外科學(xué)課件：Liver diseases2016Sep 肝臟疾病

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1、 肝臟疾病肝臟疾病This talk was based on but not limited to:2鄭樹森鄭樹森陳孝平陳孝平吳在德吳在德David C.SabistonLawrence W.Way肝膽外科肝癌肝膽外科肝癌診療涉及的指南診療涉及的指南n原發(fā)性肝癌規(guī)范化診治專家共識（2011）CSLC,CSCOn中國肝癌肝移植臨床實(shí)踐指南(2014版)n肝膽管癌臨床實(shí)踐指南（2015年NCCN-V1版）n原發(fā)性肝癌規(guī)范化病理診斷指南（2015版）CSLC,CSCOn肝癌局部消融治療規(guī)范的專家共識（2011）CSLC,CSCOnISGLS關(guān)于肝切除術(shù)后并發(fā)癥的定義（ISGLS definitio

2、n of Bile leakage after hepatobiliary and pancreactomy；ISGLS definition of Post-hepatectomy haemorrhage；Posthepatectomy liver failure-a definition and grading by the ISGLS）n肝衰竭診治指南（2012年版）中華醫(yī)學(xué)會(huì)感染病學(xué)分會(huì)肝衰竭與人工肝學(xué)組nThe Clavien-Dindo Classification of Surgical Complicationsn腹腔鏡肝切國際共識盛岡宣言（Recommendations fo

3、r laparoscopic liver resection a report from the second international consensus conference held in Morioka，2015）n腹腔鏡肝切除專家共識與手術(shù)操作指南（2013版）中華醫(yī)學(xué)會(huì)外科學(xué)分會(huì)肝臟外科學(xué)組n肝細(xì)胞癌合并門靜脈癌栓多學(xué)科診治東方肝膽外科醫(yī)院專家共識；廣東專家共識(2015版)n2015+普通外科圍手術(shù)期疼痛處理專家共識n肝切除術(shù)圍手術(shù)期過度炎癥反應(yīng)調(diào)控的多學(xué)科專家共識(2014版)n倡用圖文外科手術(shù)記錄專家共識（2015西安；中華醫(yī)學(xué)會(huì)外科學(xué)分會(huì)外科手術(shù)學(xué)學(xué)組）n肝切除術(shù)前肝臟儲(chǔ)

4、備功能評估的專家共識（2011）中華消化雜志n常用肝臟生物化學(xué)試驗(yàn)的臨床意義及評價(jià)共識（2010）中華醫(yī)學(xué)會(huì)肝病學(xué)分會(huì) n結(jié)直腸肝轉(zhuǎn)移診斷和綜合治療指南（2013）中華醫(yī)學(xué)會(huì)外科學(xué)分會(huì)胃腸外科學(xué)組 n結(jié)直腸癌肝轉(zhuǎn)移腹腔鏡一期聯(lián)合切除專家共識（2014）中華醫(yī)學(xué)會(huì)外科學(xué)分會(huì)胃腸外科學(xué)組n肝超聲造影應(yīng)用指南(中國)(2012年修改版)n美國肝病學(xué)會(huì)肝活檢推薦意見（2009）美國肝病學(xué)會(huì)n慢性乙型肝炎防治指南（2010）中華醫(yī)學(xué)會(huì)肝病學(xué)分會(huì) 中華醫(yī)學(xué)會(huì)感染病學(xué)分會(huì)n中國肝病診療管理規(guī)范白皮書（2014）中國醫(yī)院協(xié)會(huì)n慢性乙型肝炎特殊患者抗病毒治療專家共識：2014年更新n腫瘤藥物相關(guān)性肝損傷防治專家

5、共識（2014版）p1-43n抗癌藥物常見毒副反應(yīng)分級標(biāo)準(zhǔn)(WHO)n原發(fā)性肝細(xì)胞癌經(jīng)導(dǎo)管肝動(dòng)脈化療性栓塞治療技術(shù)操作規(guī)范專家共識（2011）中華醫(yī)學(xué)會(huì)放射學(xué)分會(huì)介入學(xué)組協(xié)作組n肝臟的傳說n普羅米修斯的傳說n肝臟不可或缺：動(dòng)物摘除肝臟，只能存活50小時(shí)n肝臟的功能：化工廠n代謝（糖、蛋白、脂肪、維生素、激素）、膽汁、解毒、免疫、凝血、再生n損害肝臟的原因：n病毒、藥物、酒精、食物污染、肥胖、不良習(xí)慣、情緒Catalogue nAnatomy&PhysiologynNeoplasms of liver1.Primary liver cancer 2.Metastasis neoplasms3.B

6、enign lesionsnLiver abscess56Essentials of Anatomy-1nThe liver lies in the right upper quadrant of the abdomen,under the protective rib cage,beneath the diaphragm and connected to the digestive tract by means of portal vein and biliary drainage system.nGilssons capsule,bare area,falciform lig.,coron

7、ary lig.,gastrohepatic lig.,hepatoduodenal lig.Winslows foramen1:liver;2:ribcage;3:spine;4:pelvisHistory-Childhood of liver cancer surgery 1888年，Langenbuch,1st hepatectomy(mass)1891年，Lucke,left hepatectomy(liver tumor)1899年，William,3 cases successful hepatectomy 1911年，Wendel,first right hepatectomy(

8、liver tumor)Carl Langenbuch(1846-1901)2.Huang ZQ.Digestive Surgery,2002,1(1):1-6.3.YM Jiang.J Shandong Med Univ 2000;3:20-3.Difficulty:complex anatomy,bleeding controlDifficulty:complex anatomy,bleeding controlHistory-Anatomy boost liver surgeryCouinaud segmental system Since mid-20 Since mid-20thth

9、 century,liver anatomy development century,liver anatomy development ensure dominant role of surgery in liver cancer therapyensure dominant role of surgery in liver cancer therapy1951，Hjortsjo(Switzerland)-segmental distribution of hepatic artery&biliary tracts1954，Couinaud segmental system2.Huang Z

10、Q.Digestive Surgery,2002,1(1):1-6.3.YM Jiang.J Shandong Med Univ 2000;3:20-3.9Essentials of anatomy-2nAmerican(lobar)system nFrench(Couinaud segmental)system.Claude Couinaud(16 February 1922,-4 May 2008)Claude Couinaud(16 Feb 1922,-May 2008)10Epitaph:a belated advertisement for a line of goods that

11、has permanently discontinued.(墓志銘:是一則已經(jīng)永久斷市的貨物的過時(shí)廣告)Claude Couinaud(16 Feb 1922,-May 2008)nCLAUDE COUINAUD is a French surgeon and anatomist who made significant contributions in the field of hepatobiliary surgery.He performed detailed anatomic studies of the liver and was the first to describe its

12、segmental anatomy.He developed the concept of plates and vasculobiliary sheaths of the liver,and performed the first controlled hepatectomy by isolating and dividing the Glissonian sheaths going into the liver,prior to parenchymal dissection.He also performed the first biliary bypass to the left hep

13、atic duct and the first segment III bypass.His book Le Foie:Etudes Anatomique et Chirurgicales stands as the seminal work on hepatobiliary surgery and anatomy of the 20th century.11Arch Surg.2002;137(11):1305-1310.doi:10.1001/archsurg.137.11.1305.12Essentials of Anatomy-313Essentials of Anatomy 4-Ca

14、uinaud Segmentation14Essentials of Anatomy 5-left hepatic vein15Essentials of anatomy 6-middle hepatic vein16Essentials of anatomy 7-portal vein planea web-based interactive 3D teaching model ofsurgical liver anatomy:http:/pie.med.utoronto.ca/VLiver/1718Essentials of anatomy 8-How good we could do?“

15、Era of Precision Liver Surgery”-accurate imaging,advanced tools,meticulous skills南方醫(yī)科大學(xué)珠江醫(yī)院：數(shù)字影像技術(shù)應(yīng)用于肝膽胰外科（三維可視南方醫(yī)科大學(xué)珠江醫(yī)院：數(shù)字影像技術(shù)應(yīng)用于肝膽胰外科（三維可視+虛擬手術(shù)）虛擬手術(shù)）Base of Precision Liver Surgery-Accurate imaging technologyItalian National Tumor Institute（INT）-Imaging：CT 3-D reconstruction Pre-operation evaluat

16、ion-1Italian National Tumor Institute（INT）-Imaging：liver volume estimationPre-operation evaluation-2GMU 1st Affiliated Hospital-EDDA Imaging：CT 3-D reconstruction 23Pre-operation evaluation-2Pre-operation evaluation-3Italian National Tumor Institute（INT）-liver fibrosis evaluation：fibroscan25“Era of

17、Precision Liver Surgery”Leftloberesection(preservingMHV)26“Era of Precision Liver Surgery”Seg.6,7resection(preservingRHV)“Era of Precision Liver Surgery”Seg 5,6 accurate allocation“Era of Precision Liver Surgery”block Seg-5 Glisson sheath“Era of Precision Liver Surgery”-Block Seg-5，8 Glisson sheath“

18、Era of Precision Liver Surgery”-Block Seg-6 Glisson sheath“Era of Precision Liver Surgery”-gross inspection pathology“Era of Precision Liver Surgery”-removal of Seg.5&6Video：20140923王應(yīng)勛右葉切除-錄像RHV MHV搏動(dòng)33341.The liver receives dual blood supply(75%via portal vein&25%via hepatic artery).2.50%oxygen su

19、pply via portal vein&50%via hepatic artery 3.Ligation of portal vein is catastrophic4.Pringles maneuver:15-20minEssentials of anatomy 9-circulation35nMetabolism:bilirubin,carbohydrate,lipid,protein,vitamin,drugs&toxins,.nCoagulationnImmune regulationnRegenerationnIndices of liver function:1.Liver tr

20、ansaminases:aspartate phosphatase(AST),alanine phosphatase(ALT)2.Alkaline phosphatases(ALP),Gamma-glutamyl transpeptidase(GGT)3.Albumin,pre-albumin4.Child-Pugh classification;ICG-15Essentials of physiology-liver function Child-Pugh classification36Pugh RNH,Murray-Lyon IM,Dawson JL,Pietroni MC and Wi

21、lliams R.Transection of the esophagus for bleeding esophageal varices.Brit.J.Surg.60:646-654,1973.*Lucey MR,Brown KA,Everson GT,Fung JJ,Gish R,Keeffe EB,et al.Minimal Criteria for Placement of Adults on the Liver Transplant Waiting ListLiver Transplantation ans Surgery,Vol.3,No 6(November),1997:pp 6

22、28-637Pre-operation evaluation-4Italian National Tumor Institute（INT）-liver function evaluation：ICG retention ratePre-operation evaluation-5Hepatic Trauma(skip)Liver Neoplasms問題：肝臟可以有多少種腫瘤？問題：肝臟可以有多少種腫瘤？生物學(xué)特性生物學(xué)特性 40 000例手術(shù)切除肝膽腫瘤病理診斷例手術(shù)切除肝膽腫瘤病理診斷 蛋白表型蛋白表型 肝膽系統(tǒng)腫瘤組織學(xué)分類肝膽系統(tǒng)腫瘤組織學(xué)分類(n=103)3大型大型:瘤樣病變、瘤樣病變

23、、良性腫瘤、惡性腫瘤良性腫瘤、惡性腫瘤6亞型亞型:肝細(xì)胞性、膽管上皮性、血管淋巴肝細(xì)胞性、膽管上皮性、血管淋巴性、肌纖維脂肪性、神經(jīng)內(nèi)分泌性、雜類性、肌纖維脂肪性、神經(jīng)內(nèi)分泌性、雜類 免疫病理學(xué)免疫病理學(xué) 組織起源組織起源 組織病理學(xué)組織病理學(xué) 惡性程度惡性程度Courtesy from Dr.Chong Wen Ming41Categorization benign：hemangioma，adenoma primary liver cancer malignant：secondary：metastasisPrimary Liver Cancer 43Primary Liver CancerH

24、istopathology types:n肝細(xì)胞癌肝細(xì)胞癌：Hepatocellular carcinoma(HCC);90%；n膽管細(xì)胞癌膽管細(xì)胞癌：Cholangiocellular carcinoma(cholangiocarcinoma);5%n混合細(xì)胞型肝癌混合細(xì)胞型肝癌：Mixed form(hepatocholangioma).1%2%nAnd more:-中國中國原發(fā)性肝癌診療規(guī)范（原發(fā)性肝癌診療規(guī)范（2011年版）年版）44ICCpathologist could make mistakes!45Background-overview 1.Hepatocellular car

25、cinoma(HCC)is a relatively rare malignancy in the western world,but one of the most frequent fatal tumors in the sub-Saharan African,Southeast Asia,Japan,the pacific Islands,Greece and Italy where the majority mankind lives.2.Had been considered as“in-curable disease”.3.Frequently detected only when

26、 palpable mass or dramatic clinical symptoms encouraged through clinical investigation.4.Diagnosis and treatment have been improved a lot in the past decades5.Optimized 5-yrs survival after radical resection is 3070%.46Background -etiology1.Hepatitis virus infection(HBV,HCV et al.)2.Mycotoxins(aflat

27、oxins)3.Contaminated water(pond or ditch water)4.Other causes1)Genetic factors2)Alcoholic cirrhosis3)Alpha-antitrypsin deficiency4)Hemochromatosis5)Plant alkaloid6)Oral contraceptives7)Androgens8)Vinyl chloride9)Trace elements(?):Cu,Zn,Ni and Co10)Parasites:Clonorchis sinensis 47壞死Multiple mechanism

28、s implicated in hepatocarcinogenesis-complexity of HCCFarazi PA,DePinho RA.Nat Rev Cancer.2006;6:674-687.Abnormal livernodulesExtensive scarring(collagen)HepatocellularcarcinomaDysplasticnoduleHyperplasticnoduleProliferation HBV HCV Alcohol Aflatoxin B1InjuryHepatocyteproliferativearrestStellate cel

29、lactivationChronic liver diseaseLiver cirrhosisModerate genomicinstability Marked genomicinstability Loss of p53Well differentiatedModerately differentiatedPoorly differentiatedNecrosis49Epidemiology -Worldwide1.HCCs are increasing in frequency in many parts of the world.2.HCC is more common in cert

30、ain areas.3.Incidence in Africa:164.6/100 000 (Mozambique)4.Standardized incidence rates 1-7/100 000/year (USA)5.49 times more frequently in men than in women;1:1 in group without preexistent liver disease.6.6 times higher for Orientals in USA than white population.50Epidemiology-China 1.1995 nation

31、wide survey of cancer mortality1)mortality 20.40/100,0002)29.07/100 000(men)11.23/100,000(women)2.Since 1990s,NO 2.tumor killer(following lung cancer in urban areas and,gastric cancer in countryside)and the leading cause of cancer death among Chinese aged 15 34.3.The main endemic areas are along the

32、 southeast seacoast of China,where the climate is warm and humid.4.The counties with the highest mortality(30/100 000)are:Fusui(Guangxi Zhuang Autonomous Region),Qidong(Jiangsu),Zhoushan(Zhejiang)and Tung an(Fujian).ChinaHCC pandemic areaGLOBOCAN 2008(IARC),Section of Cancer Information(19/10/2010)h

33、ttp:/globocan.iarc.fr/factsheets/cancers/liver.asp0 3.0 5.3 8.3 17.6 117 Age-standardised incidence rates per 100,000 Male morbidity:34.7/100,000（292,966例）Female morbidity:13.7/100,000（109,242 例）Male mortality:34.1/100,000（226,830例）Female mortality:13.1/100,000（105,249例）Over Over 55%55%of Global HCC

34、of Global HCCMales:females(Males:females(2.67:12.67:1)Epidemiology-1 Epidemiology-2HCC mortality distribution(China)Guangxi is high-risk area for HCCPopulation:45 million(40%are Zhuang minorities)Climate:generally hot and humid.The Tropic of Cancer across the middle of Guangxi,separates the northern

35、&southern part.Guangxi has the highest crude mortality rate of HCCHCC accounts for 1/3 of all cancer deaths(50%in males and 25%in females).Most HCC patients are farmers.Hepatitis virus,aflatoxin and contaminated water are recognized risk factors.Epidemiology-3HCC mortality distribution(Guangxi)Epide

36、miology-455Pathology nGross classification:1.Massive form:single predominant mass2.Nodular form:multiple nodules3.Diffuse form:infiltrative tumors throughout the parenchyma.nDifferentiation:nEncapsulated tumors have a relatively favorable prognosis.(Fibrolamellar hepatoma)nMetastasis:1.Lymph nodes(h

37、ilar,celiac)2.Lung3.Peritoneal cavity4.Portal or hepatic veins 56nEarly-stage HCC(sub-clinical HCC):no symptoms&signs n“Micro-HCC”微小肝癌微小肝癌：2.0cmn“Small HCC”小肝癌小肝癌：2.0cm 5.0cmn“Large HCC”大肝癌大肝癌：5.0cm 10.0cm57Hepatocellular carcinoma,liver,grossnA 2.0 cm HCC arising in a chronic viral hepatitis;the tu

38、mor,which had a predominant acinar architecture,produced abundant bile.58Hepatocellular carcinoma,liver,grossnNodule of hepatocellular carcinoma in chronic hepatitis C;the pale golden yellow color is common.59Hepatocellular carcinoma,liver,gross nThe neoplasm is large and bulky and has a greenish ca

39、st because it contains bile.To the right of the main mass are smaller satellite nodules.Thesatellitenodulesof this hepatocellular carcinoma represent either intrahepatic spread of the tumor or multicentric origin of the tumor.Satellite nodules&Tumor embolus6061Hepatocellular carcinoma,liver,grossnAn

40、other hepatocellular carcinoma with a greenish yellow hue.Such masses may also focally obstruct the biliary tract and lead to an elevated alkaline phosphatase 62HCC(fibrolamellar carcinoma),grossnWell demarcated fibrolamellar carcinoma with central scar;the surrounding liver is normal.Coarse lamella

41、r fibrosis is characteristic histologically;note the pale body in the large eosinophilic malignant hepatocyte(X40).63Hepatocellular carcinoma,liver,microscopic nThe malignant cells of this HCC(seen mostly on the right)are well differentiated and interdigitate with normal,larger hepatocytes(seen most

42、ly at the left)ThisHCCiscomposedoflivercordsthataremuchwiderthanthenormalliverplatethatistwocellsthick.Thereisnodiscernablenormallobulararchitecture,thoughvascularstructuresarepresent.64Clinical findings-1 Symptoms and signs:1.Right upper quadrant pain or discomfort with or without referred pain in

43、the right shoulder.2.With or without hepatomegaly3.Sudden deterioration in a cirrhotic patient:weight loss,weakness,intermittent fever,jaundice,variceal bleeding,ascites with or without blood.4.Rare cases may manifest metabolic or endocrine abnormalities:erythrocytosis,hypercalcemia,hypoglycemic att

44、acks,Cushings syndrome,or virilization.65Clinical findings-2 Laboratory findings:nSerum bilirubin:nonspecificnAlkaline phosphatase:nonspecificnHBsAg,HCV-Ab:nonspecificnAFP(alpha-fetoprotein):1.elevate in about 7080%HCCs;2.May be false positive among chronic active hepatitis,acute hepatitis,testicula

45、r tumors and pregnant women.3.Marker for postoperative follow-up(HL 67d).4.Upper limit in serum is 20ng/ml;200ng/ml is suggestive of HCC.66Clinical findings-3 Imaging findings:(number,location,size,neighboring,PVTT,cirrhosis,HPV)nUltrasound scan(screening):resolution2cm nCT scan(portography or CE):r

46、esolution 12cmnMRI scan is superior in showing the lesion evolving hepatic veins.resolution 12cmnAngiography:resolution 1cm1)HCC is more vascular than the adjacent parenchyma2)Cholangiocarcinoma is less vascular3)Hemangioma has patchy vascular pooling4)Venous phase of a superior mesenteric arterial

47、injection may show occupation in the portal vein.5)Angiography with iodized oil(Lipiodol)followed 2-weeks later by CT scan could demonstrate small HCC.67HCC-Imaging findings(DSA)68HCC-Imaging findingsnBefore intervention therapynAfter intervention therapy69HCC-Imaging findings Arterial phase Portal

48、vein phase70Biopsy&screeningnLiver biopsy:percutaneous core biopsy or aspiration biopsy(not so risky for bleeding if doing under US-guidance,but seeding of tumor cells along puncture channel is possible.)nScreening:using US+AFP for screening HCC among high-risk population(chronic liver diseases),man

49、y early-stage HCC were found and treated,resulting in more favorable outcomes.71HCC is amenable to biopsy by percutaneous needle biopsynThe architectural distortion due to cirrhosis is evident;at one end the tissue appears quite fragmented(X8).Thepresenceofmacrotrabeculararchitectureinthisfragmented

50、areaallowedforestablishingthediagnosisofHCC(X40).72 Essentials for Diagnosis 1.High-risk population:male,40yrs,HBV/HCV(+),alcohol,cirrhosis,family history2.Symptoms&signs:3.AFP:RI-AFP400ng/ml,4weeks,exclusion of pregnancy,active hepatitis,embryonic tumors4.Imaging:B-US,CT,MRI,DSA5.Biopsy:Diag.Criter

51、ia from different societies are fundamentally identical73原發(fā)性肝癌的診斷原發(fā)性肝癌的診斷-pathology criterian肝臟占位病灶或者肝外轉(zhuǎn)移灶活檢或手術(shù)切除組織標(biāo)本，經(jīng)病理組織學(xué)和/或細(xì)胞學(xué)檢查診斷為HCC，此為金標(biāo)準(zhǔn)。74-中國中國原發(fā)性肝癌診療規(guī)范（原發(fā)性肝癌診療規(guī)范（2011年版）年版）原發(fā)性肝癌的診斷原發(fā)性肝癌的診斷-clinical criterian在所有的實(shí)體瘤中，唯有HCC可采用臨床診斷標(biāo)準(zhǔn)，一般認(rèn)為主要取決于三大因素，即慢性肝病背景慢性肝病背景，影像學(xué)影像學(xué)檢查結(jié)果以及血清AFP水平。75-中國中國原發(fā)性肝

52、癌診療規(guī)范（原發(fā)性肝癌診療規(guī)范（2011年版）年版）原發(fā)性肝癌的診斷原發(fā)性肝癌的診斷-clinical criteria要求在同時(shí)滿足以下條件中的要求在同時(shí)滿足以下條件中的（1）+（2）a兩項(xiàng)或者（兩項(xiàng)或者（1）+（2）b+（3）三項(xiàng)時(shí)，可以確立三項(xiàng)時(shí)，可以確立HCC的臨床診斷：的臨床診斷：（1）具有肝硬化以及HBV和/或HCV感染（HBV和/或HCV抗原陽性）的證據(jù)；（2）典型的HCC影像學(xué)特征:同期多排CT掃描和/或動(dòng)態(tài)對比增強(qiáng)MRI檢查顯示肝臟占位在動(dòng)脈期快速不均質(zhì)血管強(qiáng)化（Arterial hypervascularity），而靜脈期或延遲期快速洗脫(Venous or delayed

53、 phase washout)a.如果肝臟占位直徑2cm，CT和MRI兩項(xiàng)影像學(xué)檢查中有一項(xiàng)顯示肝臟占位具有上述肝癌的特征，即可診斷HCC；b.如果肝臟占位直徑為1-2cm，則需要CT和MRI兩項(xiàng)影像學(xué)檢查都顯示肝臟占位具有上述肝癌的特征，方可診斷HCC，以加強(qiáng)診斷的特異性（3）血清AFP400g/L持續(xù)1個(gè)月或200g/L持續(xù)2個(gè)月，并能排除其他原因引起的AFP升高，包括妊娠、生殖系胚胎源性腫瘤、活動(dòng)性肝病及繼發(fā)性肝癌等76-中國中國原發(fā)性肝癌診療規(guī)范（原發(fā)性肝癌診療規(guī)范（2011年版）年版）77Differential diagnosis 1.Other abdominal tumors2

54、.Metastatic tumors3.Liver abscess4.Liver cirrhosis l Early-detection hard 1l Progression fastl Natural history（without treatment、literatures）HCC:natural history&prognosisHCC:natural history&prognosis1.Bruix J and Sherman M,Hepatology 2005;42:1208-362.Villa E et al.Hepatology 2000;32:2333.Llovet JM a

55、nd Bruix J.J Hepatol 2008;48:S20-S374.Llovet JM et al,Lancet 2003;362:1907*Best reports in literatures79Principles of treatment for HCCPrinciples of treatment for HCCnEarlydetection，earlyinterventionnSurgicalresectionofferthebestprognosisforearlyHCCsnSystemic&individualizedtherapiesarecrucialforbett

56、erprognosisnAggressivetherapyforrecurrentHCCcouldimprovesurvivalEvolution of HCC therapy19世紀(jì)末世紀(jì)末1950s1960s肝切除術(shù)肝葉切除肝移植197080s介入治療術(shù)后輔助化療2000s分子靶向治療 SHARP Oriental 1994年首項(xiàng)術(shù)后TACE RCT 發(fā)表 Br J Surg 1995;82:1221990s 2001發(fā)表首項(xiàng)術(shù)后化療Meta分析 Cancer.2001,91(12):2378免疫治療 90年代初興起IFN等治療病毒肝炎性HCC 1888年，Langenbuch有目的地成功

57、施行了第一例肝切除術(shù) 1954 年，Couinaud提出較為完備的肝臟八段法功能解剖 1963年Thomas Starzl等人完成了首例人肝移植放療 1965年，Ingold等首次報(bào)道了40例肝癌患者的放療效果小肝癌切除化療 多項(xiàng)化療RCT未顯示生存獲益Treatmentavailable weaponsnFactors influencing decision-makingnTumor：size,number,locationnLiver background：cirrhosis,hepatitis,functionnGeneral conditionnRadical therapy for

58、 early HCCnresectionnLiver transplantationnRegional ablationnSystemic therapy for mid/endstage HCCnRegional therapy：TAE、TAC、TACE、TARE ablation(RF、PEI、MCT；radiation；HIFU)nSystemic therapy：chemo、immuno、targeted therapyAlgorithm of decision makingnSlightly difference among different guidelines(societie

59、s)8283極早期極早期(0)PS 0,CPA早期早期(A)PS 0,CPA-B中期中期(B)PS 0,CPA-B晚期晚期(C)PS 1-2,CPA-B終末期終末期(D)PS 2,CPCHCC隨機(jī)對照試驗(yàn)（隨機(jī)對照試驗(yàn)（50%）中位生存時(shí)間中位生存時(shí)間11-20月月 對癥對癥(20%)生存期生存期3月月HCCHCC BCLC staging and treatmentBCLC staging and treatmentSem Liv Dis 1999 to J Hepatol 2008;48:S20-S37治愈性治療（治愈性治療（3030）5 5年生存率年生存率40%-70%40%-70%LT

60、RF/PEIresection伴隨疾病伴隨疾病有有無無3 個(gè)結(jié)節(jié)個(gè)結(jié)節(jié),3cm上升上升正常正常單發(fā)結(jié)節(jié)單發(fā)結(jié)節(jié),2cm門脈壓力門脈壓力/膽紅素膽紅素單發(fā)結(jié)節(jié)單發(fā)結(jié)節(jié)多多結(jié)節(jié)結(jié)節(jié),3cmTACE多個(gè)腫瘤多個(gè)腫瘤門脈轉(zhuǎn)移門脈轉(zhuǎn)移,N1,M1PS:performance status，ECOG體能狀態(tài)評分體能狀態(tài)評分 CP:Child-Pugh 評級評級新藥治療新藥治療SorafenibSorafenibJapanese algorithmHong Kong algorithmItalian algorithm中國決策樹中國決策樹-衛(wèi)生部肝細(xì)胞癌診療規(guī)范（衛(wèi)生部肝細(xì)胞癌診療規(guī)范（2011版）版）根治

61、手術(shù)姑息手術(shù) 無法手術(shù)中國肝癌診療HCCPS 02PS 34血管侵犯Child-Pugh C無有全身狀況肝功能肝外轉(zhuǎn)移Child-Pugh A/B無有腫瘤數(shù)目TACE手術(shù)切除放療分子靶向治療系統(tǒng)化療1個(gè)23個(gè)4個(gè)腫瘤大小3cm3cm治療選擇TACE手術(shù)切除+局部消融肝移植手術(shù)切除局部消融3cm肝移植手術(shù)切除TACE+消融肝移植50yrs2.Coexistence of liver diseases(cirrhosis)3.Vascular invasion4.Portal vein thrombosis5.Located deep inside liver6.intracapsular inf

62、iltration of tumor cells7.bilobar involvement8.More than one deposit of tumor 90Treatment-Partial hepatectomy Prognosis:1.70%recurrence in 5yrs,could be mono-center or multi-center in origin.2.Follow-up using US+AFP could detect relapsed tumor at early stage,and repeat resections provide favorable o

63、utcomes to some cases.3.In China,30%5-year survival(overall);60%5-year survival(early stage HCC)*4.Many patients die of cirrhosis(variceal bleeding,liver failure)rather than recurrence.*中華醫(yī)學(xué)雜志中華醫(yī)學(xué)雜志,2003,83(12):1053-7.Reality-concominant chronic liver diseases肝癌肝炎肝硬化Med Clin N Am 89(2005)371389N Eng

64、l J Med.1997 Dec 11;337(24):1733-45HCCHepatitisCirrhosis1520%在5年內(nèi)發(fā)展至肝硬化肝硬化患者的HCC年發(fā)病率約為3-6%90%的肝癌患者伴發(fā)肝炎、肝硬化預(yù)后這意味著隨訪100例肝硬化患者5年，有可能發(fā)現(xiàn)15例肝癌10/6/202292Survivalover14yrsSurvivalover25yrsHepatobiliary Surgery DepartmentOf The 1st Affiliated Hospital of GMUGuangxiisanepidemicareaforHapetocellularcarcinoma(

65、HCC).Overall5-yrs-survivalpost-resectionisabout30%.Future：robotic hepatectomy（imageguidedsurgery）港東醫(yī)院(PYNEH)94Treatment-Liver transplantation nOf theoretic advantage because:1.Applicable for tumors too large or multifocal distribution.2.Applicable for cirrhotic patients.3.Applicable for hepatitis pa

66、tients because effective antiviral therapy is now available4.Ensuing better quality of life for cirrhotic patients.nIt is of evident now that LT provides equivalent survival to early stage HCCs,in contrast to hepatectomy.10/6/202295Child-born 10yrs after liver transplantation for HCC97Treatment-Palliative therapy nPercutaneous ethanol injection(PEI)or radiofrequency ablation(RF):produce necrosis of small HCC.It is best suited to peripheral lesions,less than 3 cm in diameter.nArterial chemoemboli