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1、The normal liver,The largest organ inside the bodyLocated just below the ribs on the right sideLiver cells are called hepatocytesHas many functions(filter,produces enzymes and bile),Numbers about HCC,Number 5 in the worldNumber 3 among cancer mortality5 year survival rate is approximately 6.9%About
2、50%of the worlds cases occur in China,The king of cancer,Global Incidence of HCC Distribution,Definition,A primary malignancy of hepatocellular origin,CT image,HCC,Risk factors,Hepatitis B：an infectious disease caused by hepatitis B virus(HBV)Hepatitis C,HBV,HCV,Evidence of association between HBV a
3、nd HCC,Prevention of HBV reduces risk of subsequent HCCHBV carriers have shown very high relative risks for HCCHBV sequences are present in HCC tissuesHigh mortality rates for HCC also have high HBV infection rates,Global Incidence of Hepatitis B Distribution,Risk factors,Cirrhosis of the liver(肝硬化)
4、A consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis(纤维化),scar tissue and regenerative nodules(再生结节).,Which one is normal?,Basic Mechanism of Liver Fibrosis,AlcoholHepatitis VirusCongenital DisordersCholestasisNonalcoholic Steatohepatitis,肌纤维母细胞,细胞外基质,Aflat
5、oxin(黄曲霉素)Toxic and carcinogenic substancesMetabolized by the liver,Risk factors,Peanut,Risk factors,Water pollution：blue-green algae,blue-green algae(蓝绿藻）,AlcoholNonalcoholic Fatty Liver DiseaseType 2 DiabetesObesityGender,Risk factors,GASTROENTEROLOGY 2004;127,GASTROENTEROLOGY 2007;132:25572576,Th
6、e development of hepatocellular carcinoma in human,Pathology(病理),Three morphologic types Block type（块状型）Diameter 5,associated with cirrhosisNodular type（结节型）Diameter5,associated with noncirrhotic liverDiffuse type（弥漫型）less commonCytological typesHepatoma（肝细胞癌）Cholangiocarcinomas（胆管癌）,大小 21 14 12 CM,
7、巨块型,癌块的直径在厘米以上,大小 4.5 3 3 CM,结节型,大小1.51.0 CM,小肝癌,弥漫型,不易与肝硬化区分,病理,细胞分型肝细胞型：占90%，由肝细胞发展而来 胆管细胞型：少见，由胆管上皮细胞发展而来混合型：更少见，癌细胞呈过渡形态,Liver metastasis pathway,Intrahepatic metastasis（肝内转移）Out hepatic metastasis（肝外转移）,主要临床表现：1、肝区疼痛：最常见 性质：持续性胀痛或钝痛 机制：肿瘤增长快，肝包膜受牵拉 疼痛的有无、早晚及程度：与肿瘤生长速 度和所在部位有关 剧痛：癌结节破裂,临床表现,起病隐匿
8、，早期缺乏典型症状。就诊 时多为中晚期,2、肝肿大：为重要基本体征 特点：进行性肿大 典型体征：质硬、凹凸不平、有结节或 巨块、边缘不整、有压痛。血管杂音：肝癌动脉血管丰富而纡曲，粗动脉突然变细；巨大癌肿压迫肝动脉或腹主动脉 肝肋下不大非典型体征 早期；癌肿位于膈面,临床表现,3、黄疸晚期征象肝细胞性黄疸；阻塞性黄疸 机制：肝细胞大面积损害 癌肿压迫或侵犯肝门胆道 癌组织堵塞胆道4、肝硬化征象：脾大、腹水、食道胃底静脉曲张 腹水特点：增长快、血性,临床表现,5、恶性肿瘤全身表现发热：低热肿瘤代谢旺盛；肿瘤坏死产物吸收 高热并发胆道感染食欲不振，乏力，进行性消瘦，恶病质6、转移灶症状7、伴癌综合
9、症 表现：自发性低血糖症 红细胞增多症 高钙血症、高脂血症、类癌综合症,临床表现,Caput medusae(脐周静脉曲张,海蛇头),Spider Angiomas(蜘蛛志),Palmar Erythema(肝掌),Jaundice（黄疸）,Ascites（腹水）,Accumulation of plasma in the peritoneal cavityCaused by increased pressure forcing fluid out of intravascular space into cavityPlasma contains albumin，so circulating
10、proteins decreased serum osmotic pressureIntravascular fluid depletion stimulates kidney to conserve sodium and water,Ascites（腹水）,Complications,Hepatic encephalopathy（肝性脑病）Usually protein breaks down into ammonia in GI tract,then ammonia into urea-excreted by the kidneysLiver cannot convert ammonia
11、into urea，Results in serum ammonia levels Toxic to the central nervous systemTreatmentsLow protein dietControl GI bleeding,Gastrointestinal bleeding（消化道出血）Treatments,Complications,Blakemore Tube三腔二囊管,Sclerosing Procedure硬化剂注射止血,Liver cancer rupture and bleeding(肝癌结节破裂出血)Treatment：surgery Infection,C
12、omplications,1、肝性脑病(占1/3死因，提示预后差）2、上消化道出血(占15%死因）食管胃底静脉曲张破裂胃肠道粘膜糜烂、凝血机制异常3、肝癌结节破裂出血（包膜下或腹腔，血性腹水、休克）4、继发感染（肺炎或原发性腹膜炎等）,并发症,Laboratory examination,Alpha-fetoprotein Blood Test(AFP)1.Diagnosis AFP produced by 70%of HCC 500ng/ml for 4 weeks 200ng/ml for 8 weeks AFP over time 2.Monitor a patients respons
13、e to therapy and for cancer recurrenceBlood tests of liver function Blood tests for Hepatitis B and C,Ultrasound test,Tumors may produce different echoes,A procedure that makes a series of detailed pictures,CT:Venous Phase,CT:Arterial Phase,CT scan,Magnetic resonance imaging(MRI),Liver biopsy,一、肝癌标记
14、物甲胎蛋白（AFP）1.临床意义：诊断原发性肝癌特异性强，阳性率 70-90%，假阳性极少；早期诊断肝癌，先于症状8-11月；适用于普查、诊断、判断疗效、预测复发,临床检查,甲胎蛋白（AFP）2.诊断标准：AFP500g/l，持续4周AFP由低浓度逐渐升高不降AFP200g/l，持续8周3假阳性：妊娠、生殖腺胚胎瘤、肝病活动期4假阴性：与肿瘤分化程度、病理 变 化、检测方法有关,临床检查,其它肝癌标记物1、-GT-2同功酶2、APT（异常凝血酶原）3、血清岩藻糖苷酶（AFu）4、其他,临床检查,价值有限，临床少开展,二、影像学检查1、B超（筛查首选，d=2cm，彩超可提高阳性率）2、CT（诊断
15、、术前常规检查）3、MRI（多断面，血管结构清晰，非放射）4、肝血管造影（有创，未能定性定位者，行动脉栓塞治疗者）影像学进展：高清晰度CT，超声造影，PET-CT三、肝穿刺活检,临床检查,How is liver cancer diagnosed?,Medical historyPhysical exam,If a patient has symptoms that suggest liver cancer,Blood tests,Image USCTMRI,Biopsy may not be required,Workup,A 55-year-old man was admitted to
16、hospital:Due to numbness and weakness on his right sideHis initial laboratory examination:AST:160 U/L,ALT 88 U/L,GGT 55 U/L,alkaline phosphatase 288 mg/DlThe patients medical history was significant for chronic HBV-related hepatitisWhat should doctors do with this patient?AFP 400 U/LCT scanNeedle bi
17、opsy-Pathological examination,Case 1:hepatocellular carcinoma,World J Gastroenterol 2004;10(11):1688-1689,高危人群的普查：1、有乙、丙肝炎病毒感染史2、35岁（特别是男性）3、慢性活动性肝炎4、各种病因所致的肝硬化5、报警征像：肝区疼痛、进行性肝大、贫血、消瘦普查措施：AFP、B超（随诊）,诊断,一、非侵入性诊断标准1、影像学（两种影像学均显示2cm的肝癌特征性占位病灶）2、影像学结合AFP（一种影像学检查+AFP400ug/L 排除妊娠、生殖性肿瘤、继发性肝癌等）二、侵入性诊断标准影像学
18、不能确诊的2cm的肝内结节肝穿刺活检,诊断,1、继发性肝癌（原发癌表现，AFP一般不高）2、肝硬化（难点，随访）3、病毒性肝病（AFP和ALT动态 曲线分离）4、肝脓肿（发热、WBC高、影像学）5、肝局部脂肪浸润（增强CT）6、肝外邻近器官肿瘤（影像学，AFP）7、肝内非癌性占位病变（影像学，肝穿）8、其它AFP升高的非肝癌病变（生殖性肿瘤）,鉴别诊断,肝癌治疗方法,外科：肿瘤切除、姑息性手术（肝A结扎、插管、门V插管、冷冻、热凝）、肝移植经导管介入：肝A化疗栓塞（TACE）、门V 化疗栓塞经皮局部毁除术：瘤内注射、瘤内加热（射频、激光、微波、高强聚焦超声）、冷冻（氦氩）化疗放射免疫、导向、中
19、医,肿瘤靠近大血管,PV.R,LIMITATION of HEPATECTOMY,Treatments,SurgeryThe only proven potentially curative therapy for HCC(Hepatic resection or liver transplantation)Chemotherapy and radiation treatments are not usually effective,肝癌序贯治疗选择,肝癌,期,期,期,外科切除,外科姑息手术（不能切除者）,导管介入(TACE)(癌肿范围大者),经皮毁除术(PEI,PRFE,HIFU)(癌肿范围
20、小者),晚期,追踪,外科切除,化疗免疫治疗中药核素照射,高强超声聚焦疗法(High intensity focused ultrasound,HIFU),原理：利用超声瞬间高温能量聚集适应症：肝癌、乳腺癌、骨肿瘤、软组 织肿瘤、肾癌等实体肿瘤优点：无创（不需穿刺），B超监视下适 形实时毁除，可治分散病灶缺点：设备要求高，手术时间长，全麻,高强超声聚焦刀（HIFU）,HIFU治疗原理,焦域,组织,探头示意图,HIFU治疗前 HIFU治疗后5个月,Contrast-Enhanced MRI,T1W,原发性肝癌HIFU治疗前后MR表现,多极射频肿瘤消融术,原理：高频震荡电流经过射频消融电极，使电极周
21、围离子发生震荡，离子相互 碰撞产生热量，使周围组织温度达到 80100，局部肿瘤组织因此发生凝 固性坏死甚至炭化。适应症：肝癌、肺癌、肾癌、脾脏及 肾上腺肿瘤等,多极射频肿瘤消融仪,射频肿瘤消融电极（多极）,原发性肝癌射频消融术,原发性肝癌射频消融术,治疗前,治疗中,经导管肝动脉化疗栓塞术(TACE)原理,肝血液供应：正常 肝A 25%、门V 75%肝癌 肝A 90%、门V 10%肝A栓塞癌区供血减90%，正常区30-40%肿瘤内血管迂曲，缺N支配，通透性高，碘油、带药微球易滞留,TACE疗效和适应征,短期疗效：75%癌块缩小，90%AFP下降远期疗效：复发率高，需联用其他疗法适应症：不能手术
22、的中晚期肝癌,介入治疗前肝脏CT示肝右叶后下段结节型肝癌,微导管肝右后叶下亚段(段)动脉高超选择性插管造影，显示富血管型肿瘤病灶,肝癌TACE治疗-病例1,经门V栓塞化疗,经脐V或经皮穿刺插管，操作复杂单用疗效不好，需和TACE联用,经皮乙醇注射（PEI）,方法：超声（其他影像）指导下单点、连锁注射优点：简便、有效，便于基层推广，有效率60-80%缺点：并发症（术后疼痛、发热、乙醇 中毒，罕有出血、气胸、感染等）适应症：多数，失去手术机会；多数，小肝癌（和手术疗效相近？）,经皮穿刺冷冻疗法氩氦刀,原理：导针穿刺癌瘤，接氩氦冷冻系统 输氩气-140 靶组织冰球 输氦气 25-40 复温优点：和经
23、皮热凝固疗效相似，较安全缺点：穿刺并发症,原则：早期诊断、手术根除 不能切除者采取综合治疗 个体化,治疗,多学科融合的序贯治疗,外科,化疗,放疗,生物治疗,介入治疗,中医治疗,肝癌,治疗,一、手术治疗适应症：1、诊断明确，病变局限于一叶或半肝者，未侵及肝门及下腔静脉者；2、肝功能代偿良好，PT不能低于正常50%；3、无明显黄疸、腹水或远处转移者、慢性活动性肝炎4、心、肺、肾功能良好，能耐受手术者5、术后复发，病变局限于肝的一侧者；6、经其它治疗，病灶明显缩小，估计能手术切除者。,治疗,病案,男性，40岁，肝区疼痛半月余，伴有乏力、纳差、消瘦。PE：巩膜黄染，肝肋下6cm，剑突下4cm，质硬，表面不平，有大小不等的结节，缘钝，压痛。脾肋下3cm，移动性浊音（+）初步诊断？下一步处理？,初步诊断,鉴别诊断,进一步检查,治疗原则,执业医师考试 肝癌病例分析,局部与全身并重的原则分期治疗的原则个体化治疗的原则生存率与生活质量并重的原则成本与效果并重的原则中西医并重的原则,治疗规范化,预后好的因素：瘤体小于5cm，能早期手术；癌肿包膜完整，无癌栓；机体免疫状态良好；预后差：合并肝硬化、远处转移、发生肝癌破裂、消化道出血等并发症,预后,
