外科學總論課件：cancer

2023/8/24CANCER

—Principles&PracticeofOncology2023/8/24Neoplasms(Tumor,Mass)

Analteredcellpopulationcharacterizedbyanexcessive,nonusefulproliferationofcellsthathavebecomeunresponsivetonormalcontrolmechanismsandtotheorganizinginfluencesofadjacenttissues.2023/8/24ClassificationofNeoplasmsBenigntumorMalignanttumor(Cancer)CarcinomaSarcomaBorderingtumor2023/8/24EssentialsofModernOncologicScienceEssentialsofMoledularBiology:GenomicsandCancerEssentialsofSignalTransductionEssentialsofImmunology2023/8/24PrinciplesofOncologyMolecularBiologyofCancer:OncogenesIdentificationofOncogenesandTumorSuppressorGenesFunctionofOncogenesandTumorSuppressorGenes2023/8/24TumorRelatedGenesOncogene,proto-oncogene

ras,myc,erb2,src,c-fos,c-junetc.Tumorsuppressgene

RB,p53,APC,WT1etc.

DNAdamageandrepairrelatedgene

hMSH2,hMLH1,PMS1,PMS22023/8/24FunctionofOncogenesandTumorSuppressorGenes

SignalTransduction(ras)ExtracellularGrowthFactors(Sis)ReceptorTyrosineKinases(RET)NuclearProteinsandTranscriptionfactors(jun,BRCA1,2,myc,myb)CellCycle/DNADamageResponse(p53,RB,hMSH,MDM-2)2023/8/24MolecularMarkersinCancerDiagnosisChromosomalrearrangementsDNArearrangementsSmallMutation:K-ras,p53,APCTissue-specifictranscriptsViralgenomes2023/8/242023/8/24高通量分析技術——TissueArray2023/8/242023/8/24檢測大腸癌及轉移灶的不同組織基因表達研究 正常組織、結腸癌及癌旁組織 肝轉移組織及淋巴結轉移灶

FAP的不同部位的組織塊高通量分析技術——基因芯片(GeneChip)基因芯片技術日益成熟，在生命科學領域的應用更為廣泛GenePMMMOligo2023/8/24Telomerase,CellAgingandCancer

TimeTelomereLengthCriticalTelomereLengthNormalCellsStem&TumorCells2023/8/24MoledularBiologyofCancerCytogeneticsTheCellCycleApoptosisAngiogenesisInvasionandMetastasis2023/8/242023/8/242023/8/242023/8/24組織細胞數(shù)量＝細胞增殖－細胞死亡TissueCellNo.=CellProliferation-CellDeath

癌基因和抗癌基因OncogenesandTumorSuppressorGenes凋亡和抗凋亡基因ApoptosisGeneandAnti-apoptosisGene2023/8/24正常粘膜I

癌轉移APCK-rasDCCP53nm23?其它甲基化5q突變.缺失12p突變18q突變?缺失17p突變.缺失IIIIIIVAdenomaMCChMSH2hMLH1hPMS1hPMS2ACFCOX-2SNC6，SNC73SNC19，maspin，osteo2023/8/242023/8/24EtiologyofCancerViruses(DNAandRNAViruses)ChemicalFactorsPhysicalFactorsHormonalFactorsCancerGenetics(Hereditaryfactors)2023/8/24腫瘤發(fā)生機制環(huán)境、飲食生物性因素遺傳易感性酶的多態(tài)性基因不穩(wěn)定MSIIntereactionDNA損傷修復修復DNA突變癌變?nèi)旧w不穩(wěn)定作用后出現(xiàn)的分子產(chǎn)物（基因與蛋白）

2023/8/24CancerGeneticsCancerasaGeneticDiseaseMechanismsofCancerPredispositionClinicalCharacteristicsofCancerFamiliesMultisystemGeneticSyndromesWithaHighRiskofCancerNonsyndromicHereditaryCancer2023/8/24EpidemiologyofCancerHumanCarcinogenesis:TheNatureoftheEvidenceCancerEpidemiologybySiteAnOverviewofCancerCauses2023/8/24CancerPrevention:PreventingTobacco-RelatedCancersDietandChemopreventiveAgents:Fat:BreastCancer,ColonCancer,ProstateCancerandotherCancerDietaryFibersRetinoids,Carotenoids,andMicronutrientsNaturallyOccurringDietaryAnticarcinogensDietaryCarcinogensAspirinandOtherNonsteroidalAntiinflammatoryDrugsandtheRiskofCancerDevelopmentPhysicalActivityandBodyWeightRoleofSurgeryinCancerPrevention2023/8/24CancerScreeningWhatisCancerScreening?EvaluationofAscreeningTestBreastCancerScreeningCervicalCancerScreeningSkinCancerScreeningProstateCancerScreeningColorectalCancerScreeningLungCancerScreening2023/8/24PathologyofNeoplasmsCarcinogenesisandTumorigenesisTumorcelldifferentiationGrowthpatternGrowthrate(speed)MetastasisDirectExtensionLymphaticSpreadVascularSpreadSpreadthroughSerousCavities2023/8/24CancerDiagnosis:MolecularPathologyImmunohistochemistryDNAContentDiagnosticMolecularGeneticsTechniquesintheMolecularGeneticDiagnosisofCancerMolecularMarkersinCancerDiagnosisSmallMutationsFutureExpectations2023/8/24ClinicalManifestationsCancer’ssevenwarningsignalsChangeinbowelorbladderhabitsAsorethatdoesnothealUnusualbleedingordischargeThickeningorlumpinbreastorelsewhereIndigestionordifficultyinswallowingObviouschangeinwartormoleNaggingcoughorhoarseness2023/8/24LocalmanifestationsofcancerMassPainUlcerBleedingObstructionMetastaticManifestations2023/8/242023/8/242023/8/242023/8/24SystemicManifestationofcancerNon-specific:AnemiaLowfeverWeightlossInertiaAnorexia-cachexiaandothers2023/8/242023/8/24Diagnosisofcancershouldproceedinonorderlyfashion:Carefulhistory(Detailsofriskfactorsincludingfamilyhistoryandcurrentmedicationshouldbenotedinthepatientsrecords)ThoroughphysicalexaminationLaboratoryexaminationImagingexaminationCancerDiagnosis2023/8/24ClinicalBreast

ExaminationInspectionAsymmetrySkinlesionsSkinchangesNippleandareolaabnormalitiesPalpationtechniqueExaminationoftheNippleExaminationofregionallymphnodes(supraclavicular,infraclavicular,axillary)2023/8/24CancerDiagnosis:Imaging—UltrasonographyUltrasonographyisparticularlysuitableforthefollowingpatientgroups:Liver,gallbladder,spleenandpancreaseRetro-peritonealKidneyandadrenalglandBreastandthyroidUltrasoundobservationsBoundariesandshapeInternalechoesPosteriorshadowing2023/8/24CancerDiagnosis:Imaging—ComputedTomographyLiverandgallbladderPancreasandspleenKidneyandAdrenalGlandSmallBowelandColonEsophagusandStomachLungsandMediastinumMusculoskeletalSystemCentralNervousSystem2023/8/24CancerDiagnosis:Imaging—MagneticResonanceImagingBrain,SpineHeadandNeckBreastLiverAdrenalGlands,KidneyUterus,OvaryProstate,BladderMusculoskeletalSystem2023/8/24CancerDiagnosis:

OtherImagingsFunctionalandMetabolicImaging—PositronEmissionTomography(PET)InterventionalRadiologyRadionuclideImaging2023/8/242023/8/24CancerDiagnosis:EndoscopyUpperGastrointestinalEndoscopyEndoscopicUltrasonographySignoidoscopy,ColonoscopyLaparoscopyEndoscopicRetrogradeCholangiopancreatographySmallIntestinalEndoscopy:EnteroscopyPercutaneoisEndoscopicGastrostomyBronchoscopyMediastinoscopyThoracoscopy2023/8/24SpecializedTechniquesinCancerManagemntLaparoscopyVascularAccessandSpecializedTechniquesofDrugDeliveryIsolationPerfusionIntensity-ModulatedRadiationTherapy2023/8/24FineNeedleAspirationIndicationforFNAWhenphysicalexaminationormammographyofthebreastshowsasuspiciousabnormality,eitheradefinitemassorathickeningnotwithinthenormalrange,FNAisindicated.TodistinguishbetweenacystandacarcinomaFNAbiopsyorFNAcytologyUltrasound-guidedFNA2023/8/24BiopsyIndicationsforbiopsyaregenerallyderivedfromtheresultsofphysicalexaminationormammography.Twotechniquesareusedforobtainingtissuesuitableforhistologicalexamination,coreneedlebiopsy,andopenbiopsy.2023/8/24Core-cuttingneedlebiopsyStereotacticallyguidedneedlebiopsyNon-palpablelesionsOpenbiopsyIncisionalbiopsyExcisionalbiopsy(excision,marking,inking,review)Openbiopsyofnon-palpablelesionsHooked-wirelocalizationSpotlocalizationSkinbiopsy(Paget’sdisease,inflammatorycarcinoma)Biopsyofregionaladenopathy2023/8/24StagingCurrently,StagingofcancerisdeterminedbytheTNMsystemofclassification.T tumorN regionallymphnodesM distantmetastases(Primary,Local,RegionalandDistant)2023/8/24PrinciplesofCancerManagement:Goalsoftherapy–CureorPalliationThegoalsoftherapyvarywiththeextentofthecancer.Ifthecancerislocalizedwithoutevidenceofspread,thegoalistoeradicatethecancerandcurethepatient.Whenthecancerisspreadbeyondlocalcure,thegoalistocontrolthepatient’ssymptomsandtomaintainmaximumactivityforthelongestpossibleperiodoftime.2023/8/24PrinciplesofCancerManagement:SurgicalOncologyHistoricalPerspectiveAnesthesiaforOncologicSurgeryDeterminationofOperativeRiskRolesforSurgeryTheSurgicalOncologist2023/8/24SurgicalTherapyCancersurgeryhasbeenbasedupontheconceptthatcancerbeginsasalocaldiseaseandspreadsinanorderlyfashionfromtheprimarysitetoadjacenttissuesbydirectextensiontotheregionallymphnodesbylymphaticsandthroughthebloodvessels.Thesurgicalprocedurewasdesignedtoremovetheprimaryneoplasmsandtheusualcontiguousroutesofspreadwithaimofremovingeverycancercellfromthebody.2023/8/24SurgicalTherapyOnlyaboutone-thirdofcancerpatientsarecuredbysurgeryalone,sincesurgicaltherapy,withfewexceptions,iscurativeonlyinthosepatientsinwhomthediseaseislocalizedtotheprimarysiteandregionalnodes.Advancesinsurgicaltechniques,anesthesia,andsupportivecare(bloodtransfusion,antibiotics,etc)havepermittedthedevelopmentofmoreradicalandextensiveoperativeprocedures.2023/8/24SurgicalTherapyItisessentialtorealizethatthebest,andoftentheonly,opportunityforcureisatthetimeofthefirstoperation,sotheoperativeprocedureshouldbeplannedcarefully.Preventionofcancercellimplantationduringsurgery—localrecurrence.Preventionofvasculardisseminationatsurgery—blood-bornemetastases.“No-touch”technique,earlyligationofthevascularpedicle,etc.2023/8/24SurgicalTherapy:TypesofCancerOperationsLocalresection(atleastincludingsomenormaltissuessurrounding)RadicallocalresectionRadicalresectionwithenblocexcisionoflymphaticsExtensivesurgicalproceduresSurgeryofrecurrentcancerResectionofmetastasesPalliativesurgery2023/8/242023/8/24PrinciplesofCancerManagement:RadiationTherapyPhysicalConsiderationBiologicConsiderationsTumorradiobiologyClinicalConsiderations2023/8/24RadiotherapyObjectivesofRadiotherapyToday,it’srecognizedthatradiologistsmustoptimizetechniquesanddosesofradiotherapyinordertominimizetheriskoflocalrecurrence,achieveexcellentcosmeticresults,andavoidbothshort-andlong-termcomplications.2023/8/24TreatmentPlanningObtainCTScans

DefineTargetArea

EstablishIrradiationField

Construct3DImage

CreateBlocks

ConfirmDoseDistribution2023/8/24ThetechniqueofradiotherapyPatientmarkingsScheduleDoseBoostdoseExternal-beamradiotherapy(X-raysorelectrons)Interstitialimplantation2023/8/24ChemotherapyHistoryChemotherapyasPartoftheInitialTreatmentofCancerClinicalEndpointsinEvaluatingResponsetoChemotherapyPrinciplesGoverningtheUseofCombinationChemotherapyResponsetoChemotherapyIsAffectedbytheBiologyofTumorGrowthThecellCycle,DrugResistance,andtheP53TumorSuppressorGenePathwayTheconceptofDoseIntensityInVitroDrug-ResponseAssays2023/8/24TypesofChemotherapy

TheroleofchemotherapyAdjuvantchemotherapyNeo-adjuvantchemotherapyPalliativechemotherapyHigh-dosechemotherapy2023/8/24AdjuvantchemotherapyRationalforadjuvanttherapySubclinicalmetastases,therapydirectedattheprimarytumorisnothelpful,Systemictherapyaftersurgery,atatimewhenpatientsareclinicallyfreeofdiseasebutareathighriskofhavingresidualmicrometastases.Twotypesofsystemicapproachesareeffective,chemotherapy(cytotoxicagents)andhormonetherapy.2023/8/24AdjuvantchemotherapyTimingofAdjuvantchemotherapyChoiceofchemotherapySingle-agentchemotherapyCombinationchemotherapyNewcytotoxicagentsDoseDurationoftherapy2023/8/24ToxicityofadjuvantchemotherapyCommon:Myelosuppression AlopeciaNausea PrematureovarianfailureVomiting WeightgainLessCommon:SystemicinfectionsThrombosisNeurologicalproblems2023/8/24PalliativechemotherapyBenefits:Metastaticbreastcancerisverytreatableandisoneofthesolidtumormostresponsivetocytoto