上海交大外科腫瘤學課件

外科腫瘤學

SurgicalOncologyDepartmentofSurgeryRuiJinHospitalSchoolofMedicineShanghaiJiaoTongUniversity腫瘤的定義

DefinitionofTumor

腫瘤是機體中正常細胞,在不同的始動與促進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)或促進腫瘤生長3.免疫因素:機體免疫功能降低,腫瘤發(fā)病率升高4.其它因素:精神,營養(yǎng)(微量元素缺乏)等吸煙相關腫瘤

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

（MajorGenesinDevelopmentofCancer）●

癌基因 Oncogenes●

抑癌基因

Tumorsuppressorgenes●

DNA修復基因

DNArepairgenes癌基因

Oncogenes●Growthfactors生長因子

EGF,TGF-α●Growthfactorreceptors生長因子受體

EGFR,PTK●Intracellulartransducers細胞內(nèi)傳導素

cAMP●Transcriptionfactors轉(zhuǎn)錄因子

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

結(jié)直腸腫瘤發(fā)生的遺傳模型——腫瘤的發(fā)生經(jīng)歷了一系列遺傳學上的變化，如數(shù)個癌基因的激活和/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

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

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

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)單個癌細胞轉(zhuǎn)移灶(CAM5.2×100)淋巴結(jié)內(nèi)數(shù)個癌細胞形成的轉(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分期標準是由各專業(yè)會議協(xié)定的分期目的：制定合理治療方案正確評價治療效果判斷預后有利于交流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實驗室檢查

(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

●

飲食習慣改變Alterationineatinghabit●

食欲下降Lossofappetite●

吞咽困難Problemsinswallowing●

排便習慣改變Changeinbowelhabit●局部腫塊Thepresenceofalumpatanysite●

出血 Theappearanceofbleeding●

反復疼痛 Unexplainedrecurrentpain●

反復發(fā)熱 Recurrentfevers●

消瘦 Unexplainedweightloss●

反復難治性感染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腫瘤的預防(PreventionofTumor)三級預防的概念:一級預防:環(huán)境因素包括飲食習慣的改造與預防,減少致癌因素,降低癌腫發(fā)生率二級預防:強調(diào)早期發(fā)現(xiàn),早期診斷,早期治療三級預防: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間正確用藥途徑ThePrinciplesofCancerSurgery外科腫瘤學的基本原則PrinciplesofCancerSurgeryNoinvolvementofsurgicalstumpSufficientlymphaticdissection(Dn>Nn)NodistantmetastasesRemovalofinvolvedadjacentorgansandstructuresbycombinedenblocresection腫瘤外科治療的關鍵問題

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，進行轉(zhuǎn)移灶的治療。惡性腫瘤第一次治療的正確與否對預后有密切關系。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

TreatmentPrinciplesofCancerTreatmentareBasedUpon●

腫瘤生物學特性●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

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(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

腫瘤的三級預防腫瘤的治療手段外科治療的原則藥物分類二1)細胞毒素類藥物；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、細胞周期特異性2、細胞周期非特異性3。細胞周期時相特異性化療

細胞毒藥物:

依賴腫瘤細胞與正常細胞生長、修復、死亡的動力學間的差異來殺傷腫瘤細胞，選擇性差。靶向治療：具有針對致癌機制，直接攻擊致癌病因，選擇性強AntisenseDNACytoplasmmRNADNAproteinSG2MG1G0細胞周期與抗癌藥物TheCellCycle&AnticancerDrugs抗代謝藥物抗細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