上海交大外科肿瘤学课件

外科肿瘤学

SurgicalOncologyDepartmentofSurgeryRuiJinHospitalSchoolofMedicineShanghaiJiaoTongUniversity肿瘤的定义

DefinitionofTumor

肿瘤是机体中正常细胞,在不同的始动与促进因素长期作用下所产生的增生与异常分化所形成的新生物

TumorsarecharacterizedbycellsthathavelosttheirnormalcontrolmechanismsandthushaveunregulatedgrowthThetop10cancerincidenceandmortalityinChina,2011incidencemortalityAge-standardizedincidencerate(1/105)---ChenWQ,etal.ChinCancer2015;24(1):1-10Thetop10cancerincidenceandmortalityinChina,2011(Male)%%incidenceAge-standardizedincidencerate(1/105)---ChenWQ,etal.ChinCancer2015;24(1):1-10mortality%Thetop10cancerincidenceandmortalityinChina,2011(Female)%%Age-standardizedincidencerate(1/105)---ChenWQ,etal.ChinCancer2015;24(1):1-10mortalityincidence

肿瘤病因学

TheEtiologyofCancer●

病毒

Viruses(papilloma,Epstein-Barr, HepatitisB,retroviruses,HIV)●

射线

Radiationexposure●

环境、工业因素

Environmentalindustrialcarcinogens●

吸烟/饮酒Tobaccoandalcoholconsumption●

基因易感性Geneticsusceptibilitysyndromes肿瘤相关病毒

VirusesAssociatedwithCancerVirus CancerHepatitisB,C HepatocellularCancerHIV Kaposi’ssarcomaEpstein-Barrvirus Nasopharyngealcancer Burkitt’slymphomaHumanPapillomavirus Cervicalcancer肿瘤发病率与生活/环境因素

CancerMortality&Behavior/environmentalFactorsFactor PercentageofcancerdeathsSmoking 30Diet 30Infectiousagents 5Alcohol 3Sedentarylifestyle 3Ultraviolet 2Airpollution 2人体内在因素(InherentFactors)1.遗传因素:遗传易感性(hereditarysusceptibility)2.内分泌因素:某些激素代谢紊乱可诱发或促进肿瘤生长3.免疫因素:机体免疫功能降低,肿瘤发病率升高4.其它因素:精神,营养(微量元素缺乏)等吸烟相关肿瘤

Smoking-relatedcancers●Lungcancer●Oropharyngealcancer●Stomachcancer●Cervicalcancer●Pancreaticcancer●Renalcancer●Bladdercancer●Livercancer●Leukemia与肿瘤发生相关的基因

（MajorGenesinDevelopmentofCancer）●

癌基因 Oncogenes●

抑癌基因

Tumorsuppressorgenes●

DNA修复基因

DNArepairgenes癌基因

Oncogenes●Growthfactors生长因子

EGF,TGF-α●Growthfactorreceptors生长因子受体

EGFR,PTK●Intracellulartransducers细胞内传导素

cAMP●Transcriptionfactors转录因子

c-mycDNA修复基因失活抑癌基因失活癌基因激活癌细胞肿瘤的发生和发展恶性肿瘤病因和发病机制模式图

结直肠肿瘤发生的遗传模型——肿瘤的发生经历了一系列遗传学上的变化，如数个癌基因的激活和/或抑癌基因的失活，及其他基因变化。ModernViewpointofCancerasaLong-termProcess癌前期广泛播散期侵袭期原位癌期Upto10~30years3~10years1~5years1~5years肿瘤病理学

ThePathology

of

Cancer恶性肿瘤的命名

NomenclatureofMalignantTumorNamesoftumor TissueoforiginExamples Carcinoma Epithelium AdenocarcinomasSarcoma Mesenchymal LiposarcomaMalig.lymphoma Lymphocytes LymphomaMalig.melanoma Melanocytes MalignantmelanomaMalig.Mesothelioma Mesothelium Pleuralmalig.MesotheliomaTeratoma GermCells TesticularteratomaChoriocarcinoma Trophoblast Uterinechoriocarcinoma良性肿瘤

BenignTumors●Alimitedgrowthpotential●theneoplasticcellscloselyresemblethoseoftheparenttissue(welldiff.)●growthslowlybyexpansion●awell-encapsulatedlesion●donotusuallyproduceseriouseffect恶性肿瘤

MalignantTumors●proliferaterapidly●morepoorlydifferentiatedcells●progressivegrowthandinvasionofthesurroundingtissues●metastasesbylymphatic&bloodvessels●ifnottreatedearly,eventuallycausedeath

Peritonealcarcinomatosisofgastriccancer

癌肿分期和组织学分类的目的●有助于制订治疗方案●有助于判定预后●有助于评判疗效●有助于资源共享和学术交流●有助于癌肿临床研究的开展组织病理学分期与分类

HistopathologicalStaging

&Classification●Adenocarcinomas●Squamouscarcinomas●Smallcellcarcinomas●Largecellcarcinomas●Sarcomas ●Lymphomas●Leukemias ●Gliomas ●Seminomas ●Teratomas恶性肿瘤特性

TheHallmarkofMalignancy●

局部破坏性浸润

Localdestructiveinvasion●

远处转移

Distantmetastasis------thecardinalbehaviortodistinguishbenign&malignanttumor恶性肿瘤病理特征

PathologicalFeatures

ofMalignancy●aninfiltrativeuncapsulatedmargin●invasionofbaselinemembraneorsurroundingstructure●evidenceofinvasionofbloodvesselsorlymphaticsormetastases●tumornecrosis●architectureabnormalities e.g.increasedgland/stromaratio●cytologicalabnormalities e.g.increasednuclear/cytoplasmratio●numerousmitoticfigures&abnormalmitoses恶性肿瘤病理特征

PathologicalFeatures

ofMalignancy

癌的大体分型GrossTypesofCarcinomaPapillaryNodularUlcerativeCysticMultipleDiffuseStrictureBorrmann’sClassificationI型II型III型Ⅳ型左肺上叶中央型肺癌胃癌肝转移ThreeImportantTerms●

Metaplasia----thereplacementofonefullydifferentiatedtissuebyanother●

Carcinomainsitu----thehistologicalabnormalitiesaresufficientlyseveretosuggestcarcinoma,butintheabsenceofbasementmembraneinvasion●Bordertumor-----Atumorwithbiologicbehaviorbetweenbenignandmalignant分化程度

TheDegreeofDifferentiation●

高度分化(I级)

Welldifferentiated●

中度分化(II级)Moderatelydifferentiated●

低度分化(III级)Poorlydifferentiated恶性肿瘤的后果

EffectsofMalignancy●Tumorarisingwithinahollowviscus

梗阻

obstruction●tumorarisingfromsurfaceoforgan

溃疡/出血

ulcerationandbleeding恶性肿瘤的波散

SpreadofMalignantTumors●直接浸润(directinvasion)---rectalcancer●

区域淋巴结转移(lymphaticspread) --breastcarcinoma,gastriccancer●

血行播散至远处(metastasisbybloodstream)--liver,lung&brain●

体腔内种植

(cavityimplantation)--ovariancarcinoma(Krukenberg’stumor)TNMStagingofGCTstagearedefinedbydepthofpenetrationintothegastricwallLaminapropriaT1aT1bT4aT4bT3Subserosal

connectivetissueT1bT1aT4aT4bTstageLymphaticSpreadofGastricCancer淋巴结内单个癌细胞转移灶(CAM5.2×100)淋巴结内数个癌细胞形成的转移簇(CAM5.2×100)肿瘤分期国际癌症联盟（UICC）

TNM分期T（tumor）：1，2，3，4，xN(lymphnode)：1，2，3M(metastasis)：0，1临床分期（CTNM）术后的临床病理分期（PTNM）各种肿瘤的TNM分期标准是由各专业会议协定的分期目的：制定合理治疗方案正确评价治疗效果判断预后有利于交流TNM分期T---原发肿瘤

primarytumorN---区域淋巴结

regionallymphnodeM---远处转移

metastases癌症的诊断步骤

TheDiagnosticProcedures

ofCancer病史History●Familyhistory ●Individualhabits●Socialhistory ●Occupation●Marital&Sexhistory ●Pasthistory体检

PhysicalExamination

●

系统体检 ●

局部体检

Tumor Metastaticfoci

癌症的诊断步骤

TheDiagnosticProcedures

ofCancer特殊检查SpecialProcedures●

DiagnosticRadiology ChestX-rays Bariumenemaradiography Gastro-intestinalseriesradiography

Arteriography Computerizedtomography(CT) Radioisotopescanningtechniques Mammography Positronemissiontomography(PET)癌肿诊断步骤

TheDiagnosticProcedures

ofCancer特殊检查SpecialProcedures●Ultrasonicexamination●Endoscopy●Cytology●Biopsy bone-marrowbiopsy needlebiopsy endoscopicbiopsy●Magneticresonanceimagine(MRI)癌肿诊断步骤

TheDiagnosticProcedures

ofCancer实验室检查

(LabTest)●

Routinetest: blood,urine,stool●Serumtest: enzyme,hormone glycoprotein,tumormarkers●Immunologytest: AFP,CEA, tumor-relatedantigens●Flow-cytometry(FCM): DNAploidy DNAindex●GeneTest: Oncogenes,DNArepairgenes Tumorsuppressorgenes癌症诊断步骤

TheDiagnosticProceduresofCancer早期肿瘤诊断的工具

ToolsForEarlyClinicalDetection●

Completephysicalexamination●Regularmammographyandbreastselfexam●Haemoccultforoccultbloodinfeces●Urinanalysisandbloodcount●Acompleteclinicalhistory●Anin-depthfamilymedicalhistory癌症的症状和体征

Symptoms

orSigns

ofCancer

●

饮食习惯改变Alterationineatinghabit●

食欲下降Lossofappetite●

吞咽困难Problemsinswallowing●

排便习惯改变Changeinbowelhabit●局部肿块Thepresenceofalumpatanysite●

出血 Theappearanceofbleeding●

反复疼痛 Unexplainedrecurrentpain●

反复发热 Recurrentfevers●

消瘦 Unexplainedweightloss●

反复难治性感染Repeatedinfections

whichdonotclearwithtreatment癌症的症状与体征

Symptoms

orSigns

ofCancer

乳房癌BreastCancer伴癌综合症

Para-neoplasticSyndrome●SmallcellcarcinomassecretACTH Cushing’ssyndrome

●Renalcarcinomassecreterythropoitin polycythaemia●Mucin-secretingadenomasincreasingthecoagulability thromboembolism恶液质Cachexia肿瘤标记物

TumorMarkersTumormarker Examples肿瘤抗原

AFP,CEA酶

PSA激素

β-HCG癌基因

Ras,c-myc肿瘤相关抗原

CA19-9,CA-242BariumSwallowBorr-IBorr-IIIBorr-IVPreoperativeStagingbySpiralCT螺旋CT显示肾脏肿瘤

MSCTrenaltumor螺旋CT显示转移淋巴结

MSCTMetastaticLN内窥镜检查Endoscopy超声胃镜EndoscopicUltrasonographyEUS-T1EUS-T2EUS-T3EUS-T4MSCT-T1MSCT-T2MSCT-T3MSCT-T4MSCT-N1MSCT-N2MSCT-M1（PeritonealMetastasis）PETImaging

ofGCDetectionofPeritonealMetastasis

byLaparoscopy肿瘤的预防(PreventionofTumor)三级预防的概念:一级预防:环境因素包括饮食习惯的改造与预防,减少致癌因素,降低癌肿发生率二级预防:强调早期发现,早期诊断,早期治疗三级预防:改善生活质量,对症处理,减轻病痛延长患者生命世界卫生组织三阶梯止痛方案

癌痛缓解

强阿片类药物±非阿片类镇痛药±辅助药物疼痛持续或加重

弱阿片类药物±非阿片类镇痛±辅助药物疼痛持续或加重

非阿片类药物±辅助药物

疼痛发生

321WHO癌症疼痛三阶梯给药原则

从小剂量开始视止痛效果渐增量口服为主无效时直肠给药最后才注射给药90％以上满意正确的药物正确的剂量正确间隔时间正确用药途径ThePrinciplesofCancerSurgery外科肿瘤学的基本原则PrinciplesofCancerSurgeryNoinvolvementofsurgicalstumpSufficientlymphaticdissection(Dn>Nn)NodistantmetastasesRemovalofinvolvedadjacentorgansandstructuresbycombinedenblocresection肿瘤外科治疗的关键问题

KeyPointsofCancerSurgery●Combinedtreatmentmodalities(Multipledisciplinaryteam,MDT)●Preoperativechemotherapy●Postoperativechemotherapy●Preoperativeradiotherapy●Postoperativeradiotherapy●Perioperativechemotherapy

辅助治疗Adjuvanttherapy

Administrationofsystemictherapyafteroptimalloco-regionaltherapy(surgery/radiotherapy)新辅助治疗Neo-adjuvanttherapy

Chemotherapy/Radiotherapyisadministeredpriortoloco-regionaltherapytoreducethetumorcellburdenSurgery根据肿瘤位置局部LN组的清扫情况D14d4d4d653D211p12a14v1998a97LD/L

SurgicaltreatmentforgastriccancerGastricresectionshouldincludetheregionallymphatic--perigastriclymphnodes(D1)andthosealongthenamedvesselsoftheceliacaxis(D2),withagoalofexamining15orgreaterlymphnodes.腹腔镜结肠癌手术腹腔镜结肠吻合技术胃癌手术标本整块切除（enblocresection)肿瘤治疗原则

良性肿瘤及交界性肿瘤:

以手术切除为主。尤其交界性肿瘤必须切除，否则极易复发或恶性变。恶性肿瘤:

拟定综合治疗方案，在控制原发病灶后，进行转移灶的治疗。恶性肿瘤第一次治疗的正确与否对预后有密切关系。I期：手术为主。II期：局部治疗为主，原发肿瘤切除或放疗，并必须包括转移灶的治疗，辅以有效的全身化疗。III期：采取综合治疗，手术前、后及术中放疗或化疗。IV期：有全身治疗为主，辅以局部对症治疗。

肿瘤治疗方案制订的基础

TreatmentPrinciplesofCancerTreatmentareBasedUpon●

肿瘤生物学特性●治疗手段的并发症发生率和死亡率●治疗手段的效果●病人生活质量肿瘤治疗方案制订的基础

TreatmentPrinciplesofCancer

TreatmentareBasedUpon●

withlocalizedcancersarecurable●presentingwithpositiveLymphNodestendtobadoutcome●withdistantmetastasesarerarelycurable●themostcommonlyparametertomeasuresurvivalandbenefitoftreatment --5-yrsurvivalrates肿瘤治疗新手段

NewApproachestoCancer●Immunology●Biologicalresponsemodifiers●Interferonsandinterleukins●Adoptiveimmunotherapy●Monoclonalantibodies●Tumorvaccines●Genetherapy本课重点(keypoints)肿瘤的分类与命名肿瘤的病理:发生发展过程,肿瘤细胞的分化生长方式,转移方式肿瘤的临床表现:局部表现肿瘤的主要诊断方法

肿瘤的三级预防肿瘤的治疗手段外科治疗的原则药物分类二1)细胞毒素类药物；2)抗代谢类药；3)抗生素类；4)生物碱类；5)激素类；6)其他增殖周期

M

G1

G0

G2

S

静止期

药物分类一1、细胞周期特异性2、细胞周期非特异性3。细胞周期时相特异性化疗

细胞毒药物:

依赖肿瘤细胞与正常细胞生长、修复、死亡的动力学间的差异来杀伤肿瘤细胞，选择性差。靶向治疗：具有针对致癌机制，直接攻击致癌病因，选择性强AntisenseDNACytoplasmmRNADNAproteinSG2MG1G0细胞周期与抗癌药物TheCellCycle&AnticancerDrugs抗代谢药物抗细胞分裂药长春碱类泰素化疗药物的分类

ClassificationofChemotherapeuticDrugsClasses ExamplesAlkalatingagents CisplatinAntimetabolites 5-FU,MTXMitoticinhibitors VP-16,Ta