上海交大外科腫瘤學(xué)課件

外科腫瘤學(xué)

SurgicalOncologyDepartmentofSurgeryRuiJinHospitalSchoolofMedicineShanghaiJiaoTongUniversity腫瘤的定義

DefinitionofTumor

腫瘤是機(jī)體中正常細(xì)胞,在不同的始動(dòng)與促進(jìn)因素長期作用下所產(chǎn)生的增生與異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

腫瘤病因?qū)W

TheEtiologyofCancer●

病毒

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

射線

Radiationexposure●

環(huán)境、工業(yè)因素

Environmentalindustrialcarcinogens●

吸煙/飲酒Tobaccoandalcoholconsumption●

基因易感性Geneticsusceptibilitysyndromes腫瘤相關(guān)病毒

VirusesAssociatedwithCancerVirus CancerHepatitisB,C HepatocellularCancerHIV Kaposi’ssarcomaEpstein-Barrvirus Nasopharyngealcancer Burkitt’slymphomaHumanPapillomavirus Cervicalcancer腫瘤發(fā)病率與生活/環(huán)境因素

CancerMortality&Behavior/environmentalFactorsFactor PercentageofcancerdeathsSmoking 30Diet 30Infectiousagents 5Alcohol 3Sedentarylifestyle 3Ultraviolet 2Airpollution 2人體內(nèi)在因素(InherentFactors)1.遺傳因素:遺傳易感性(hereditarysusceptibility)2.內(nèi)分泌因素:某些激素代謝紊亂可誘發(fā)或促進(jìn)腫瘤生長3.免疫因素:機(jī)體免疫功能降低,腫瘤發(fā)病率升高4.其它因素:精神,營養(yǎng)(微量元素缺乏)等吸煙相關(guān)腫瘤

Smoking-relatedcancers●Lungcancer●Oropharyngealcancer●Stomachcancer●Cervicalcancer●Pancreaticcancer●Renalcancer●Bladdercancer●Livercancer●Leukemia與腫瘤發(fā)生相關(guān)的基因

（MajorGenesinDevelopmentofCancer）●

癌基因 Oncogenes●

抑癌基因

Tumorsuppressorgenes●

DNA修復(fù)基因

DNArepairgenes癌基因

Oncogenes●Growthfactors生長因子

EGF,TGF-α●Growthfactorreceptors生長因子受體

EGFR,PTK●Intracellulartransducers細(xì)胞內(nèi)傳導(dǎo)素

cAMP●Transcriptionfactors轉(zhuǎn)錄因子

c-mycDNA修復(fù)基因失活抑癌基因失活癌基因激活癌細(xì)胞腫瘤的發(fā)生和發(fā)展惡性腫瘤病因和發(fā)病機(jī)制模式圖

結(jié)直腸腫瘤發(fā)生的遺傳模型——腫瘤的發(fā)生經(jīng)歷了一系列遺傳學(xué)上的變化，如數(shù)個(gè)癌基因的激活和/或抑癌基因的失活，及其他基因變化。ModernViewpointofCancerasaLong-termProcess癌前期廣泛播散期侵襲期原位癌期Upto10~30years3~10years1~5years1~5years腫瘤病理學(xué)

ThePathology

of

Cancer惡性腫瘤的命名

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

BenignTumors●Alimitedgrowthpotential●theneoplasticcellscloselyresemblethoseoftheparenttissue(welldiff.)●growthslowlybyexpansion●awell-encapsulatedlesion●donotusuallyproduceseriouseffect惡性腫瘤

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

Peritonealcarcinomatosisofgastriccancer

癌腫分期和組織學(xué)分類的目的●有助于制訂治療方案●有助于判定預(yù)后●有助于評判療效●有助于資源共享和學(xué)術(shù)交流●有助于癌腫臨床研究的開展組織病理學(xué)分期與分類

HistopathologicalStaging

&Classification●Adenocarcinomas●Squamouscarcinomas●Smallcellcarcinomas●Largecellcarcinomas●Sarcomas ●Lymphomas●Leukemias ●Gliomas ●Seminomas ●Teratomas惡性腫瘤特性

TheHallmarkofMalignancy●

局部破壞性浸潤

Localdestructiveinvasion●

遠(yuǎn)處轉(zhuǎn)移

Distantmetastasis------thecardinalbehaviortodistinguishbenign&malignanttumor惡性腫瘤病理特征

PathologicalFeatures

ofMalignancy●aninfiltrativeuncapsulatedmargin●invasionofbaselinemembraneorsurroundingstructure●evidenceofinvasionofbloodvesselsorlymphaticsormetastases●tumornecrosis●architectureabnormalities e.g.increasedgland/stromaratio●cytologicalabnormalities e.g.increasednuclear/cytoplasmratio●numerousmitoticfigures&abnormalmitoses惡性腫瘤病理特征

PathologicalFeatures

ofMalignancy

癌的大體分型GrossTypesofCarcinomaPapillaryNodularUlcerativeCysticMultipleDiffuseStrictureBorrmann’sClassificationI型II型III型Ⅳ型左肺上葉中央型肺癌胃癌肝轉(zhuǎn)移ThreeImportantTerms●

Metaplasia----thereplacementofonefullydifferentiatedtissuebyanother●

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

TheDegreeofDifferentiation●

高度分化(I級)

Welldifferentiated●

中度分化(II級)Moderatelydifferentiated●

低度分化(III級)Poorlydifferentiated惡性腫瘤的后果

EffectsofMalignancy●Tumorarisingwithinahollowviscus

梗阻

obstruction●tumorarisingfromsurfaceoforgan

潰瘍/出血

ulcerationandbleeding惡性腫瘤的波散

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

區(qū)域淋巴結(jié)轉(zhuǎn)移(lymphaticspread) --breastcarcinoma,gastriccancer●

血行播散至遠(yuǎn)處(metastasisbybloodstream)--liver,lung&brain●

體腔內(nèi)種植

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

connectivetissueT1bT1aT4aT4bTstageLymphaticSpreadofGastricCancer淋巴結(jié)內(nèi)單個(gè)癌細(xì)胞轉(zhuǎn)移灶(CAM5.2×100)淋巴結(jié)內(nèi)數(shù)個(gè)癌細(xì)胞形成的轉(zhuǎn)移簇(CAM5.2×100)腫瘤分期國際癌癥聯(lián)盟（UICC）

TNM分期T（tumor）：1，2，3，4，xN(lymphnode)：1，2，3M(metastasis)：0，1臨床分期（CTNM）術(shù)后的臨床病理分期（PTNM）各種腫瘤的TNM分期標(biāo)準(zhǔn)是由各專業(yè)會(huì)議協(xié)定的分期目的：制定合理治療方案正確評價(jià)治療效果判斷預(yù)后有利于交流TNM分期T---原發(fā)腫瘤

primarytumorN---區(qū)域淋巴結(jié)

regionallymphnodeM---遠(yuǎn)處轉(zhuǎn)移

metastases癌癥的診斷步驟

TheDiagnosticProcedures

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

PhysicalExamination

●

系統(tǒng)體檢 ●

局部體檢

Tumor Metastaticfoci

癌癥的診斷步驟

TheDiagnosticProcedures

ofCancer特殊檢查SpecialProcedures●

DiagnosticRadiology ChestX-rays Bariumenemaradiography Gastro-intestinalseriesradiography

Arteriography Computerizedtomography(CT) Radioisotopescanningtechniques Mammography Positronemissiontomography(PET)癌腫診斷步驟

TheDiagnosticProcedures

ofCancer特殊檢查SpecialProcedures●Ultrasonicexamination●Endoscopy●Cytology●Biopsy bone-marrowbiopsy needlebiopsy endoscopicbiopsy●Magneticresonanceimagine(MRI)癌腫診斷步驟

TheDiagnosticProcedures

ofCancer實(shí)驗(yàn)室檢查

(LabTest)●

Routinetest: blood,urine,stool●Serumtest: enzyme,hormone glycoprotein,tumormarkers●Immunologytest: AFP,CEA, tumor-relatedantigens●Flow-cytometry(FCM): DNAploidy DNAindex●GeneTest: Oncogenes,DNArepairgenes Tumorsuppressorgenes癌癥診斷步驟

TheDiagnosticProceduresofCancer早期腫瘤診斷的工具

ToolsForEarlyClinicalDetection●

Completephysicalexamination●Regularmammographyandbreastselfexam●Haemoccultforoccultbloodinfeces●Urinanalysisandbloodcount●Acompleteclinicalhistory●Anin-depthfamilymedicalhistory癌癥的癥狀和體征

Symptoms

orSigns

ofCancer

●

飲食習(xí)慣改變Alterationineatinghabit●

食欲下降Lossofappetite●

吞咽困難Problemsinswallowing●

排便習(xí)慣改變Changeinbowelhabit●局部腫塊Thepresenceofalumpatanysite●

出血 Theappearanceofbleeding●

反復(fù)疼痛 Unexplainedrecurrentpain●

反復(fù)發(fā)熱 Recurrentfevers●

消瘦 Unexplainedweightloss●

反復(fù)難治性感染Repeatedinfections

whichdonotclearwithtreatment癌癥的癥狀與體征

Symptoms

orSigns

ofCancer

乳房癌BreastCancer伴癌綜合癥

Para-neoplasticSyndrome●SmallcellcarcinomassecretACTH Cushing’ssyndrome

●Renalcarcinomassecreterythropoitin polycythaemia●Mucin-secretingadenomasincreasingthecoagulability thromboembolism惡液質(zhì)Cachexia腫瘤標(biāo)記物

TumorMarkersTumormarker Examples腫瘤抗原

AFP,CEA酶

PSA激素

β-HCG癌基因

Ras,c-myc腫瘤相關(guān)抗原

CA19-9,CA-242BariumSwallowBorr-IBorr-IIIBorr-IVPreoperativeStagingbySpiralCT螺旋CT顯示腎臟腫瘤

MSCTrenaltumor螺旋CT顯示轉(zhuǎn)移淋巴結(jié)

MSCTMetastaticLN內(nèi)窺鏡檢查Endoscopy超聲胃鏡EndoscopicUltrasonographyEUS-T1EUS-T2EUS-T3EUS-T4MSCT-T1MSCT-T2MSCT-T3MSCT-T4MSCT-N1MSCT-N2MSCT-M1（PeritonealMetastasis）PETImaging

ofGCDetectionofPeritonealMetastasis

byLaparoscopy腫瘤的預(yù)防(PreventionofTumor)三級預(yù)防的概念:一級預(yù)防:環(huán)境因素包括飲食習(xí)慣的改造與預(yù)防,減少致癌因素,降低癌腫發(fā)生率二級預(yù)防:強(qiáng)調(diào)早期發(fā)現(xiàn),早期診斷,早期治療三級預(yù)防:改善生活質(zhì)量,對癥處理,減輕病痛延長患者生命世界衛(wèi)生組織三階梯止痛方案

癌痛緩解

強(qiáng)阿片類藥物±非阿片類鎮(zhèn)痛藥±輔助藥物疼痛持續(xù)或加重

弱阿片類藥物±非阿片類鎮(zhèn)痛±輔助藥物疼痛持續(xù)或加重

非阿片類藥物±輔助藥物

疼痛發(fā)生

321WHO癌癥疼痛三階梯給藥原則

從小劑量開始視止痛效果漸增量口服為主無效時(shí)直腸給藥最后才注射給藥90％以上滿意正確的藥物正確的劑量正確間隔時(shí)間正確用藥途徑ThePrinciplesofCancerSurgery外科腫瘤學(xué)的基本原則PrinciplesofCancerSurgeryNoinvolvementofsurgicalstumpSufficientlymphaticdissection(Dn>Nn)NodistantmetastasesRemovalofinvolvedadjacentorgansandstructuresbycombinedenblocresection腫瘤外科治療的關(guān)鍵問題

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

輔助治療Adjuvanttherapy

Administrationofsystemictherapyafteroptimalloco-regionaltherapy(surgery/radiotherapy)新輔助治療Neo-adjuvanttherapy

Chemotherapy/Radiotherapyisadministeredpriortoloco-regionaltherapytoreducethetumorcellburdenSurgery根據(jù)腫瘤位置局部LN組的清掃情況D14d4d4d653D211p12a14v1998a97LD/L

SurgicaltreatmentforgastriccancerGastricresectionshouldincludetheregionallymphatic--perigastriclymphnodes(D1)andthosealongthenamedvesselsoftheceliacaxis(D2),withagoalofexamining15orgreaterlymphnodes.腹腔鏡結(jié)腸癌手術(shù)腹腔鏡結(jié)腸吻合技術(shù)胃癌手術(shù)標(biāo)本整塊切除（enblocresection)腫瘤治療原則

良性腫瘤及交界性腫瘤:

以手術(shù)切除為主。尤其交界性腫瘤必須切除，否則極易復(fù)發(fā)或惡性變。惡性腫瘤:

擬定綜合治療方案，在控制原發(fā)病灶后，進(jìn)行轉(zhuǎn)移灶的治療。惡性腫瘤第一次治療的正確與否對預(yù)后有密切關(guān)系。I期：手術(shù)為主。II期：局部治療為主，原發(fā)腫瘤切除或放療，并必須包括轉(zhuǎn)移灶的治療，輔以有效的全身化療。III期：采取綜合治療，手術(shù)前、后及術(shù)中放療或化療。IV期：有全身治療為主，輔以局部對癥治療。

腫瘤治療方案制訂的基礎(chǔ)

TreatmentPrinciplesofCancerTreatmentareBasedUpon●

腫瘤生物學(xué)特性●治療手段的并發(fā)癥發(fā)生率和死亡率●治療手段的效果●病人生活質(zhì)量腫瘤治療方案制訂的基礎(chǔ)

TreatmentPrinciplesofCancer

TreatmentareBasedUpon●

withlocalizedcancersarecurable●presentingwithpositiveLymphNodestendtobadoutcome●withdistantmetastasesarerarelycurable●themostcommonlyparametertomeasuresurvivalandbenefitoftreatment --5-yrsurvivalrates腫瘤治療新手段

NewApproachestoCancer●Immunology●Biologicalresponsemodifiers●Interferonsandinterleukins●Adoptiveimmunotherapy●Monoclonalantibodies●Tumorvaccines●Genetherapy本課重點(diǎn)(keypoints)腫瘤的分類與命名腫瘤的病理:發(fā)生發(fā)展過程,腫瘤細(xì)胞的分化生長方式,轉(zhuǎn)移方式腫瘤的臨床表現(xiàn):局部表現(xiàn)腫瘤的主要診斷方法

腫瘤的三級預(yù)防腫瘤的治療手段外科治療的原則藥物分類二1)細(xì)胞毒素類藥物；2)抗代謝類藥；3)抗生素類；4)生物堿類；5)激素類；6)其他增殖周期

M

G1

G0

G2

S

靜止期

藥物分類一1、細(xì)胞周期特異性2、細(xì)胞周期非特異性3。細(xì)胞周期時(shí)相特異性化療

細(xì)胞毒藥物:

依賴腫瘤細(xì)胞與正常細(xì)胞生長、修復(fù)、死亡的動(dòng)力學(xué)間的差異來殺傷腫瘤細(xì)胞，選擇性差。靶向治療：具有針對致癌機(jī)制，直接攻擊致癌病因，選擇性強(qiáng)AntisenseDNACytoplasmmRNADNAproteinSG2MG1G0細(xì)胞周期與抗癌藥物TheCellCycle&AnticancerDrugs抗代謝藥物抗細(xì)胞分裂藥長春堿類泰素化療藥物的分類

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