/AJCC TNM stage, there are total of more than ten kinds of staging system and a variety of biological prognostic molecular markers. Due to the different causes of primary liver cancer epidemiological data around the world, different merger lesions of the liver, the diagnosis and treatment of liver cancer is not the same. There are many different liver cancer staging systems but there has not yet been a standardization that is identified as the best.
In China, more than90%of liver cancer patients who have received Chinese medicine treatment in the recent years (The role of Chinese medicine in advanced hepatocellular carcinoma had greater emphasis recently) have displayed improvement in symptoms, prolonged survival and an improved quality of life. But there is absence of prognostic and evaluation system of Chinese medical treatments malignant tumors today. According to prominent scholars on the issue, the various installments or biomarkers can reflect the efficacy of Chinese medicine in the treatment of advanced liver cancer. The Jianpiliqi method is the mainstay of treatment of liver cancer. In the Guangdong Provincial Hospital, the mentioned method is widely used and achieved certain results. This study of comparing the different staging methods to the prognostic value of the New JianpiLiqi fomula (XJPLQF) treatment of hepatocellular carcinoma is required in order to explore the installment method suitable for the evaluation of Chinese medicine treatment of liver cancer.
Objective:
An assessment of primary liver cancer staging/socring systems (including China liver cancer stage, Okuda stage, CLIP score, French stage and BCLC stage) of the prognostic value of the XJPLQF treat liver cancer. It is to explore each staging/scoring system for evaluating Chinese medical treatment of liver cancer.
Methods:
This study is divided into two parts. First, by looking through prior research, the advantages and disadvantages of different staging/scoring systems can be used in the assessment of viable prognosis staging/scoring system. In the last retrospective study,151patients with primary liver cancer patients to accept the XJPLQF treatment from May2007to December2009in the Guangdong Provincial Hospital for treatment as the research object. All patients were in accordance with the screened out of the installment method or scoring system restaging. The survival rate calculated using the Kaplan-Meier method, rank test (log-rank test). The survival rate of the single factors compared with the proportional hazards model for multivariate analysis of the AIC value evaluation model prognostic value contribution. Linear trend chi-square test, the likelihood ratio chi-square test, Harrell.'s c-index (concordant index, c-index) to assess staging systems for homogeneity, monotonous, discriminant force, with the AIC (Akaike Information Criterion, AIC) finding the best prognostic model.
Results:
Found by searching the literature, various staging or scoring system has its advantages and disadvantages. The TNM staging including vascular invasion, vascular invasion by surgical resection, confirmed by imaging to confirm whether vascular invasion is not accurate. For non-surgical treatment of patients, the Izumi improved staging, TNM staging simplified, the sixth edition of the UICC/TNM classification of the AJCC TNM staging of Japan, Japanese JIS integration method, and the Chinese University of Hong Kong prognosis coefficient scoring system including TNM stage's reliability is also questionable. With the China liver cancer staging, Okuda staging, CLIP scoring, French staging and the BCLC staging (cancer that does not include vascular invasion), through imaging and clinical factors to determine the stage of cancer-suitable for non-surgical patients-can be used in the assessment of prognosis of Chinese medical treatment efficacy.
Using the retrospective research method by comparing different staging/scoring system (China liver cancer stage, Okuda stage, CLIP score, French stage and BCLC stage), one can accept the XJPLQF treatment in patients with primary liver cancer prognosis value. This study included151patients with primary liver cancer patients of whom127(84.1%) are males while24(15.9%) are females, aged ranging from27to81years old, with a median age of56years old. In univariate analysis, treatment symptoms, ascites, total bilirubin level, albumin level, AFP level, portal vein tumor thrombus, lesion proportion, TCM syndrome, Pugh, Okuda stage, CLIP score, French stage, BCLC stage and China liver cancer staging having prognosis statistically significant. Multivariate analysis shows the classification of albumin, ascites graded cirrhosis, lesions proportion of abdominal lymph node metastasis and prognosis, classification AFP made are significant differences.
After using the linear trend chi-square test, likelihood ratio chi-square test, Harrell's c-index to assess the homogeneity of the staging system and discriminant forces, the CLIP score is better than the other installments in homogeneity and monotonicity. The size of the contribution to the pre-value of the AIC value evaluation model found by Okuda stage and the CLIP score model constituted the lowest AIC value, which is the most effective model. The CLIP score, homogeneity and monotonicity are better than the other installments (including Okuda stage. etc.). The CLIP score also has a better prognostic value. Integrating the different stages of the prognostic value of homogeneity, monotonicity and model results, the CLIP score on the prognostic value of the contribution is greater than the other installments.
Conelusions:
1. A single factor analysis shows that the treatment symptoms and ascites had statistically significant differences in the impact of factors such as the level of total bilirubin, albumin level, AFP level, portal vein tumor thrombus and the lesions proportion XJPLQF in the treatment of liver cancer prognosis influential.
2. The multifactorial analysis suggests that cirrhosis, lesions proportional abdominal lymph node metastases, ascites, and hierarchical classification of albumin and AFP levels have a significant impact on the XJPLQF treatment of liver cancer prognosis statistics.
3. Prognostic risk model assessment showed, through experimental results, that the Okuda stage and CLIP score are reliable prognostic models. The CLIP score homogeneity, monotonicity are better than the other installments (including Okuda stage etc.) CLIP score has a higher prognostic value, superior to Okuda stage, French stage, BCLC score and China stage stratification stage. CLIP score also has more prognostic discriminant force to Chinese medicine in the treatment of advanced liver cancer. In fact, CLIP score is rather simple and easy to use and is worthy for further reference and research.
原发性肝癌是全世界高发病率中的第5大癌症,是高致死率中的第2大癌症。世界范围内,高发地区主要集中在东亚及非洲,该地区的病因主要是感染乙型肝炎病毒(HBV)及暴露于黄曲霉毒素B1环境；相反在北美、欧洲及日本,其病因主要是感染HCV病毒及酗酒。中国是HBV感染高发区,全世界约75%的乙肝患者集中在中国,而最终约30%的慢性HBV感染病人最终会发展为肝硬化。肝硬化是肝癌的易患因素,约有1/3的肝硬化患者最终将发生肝癌。
目前现代医学对原发性肝癌有多种方法治疗,并取得了一定成效；使用那种治疗方法治疗要根据肝癌的种类、大小、分期和病人的健康状况等因子来作决定。其中病人的肝癌分期尤其重要。所以应有一个适合的肝癌分期,才能作出最适合的治疗方法,又能初步评估患者的预后。但目前肝癌有多种分期方法或评分系统。从1971年的Kampala分期到目前NCCN/AJCC的TNM分期,共有十余种分期系统及各种生物预后分子标志物。由于世界各地原发性肝癌病因的流行病学资料不同,肝脏合并病变各异,诊断水平及治疗水平也不一样,出现了许多不同的肝癌分期方法,至今尚未形成一个公认的、最好的分期方法。
在中国,90%以上的肝癌患者曾接受中医药治疗。近年来,中医药在晚期肝癌的作用也越来越受重视,中医药在改善症状、延长生存期及提高生活质量等方面有一定作用,但目前缺乏中医药治疗恶性肿瘤的疗效评价标准及预后评价系统。目前常用的各种分期或生物标记物能否反映中医药治疗中晚期肝癌的疗效是许多学者思考的问题。健脾理气法是肝癌最主要的治疗方法,其在广东省中医院广泛应用,取得一定的效果。本研究拟采用不同的分期方法对新健脾理气方治疗肝癌的预后价值进行比较研究,以期探索适合评价中医药治疗肝癌的分期方法。
目的：
评估原发性肝癌不同分期方法或评分系统(包括中国肝癌分期、Okuda分期、CLIP评分、French分期及BCLC分期)对新健脾理气方治疗肝癌的预后价值,探索适合评价中医药治疗肝癌的分期方法或评分系统。
方法：
本研究分两部份。首先通过检索国内外文献,分析不同分期的优点及不足,筛选出能用于评估中医药治疗预后的分期或评分系统。最后采用回顾性的研究方法,以2007年5月至2009年12月在广东省中医院就诊接受新健脾理气方治疗的151例原发性肝癌患者为研究对象。所有患者按照筛选出来的各种分期方法或评分系统进行再分期。生存率计算采用Kaplan-Meier方法,用时序检验(log-rank test)进行生存率的单因素比较,用比例风险模型进行多因素分析,采用AIC值评价模型预后价值的贡献大小。用线性趋势卡方检验、似然比卡方检验、Harrell's c-指数(concordant index, c-指数)评估各分期系统的同质性、单调性、判别力,用AIC (Akaike Information Criterion, AIC)寻找最佳的预后模型。
结果：
通过检索国内外文献发现,各种分期或评分系统均有其优点及缺点。目前常用的TEM分期包括血管侵犯,有无血管侵犯主要通过手术切除确认,通过影像学来确认是否有血管侵犯并不准确。Izumi改良分期、简化的TNM分期、第六版UICC/AJCC的TNM分期、日本TNM分期法、日本JIS积分法、香港中文大学预后系数评分系统均包括TNM分期,其用于非手术治疗患者的真确性有待商榷；中国肝癌分期、Okuda分期、CLIP评分、French分期及BCLC分期不含血管侵犯,能通过影像学及临床因素来确定分期,适合用于非手术患者,可用于评估中医药治疗疗效的预后。
采用回顾性的研究方法,比较不同分期或评分系统(中国肝癌分期、Okuda分期、CLIP评分、French分期及BCLC分期)对接受新健脾理气方治疗的原发性肝癌患者预后的价值。本研究共纳入151例原发性肝癌患者,其中男性127例(84.1%),女性24例(15.9%),年龄为27-81岁,中位年龄为56岁。单因素分析中,就诊症状、腹水、总胆红素水平、白蛋白水平、AFP水平、门脉癌栓、病灶比例、中医证型、肝功能分级、Okuda分期、CLIP分期评分、French分期、BCLC评分、中国肝癌分期对预后的影响有统计学显著意义。多因素分析示白蛋白分级、腹水分级、肝硬化、病灶比例、腹腔淋巴结转移及AFP分级对预后有统计学差异。
随后采用线性趋势卡方检验、似然比卡方检验、Harrell's c-指数评估各分期系统的同质性、单调性、判别力发现,CLIP评分的同质性、单调性优于其他分期。采用AIC值评价模型预后价值的贡献大小发现,由Okuda分期、CLIP评分构成的模型AIC值最低,说明其是最有效的模型。CLIP评分的同质性、单调性优于其他分期(包括Okuda分期等),因此CLIP评分具有较好的预后价值。综合不同分期的同质性、单调性及模型预后价值结果,CLIP评分对预后价值的贡献大于其他分期。
结论：
1.单因素分析发现就诊症状、腹水、总胆红素水平、白蛋白水平、AFP水平、门脉癌栓及病灶比例等因素对新健脾理气方治疗肝癌预后有影响。
2.多因素分析提示肝硬化、病灶比例、腹腔淋巴结转移、腹水分级、白蛋白分级及AFP水平对新健脾理气方治疗肝癌预后的影响有统计学差异。
3.预后风险模型评估,结果发现Okuda分期及CLIP评分的预后模型较佳。CLIP评分的同质性、单调性优于其他分期(包括Okuda分期等),因此CLIP评分具有较好的预后价值,比Okuda分期、French分期、BCLC评分、中国肝癌分期分层更好,具有对中医药治疗中晚期肝癌更高的预后判别力,而且简便易行,值得进一步借鉴与研究。
Background:
Out of the all incidents of cancer, primary liver cancer is the fifth most common type of cancer one can develop, and, including every variation, is the second most common cause of death in the world. High-risk areas within the world are mainly concentrated in East Asia and Africa. In these regions, the main cause of liver cancer is exposure to the hepatitis B virus (HBV) infection and/or to aflatoxin B1environment. The etiology of this type of cancer in North America, Japan and Europe, however, is mostly due to the HCV (Hepatitis C) virus and alcoholism. China in particular has a high incidence of HBV infection, making up approximately75%of all Hepatitis B carriers in the world. Eventually, about30%of chronic HBV infected patients will develop cirrhosis. Cirrhosis increases the risk of liver cancer; about one-third of the patients with this disease will eventually develop Hepatocellular Carcinoma.
Modern medicine utilizes a variety of methods in the treatment of primary liver cancer and has achieved some success; these treatments involve prescribing remedies depending on the type, size or stage and also the patient's health status to make a decision. The stage of the patient's liver cancer is essential as well. To improve treatment, there should be a streamlined/standardized liver cancer staging method not only to choose the most appropriate treatment, but also a preliminary assessment of the patient's prognosis. Nowadays, the primary liver cancer had a variety of staging or scoring system. Installments from1971Kampala to the current NCCN/AJCC TNM stage, there are total of more than ten kinds of staging system and a variety of biological prognostic molecular markers. Due to the different causes of primary liver cancer epidemiological data around the world, different merger lesions of the liver, the diagnosis and treatment of liver cancer is not the same. There are many different liver cancer staging systems but there has not yet been a standardization that is identified as the best.
In China, more than90%of liver cancer patients who have received Chinese medicine treatment in the recent years (The role of Chinese medicine in advanced hepatocellular carcinoma had greater emphasis recently) have displayed improvement in symptoms, prolonged survival and an improved quality of life. But there is absence of prognostic and evaluation system of Chinese medical treatments malignant tumors today. According to prominent scholars on the issue, the various installments or biomarkers can reflect the efficacy of Chinese medicine in the treatment of advanced liver cancer. The Jianpiliqi method is the mainstay of treatment of liver cancer. In the Guangdong Provincial Hospital, the mentioned method is widely used and achieved certain results. This study of comparing the different staging methods to the prognostic value of the New JianpiLiqi fomula (XJPLQF) treatment of hepatocellular carcinoma is required in order to explore the installment method suitable for the evaluation of Chinese medicine treatment of liver cancer.
Objective:
An assessment of primary liver cancer staging/socring systems (including China liver cancer stage, Okuda stage, CLIP score, French stage and BCLC stage) of the prognostic value of the XJPLQF treat liver cancer. It is to explore each staging/scoring system for evaluating Chinese medical treatment of liver cancer.
Methods:
This study is divided into two parts. First, by looking through prior research, the advantages and disadvantages of different staging/scoring systems can be used in the assessment of viable prognosis staging/scoring system. In the last retrospective study,151patients with primary liver cancer patients to accept the XJPLQF treatment from May2007to December2009in the Guangdong Provincial Hospital for treatment as the research object. All patients were in accordance with the screened out of the installment method or scoring system restaging. The survival rate calculated using the Kaplan-Meier method, rank test (log-rank test). The survival rate of the single factors compared with the proportional hazards model for multivariate analysis of the AIC value evaluation model prognostic value contribution. Linear trend chi-square test, the likelihood ratio chi-square test, Harrell.'s c-index (concordant index, c-index) to assess staging systems for homogeneity, monotonous, discriminant force, with the AIC (Akaike Information Criterion, AIC) finding the best prognostic model.
Results:
Found by searching the literature, various staging or scoring system has its advantages and disadvantages. The TNM staging including vascular invasion, vascular invasion by surgical resection, confirmed by imaging to confirm whether vascular invasion is not accurate. For non-surgical treatment of patients, the Izumi improved staging, TNM staging simplified, the sixth edition of the UICC/TNM classification of the AJCC TNM staging of Japan, Japanese JIS integration method, and the Chinese University of Hong Kong prognosis coefficient scoring system including TNM stage's reliability is also questionable. With the China liver cancer staging, Okuda staging, CLIP scoring, French staging and the BCLC staging (cancer that does not include vascular invasion), through imaging and clinical factors to determine the stage of cancer-suitable for non-surgical patients-can be used in the assessment of prognosis of Chinese medical treatment efficacy.
Using the retrospective research method by comparing different staging/scoring system (China liver cancer stage, Okuda stage, CLIP score, French stage and BCLC stage), one can accept the XJPLQF treatment in patients with primary liver cancer prognosis value. This study included151patients with primary liver cancer patients of whom127(84.1%) are males while24(15.9%) are females, aged ranging from27to81years old, with a median age of56years old. In univariate analysis, treatment symptoms, ascites, total bilirubin level, albumin level, AFP level, portal vein tumor thrombus, lesion proportion, TCM syndrome, Pugh, Okuda stage, CLIP score, French stage, BCLC stage and China liver cancer staging having prognosis statistically significant. Multivariate analysis shows the classification of albumin, ascites graded cirrhosis, lesions proportion of abdominal lymph node metastasis and prognosis, classification AFP made are significant differences.
After using the linear trend chi-square test, likelihood ratio chi-square test, Harrell's c-index to assess the homogeneity of the staging system and discriminant forces, the CLIP score is better than the other installments in homogeneity and monotonicity. The size of the contribution to the pre-value of the AIC value evaluation model found by Okuda stage and the CLIP score model constituted the lowest AIC value, which is the most effective model. The CLIP score, homogeneity and monotonicity are better than the other installments (including Okuda stage. etc.). The CLIP score also has a better prognostic value. Integrating the different stages of the prognostic value of homogeneity, monotonicity and model results, the CLIP score on the prognostic value of the contribution is greater than the other installments.
Conelusions:
1. A single factor analysis shows that the treatment symptoms and ascites had statistically significant differences in the impact of factors such as the level of total bilirubin, albumin level, AFP level, portal vein tumor thrombus and the lesions proportion XJPLQF in the treatment of liver cancer prognosis influential.
2. The multifactorial analysis suggests that cirrhosis, lesions proportional abdominal lymph node metastases, ascites, and hierarchical classification of albumin and AFP levels have a significant impact on the XJPLQF treatment of liver cancer prognosis statistics.
3. Prognostic risk model assessment showed, through experimental results, that the Okuda stage and CLIP score are reliable prognostic models. The CLIP score homogeneity, monotonicity are better than the other installments (including Okuda stage etc.) CLIP score has a higher prognostic value, superior to Okuda stage, French stage, BCLC score and China stage stratification stage. CLIP score also has more prognostic discriminant force to Chinese medicine in the treatment of advanced liver cancer. In fact, CLIP score is rather simple and easy to use and is worthy for further reference and research.
引文
[1]Jemal A, Bray F, Melissa M, et al. Global cancer statistics,2011 [J]. CA Cancer J Clin, 2011,61:69-90.
[2]Bosetti C, Levi F, Boffetta P, et cl. Trends in mortality from hepatocellular carcinoma in Europe,1980-2004[J]. Hepatology,2008; 48:137-45.
[3]El-Serag HB. Hepatocellular carcinoma[J]. N Engl J Med,2011,365:1118-1127.
[4]El-Serag HB, Tran T, Everhart JE. Diabetes increases the risk of chronic liver, disease and hepatocellular carcinoma[J]. Gastroenterology,2004,126:460-468.
[5]Marrero JA, Fontana RJ, Fu S, Conjeevaram HS, Su GL, Lok AS. Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma[J]. J Hepatol,2005, 42:218-24.
[6]Bravi F, Bosetti C, Tavani A, La Vecchia C. Coffee drinking and hepatocellular carcinoma:an update[J]. Hepatology,2009,50:1317-18.
[7]Sherman M. Hepatocellular carcinoma:epidemiology, surveillance, and diagnosis[J]. Semin Liver Dis,2010,30:3-16.
[8]Chen JD, Yang HI, Iloeje UH, et al. Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death [J]. Gastroenterology; 2010,138:1747-54.
[9]Schwardz M, Roayaie S, Konstadoulakis M. Strategies for the management of hepatocellular carcinoma [J]. Nat Clin Pract Oncol,2007,4(7):424-432.
[10]Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma[J]. Lancet,2003,362(9399): 1907-1917.
[11]Liaw YF, Tai DI, Chu CM, et al. Early detection of hepatocellulare creinoma in patients with chronic type B hepatitis.A Prospective study. Gastroenierology[J],1986,90:263-67.
[12]Llovet JM. Updated treatment approach to hepatoeellular careinoma[J].J Gastroenterol,2005,40(3):225-235.
[13]严律南,曾勇,文天夫,等.原发性肝癌分期探讨[J].中华普通外科杂志,2001,16(8)：455-456.
[14]唐合兰,叶胜龙,任正刚,等.原发性肝癌临床分期标准的探讨[J].实用癌症杂志,2002,17(5)：523-526,529.
[15]盛建明,赵文和,马志敏,等.原发性肝癌的中国分期与TNM分期对肝癌切除的预后价值的比较研究[J].中华普通外科杂志,2005,20(10)：644-646.
[16]陆敏强,陈规划,杨扬,等.中国原发性肝癌临床分期预测肝癌肝移植预后的临床研究[J].中华肝胆外科杂志.2005,11(4)：224-226.
[17]汤钊猷.汤钊猷临床肝癌学[M].上海：上海科技教育出版社,2001,2-3.
[18]Child CG, Turcotte JG. The Live rand Portal Hypertension[M]. PhiladelPhia, W. B. Saunders.1964, PP50-51.
[19]Campell DP, Parker DE, Anagnostopoulos CE. Suvrival perdietion in portacaval shunts: a computerized statistical analysis[J]. AmJSurg,1973:126:748-751.
[20]中国抗癌协会肝癌专业委员会.原发性肝癌的临床诊断与分期标准[J].肝脏,2004,9：67-68.
[21]任正刚,杨秉辉,汤钊猷.原发性肝癌临床分期建议及可行性分析[J].中华肝胆外科杂志,2000,6(1)：48-49.
[22]Vauthey JN. Simplified staging system for hepatocellul carcinoma[J]. J Clin Oncol,2002,20:1527-1536.
[23]Ishak K. Histological grading and staging of chronic hepatitis[J]. J HePatol.1995, 22:696-699.
[24]Sobin LH, Wittekind CH. TNM classification of malignant tumors[M].5th ed. NEW YORK: Wile y-Liss,Inc,1997.
[25]Liver including intrahepatic bile ducts. In:Greene FL, Page DL, Fleming ID, Fritz AG, Balch CM, Haller DG, Morrow M, editors. American Joint Com mittee on Cancer Staging Manual[M].6th ed. New York, NY:Springer,2002.131-144.
[26]Leung TW, Tang AM, Zee B, et al. Construction of the Chinese University Prognostic Index of the hepatocellular carcinoma and comparison with the TNM staging system, the Okuda staging system, and the Cancer of the liver Italian Program staging system:a study based on 926 patients[J]. Cancer,2002,294(6:)1760-1769.
[27]Okuda K, Ohtsuki T, Obata H. Natural history of hepatocellular carcinoma and Prognosis in relation to treatment:study of 850 Patients[J]. Cancer,1985,56:918-928.
[28]Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma:the BCLC stagingelassification[J].Semin Liver Dis,1999,19:329-338.
[29]Kudo M. Prognostic staging system for hepatocellular carcinoma(CLIPseore):it's value and limitations, and a proposal for a new staging system, the Japan Integrated Staging score(JIS score) [J].J Gastroenterol,2003,38:207-215.
[30]The Cancer of the Liver Italian Program (CLIP) Investigators. A new prognost ic system for hepatocellular carcinoma:a retrospect ive study of 435 patients[J]. Hepatology, 1998,28:751-755.
[31]The Cancer of the Liver Italian Program(CLIP) Investigators. Prospective validation of the CLIP score:a new prognostic system for patients with cirrhosis and hepatocellular carcinoma [J]. Hepatology,2000:31:840.
[32]Farinati F, Rinaldi M, Gianni S, et al. How should patients with hepatoeellular carcinoma be staged? Validation of a new staging system[J]. Cancer,2000,89:2266-2273.
[33]曲强,苗静安,王少斌,等.肝细胞肝癌临床分期系统的比较[J].中华肿瘤杂志,2006,28：155-158.
[34]Llovet JM, Bruix J, BCLC group. Prospective validation of the Cancer of the Liver Italian Program (CLIP) score:a new prognostic system for Pptients with cirrhosis and hepatocellular carcinoma:correspondence[J].Hepatology,2000,32:679-680.
[35]Bruix J, Castells A, Boseh J, et al. Surgical resection of hepatoeellular carcinoma in cirrhotic Patients. Prognostic value of Preoperative portal ressure[J].Gastorenterology,1996,111:1018-1022.
[36]Llovet JM, BurixJ, FusterJ, et al. Long-term outcome after radical treatment for hepatocellular carcinoma:a single center experience[J]. Hepatology,1998,224(5): 628-638.
[37]Cillo U, Bassanello M, Vitale A, et al. The critical issue of hepatocellular carcinoma prognostic classification:which is the best tool available? [J].J Hepatol,2004, 40:124-131.
[38]Chevret S. Chastang C for the Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire. A new prognostic classification for predicting survival in patients with hepatocellular carcinoma[J]. Hepatol,1999,31:133-141.
[39]Levy I, Sherman M.. The liver cancer study group of the university of Toronto. Staging of hepatocellular carcinoma:assessment of the CLIP, Okuda, and Child-Pugh staging systems in a cohort of 257 patients in Toronto[J]. Gut,2002,50:881-885.
[40]Liver Cancer Study Group of Japan. The general rules for the clinical and pathological study of primary 1 iver can cer (in Japanese) [M].4th ed. Tokyo:K anehara,2000. 19.
[41]Toyoda H, KumadaT, KiriyamaS, et al. Comparison of the usefulness of three staging systems for hepatocellular carcinoma (CLIP, BCLC, and JIS) in Japan[J]. Am J Gastroenterol, 2005,100:1764-1771.
[42]Izumi R, Shimizu K, Ii T, et al. Prognostic factors of hepatocellular carcinoma in patients undergoing hepatic resection[J]. Gastroenterology,1994,106:720-727.
[43]Staudaeher C, Chiappa A, Biella F, et al.Validation of the modifiedTNM-Izumi classifieation for hepatocellular carcinoma[J]. Tumor,2000:86:8.
[44]Marsh JW, Dvorehik I, Bonham CA, et al. Is the pathologic TNM staging system for patients with hepatoma predictive of outcome? [J]. Caneer,2000,88:53.
[45]Okuda K, Obata H, Nakajima Y, etal. Prognosis in primary hepatoeellular careinoma[J]. HePatology,1984,4:35-65.
[46]Primack A, Vogel CL, Kyalwazi SK, et al.A staging system of hepatoeellular carcinoma:prognostic factors in Ugandan patients[J]. Caneer,1975,35:1357-1364.
[47]Bae SH, Jung ES, Park YM, et al. Expression of cyclooxygenase-2 (COX-2) in hepatocellular carcinoma and growth inhibition of hepatoma cell lines by a COX-2 inhibitor NS-398[J].Clin Cancer Res2001,7(5):1410-1418.
[48]Chang YC,Ho CL, Chen HH, et al. Molecular diagnosis of primary liver cancer by microsatellite DNA analysis in the serum [J].Br J Cancer 2002,87(12):1449-1453.
[49]Ikeguchi M, Ueta T, Yamane Y, et al. Inducible niteic oxide synthase and surviving messenger RNA expression in hepatocellular carcinoma[J]. Clin Cancer Res,2002,8(10):3131-3136.
[50]Iizuka N, Oka M, Yamada-Okabe H, et al. Oligonucleotide microarray for prediction of early intrahepatic recurrence of hepatocellular carcinoma afer curative resection[J]. Lancet,2003,361(9361):923-929.
[51]Pugh RN, Murray-Lyon IM, Dawson JL, et al. Transection of the oesophagus for bleeding oesophageal varices[J]. Br J Surg,1973,60:646-49.
[52]Llovet JM, Schwartz M, Mazzaferro V. Resection and liver transplantation for hepatocellular carcinoma[J]. Semin Liver Dis,2005,25:181-200.
[53]Imamura H, Matsuyama Y, Tanaka E, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy[J]. J Hepatol,2003,38:200-207.
[54]Sala M, Fuster J, Llovet JM, et al. High pathological risk of recurrence after surgical resection for hepatocellular carcinoma:an indication for salvage liver transplantation[J]. Liver Transpl,2004,10:1294-1300.
[55]Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis[J]. N Engl J Med,1996,334: 693-699.
[56]Bismuth H, Chiche L, Adam R, et al. Liver resection versus transplantation for hepatocellular carcinoma in cirrhosis[J]. Ann Surg,1993,218,145-151.
[57]Jonas S, Bechstein WO, Steinmuller T, et al. Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosist[J]. Hepatology,2001,33,1080-1086.
[58]Bruix J, Sherman M, Llovet JM, et al, for the EASL panel of experts on HCC. Clinical management of hepatocellular carcinoma:conclusions of the Barcelona-2000 EASL conference [J]. J Hepatol 2001,35:421-430.
[59]Clavien P-A, Lesurtel M, Bossuyt PMM, et al. Recommendations for liver transplantation for hepatocellular carcinoma:an international consensus conference report [J]. Lancet Oncol,2012,13:11-12.
[60]Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival [J]. Hepatology, 2001,33,1394-1403.
[61]Schnitzbauer AA, Zuelke C, Graeb C, et al. A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma [J]. BMC Cancer, 2010,10:190.
[62]Ikai I, Arii S, Kojiro M, Ichida T, et al. Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey[J]. Cancer,2004,101:796-802.
[63]Arii S, Yamaoka Y, Futagawa S, et al. Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas:a retrospective and nationwide survey in Japan[J]. Hepatology 2000,32:1224-1229.
[64]Venook AP, Ferrell LD, Roberts JP, et al. Liver transplantation for hepatocellular carcinoma:Results wiihpreoperative chemoembolization[J]. Liver Transplant Surgl,1995, 1:142-248.
[65]Harnois DM, Steere J, Andrews JC, et al. Preoperative hepatic artery chemoembolization followed by orthotopic liver transplantation for hepatocellular carcinoma[J]. Liver Transplant Surg.1999,5:192-199.
[66]Siernlicht M, Daniels JR, Sales SF, et al. Effect of antimicrobial protection on tolerance to hepatic chemoembolization with a fibrous collagen carrier [J]. Radiology.1989,170:1067-1071.
[67]Marchiori L, Mansueto GC, Nifosi F, et al. The treatment of hepatocellular carcinoma by chemoembolization[J]. Chir Ital,1994,46:17-22.
[68]Onohara S, Kobayashi H, ltoh Y, et al. Intra-arterial cis-platinum infusion with sodium thiosulfate protection and angiotensin II induced hypertension for treatment of hepatocellular carcinoma [J]. Acta Radiol,1988,29:197-202.
[69]Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma:chemoembolization improves survival. Hepatology[J].2003,37, 429-442.
[70]Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, et al. Arterial embolisation or chemoembolisation versus symp-tomatic treatment in patients with unresectable hepatocellular carcinoma:a randomised controlled trial [J]. Lancet.2002,359,1734-1739.
[71]Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, et al. Randomized controlled trial of transarterial lipiodol chemoemb-olization for unresectable hepatocellular carcinoma[J]. Hepatology,2002,35:1164-1171.
[72]Bruix J, Sala M, Llovet JM. Chemoembolization for hepatocel-lular carcinoma [J]. Gastroenterology,2004,127:S179-S188.
[73]Sala M, Llovet JM, Vilana R, Bianchi L, Sole'M, Ayuso C, et al. Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma [J]. Hepatology,2004,40:1352-1360.
[74]Arii S, Okamoto E, Imamura M:Registries in Japan:Current status of hepatocellular carcinoma in Japan. Liver Cancer Study Group of Japan [J]. Semin Surg Onco,1996,12: 204-211.
[75]Oliveri RS, Wetterslev J, Gluud C. Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma [J]. Cochrane Database Syst Rev,2011,3:CD004787.
[76]Chapman WC, Majella Doyle MB, Stuart JE, et al. Outcomes of neoadjuvant transarterial chemoembolization to downstage hepatocellular carcinoma before liver transplantation [J]. Ann Surg,2008,248:617-25.
[77]Decaens T, Roudot-Thoraval F, Bresson-Hadni S, et al. Impact of pretransplantation transarterial chemoembolization on survival and recurrence after liver transplantation for hepatocellular carcinoma [J]. Liver Transpl,2005,11:767-775.
[78]Takayasu K, Arii S, Ikai I, et al. Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients [J]. Gastroenterology,2006,131:461-469.
[79]Bargellini I, Sacco R, Bozzi E, et al. Transarterial chemoembolization in very early and early-stage hepatocellular carcinoma patients excluded from curative treatment:a prospective cohort study [J]. Eur J Radiol (published online April 3,2011). OI:10.1016/j.e jrad.2011.03.046.
[80]Varela M, Real MI, Burrel M, et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads:efficacy and doxorubicin pharmacokinetics [J]. J Hepatol,2007, 46:474-481.
[81]Hilgard P, Hamami M, Fouly AE, et al. Radioembolization with yttrium-90 glass microspheres in hepatocellular carcinoma:European experience on safety and long-term survival [J]. Hepatology,2010,52:1741-1749.
[82]Salem R, Lewandowski RJ, Mulcahy MF, et al. Radioembolization for hepatocellular carcinoma using yttrium-90 microspheres:a comprehensiv outcomes [J]. e report of long-term Gastroenterology,2010,138:52-64.
[83]Sangro B, Carpanese L, Cianni R, et al, on behalf of the European Network on Radioembolization with Yttrium-90 Resin Microspheres (ENRY). Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages:a European evaluation [J]. Hepatology,2011,54:868-878.
[84]汤雨,周晓东.超声介入治疗原发性肝癌的研究进展[J].第四军医大学学报.2008；29：89-92.
[85]Germani G, Pleguezuelo M, Gurusamy K, et al. Clinical outcomes of radiofrequency ablation, percutaneous alcohol and acetic acid injection for hepatocelullar carcinoma: a meta-analysis [J]. J Hepatol,2010,52:380-88.
[86]Cho YK, Kim JK, Kim MY, et al. Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies [J]. Hepatology, 2009,49:453-59.
[87]0rlando A, Leandro G, Olivo M, et al. Radiofrequency thermal ablation vs. percutaneous ethanol injection for small hepatocellular carcinoma in cirrhosis: meta-analysis of randomized controlled trials [J]. Am J Gastroenterol,2009,104: 514-524.
[88]Lencioni R. Loco-regional treatment of hepatocellular carcinoma[J]. Hepatology, 2010,52:762-773.
[89]Cormier JN, Thomas KT, Chari RS, et al. Management of hepatocellular carcinoma [J].Gastrointest Surg,2006,10:761-780.
[90]Zhou XD, Tang ZY, Yu Y, et al. Cryohepatectomy for hepatocellular carcinoma-results in 84 patients [J]. Asian J Surg,2002,25(1):68-72.
[91]Kennedy JE. High-intensity focused ultrasound in the treatment of solid tumours[J]. Nat Rev Cancer,2005,5:321-327.
[92]张卫星,邓卫萍,黄耀.高强度聚焦超声治疗中晚期肝癌[J].中国临床医学200 14：491-492.
[93]Sugiyama S, Beppu T, Ishiko T, et al. Efficacy of radiotherapy for PV and IVC tumor thrombosis in unresectable HCC[J]. Hepatogastroenterology,2007,54(78):1779-82.
[94]Zhao JD, Xu ZY, Zhu J, et al. Application of active breathing control in 3-dimensional conformal radiation therapy for hepatocellular carcinoma, the feasibilitv and benefit[J]. Radiother Oncol,2008,87:439-444.
[95]Lopez P, Villanueva A, Llovet JM. Up-dated systematic review of randomized controlled trials in hepatocellular carcinoma.2002-2005[J]. Aliment Pharmacol Ther.2006, 23:1535-1547.
[96]DranOff G. Cytokines in cancer pathogenesis and cancer therapy[J]. Nat Rev Cancer, 2004,4(1):11-22.
[97]Weng Ds, zhou J, zhu QM, et al. Minimally invasive treatment combined with cytokine-induced killer cell therapy lower the short-term recurrence rates of hepatocellular carcinomas[J]. J Immunotherapy.2008,31 (1):63-71.
[98]Peng BG, Uang U, He Q, et al. Tumor vaccine against recurrence of hepatocellular carcinoma[J]. World J Gastroenterol,2005,11(5):700-704.
[99]陈世晞,徐卫东,尹国文,等.p53基因治疗晚期肝癌的临床观察及生物学监测[J].中华医学杂志,2010,90(31)：2182-2186.
[100]Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma [J]. N Engl J Med,2008,359:378-90.
[101]Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacif i c region with advanced hepatocellular carcinoma:a phase III randomised, double-blind, placebo-controlled trial[J]. Lancet Oncol,2009,10:25-34.
[102]张辉,方肇勤.健脾理气法应用于肝癌的临床进展[J].河南中医,2007,27(7)：78-81.
[103]曹继刚,邱幸凡,陈月雀.原发性肝癌的基本病机及治则探讨[J].中医药学报,2008,36(4)：28-29.
[104]方肇勤,李永健,唐辰龙,等.2060例原发性肝癌患者证候特点分析[J].中医杂志,2004,45(1)：53-54.
[105]陈喆,侯风刚,孙克兴.肝癌中医证型的文献分析[J].安徽中医杂志,2002,21(2)：24-26.
[106]李永健,方肇勤,邸若虹.2492例肝癌辨证分型临床报道的统计分析[J].中国中医基础医学杂志,2001,7(6)：69-71.
[107]郑筱萸主编.中药新药临床研究指导原[M].北京：中国医药科技出版社,2002：210-211.
[108]刘伟胜主编.肿瘤科专病中医临床诊治[M].北京：人民卫生出版社,2005：237-238.
[109]张维彬,谭敏,肖刚,等.莪术油诱导小鼠Hep肝癌细胞凋亡及其对bcl-2蛋白表达的影响[J].现代中西医结合杂志,2009,18(4)：370-371.
[110]赵军艳,郑艳敏,赵红艳,等.苦参碱和氧化苦参碱对肝癌细胞增殖凋亡及JAK-STAT信号通路的影响[J].中药药理与临床,2008,24(4)：18-20.
[111]黄修燕,黄自丽,晁愚,等.中药“松友饮”对高转移人肝癌侵袭性及小鼠免疫功能的影响[J].肿瘤,2005,28(6)：489-493.
[112]黄挺,陈震,杨雪飞,等.康莱特注射液抗恶性肿瘤肝转移疗效及机理的实验研究[J].中华中医药学刊,2009,27(3)：509-511.
[113]金沈锐,张新胜,祝彼得,等.西黄丸对肝癌细胞SMMC7721分泌的血管内皮生长因子及基质金属蛋白酶2、9的影响[J].中成药,2008,30(7)：1079-1081.
[114]王济,张前,解华,等.轻基红花黄色素A对肿瘤上清诱导的人脐静脉内皮细胞增殖的影响[J].中华中医药杂志,2009,24(5)：572-575.
[115]李磷,邱蓉丽,程革,等.女贞子多糖抗肿瘤作用研究[J].中国药理学通报,2009,24(12)：1619-1622.
[116]胡玲,王洪琦,崔娜娟,等.白花蛇舌草对小鼠活体腹水H22肝癌细胞及T细胞的影响[J].广州中医药大学学报,2007,24(4)：313-316.
[117]杨传标,郭德鸿,张曼,等.中医药辨证治疗中晚期肝癌临床疗效观察[J].南方医科大学学报,2007,27(8)：1229-1230.
[118]王俊显,周超凡,郑伟达.应用慈丹胶囊治疗原发性肝癌325例临床疗效观察[J].中国肿瘤临床,2005,32(21)：1255-1256.
[119]白广德,练祖平,黄丁平,等.中西医结合治疗原发性中晚期肝癌疗效对照观察[J].辽宁中医杂志,2008,35(1)：98-100.
[120]程剑华,常纲,吴万垠,等.莪术油和化疗药对照肝动脉灌注栓塞治疗原发性肝癌的临床研究[J].中国中西医结合杂志,2001;21(3)：165-167.
[121]朱晓锋.康莱特注射液联合介入化疗栓塞治疗原发性中晚期肝癌[J].肿瘤基础与临床,2006,19(2)：132-134.
[122]Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors[J]. JNCI,2000,92:205-216.
[123]刘鲁明主编.肝癌中西医综合治疗[M].人民卫生出版社,2002,11,第一版：139-155,165,179,183,194-195,205-208,254-265,279,302,312,323-330.
[124]于尔辛.中药扶正培本在恶性肿瘤治疗方面的应用[J].医学理论与实践,1994；7(8)：21-23.
[125]于尔辛.肝癌的健脾理气方治疗[J].中国肿瘤,2000,9(8)：344.
[126]于尔辛,刘鲁明,宋明志,等.全肝移动条野放射结合中药治疗大肝癌临床研究[J].中华肿瘤杂志,1992,14(1)：57-60.
[127]任莉莉,于尔辛,宋明志,等.人参抗肿瘤作用研究进展[J].中成药,2005,27(8)：947-950.
[128]赵增虎,丁瑞亮,李海.健脾理气中药治疗原发性肝癌的依据及作用[J].现代中西医结合杂志,2011,20(9)：1158-1159.
[129]林均华,徐益语.中药及中药结合化疗治疗原发性肝癌术后残瘤与复发[J].中医杂志,1994,35(4)：220-221.
[130]赵增虎,杜欣,刘秀芳,等.肝动脉化疗栓塞联合健脾理气中药治疗中晚期肝癌临床研究[J].中国中医药信息杂志,2006,13(1)：62-63.
[13l]Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors (RECIST Guidelines) [J]. J Nat/Cancer Inst,2000,92:205-216.
[132]储大同.肿瘤中医药治疗评价标准的新共识及其启迪[J].中国处方药,2004,29(8)：42.
[133]周岱翰,林丽珠,陶志广.中医肿瘤疗效评价系统在晚期非小细胞肺癌中的应用[J].中国肿瘤,2005,14(10)：654-657.
[134]林洪生,李树奇,朴炳奎.中医治疗晚期肺癌的疗效评价方法[J].中国肿瘤,2000,9(8)：354-355.
[135]张培彤,于明薇,杨宗艳,等.中晚期非小细胞肺癌中西医疗效评价方法比较研究[J].中国中西医结合杂志,2010,30(7)：702-705.
[136]林丽珠.生存质量在中医肿瘤学综合疗效评价中的作用[J].中国肿瘤,2010,10(2)：80-82.
[137]杨宇飞,朱尧武,吴煜,等.中医药治疗恶性肿瘤综合疗效标准探讨及初步运用[J].中国中西医结合杂志,1999,19(6)：340-343.
[138]Choi H, Charnsangav C, de Castro FS, et al. CT evaluation of the response of gastrointestinal stromal tumors after imatinib mesylate treatment:a quantitative analysis correlated with FDG PET findings[J]. Am J Roentgenal,2004,183:1619-1628.
[139]Choi H, Charnsangavej C, Faria SC, et al. Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate:proposal of new computed tomography response criteria[J]. J Clin Oncol,2007,25(13):1753-1759.
[140]Choi H. Critical issues in response evaluation on computed tomography:lessons from the gastrointestinal stromal tumor model[J]. Curt Oncol Rep,2005,7(4):307-311.
[141]Choi H. Response evaluation of gastrointestinal stromal tumors [J]. Oneologist, 2008,13(Suppl 2):4-7.
[142]李东涛,凌昌全,郎庆波,等.以证候为内容的原发性肝癌中医疗效评价体系研究[J].中西医结合学报,2007,5(1)：15-22.
[143]余松林.医学统计学[M].北京：人民卫生出版社.2002：386-390.
[144]许致远.不同临床分期对中医药治疗原发性肝癌的预后评估和疗效分析[D].广州中医药大学,2005.
[145]王海鹏.原发性肝癌分期方法的比较研究[D].北京：中国协和医科大学,2006.
[146]中国抗癌协会.新编常见恶性肿瘤诊治规范[M].北京：中国协和医科大学出版社,1999：450.
[147]Custer B, Sullivan SD, Hazlet T K, et al. Global epidemiology of hepatitis B virus[J].J Clin Gastroenterol,2004,38(10 Suppl 3):S158-168.
[148]Llovet JM, Burmughs A,Bruix J. Hepatocellular carcinoma [J].Lancet,2003,362:1907-1917.
[149]Bruix J, Sherman M, LlovetJM, et al. Clinical management of hepatocellular carcinoma.Conelusions of the 2000 EASL conferenee[J]. J Hepatol,2001,35:421-430.
[150]Levy I, Sherman M. Staging of hepatocellular carcinoma:assessment of the CLIP, Okuda, and Child-Pugh staging systems in a cohort of 257 patients in Toronto[J]. Gut,2002, 50:881-885.
[151]Poon RT, Ng IO, Fan ST, et al. Clinicopathologic featurescofclong-term survivors and disease-free survivors after rescetion of hepatocellular careinoma:a study of a prospective cohort[J].J Clin Oncol,2001,19:3037-3044.
[152]Pompili M, Rapaccini GL, Covino M, et al. Prognostic factors for survival in patients with compensated cirrhosis and small hepatocellular carcinoma after pereutaneous ethanol injeetion therapy [J]. Caneer,2001,92:126-135.
[153]Farinati F, Rinaldi M, Gianni S, et al. How should patients with hepatocellular carcinoma be staged? Validation of a new prognostic system [J]. Cnaeer,2000,89:2266-2273.
[154]The cancer of the Liver Italian Program (CLIP) Investigators. Prospective validation of the CLIP seore:a new prognostic system for patients with cirrhosis and hepatocellular carcinoma[J].Hepatology,2000,31:840.
[155]Nanashima A, Sumida Y, Abo T, et al. Modified Japan Integrated Staging is currently the best available staging system for hepatocellular carcinoma patients who have undergone hepatectomy[J]. J Gastroenierol,2006,41:250-256.
[156]中国抗癌协会肝癌专业委员会.原发性肝癌的临床诊断与分期标准[J].肝脏,2004,9：67-68.
[157]Sangiovanni A, Del Ninno E, Fasani P, etal. Inereased survival of cirrhotic patients with hepatocellular carcinoma detected during surveillance[J]. Gastroenierology,2004, 126:1005-1014.
[158]Adachi E, Maeda T, Matsuma T, et al. Risk factors of introhepatic recurrence in human small hepatocellular carcinoma[J]. Gastroenterology,1995,108:768-775.
[159]Chen MF, Hwang TL, Jeng LB, et al. Postoperative recurrence of hepatocellular carcinoma. Two hundred five consecutive patients who underwent hepaticresection in 15 years[J]. Areh Sug,1994,129:738-742.
[160]The liver Cancer Study Group of Japan. Survey and follow-up study of primary liver cancer in Japan Report 11[J]. Liver,1995,36:208-217.
[161]Hanazaki K, Kajikawa S, Koide N, et al. prognostic factor after hepaticresection for hepatocellular carcinoma with hepatitis C viral infection:univariate and multiviate analysis[J]. Am J Gastorenterol,2001,96:1243-1250.
[162]张智坚,吴孟超,沈锋,等.TNM分期对评价肝细胞癌切除术预后的价值[J].中华肿瘤杂志,1999,21,293-295.
[163]Ueno S, Tanabe G, Sako K, et al. Diserimination value of the new western prognostic system (CLIPseore) for hepatocellular carcinoma in 662 Japanese patients [J]. Hepatolory,2001,34,529-534.
[164]赵文和,马志敏,周杏仁,等CLIP评分系统对评价手术切除肝癌预后的意义[J].中华外科杂志,2002,40：321-325.
[165]何招才.肝细胞癌不同分期方法对肝癌肝切除患者预后价值的比较研究[D].湖南：中南科大学,2009.
[2]Bosetti C, Levi F, Boffetta P, et cl. Trends in mortality from hepatocellular carcinoma in Europe,1980-2004[J]. Hepatology,2008; 48:137-45.
[3]El-Serag HB. Hepatocellular carcinoma[J]. N Engl J Med,2011,365:1118-1127.
[4]El-Serag HB, Tran T, Everhart JE. Diabetes increases the risk of chronic liver, disease and hepatocellular carcinoma[J]. Gastroenterology,2004,126:460-468.
[5]Marrero JA, Fontana RJ, Fu S, Conjeevaram HS, Su GL, Lok AS. Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma[J]. J Hepatol,2005, 42:218-24.
[6]Bravi F, Bosetti C, Tavani A, La Vecchia C. Coffee drinking and hepatocellular carcinoma:an update[J]. Hepatology,2009,50:1317-18.
[7]Sherman M. Hepatocellular carcinoma:epidemiology, surveillance, and diagnosis[J]. Semin Liver Dis,2010,30:3-16.
[8]Chen JD, Yang HI, Iloeje UH, et al. Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death [J]. Gastroenterology; 2010,138:1747-54.
[9]Schwardz M, Roayaie S, Konstadoulakis M. Strategies for the management of hepatocellular carcinoma [J]. Nat Clin Pract Oncol,2007,4(7):424-432.
[10]Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma[J]. Lancet,2003,362(9399): 1907-1917.
[11]Liaw YF, Tai DI, Chu CM, et al. Early detection of hepatocellulare creinoma in patients with chronic type B hepatitis.A Prospective study. Gastroenierology[J],1986,90:263-67.
[12]Llovet JM. Updated treatment approach to hepatoeellular careinoma[J].J Gastroenterol,2005,40(3):225-235.
[13]严律南,曾勇,文天夫,等.原发性肝癌分期探讨[J].中华普通外科杂志,2001,16(8)：455-456.
[14]唐合兰,叶胜龙,任正刚,等.原发性肝癌临床分期标准的探讨[J].实用癌症杂志,2002,17(5)：523-526,529.
[15]盛建明,赵文和,马志敏,等.原发性肝癌的中国分期与TNM分期对肝癌切除的预后价值的比较研究[J].中华普通外科杂志,2005,20(10)：644-646.
[16]陆敏强,陈规划,杨扬,等.中国原发性肝癌临床分期预测肝癌肝移植预后的临床研究[J].中华肝胆外科杂志.2005,11(4)：224-226.
[17]汤钊猷.汤钊猷临床肝癌学[M].上海：上海科技教育出版社,2001,2-3.
[18]Child CG, Turcotte JG. The Live rand Portal Hypertension[M]. PhiladelPhia, W. B. Saunders.1964, PP50-51.
[19]Campell DP, Parker DE, Anagnostopoulos CE. Suvrival perdietion in portacaval shunts: a computerized statistical analysis[J]. AmJSurg,1973:126:748-751.
[20]中国抗癌协会肝癌专业委员会.原发性肝癌的临床诊断与分期标准[J].肝脏,2004,9：67-68.
[21]任正刚,杨秉辉,汤钊猷.原发性肝癌临床分期建议及可行性分析[J].中华肝胆外科杂志,2000,6(1)：48-49.
[22]Vauthey JN. Simplified staging system for hepatocellul carcinoma[J]. J Clin Oncol,2002,20:1527-1536.
[23]Ishak K. Histological grading and staging of chronic hepatitis[J]. J HePatol.1995, 22:696-699.
[24]Sobin LH, Wittekind CH. TNM classification of malignant tumors[M].5th ed. NEW YORK: Wile y-Liss,Inc,1997.
[25]Liver including intrahepatic bile ducts. In:Greene FL, Page DL, Fleming ID, Fritz AG, Balch CM, Haller DG, Morrow M, editors. American Joint Com mittee on Cancer Staging Manual[M].6th ed. New York, NY:Springer,2002.131-144.
[26]Leung TW, Tang AM, Zee B, et al. Construction of the Chinese University Prognostic Index of the hepatocellular carcinoma and comparison with the TNM staging system, the Okuda staging system, and the Cancer of the liver Italian Program staging system:a study based on 926 patients[J]. Cancer,2002,294(6:)1760-1769.
[27]Okuda K, Ohtsuki T, Obata H. Natural history of hepatocellular carcinoma and Prognosis in relation to treatment:study of 850 Patients[J]. Cancer,1985,56:918-928.
[28]Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma:the BCLC stagingelassification[J].Semin Liver Dis,1999,19:329-338.
[29]Kudo M. Prognostic staging system for hepatocellular carcinoma(CLIPseore):it's value and limitations, and a proposal for a new staging system, the Japan Integrated Staging score(JIS score) [J].J Gastroenterol,2003,38:207-215.
[30]The Cancer of the Liver Italian Program (CLIP) Investigators. A new prognost ic system for hepatocellular carcinoma:a retrospect ive study of 435 patients[J]. Hepatology, 1998,28:751-755.
[31]The Cancer of the Liver Italian Program(CLIP) Investigators. Prospective validation of the CLIP score:a new prognostic system for patients with cirrhosis and hepatocellular carcinoma [J]. Hepatology,2000:31:840.
[32]Farinati F, Rinaldi M, Gianni S, et al. How should patients with hepatoeellular carcinoma be staged? Validation of a new staging system[J]. Cancer,2000,89:2266-2273.
[33]曲强,苗静安,王少斌,等.肝细胞肝癌临床分期系统的比较[J].中华肿瘤杂志,2006,28：155-158.
[34]Llovet JM, Bruix J, BCLC group. Prospective validation of the Cancer of the Liver Italian Program (CLIP) score:a new prognostic system for Pptients with cirrhosis and hepatocellular carcinoma:correspondence[J].Hepatology,2000,32:679-680.
[35]Bruix J, Castells A, Boseh J, et al. Surgical resection of hepatoeellular carcinoma in cirrhotic Patients. Prognostic value of Preoperative portal ressure[J].Gastorenterology,1996,111:1018-1022.
[36]Llovet JM, BurixJ, FusterJ, et al. Long-term outcome after radical treatment for hepatocellular carcinoma:a single center experience[J]. Hepatology,1998,224(5): 628-638.
[37]Cillo U, Bassanello M, Vitale A, et al. The critical issue of hepatocellular carcinoma prognostic classification:which is the best tool available? [J].J Hepatol,2004, 40:124-131.
[38]Chevret S. Chastang C for the Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire. A new prognostic classification for predicting survival in patients with hepatocellular carcinoma[J]. Hepatol,1999,31:133-141.
[39]Levy I, Sherman M.. The liver cancer study group of the university of Toronto. Staging of hepatocellular carcinoma:assessment of the CLIP, Okuda, and Child-Pugh staging systems in a cohort of 257 patients in Toronto[J]. Gut,2002,50:881-885.
[40]Liver Cancer Study Group of Japan. The general rules for the clinical and pathological study of primary 1 iver can cer (in Japanese) [M].4th ed. Tokyo:K anehara,2000. 19.
[41]Toyoda H, KumadaT, KiriyamaS, et al. Comparison of the usefulness of three staging systems for hepatocellular carcinoma (CLIP, BCLC, and JIS) in Japan[J]. Am J Gastroenterol, 2005,100:1764-1771.
[42]Izumi R, Shimizu K, Ii T, et al. Prognostic factors of hepatocellular carcinoma in patients undergoing hepatic resection[J]. Gastroenterology,1994,106:720-727.
[43]Staudaeher C, Chiappa A, Biella F, et al.Validation of the modifiedTNM-Izumi classifieation for hepatocellular carcinoma[J]. Tumor,2000:86:8.
[44]Marsh JW, Dvorehik I, Bonham CA, et al. Is the pathologic TNM staging system for patients with hepatoma predictive of outcome? [J]. Caneer,2000,88:53.
[45]Okuda K, Obata H, Nakajima Y, etal. Prognosis in primary hepatoeellular careinoma[J]. HePatology,1984,4:35-65.
[46]Primack A, Vogel CL, Kyalwazi SK, et al.A staging system of hepatoeellular carcinoma:prognostic factors in Ugandan patients[J]. Caneer,1975,35:1357-1364.
[47]Bae SH, Jung ES, Park YM, et al. Expression of cyclooxygenase-2 (COX-2) in hepatocellular carcinoma and growth inhibition of hepatoma cell lines by a COX-2 inhibitor NS-398[J].Clin Cancer Res2001,7(5):1410-1418.
[48]Chang YC,Ho CL, Chen HH, et al. Molecular diagnosis of primary liver cancer by microsatellite DNA analysis in the serum [J].Br J Cancer 2002,87(12):1449-1453.
[49]Ikeguchi M, Ueta T, Yamane Y, et al. Inducible niteic oxide synthase and surviving messenger RNA expression in hepatocellular carcinoma[J]. Clin Cancer Res,2002,8(10):3131-3136.
[50]Iizuka N, Oka M, Yamada-Okabe H, et al. Oligonucleotide microarray for prediction of early intrahepatic recurrence of hepatocellular carcinoma afer curative resection[J]. Lancet,2003,361(9361):923-929.
[51]Pugh RN, Murray-Lyon IM, Dawson JL, et al. Transection of the oesophagus for bleeding oesophageal varices[J]. Br J Surg,1973,60:646-49.
[52]Llovet JM, Schwartz M, Mazzaferro V. Resection and liver transplantation for hepatocellular carcinoma[J]. Semin Liver Dis,2005,25:181-200.
[53]Imamura H, Matsuyama Y, Tanaka E, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy[J]. J Hepatol,2003,38:200-207.
[54]Sala M, Fuster J, Llovet JM, et al. High pathological risk of recurrence after surgical resection for hepatocellular carcinoma:an indication for salvage liver transplantation[J]. Liver Transpl,2004,10:1294-1300.
[55]Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis[J]. N Engl J Med,1996,334: 693-699.
[56]Bismuth H, Chiche L, Adam R, et al. Liver resection versus transplantation for hepatocellular carcinoma in cirrhosis[J]. Ann Surg,1993,218,145-151.
[57]Jonas S, Bechstein WO, Steinmuller T, et al. Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosist[J]. Hepatology,2001,33,1080-1086.
[58]Bruix J, Sherman M, Llovet JM, et al, for the EASL panel of experts on HCC. Clinical management of hepatocellular carcinoma:conclusions of the Barcelona-2000 EASL conference [J]. J Hepatol 2001,35:421-430.
[59]Clavien P-A, Lesurtel M, Bossuyt PMM, et al. Recommendations for liver transplantation for hepatocellular carcinoma:an international consensus conference report [J]. Lancet Oncol,2012,13:11-12.
[60]Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival [J]. Hepatology, 2001,33,1394-1403.
[61]Schnitzbauer AA, Zuelke C, Graeb C, et al. A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma [J]. BMC Cancer, 2010,10:190.
[62]Ikai I, Arii S, Kojiro M, Ichida T, et al. Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey[J]. Cancer,2004,101:796-802.
[63]Arii S, Yamaoka Y, Futagawa S, et al. Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas:a retrospective and nationwide survey in Japan[J]. Hepatology 2000,32:1224-1229.
[64]Venook AP, Ferrell LD, Roberts JP, et al. Liver transplantation for hepatocellular carcinoma:Results wiihpreoperative chemoembolization[J]. Liver Transplant Surgl,1995, 1:142-248.
[65]Harnois DM, Steere J, Andrews JC, et al. Preoperative hepatic artery chemoembolization followed by orthotopic liver transplantation for hepatocellular carcinoma[J]. Liver Transplant Surg.1999,5:192-199.
[66]Siernlicht M, Daniels JR, Sales SF, et al. Effect of antimicrobial protection on tolerance to hepatic chemoembolization with a fibrous collagen carrier [J]. Radiology.1989,170:1067-1071.
[67]Marchiori L, Mansueto GC, Nifosi F, et al. The treatment of hepatocellular carcinoma by chemoembolization[J]. Chir Ital,1994,46:17-22.
[68]Onohara S, Kobayashi H, ltoh Y, et al. Intra-arterial cis-platinum infusion with sodium thiosulfate protection and angiotensin II induced hypertension for treatment of hepatocellular carcinoma [J]. Acta Radiol,1988,29:197-202.
[69]Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma:chemoembolization improves survival. Hepatology[J].2003,37, 429-442.
[70]Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, et al. Arterial embolisation or chemoembolisation versus symp-tomatic treatment in patients with unresectable hepatocellular carcinoma:a randomised controlled trial [J]. Lancet.2002,359,1734-1739.
[71]Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, et al. Randomized controlled trial of transarterial lipiodol chemoemb-olization for unresectable hepatocellular carcinoma[J]. Hepatology,2002,35:1164-1171.
[72]Bruix J, Sala M, Llovet JM. Chemoembolization for hepatocel-lular carcinoma [J]. Gastroenterology,2004,127:S179-S188.
[73]Sala M, Llovet JM, Vilana R, Bianchi L, Sole'M, Ayuso C, et al. Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma [J]. Hepatology,2004,40:1352-1360.
[74]Arii S, Okamoto E, Imamura M:Registries in Japan:Current status of hepatocellular carcinoma in Japan. Liver Cancer Study Group of Japan [J]. Semin Surg Onco,1996,12: 204-211.
[75]Oliveri RS, Wetterslev J, Gluud C. Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma [J]. Cochrane Database Syst Rev,2011,3:CD004787.
[76]Chapman WC, Majella Doyle MB, Stuart JE, et al. Outcomes of neoadjuvant transarterial chemoembolization to downstage hepatocellular carcinoma before liver transplantation [J]. Ann Surg,2008,248:617-25.
[77]Decaens T, Roudot-Thoraval F, Bresson-Hadni S, et al. Impact of pretransplantation transarterial chemoembolization on survival and recurrence after liver transplantation for hepatocellular carcinoma [J]. Liver Transpl,2005,11:767-775.
[78]Takayasu K, Arii S, Ikai I, et al. Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients [J]. Gastroenterology,2006,131:461-469.
[79]Bargellini I, Sacco R, Bozzi E, et al. Transarterial chemoembolization in very early and early-stage hepatocellular carcinoma patients excluded from curative treatment:a prospective cohort study [J]. Eur J Radiol (published online April 3,2011). OI:10.1016/j.e jrad.2011.03.046.
[80]Varela M, Real MI, Burrel M, et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads:efficacy and doxorubicin pharmacokinetics [J]. J Hepatol,2007, 46:474-481.
[81]Hilgard P, Hamami M, Fouly AE, et al. Radioembolization with yttrium-90 glass microspheres in hepatocellular carcinoma:European experience on safety and long-term survival [J]. Hepatology,2010,52:1741-1749.
[82]Salem R, Lewandowski RJ, Mulcahy MF, et al. Radioembolization for hepatocellular carcinoma using yttrium-90 microspheres:a comprehensiv outcomes [J]. e report of long-term Gastroenterology,2010,138:52-64.
[83]Sangro B, Carpanese L, Cianni R, et al, on behalf of the European Network on Radioembolization with Yttrium-90 Resin Microspheres (ENRY). Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages:a European evaluation [J]. Hepatology,2011,54:868-878.
[84]汤雨,周晓东.超声介入治疗原发性肝癌的研究进展[J].第四军医大学学报.2008；29：89-92.
[85]Germani G, Pleguezuelo M, Gurusamy K, et al. Clinical outcomes of radiofrequency ablation, percutaneous alcohol and acetic acid injection for hepatocelullar carcinoma: a meta-analysis [J]. J Hepatol,2010,52:380-88.
[86]Cho YK, Kim JK, Kim MY, et al. Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies [J]. Hepatology, 2009,49:453-59.
[87]0rlando A, Leandro G, Olivo M, et al. Radiofrequency thermal ablation vs. percutaneous ethanol injection for small hepatocellular carcinoma in cirrhosis: meta-analysis of randomized controlled trials [J]. Am J Gastroenterol,2009,104: 514-524.
[88]Lencioni R. Loco-regional treatment of hepatocellular carcinoma[J]. Hepatology, 2010,52:762-773.
[89]Cormier JN, Thomas KT, Chari RS, et al. Management of hepatocellular carcinoma [J].Gastrointest Surg,2006,10:761-780.
[90]Zhou XD, Tang ZY, Yu Y, et al. Cryohepatectomy for hepatocellular carcinoma-results in 84 patients [J]. Asian J Surg,2002,25(1):68-72.
[91]Kennedy JE. High-intensity focused ultrasound in the treatment of solid tumours[J]. Nat Rev Cancer,2005,5:321-327.
[92]张卫星,邓卫萍,黄耀.高强度聚焦超声治疗中晚期肝癌[J].中国临床医学200 14：491-492.
[93]Sugiyama S, Beppu T, Ishiko T, et al. Efficacy of radiotherapy for PV and IVC tumor thrombosis in unresectable HCC[J]. Hepatogastroenterology,2007,54(78):1779-82.
[94]Zhao JD, Xu ZY, Zhu J, et al. Application of active breathing control in 3-dimensional conformal radiation therapy for hepatocellular carcinoma, the feasibilitv and benefit[J]. Radiother Oncol,2008,87:439-444.
[95]Lopez P, Villanueva A, Llovet JM. Up-dated systematic review of randomized controlled trials in hepatocellular carcinoma.2002-2005[J]. Aliment Pharmacol Ther.2006, 23:1535-1547.
[96]DranOff G. Cytokines in cancer pathogenesis and cancer therapy[J]. Nat Rev Cancer, 2004,4(1):11-22.
[97]Weng Ds, zhou J, zhu QM, et al. Minimally invasive treatment combined with cytokine-induced killer cell therapy lower the short-term recurrence rates of hepatocellular carcinomas[J]. J Immunotherapy.2008,31 (1):63-71.
[98]Peng BG, Uang U, He Q, et al. Tumor vaccine against recurrence of hepatocellular carcinoma[J]. World J Gastroenterol,2005,11(5):700-704.
[99]陈世晞,徐卫东,尹国文,等.p53基因治疗晚期肝癌的临床观察及生物学监测[J].中华医学杂志,2010,90(31)：2182-2186.
[100]Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma [J]. N Engl J Med,2008,359:378-90.
[101]Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacif i c region with advanced hepatocellular carcinoma:a phase III randomised, double-blind, placebo-controlled trial[J]. Lancet Oncol,2009,10:25-34.
[102]张辉,方肇勤.健脾理气法应用于肝癌的临床进展[J].河南中医,2007,27(7)：78-81.
[103]曹继刚,邱幸凡,陈月雀.原发性肝癌的基本病机及治则探讨[J].中医药学报,2008,36(4)：28-29.
[104]方肇勤,李永健,唐辰龙,等.2060例原发性肝癌患者证候特点分析[J].中医杂志,2004,45(1)：53-54.
[105]陈喆,侯风刚,孙克兴.肝癌中医证型的文献分析[J].安徽中医杂志,2002,21(2)：24-26.
[106]李永健,方肇勤,邸若虹.2492例肝癌辨证分型临床报道的统计分析[J].中国中医基础医学杂志,2001,7(6)：69-71.
[107]郑筱萸主编.中药新药临床研究指导原[M].北京：中国医药科技出版社,2002：210-211.
[108]刘伟胜主编.肿瘤科专病中医临床诊治[M].北京：人民卫生出版社,2005：237-238.
[109]张维彬,谭敏,肖刚,等.莪术油诱导小鼠Hep肝癌细胞凋亡及其对bcl-2蛋白表达的影响[J].现代中西医结合杂志,2009,18(4)：370-371.
[110]赵军艳,郑艳敏,赵红艳,等.苦参碱和氧化苦参碱对肝癌细胞增殖凋亡及JAK-STAT信号通路的影响[J].中药药理与临床,2008,24(4)：18-20.
[111]黄修燕,黄自丽,晁愚,等.中药“松友饮”对高转移人肝癌侵袭性及小鼠免疫功能的影响[J].肿瘤,2005,28(6)：489-493.
[112]黄挺,陈震,杨雪飞,等.康莱特注射液抗恶性肿瘤肝转移疗效及机理的实验研究[J].中华中医药学刊,2009,27(3)：509-511.
[113]金沈锐,张新胜,祝彼得,等.西黄丸对肝癌细胞SMMC7721分泌的血管内皮生长因子及基质金属蛋白酶2、9的影响[J].中成药,2008,30(7)：1079-1081.
[114]王济,张前,解华,等.轻基红花黄色素A对肿瘤上清诱导的人脐静脉内皮细胞增殖的影响[J].中华中医药杂志,2009,24(5)：572-575.
[115]李磷,邱蓉丽,程革,等.女贞子多糖抗肿瘤作用研究[J].中国药理学通报,2009,24(12)：1619-1622.
[116]胡玲,王洪琦,崔娜娟,等.白花蛇舌草对小鼠活体腹水H22肝癌细胞及T细胞的影响[J].广州中医药大学学报,2007,24(4)：313-316.
[117]杨传标,郭德鸿,张曼,等.中医药辨证治疗中晚期肝癌临床疗效观察[J].南方医科大学学报,2007,27(8)：1229-1230.
[118]王俊显,周超凡,郑伟达.应用慈丹胶囊治疗原发性肝癌325例临床疗效观察[J].中国肿瘤临床,2005,32(21)：1255-1256.
[119]白广德,练祖平,黄丁平,等.中西医结合治疗原发性中晚期肝癌疗效对照观察[J].辽宁中医杂志,2008,35(1)：98-100.
[120]程剑华,常纲,吴万垠,等.莪术油和化疗药对照肝动脉灌注栓塞治疗原发性肝癌的临床研究[J].中国中西医结合杂志,2001;21(3)：165-167.
[121]朱晓锋.康莱特注射液联合介入化疗栓塞治疗原发性中晚期肝癌[J].肿瘤基础与临床,2006,19(2)：132-134.
[122]Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors[J]. JNCI,2000,92:205-216.
[123]刘鲁明主编.肝癌中西医综合治疗[M].人民卫生出版社,2002,11,第一版：139-155,165,179,183,194-195,205-208,254-265,279,302,312,323-330.
[124]于尔辛.中药扶正培本在恶性肿瘤治疗方面的应用[J].医学理论与实践,1994；7(8)：21-23.
[125]于尔辛.肝癌的健脾理气方治疗[J].中国肿瘤,2000,9(8)：344.
[126]于尔辛,刘鲁明,宋明志,等.全肝移动条野放射结合中药治疗大肝癌临床研究[J].中华肿瘤杂志,1992,14(1)：57-60.
[127]任莉莉,于尔辛,宋明志,等.人参抗肿瘤作用研究进展[J].中成药,2005,27(8)：947-950.
[128]赵增虎,丁瑞亮,李海.健脾理气中药治疗原发性肝癌的依据及作用[J].现代中西医结合杂志,2011,20(9)：1158-1159.
[129]林均华,徐益语.中药及中药结合化疗治疗原发性肝癌术后残瘤与复发[J].中医杂志,1994,35(4)：220-221.
[130]赵增虎,杜欣,刘秀芳,等.肝动脉化疗栓塞联合健脾理气中药治疗中晚期肝癌临床研究[J].中国中医药信息杂志,2006,13(1)：62-63.
[13l]Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors (RECIST Guidelines) [J]. J Nat/Cancer Inst,2000,92:205-216.
[132]储大同.肿瘤中医药治疗评价标准的新共识及其启迪[J].中国处方药,2004,29(8)：42.
[133]周岱翰,林丽珠,陶志广.中医肿瘤疗效评价系统在晚期非小细胞肺癌中的应用[J].中国肿瘤,2005,14(10)：654-657.
[134]林洪生,李树奇,朴炳奎.中医治疗晚期肺癌的疗效评价方法[J].中国肿瘤,2000,9(8)：354-355.
[135]张培彤,于明薇,杨宗艳,等.中晚期非小细胞肺癌中西医疗效评价方法比较研究[J].中国中西医结合杂志,2010,30(7)：702-705.
[136]林丽珠.生存质量在中医肿瘤学综合疗效评价中的作用[J].中国肿瘤,2010,10(2)：80-82.
[137]杨宇飞,朱尧武,吴煜,等.中医药治疗恶性肿瘤综合疗效标准探讨及初步运用[J].中国中西医结合杂志,1999,19(6)：340-343.
[138]Choi H, Charnsangav C, de Castro FS, et al. CT evaluation of the response of gastrointestinal stromal tumors after imatinib mesylate treatment:a quantitative analysis correlated with FDG PET findings[J]. Am J Roentgenal,2004,183:1619-1628.
[139]Choi H, Charnsangavej C, Faria SC, et al. Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate:proposal of new computed tomography response criteria[J]. J Clin Oncol,2007,25(13):1753-1759.
[140]Choi H. Critical issues in response evaluation on computed tomography:lessons from the gastrointestinal stromal tumor model[J]. Curt Oncol Rep,2005,7(4):307-311.
[141]Choi H. Response evaluation of gastrointestinal stromal tumors [J]. Oneologist, 2008,13(Suppl 2):4-7.
[142]李东涛,凌昌全,郎庆波,等.以证候为内容的原发性肝癌中医疗效评价体系研究[J].中西医结合学报,2007,5(1)：15-22.
[143]余松林.医学统计学[M].北京：人民卫生出版社.2002：386-390.
[144]许致远.不同临床分期对中医药治疗原发性肝癌的预后评估和疗效分析[D].广州中医药大学,2005.
[145]王海鹏.原发性肝癌分期方法的比较研究[D].北京：中国协和医科大学,2006.
[146]中国抗癌协会.新编常见恶性肿瘤诊治规范[M].北京：中国协和医科大学出版社,1999：450.
[147]Custer B, Sullivan SD, Hazlet T K, et al. Global epidemiology of hepatitis B virus[J].J Clin Gastroenterol,2004,38(10 Suppl 3):S158-168.
[148]Llovet JM, Burmughs A,Bruix J. Hepatocellular carcinoma [J].Lancet,2003,362:1907-1917.
[149]Bruix J, Sherman M, LlovetJM, et al. Clinical management of hepatocellular carcinoma.Conelusions of the 2000 EASL conferenee[J]. J Hepatol,2001,35:421-430.
[150]Levy I, Sherman M. Staging of hepatocellular carcinoma:assessment of the CLIP, Okuda, and Child-Pugh staging systems in a cohort of 257 patients in Toronto[J]. Gut,2002, 50:881-885.
[151]Poon RT, Ng IO, Fan ST, et al. Clinicopathologic featurescofclong-term survivors and disease-free survivors after rescetion of hepatocellular careinoma:a study of a prospective cohort[J].J Clin Oncol,2001,19:3037-3044.
[152]Pompili M, Rapaccini GL, Covino M, et al. Prognostic factors for survival in patients with compensated cirrhosis and small hepatocellular carcinoma after pereutaneous ethanol injeetion therapy [J]. Caneer,2001,92:126-135.
[153]Farinati F, Rinaldi M, Gianni S, et al. How should patients with hepatocellular carcinoma be staged? Validation of a new prognostic system [J]. Cnaeer,2000,89:2266-2273.
[154]The cancer of the Liver Italian Program (CLIP) Investigators. Prospective validation of the CLIP seore:a new prognostic system for patients with cirrhosis and hepatocellular carcinoma[J].Hepatology,2000,31:840.
[155]Nanashima A, Sumida Y, Abo T, et al. Modified Japan Integrated Staging is currently the best available staging system for hepatocellular carcinoma patients who have undergone hepatectomy[J]. J Gastroenierol,2006,41:250-256.
[156]中国抗癌协会肝癌专业委员会.原发性肝癌的临床诊断与分期标准[J].肝脏,2004,9：67-68.
[157]Sangiovanni A, Del Ninno E, Fasani P, etal. Inereased survival of cirrhotic patients with hepatocellular carcinoma detected during surveillance[J]. Gastroenierology,2004, 126:1005-1014.
[158]Adachi E, Maeda T, Matsuma T, et al. Risk factors of introhepatic recurrence in human small hepatocellular carcinoma[J]. Gastroenterology,1995,108:768-775.
[159]Chen MF, Hwang TL, Jeng LB, et al. Postoperative recurrence of hepatocellular carcinoma. Two hundred five consecutive patients who underwent hepaticresection in 15 years[J]. Areh Sug,1994,129:738-742.
[160]The liver Cancer Study Group of Japan. Survey and follow-up study of primary liver cancer in Japan Report 11[J]. Liver,1995,36:208-217.
[161]Hanazaki K, Kajikawa S, Koide N, et al. prognostic factor after hepaticresection for hepatocellular carcinoma with hepatitis C viral infection:univariate and multiviate analysis[J]. Am J Gastorenterol,2001,96:1243-1250.
[162]张智坚,吴孟超,沈锋,等.TNM分期对评价肝细胞癌切除术预后的价值[J].中华肿瘤杂志,1999,21,293-295.
[163]Ueno S, Tanabe G, Sako K, et al. Diserimination value of the new western prognostic system (CLIPseore) for hepatocellular carcinoma in 662 Japanese patients [J]. Hepatolory,2001,34,529-534.
[164]赵文和,马志敏,周杏仁,等CLIP评分系统对评价手术切除肝癌预后的意义[J].中华外科杂志,2002,40：321-325.
[165]何招才.肝细胞癌不同分期方法对肝癌肝切除患者预后价值的比较研究[D].湖南：中南科大学,2009.