內(nèi)科學(xué) 肝癌-葉勝龍

1、Primary Liver CancerLiver Cancer InstituteZhongshan HospitalFudan UniversityDefinitionMalignant tumors from Hepatocytes and intrehepatic cholangiocytes “ King of Cancer ”- Short-term survival period（3 - 6m） High incidence at age 40 - 50yEpidemiologyEtiology & PathogenesisPathologyClinical Manifestat

2、ionClinical StagingDiagnosisTreatmentPreventionIncidenceNo. 5 in the world1990Worldwide - 541000China - 318000 (58.8%)2005Worldwide - 626000China: 55%The Second Cancer Killer in ChinaUrban - Lung,Liver Rural - Stomach, LiverMortality in China - 20.4/100000 (1990-1992)High Risk AreasWorldwide Sub-Sah

3、aran Africa（Mozambique, Uganda, South Africa） Southeast Asia（China, Malaysia, Indonesia, Singapore ）China Southeast（Jiangsu, Guangxi, Guangdong, Fujian） Highest：Qidong, Haimen, Fushui, ShundeWorldwide Incidence of Liver CancerEpidemiologyEtiology & PathogenesisPathologyClinical ManifestationClinical

4、 StagingDiagnosisTreatmentPreventionHigh-Risk Factors for HCCHepatitis virus infection（HBV，HCV）CirrhosisAflatoxin B1 ingestionDrinking water pollution （Microcystin, Nodularin）Alcohol abuse（West countries and North China）Genetic susceptibilityChemical carcinogenParasitesNatural History of HCCEpidemio

5、logyEtiology & PathogenesisPathologyClinical ManifestationClinical StagingDiagnosisTreatmentPreventionPathology（Macrostructural Feature）Eggle分型（1901） 巨塊型，結(jié)節(jié)型，彌漫型我國(guó)肝癌病理協(xié)作組分型（1982） 塊狀型： 5 cm （巨塊型 10cm） 結(jié)節(jié)型： 5 cm (小癌型：?jiǎn)蝹€(gè)或相鄰2個(gè)結(jié)節(jié)直徑之和 Lymphatic Direct spread, Infiltration ImplantationPortal VeinIntrahepat

6、ic spreadHepatic VeinSystemic metastasis（Lung, Adrenal gland, Bone, Lymph nodes, Brain, Stomach, Colon）EpidemiologyEtiology & PathogenesisPathologyClinical ManifestationClinical StagingDiagnosisTreatmentPreventionClinical ManifestationSymptoms（Moderate and late stage）Hepatalgia腫瘤增大迅速、結(jié)節(jié)破裂Anorexia肝功損

7、害，胃腸道壓迫Hypodynemia, Athrepsy代謝產(chǎn)物，厭食，惡病質(zhì)Abdominal distention腫瘤巨大，腹水，肝功障礙Abdominal mass左肝劍突下，右肝肋下Fever腫瘤壞死，感染，代謝Jaundice膽道癌栓，肝膽管壓迫，合并肝細(xì)胞性黃疸Hemorrhagic tendency肝功障礙Diarrhea肝功障礙，門脈癌栓Right shoulder pain橫膈刺激Acute abdomen小破裂Clinical Manifestation SignsHepatomegaly腫瘤結(jié)節(jié)生長(zhǎng)（不同部位）Jaundice瘤栓阻塞，結(jié)節(jié)壓迫（晚期表現(xiàn)）Ascites癌

8、栓（門脈主干、肝靜脈、下腔靜脈），破裂（血性），浸潤(rùn)（癌性）Lymphadenhypertrophy左鎖骨上Splenomegaly 門脈高壓，癌栓Swollen limbs低蛋白，腹水Cirrhosis肝掌，蜘蛛痣，腹壁靜脈曲張Clinical Manifestation Paraneoplastic syndromeErythrocytosis促紅素生成Hypoglycemia胰島素異位分泌？ 糖原貯存減少？HypercalcemiaHyperlipemiaClinical Manifestation Metastatic SymptomsLung 右側(cè)多見，可有胸水Bone局部壓痛Spi

9、nal cord神經(jīng)受壓癥狀Brain神經(jīng)定位體征Complications（Main causes of death）Upper gastrointestinal hemorrhage（15）門脈高壓，癌栓，凝血機(jī)制低下，胃腸道粘膜損害、水腫Rupture of cancer nodules（10）腫瘤增大壞死液化，外力沖擊Hepatic encephalopathy（30）多見于終末期Secondary infection肺炎，敗血癥，腸道感染Systemic exhaustionEpidemiologyEtiology & PathogenesisPathologyClinical Ma

10、nifestationClinical StagingDiagnosisTreatmentPreventionTNM Staging SystemT0 No evidence of primary tumorT1 Solitary tumor without vascular invasionT2 Solitary tumor with vascular invasion; or multiple tumors none more than 5 cmT3 Multiple tumors more than 5 cm； or tumor involving a branch of the por

11、tal or hepatic veinT4 Tumor with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneumN0 No regional lymph node metastasisN1 Regional lymph node metastasisM0 No distant metastasisM1 Distant metastasisTNM StagingStage T1 N0 M0Stage T2 N0 M0Stage A T3

12、 N0 M0Stage B T4 N0 M0Stage C T1-4 N1 M0Stage T1-4 N0-1 M1我國(guó)原發(fā)性肝癌分期標(biāo)準(zhǔn)分期 腫瘤 癌栓 淋巴結(jié) 轉(zhuǎn)移 Child-Pugha 單個(gè)，3cm 無 無 無 Ab 半肝1-2個(gè),5cm 無 無 無 Aa 半肝1-2個(gè),10cm 無 無 無 A 兩半肝2個(gè),5cm 無 無 無 A b 半肝12個(gè),10cm 無 無 無 A 兩半肝2個(gè),5cm 無 無 無 A 任意 門V分支、肝V或膽管 無 無 A 任意 無 無 無 Ba 任意 門V主干或下腔V 有或無 有或無 A或B 任意 有或無 有 有或無 A或B 任意 有或無 有或無 有 A或Bb

13、 任意 有或無 有或無 有或無 C EpidemiologyEtiology & PathogenesisPathologyClinical ManifestationClinical StagingDiagnosisTreatmentPreventionDiagnosisMarkersAFPAFP-L3DCPGGT-AFUImagingUltrasonography (US)Computer tomography (CT)Magnetic resonance imaging (MRI)AngiographyScintigraphyDiagnosis Tumor markers甲胎蛋白 ( a

14、lpha-fetoprotein, AFP)Normal： 25% 良性肝病 25%單克隆抗體Diagnosis - Tumor markers異常凝血酶原（-羧基凝血酶原，des- -carboxy prothrombin，DCP）正常值 1 cm）提示占位性病變性質(zhì)：液性、實(shí)質(zhì)性、良性、惡性明確腫瘤位置及其與重要血管的關(guān)系了解肝內(nèi)播散和浸潤(rùn)情況引導(dǎo)穿刺活檢和介入治療Imaging Diagnosis Ultrasonography (US)小肝癌：薄包膜低回聲光團(tuán)（77）或暗環(huán)圍繞的不均勻高回聲光團(tuán)大肝癌：多結(jié)節(jié)，子結(jié)節(jié)，聲暈，厚包膜，壞死區(qū)彩色血流成象（CFI）：結(jié)節(jié)內(nèi)局灶性彩色血流增多

15、， RI 0.75門靜脈癌栓Imaging DiagnosisUltrasonography (US)Imaging DiagnosisCTEvaluation：明確病灶的部位、數(shù)目、大小、血管關(guān)系提示病變性質(zhì)，增強(qiáng)掃描有助鑒別放射治療定位了解肝周組織受累情況Imaging DiagnosisCT平掃：多為不均勻低密度病灶增強(qiáng)掃描：動(dòng)脈期呈高密度增強(qiáng)，門脈期低密度病灶對(duì)比更明顯，可見門脈癌栓Imaging DiagnosisCTImaging DiagnosisMRI能獲得三維圖象軟組織分辨率高無放射線損傷顯示肝內(nèi)外膽管和血管Imaging DiagnosisMRIT1加權(quán)象病灶呈高低混合區(qū)T

16、2加權(quán)象呈不規(guī)則、不均勻高信號(hào)病灶周圍可見線條狀低信號(hào)影( “假包膜” )肝內(nèi)外血管受侵犯，癌栓表現(xiàn)為 T1中強(qiáng)度信號(hào)、T2高強(qiáng)度信號(hào)Imaging DiagnosisMRIT1WIT2WIT1加權(quán)增強(qiáng)動(dòng)脈期增強(qiáng)靜脈期Imaging Diagnosis Scintigraphy肝臟平面顯象膠體99mTc單光子計(jì)算機(jī)斷層顯象( SPECT )陽(yáng)性顯象67Ga，99mTc-PMT肝血池顯象99mTc-RBCImaging DiagnosisAngiography明確肝占位病變(400 g/L，能排除活動(dòng)性肝病、妊娠、生殖系胚胎源性腫瘤及轉(zhuǎn)移性肝癌，并能觸及堅(jiān)硬腫塊的肝臟或影像學(xué)檢查有明確的肝癌特征

17、性占位性病變者。2AFP400 g/L，能排除活動(dòng)性肝病、妊娠、生殖系胚胎源性腫瘤及轉(zhuǎn)移性肝癌，并有兩種影像學(xué)檢查具有肝癌特征性占位病變或有兩種肝癌標(biāo)志物（AFP異質(zhì)體、異常PTT、GGT-、AFU等）陽(yáng)性及一種影像學(xué)檢查具有肝癌特征性占位性病變者。3有肝癌的臨床表現(xiàn)，并有肯定的肝外轉(zhuǎn)移病灶（包括肉眼可見的血性腹水或在其中發(fā)現(xiàn)癌細(xì)胞）并能排除轉(zhuǎn)移性肝癌者。 Diagnostic Procedure AFP-L3 Biopsy Pathological Diagnosis His Liver AFP Ultrasound Clinical Diagnosis Sign function Othe

18、r markers CT / MRI Isotope AngiographyDifferential DiagnosisAFP Positive無占位： 妊娠 睪丸或卵巢腫瘤 活動(dòng)性肝?。篈FP與ALT絕對(duì)值和動(dòng)態(tài)變化有占位：少數(shù)轉(zhuǎn)移癌（胃、胰腺）Differential DiagnosisAFP NegativeOccupied UltrahepaticIntrahepatic Liquid（Cyst, Abscess）Solid Benign（Hemangioma）Malignant Metastatic cancerPrimary CholangiocarcinomaHepatocell

19、ular carcinomaActive Liver DiseasesAFP多在 400 g/L 以下AFP動(dòng)態(tài)變化與ALT波動(dòng)相關(guān)AFP異質(zhì)體LCA結(jié)合型 25%定位診斷（）或?yàn)橛不Y(jié)節(jié)Liver Cyst多無癥狀，無肝病背景多合并腎囊腫，常有家族性B超表現(xiàn)為液性暗區(qū)CT增強(qiáng)掃描無造影劑填充Liver Abscess可有感染史，多有炎癥表現(xiàn)（發(fā)熱、肝區(qū)叩痛、血象增高）B超及CT呈液性暗區(qū)，四周有較厚炎癥反應(yīng)區(qū)肝穿刺抽吸可獲膿液Hemangioma無癥狀，多無肝病背景，肝硬化不明顯小病灶超聲多呈高回聲，RI0.5CT增強(qiáng)掃描造影劑由外周向中心填充并滯留核素血池掃描（）HemangiomaB超C

20、O2造影Metastatic Liver Cancer原發(fā)灶多來自胃腸道多無肝病背景超聲及CT可見肝內(nèi)大小相仿多數(shù)結(jié)節(jié)CEA、CA19-9多為陽(yáng)性EpidemiologyEtiology & PathogenesisPathologyClinical ManifestationClinical StagingDiagnosisTreatmentPreventionKey Factors for TreatmentTumor Size and NumberTumor Involvement AreaTumor Emboli of Main Portal VeinLiver Compensatio

21、nSurgical TreatmentHepatectomyNonresection Ligation Catheterization CryotherapyTransplantationSurgical TreatmentHepatectomy全身情況好，無嚴(yán)重心、肺、腎功能障礙肝功能代償（ALT, SB, A/G, GGT, PTT）無腹水、肢腫或遠(yuǎn)處轉(zhuǎn)移病變局限于一葉或半肝，未累及門靜脈主干和下腔靜脈Surgical Resection切除治療原則合并肝硬化的小肝癌，以局部切除為主腫瘤包膜完整者傾向于局部切除左葉腫瘤盡可能規(guī)則性切除，右葉腫瘤一般作部分切除亞臨床復(fù)發(fā)和單個(gè)轉(zhuǎn)移可再手術(shù)切除

22、非切除姑息外科優(yōu)于明顯殘癌的姑息切除Surgical TreatmentArterial Ligation (Embolization) / Catheterization手術(shù)探查證實(shí)腫瘤不能切除（肝內(nèi)多發(fā)、腫瘤巨大緊貼肝門、破裂出血難以控制）切后殘癌，復(fù)發(fā)可能大大肝癌二期切除準(zhǔn)備無黃疸腹水，肝功能基本代償（ALT50%）無其他主要臟器嚴(yán)重病變Surgical TreatmentCryotherapy嚴(yán)重肝硬化，不能耐受手術(shù)切除腫瘤緊靠大血管，不宜手術(shù)切除主瘤切后殘留結(jié)節(jié)不能再切除的復(fù)發(fā)癌切前應(yīng)用預(yù)防術(shù)后復(fù)發(fā)Surgical TreatmentLiver transplantation適應(yīng)證：

23、小肝癌合并嚴(yán)重肝硬化，50歲以下，無活動(dòng)性肝病，無黃疸、腹水、遠(yuǎn)處或腹腔內(nèi)廣泛轉(zhuǎn)移，無下腔靜脈癌栓，無心、肺、腎嚴(yán)重疾患，無感染病灶或糖尿病存在問題：腦死亡供體，費(fèi)用，療效Non-surgical TreatmentInterventional Radiology-TACELocal AblationRadiotherapyChemotherapyBiotherapyTraditional Chinese MedicineNon-surgical TreatmentTransarterial Chemoembolization（TACE）不能切除的肝癌：右葉為主或較大、多發(fā)腫瘤切除術(shù)前縮小腫瘤

24、，有助根治切除術(shù)后消滅殘癌減少?gòu)?fù)發(fā)肝癌破裂緊急止血復(fù)發(fā)肝癌無法切除減輕癥狀，控制疼痛、出血及動(dòng)靜脈瘺 TACENon-surgical Treatment- Local AblationPercutaneous ethanol injection (PEI)Radiofrequency ablation (RFA)Microwave coagulation therapy (MWCT)High-intensity focused ultrasound (HIFU)Argon-helium targeting cryotherapyLocal Ablation Percutaneous Etha

25、nol Injection（PEI）Indication肝功能基本正常腫瘤結(jié)節(jié)直徑小于 3 cm腫瘤結(jié)節(jié)總數(shù)不超過3個(gè)PEI小肝癌與手術(shù)治療療效相似對(duì)肝功能影響小并發(fā)癥少，易耐受纖維間隔難以均勻彌散局部復(fù)發(fā)率高反復(fù)多次注射，增加針道轉(zhuǎn)移危險(xiǎn)Radiofrequency Ablation (RFA)射頻電流使組織和細(xì)胞脫水、離子振蕩產(chǎn)生高熱（70-110 )，凝固壞死主要用于治療小肝癌多彈頭射頻和外套針冷卻可提高療效RFA for Small HCCWang ZSMao YYRFA for Small HCCRadiotherapyIndication全身狀況較好，肝功能基本正常腫瘤較局限（主要

26、位于右葉）， 10 cm肝門區(qū)腫瘤或侵入膽管致劇痛對(duì)癥或姑息治療Radiotherapy全肝照射局部照射全肝移動(dòng)條照射術(shù)中定位局部照射超分割照射適形調(diào)強(qiáng)放射ChemotherapyIndicationPost-palliative resectionCombination in non-surgical treatmentLocal administration with hepatic arterial catheterizationChemotherapy常用藥物：氟脲嘧啶（5-Fu） 順氯氨鉑（CDDP） 絲裂霉素C（MMC） 阿霉素（ADM）方法：聯(lián)合，局部，化療栓塞Biotherap

27、yCytokinesCellular TransferMonoclonal AntibodiesCancer VaccinesAnti-angiogenesisGene TherapyBiotherapyPrincipleLocal-regional administrationCombination with other therapiesPrevention of recurrence and metastasisTraditional Chinese MedicineIndication手術(shù)、放療、化療的輔助治療腫瘤巨大或彌散分布明顯肝功能損害，嚴(yán)重肝硬化晚期患者Traditional

28、Chinese Medicine 中醫(yī)治則健脾理氣理氣消導(dǎo)益氣補(bǔ)血清熱解毒活血化瘀軟堅(jiān)散結(jié)Complication TreatmentRupture & BleedingUpper GI hemorrhageObstructive jaundiceHepatic comaSymptomatic TreatmentAscitesCancer feverCancer painCachexiaHypoglycemiaManagement for Liver Cancer 亞臨床復(fù)發(fā)或轉(zhuǎn)移 根治性切除 再切除 姑息性切除 綜合治療 手術(shù)探查 姑息外科 腫瘤 5y-1261 cases, 10y-363

29、 cases (Follow-up by 2006)U.S. survivors (1905-1970) 5y-45 cases (Curutchet, 1971)EpidemiologyEtiology & PathogenesisPathologyClinical ManifestationClinical StagingDiagnosisTreatmentPreventionPrimary Prevention of HCCWater reform prevent water pollution, improve water qualityFood controlalteration of food formation, food custody, molds prevention and detoxicationHepatitis Prevention prevention and