原发性肝癌

原发性肝癌,韩国宏 第四军医大学第一附属医院内科教研室,Long-Term Relative Survival Rates for Patients (Diagnosed, SEER Program, All Races, Men and Women),一、组织学分型 肝细胞癌（HCC） 85-90% Hepatocellular carcinoma 胆管细胞癌（CCC） 5% Cholangiocellular carcinoma 混合细胞癌（HCC+CCC） 5%,二、流行病学,肝细胞癌发生于世界范围，尤其是我国等亚洲和非洲国家 全球第六位的癌症和第三位最常见引起死亡的癌症全球每年60万人新诊断，中国占50% 全球每年60万人，中国每年30万人（50%）死于肝癌,Worldwide Incidence of Hepatocellular Carcinoma,High ( 30:100,000),Low or data unavailable ( 3:100,000),Intermediate (3-30:100,000),Worldwide Incidence of Hepatocellular Carcinoma,HCC Epidemiology,El-Serag HB, Gastroenterology 2004,肝癌的全球发病情况,Parkin DM, et al. CA Cancer J Clin 2005;55:74108,* 包括HCC及胆管细胞癌（5cm，最常见,2、结节型：5cm,3、弥漫型： 较少见,4、小癌型： 单结节3cm， 两癌结节之和10 cm,块状型5 cm,结节型,Multiple smallfoci of HCC,HCV Cirrhosis and HCC,正常肝脏,病毒性肝炎,肝硬化,原发性肝癌,肝癌发生“三部曲”,: high-grade dysplastic nodule,: well-differentiated,: moderately differentiated HCC,De novo hepatocarcinogenesis,?,?,Evolution of Hepatocellular Carcinoma,五、转移（1）1、肝内转移侵犯门静脉 癌栓 肝内多发病灶门脉主干癌栓 门脉高压,五、转移（2）,2、肝外转移血行转移：最早，肺（1/2）、脑、肾上腺淋巴转移：肝门、腹主动脉旁、腹膜后种植转移：腹膜、横膈 （肝癌破裂）,肝癌肺转移,局部：肝区疼痛肝肿大血管杂音,全身： 黄疸发热肝硬化征象转移灶症状,六、临床表现 （1）,Clinical Features at Presentation,SymptomsPercent of PatientsNone23%Abdominal Pain32%Ascites 8%Jaundice 8%Anorexia/weight loss10%Malaise 6%Bleeding 4%Encephalopathy 2%,Gastroenterology 2002,HCC Diagnosis,六、临床表现（2）,肝性脑病静脉曲张上消化道出血肝癌破裂出血继发感染,并发症,Diagnosis of Hepatocellular Carcinoma,七、诊断 早发现、早诊断、早治疗,1、AFP HCC特异性最强，早期诊断指标 HCC普查、诊断、疗效判定和预测复发 HCC的阳性率70-90% 假阳性：肝炎、肝硬化、生殖胚胎瘤及肝转移瘤,2、影像学诊断,(1) 超声 肝癌影像诊断中的首选方法,(2) CT,Plain CT Dynamic CT Delayed CT,(3) MRI,(4) DSA,Dual Blood Supply of Liver,The vascular supply of HCC arises from the hepatic artery through neovascularization. Imaging of the liver has to be performed in a triple phase manner to account for the early arterial phase followed by the portal venous phase and the delayed phases,Yu JS, et al, Am J Roentgenol 1999,HCC Diagnosis,Arterial phase,Venous phase,Arterial phase,Washout in HCC,Washout in HCC,HCC Diagnosis,Venous phase,Arterial phase,Washout in HCC,Washout in HCC,HCC Diagnosis,Non-contrast,: high-grade dysplastic nodule,: well-differentiated,: moderately differentiated HCC,De novo hepatocarcinogenesis,?,?,小肝癌的早期诊断- CTAP 和 CTHA,Portal,supply,Arterial,supply,LRN,LDN, HDN,wd-HCC,Classicl HCC,Portal supply,Hepatic arterial supply,Abnormal arterial supply,Stepwise Hepatocarcinogenesis and Changes of Intranodular Blood Supply,LDN: low-grade dysplastic nodule, HDN: high-grade dysplastic nodule,S.M. vein,Celiac a.,Intestine,CT during Arterial Portography (CTAP),Contrast injection,into sup. mesenteric a.,S.M. vein,Sup. mesenteric a.,Celiac a.,Intestine,CT during Hepatic Arteriography (CTHA),Contrast injection,into hepatc a.,A combined DSA and helical CT system,(CT/ANGIO system, Toshiba,Japan),CT/ANGIO System,Moderately differentiated HCC (classical HCC),CTHA,CTAP,CTAP CTHA,肝细胞癌诊断标准 (BCLC、AASLD),病理诊断： 细胞学或组织学诊断流程1、小于1cm: 随诊 每3-4月 超声2、1-2cm: 两种特征性影像学表现 或 活检 3、大于2cm者： 肝硬化背景 + 一种特征性影像学表现 肝硬化背景 + AFP(200) + 一种影像学诊断影像学：增强CT、MRI、超声造影 特征性表现： 动脉期造影剂的摄取伴静脉期的快速清除,Guidelines for Diagnosis of HCC,Typical features of HCC = vascular nodule on arterial phase with washout in delayed phases,Ultrasound findings,Bruix J, et al, Hepatology 2005,HCC Diagnosis,Screening / Surveillance for Hepatocellular Carcinoma,Recommendations Screening,Surveillance should be performed using US (level II)AFP should not be used for screening (level II)Screening should be done / 6 months (level II)Higher risk does not imply shorter interval (level III),八、鉴别诊断,肝海绵状血管瘤肝脓肿脂肪肝肝硬化转移性肝癌邻近肝区的肝外肿瘤,转移性肝癌,九、肝癌治疗现状,外科切除： 30%（肿瘤大小、部位、多中心、肝功） 肝移植: Milan criteria (单结节5 cm 或 两到三个3 cm) 介入治疗：肝动脉化疗栓塞 (TACE) 不能手术切除或术后复发肝癌的首选疗法 消融治疗：Imaging-guided delivery of energy for ablation 经皮肝穿无水酒精注射治疗 经皮肝穿射频治疗 经皮肝穿微波治疗 经皮肝穿（或手术）冷冻治疗,BCLC 分期系统，2010,Semin Liver Dis 1999;19:329338 to 2010;30:61-74,多个肿瘤,门脉转移,N1,M1,Tumor Stage (number & size, MVI, EHS) Liver functionHealth status, PST/ECOG,单发结节,2cm,3 个结节, 3cm,Efficacy of treatment,Child Pugh A-B,Child Pugh A,Child Pugh C,随机对照试验（50%） 中位生存时间11-20月,对症(20%) 生存期3月,BCLC 分期系统及治疗策略,TACE,多个肿瘤,门脉转移,N1,M1,新药治疗,索拉非尼,Radiofrequency Ablation for Hepatocellular Carcinoma,Probe insertion,Deployment of tines and treatmentof tumor and surrounding region,HCC Treatment,大血管旁的HCC,Embolic Materials(Lipiodol+doxorubicin+contrast),Lipiodol (iodized poppy seed oil),Gelatin sponge particles,EMULSIONS,EMULSIONS,Water (Drug) in Oil (Lip) Oil (Lip) in Water (Drug),-in blood- -in blood-,D,LIP,D,LIP,Portal vein,Hepatic vein and liver Segments in Angio,Subsegmental Transarterial Chemoembolization of HCC,Subsegmental Transarterial Chemoembolization of HCC,Dynamic CT,Lipiodol CT,Celiac a.,Catheter in A8,Subsegmental TACE for small HCC in S8,原发性肝癌治疗难点,大多合并严重肝硬化易发生肝内播散和远处转移手术切除率低(20%)术后复发率高,Molecular Events in the Multi-Step Development of Hepatocellular Carcinoma,Normal liver,HBVHCValcohol,Chronichepatitiscirrhosis,p53 mutationreduced p21WAF1/CIP1expression,Rbdysfunction,EarlyHCC,Advanced/Metastatic HCC,E cadherininactivation,p16INK4inactivation,Aberrant DNAmethylation,Dysplasia,p53 mutation,Dietary aflatoxin,Molecular Events in the Multi-Step Development of Hepatocellular Carcinoma,Hui and Makuuchi, Scand J Gastroenterol 1999,HCC Pathogenesis,Llovet et al. NEJM 2008;