内科学教学课件：Primary Bronchogenic Carcinoma

PrimaryBronchogenicCarcinomaGeneralconsiderationsPrimarybronchogeniccarcinoma(lungcancer)isamalignanttumorthatarisesfromthebronchialmucosaorgland.Lungcanceristheleadingcauseofcancerdeathsanditsprognosisisamongtheworstbecauseoflateclinicalcomfirmation.

Epidemiolody流行病学In2008,thedatafromWHOshowedthatlungcancerwasfirstplaceofallcancersintheworldnomatterinthemorbidity发病率(1,600,000annually)ormortality死亡率(1,400,000).InChina,lungcanceristheleadingcauseofcancerdeathsanditsdeathratehasincreasedby464.8%inthepast3decades.70%oflungcancerpatientareover65yearsofage,whilelessthan3%oflungcanceroccurinpeopleunder45.EtiologyandPathogenesisCigarettesmoking

Cigarettesmokingisbyfarthemaincontributortothelungcancer’sdeathrate.Nicotin尼古丁,benzo-pyrene苯并芘,nitrosamine

亚硝胺

insmokehavebeenidentifiedascarcinogens致癌物,especiallyinthedevelopmentofsquamouscarcinomaandsmallcelllungcancer.Peoplewhosmokeshasahigherrisk(9-10timesinsmokerand10-25timesinheaveysmoker)forthedevelopmentoflungcancerthananonsmoker.Thereisadose-effectrelationshipbetweencigarettesmokingandincedenceoflungcancer.EtiologyandPathogenesisCigarettesmokingPassivesmokingnonsmokerswhoresidewithasmokertheriskfordevelopinglungcancerwillbedoubledwhencomparedwithnonsmokerswhodonotresidewithasmoker

Quitsmoking

About1-5yearsafterquitting,theriskforlungcancerbeinghalvedand15yearsafterquitting,riskdecreasestothelevelofsomeonewhoneversmoked.EtiologyandPathogenesisOccupationalcarcinogens职业致癌因子Asbestos石棉,arseniccompound砷化合物,chrome铬，nickel镍，uranium铀,radon氡气

(aradioactivegasfoundinrocksandsoil),etc.AirpollutionIncludingindoorandoutdoor,

fuelburning燃料燃烧,cookingoilfumes,smog雾霾

PM2.5可入肺颗粒物particulatematter微粒

（≤2.5µ）thatcangodirectlytothealveoli.

EtiologyandPathogenesisIonizingradiation电离辐射Dietandnutrition饮食与营养

β

Carotin

β胡萝卜素,vegetables,fruitsPrecipitatingfactors诱发因素

Infections(tuberculebacillus结核杆菌,virus,fungus真菌,etc)EtiologyandPathogenesisHeredityandgeneticchange遗传和基因改变Inallnormalcells,twotypeofgenes,oncogenesandanti-oncogenes,areexpressedandcontrolcellproliferation增殖anddifferentiation分化.Lungcancerisinitiatedbyactivationof

oncogene癌基因活化

orinactivationof

anti-oncogene抑癌基因失活Theoncogenesrelatingtolungcancer:rasandmycgenesfamily,c-erbB-2,bcl-2,c-fos,c-junetc.Theanti-oncogene(tumorsuppressorgenes)

p53,Rb,CDKN2,FHITetc.

PathologyandclassificationAnatomicalclassification

1.

Centrallungcancer

（3/4）locatedbetweensegmentalbronchusandmainbronchus(squamousandsmallcelllungcancer)

2.Peripherallungcancer(1/4)locatedbeyondsegmentalbronchus(adenocarcinoma)PathologyandclassificationHistologicalclassification(SCLCandNSCLC)

Non-smallcelllungcancer,NSCLC(80%)

1.Squamouscellcarcinoma(25%-35%)a.Craluminalgrowth管腔内生长

c.cavitation易形成空洞

d.secondaryinfectionandatelectasis

Pathologyandclassification

Non-smallcelllungcancer,NSCLC

2.Adenocarcinoma(35%-40%)a.peripherallocatedb.extra-luminalgrowth管腔外生长

c.earlymetastasis(localorsystemic)d.alveolarcellcarcinoma肺泡细胞癌(subtype)

3.Largecellcarcinoma(5%-10%)

4.Others(adenosquamous腺鳞癌,carcinoid类癌，etc.)PathologyandclassificationHistologicalclassification(SCLCandNSCLC)

Smallcelllungcancer,SCLC(15%-20%)1.centrallylocated2.mostaggressiveandearlymetastasis3.neuroendocrinegranules神经内分泌颗粒

thatcansecretsomeectopichormones异位激素,suchasthrombocytin5-羟色胺，catecholamine儿茶酚氨，histamine组胺

etcwhichareassociatedwithcardinoidsyndrome类癌综合征4.respondswelltochemotherapyandradiotherapy5.poorprognosisuntreatedSCLChasanaveragesurvivaltimeof2to3months，treatedonly5%have5years’survival.Staging临床分期StagingisimportantfordetermininghowaparticularcancershouldbetreatedStagingofNSCLCTNMinternationalstagingsystemTthesizeandlocationoftheprimarytumorNthepresenceandlocationofnodalmetastasisMthepresenceorabsenceofdistantmetastasisPrimarytumor(T)TX:Primarytumorcannotbeassessed;ortumorprovedbythepresenceofmalignantcellsinsputumorbronchialwashingbutnotvisualizedbyimagingorbronchoscopyT0:NoevidenceofprimarytumorTis:Carcinomainsitu原位癌T1a:

Atumor≤2cmingreatestdimension,surroundedbylungorvisceral脏层

pleural,andwithoutevidenceofinvasionproximal近端

tolobarbronchusatbronchoscopy.T1b:Tumorsizemorethan2

cmbutlessthanorequalto3

cmacrossT2a:Tumorsizemorethan3

cmbutlessthanorequalto5

cmacrossInvolvementofthemainbronchusatleast2

cmdistaltothecarinaInvasionofvisceralpleuraAtelectasis/obstructivepneumonitisextendingtothehilumbutnotinvolvingthewholelungT2b:Tumorsizemorethan5

cmbutlessthanorequalto7

cmacrossPrimarytumor(T)T3:Anyof

tumorsizemorethan7

cmacross.Invasionintothechestwall(Pancoastcancer),diaphragm,

phrenicnerve,mediastinalpleuraandpericardium.Tumorlessthan2

cmdistaltothecarina,butnotinvolvingthecarina.Atelectasis/obstructivepneumonitisofthewholelung.Separatetumornoduleinthesamelobe.T4:Anyoftumorsizewithinvasionofthemediastinum,heart,greatvessels,trachea,carina,recurrentlaryngealnerve,esophagus,orvertebra.SeparatetumornoduleinadifferentlobeofthesamelungRegionallymphnodes(N)

NxRegionallymphnodescannotbeassessedN0NoregionallymphnodesmetastasisN1Metastasistotheipsilateral同侧

peribronchial支气管旁

and/orhilar肺门

lymphnodes.N2Metastasistoipsilateralmediastinaland/orsubcarinal隆凸下lymphnodesN3

Metastasistoscalene斜角肌

orsupraclavicular锁骨上

lymphnodesorcontralateral对侧

hilarormediastinallymphnodes。Distantmetastasis(M)MxPresenceofdistantmetastasiscannotbeassessedM0NometastasisM1aSeparatetumornoduleintheotherlung.Tumorwithpleuralnodules.Malignantpleuralorpericardialeffusion.M1bDistantmetastasisTNMandclinicalstagingClinicalStagingTNMstagingOccultTxN0M0隐性癌

0Tis

ⅠAT1N0M0

ⅠBT2aN0M0

ⅡAT1N1M0;T2bN0M0;T2aN1M0

ⅡBT2bN1M0;T3N0M0ⅢAT1-3N2M0;T3N1-2M0;T4N0-1M0

ⅢBT1-4N3M0;T4N2-3M0

ⅣT1-4N0-3M1Clinicalmanifestationsthesize,type,location,stage,complication5%-15%mayhavenosymptomswhenthecancerisdiagnosed.Primarytumor,localspread,distantspreadandparaneoplasticsymptoms.ClinicalmanifestationSymptomsoftheprimarytumorCoughirritating,persistent

cough刺激性持续性干咳withmetallicsound金属音Heamoptysis(coughingupblood)centraltype,bloodysputumtomassiveheamoptysisShortnessofbreathordyspneaobstructionofbigairway,diffusealveolarcellcarcinomaandpleuraleffusionFevercancerousfever癌性发热

orobstructivepneumoniaWeightlossClinicalmanifestationsSyptomsoflocalspreadChestpaininvolvementofpleuraorchestwall,obstructivepneumoniaHoarseness

声嘶

paralysisofthevocalcordsbecauseofcompromiseofrecurrentlaryngealnerve喉返神经

bytumorormetastaticnodalsDysphagia

吞咽困难

invasionoftheesophagusmayleadtodifficultyswallowing.Pleuraleffusioninvasionofpleuraorlymphaticreturnobstacle淋巴回流受阻ClinicalmanifestationsSyptomsoflocalspreadSuperiorvenacavasyndrome

上腔静脉阻塞综合征

obstructionofSVCwithsupraclavicularvenousengorgement锁骨上静脉充盈

andedemaofface,cervico-thoracicregion面、颈胸部水肿Horner’ssyndrome(Pancoasttumor)ipsilateralptosis上睑下垂,miosis瞳孔缩小,enophthalmos眼球内陷

andanhidrosis缺汗症

frominvolvementoftheinferiorcervicalganglion颈下交感神经节ClinicalmanifestationsSymptomsrelatedtodistantmetastasis

Centralnervessystemheadache,nausea,vomit,etc.SkeletalsystempainatthesitesofboneinvolvementAbdomenadrenal,liver,pancrea,etcLymphnodessupraclavicularlymphnodes锁骨上淋巴结

ClinicalmanifestationsParaneoplasticsymptoms(10%-20%)notcorrelatedwithdistantmetastasisHypertrophicpulmonaryosteoarthropathy

肥大性肺性股关节病,fingerclubbing杵状指Ectopicgonadotropichormone

异位促性腺激素(largecellcarcinoma),gynaecomastia男性乳房发育

AdrenocorticotrophichormoneACTH

促肾上腺皮质激素

(SCLC),Cushingsyndrome库欣综合征SyndromeofinappropriatesecretionofantidiuretichormoneSIADH,overhydration水中毒

ClinicalmanifestationsParaneoplasticsymptoms(10%-20%)Neuromuscularsyndrome

神经肌肉综合征，cerebellarcorticaldegeneration小脑皮质变性，peripheralneuropathy周围神经病变，myastheniagravis重症肌无力Hypercalcemia

高钙血症

(squamouscarcinoma),metastasisofboneandproductionofasubstancesimilartoparathyroidhormone甲状旁腺激素Carcinoidsyndrome

类癌综合征，symtomesassociatedwithskin,cardiovascularsystem,gastrointestinaltract,etc.Suchasflush皮肤潮红,angioedema血管性水肿,tachycardia心动过速,diarrhoea,etc.

ImagingandothertestsImagingofchestCentraltypehilarmass,airwayobstruction(localizedemphysema,ateleatasis,pneumonia,etc.)ImagingandothertestsPeripheraltypesmallpatch,nodulewithboundarylobulated分叶

andburr毛刺，pleuralindentation胸膜凹陷,cancerouscavity,pleuraleffusion,etc.ImagingandothertestsAlveolarcellcarcinomsolitarynoduleormultiplenodulesImagingandothertestsMagneticresonanceimagingMRI

noexposuretoradiationno

needofintravenouscontrastmaterialinjectionSinglephotonemissioncomputerizedtomographyECT

单光子发射计算机断层显像

Todeterminewhetheralungcancerhasmetastasizedtothebones.ImagingandothertestsPositronemissiontomographyPETscan正电子发射计算机体层显像

Cancercellhashighermetabolicrateandtakeinmoreglucosethannormalcell.WhenFluorine-18lablieddeoxyglucose

18-氟脱氧葡萄糖（FDG）isinjectedintobody,ahigherconcentrationofFDGincancertissueswillbedetectedbyPETscan.FDG-PETcanbeusedfordiagnosis(primaryandmetastaticlesions),staging,andmonitoringtreatmentofcancers.

ImagingandothertestsSputumcytology

Themostrisk-freeandinexpensivemethodtoestablishthediagnosis,,butitsvalueislimited.Morethan3serialsamplescanincreasthepositiveyieldto80%incentraltypeand50%inperipheralone.

ImagingandothertestsBronchoscopy

支气管镜检

visualizationofthemajorairwaysthroughathin,flexibleprobeinsertedthroughthenoseormouth,cytologybrushing,washing,lavagedirectbiopsyortransbronchiallungbiopsy.ImagingandothertestsNeedleaspirationcytologyNeedleaspirationofsuperficiallymphnode浅表淋巴结针吸细胞学Transbronchoscopeneedleaspiration

经纤气管镜针吸细胞学Percutaneousneedleaspiration

经皮针吸细胞学ImagingandothertestsMediastinoscopy

纵隔镜检查Thoracoscopy

胸腔镜检查Othercytology细胞学

andhistology组织学

exam.CytologictestofpleuraleffusionHistologictestofpleura,lymphnode,liverorbonemarrow.Openlungbiopsy

开胸肺活检ImagingandothertestsTumormarkers

肿瘤标志物

(a

biomarkerortumorantigenfoundinthe

blood,

urine,orbodytissues

thatcanbeelevatedin

cancer).

CEA癌胚抗原,NSE神经特异性烯醇酶,

cyfra21-1

细胞角蛋白19片段,ProGRY胃泌素释放肽前体.DiagnosisThelong-termsurvivalrateoflungcancerlargelydependsontheearlydiagnosis.EducationofpeopleabouttheknowledgeoflungcancerThepeopleover40yearsoldwithaheaveysmokinghistoryoracontacthistorywithcarcinogenicfactorshouldhaveahealthcheck-uponceayear.Timelyidentificationoflungcancer’searlysymptomesDiagnosisCommonsignsandsymptomsoflungcancerinclude:aconstantunexplainedirritatingcoughdoesnotrespondtothetreatmentorachangeinchroniccough.coughingupblood.repeatedsamesitepneumonia,especiallysegmentaloneunexplainedlungabscesswithnotoxicsymptoms,purulentsputum,foreignbodyaspiration.unknownoriginjointpainandfingerclubbinglocalizedemphsema,segmentorlobeatelectasissolitarynoduleoripsilateralhilarshadowincreasingchangeofoldstabletuberculosis(tuberculoma结核瘤)pleuraleffusionwithnotoxicsymptoms,especiallybloodyhydrothoraxDifferentialdiagnosisPulmonarytuberculosis

tuberculoma结核球hilarlymphonodetuberculosis肺门淋巴结结核acutemiliarytuberculosis急性粟粒性肺结核Pneumonia,inflammatorypseudotumor炎性假瘤Lungabscess—cancerouscavity癌性空洞Mediastinallymphoma

纵膈淋巴瘤

bilateralsymmetricalhilarshadowsenlargementgeneralsymptomslikefeverbutlessrespiratorysymptomsPulmonarybenigntumorbronchialadenoma支气管腺瘤，hamartoma错构瘤Tuberculouspleuritis

结核性胸膜炎TreatmentThemaintreatmentoptionsinlungcancerinclude:SurgeryChemotherapyRadiationtherapyTheoptionwilldependuponthepathologic

type,

staging

aswellastheoverallhealthstatusofthepatient.

TreatmentNSCLCLimiteddisease

局限性病变Sugery

StageⅠa,Ⅰb,ⅡaandⅡbsurgicalremovalStageⅢasurgeryandneoadjuvantchemotherapy新辅助化疗Radicalradiotherapy

根治性放疗

StageⅢand,ⅠorⅡwhoisintolerantsurgeryorunwillingtoacceptsurgery.Radicalcomprehensivetherapy根治性综合治疗Postoperativechemotherapyandradiotherapy

（Pancoasttumor,ⅢaandⅢb）.

TreatmentNSCLCExtensivedisease

播散性病变

Chemotherapy,radiotherapyand/orsupportivetherapyaccordingtoperformancestatus.Chemotherapyplatinum-based

铂

chemotherapycanprolongsurvival,relievesymptomsandimprovelifequality.Radiotherapyobstructionofbigairwayandsuperiorvenacava上腔静脉.Targetedtherapy

atypeof

medication

thatblocksthegrowthof

cancercells

byinterferingwithspecifictargeted

moleculesneededforcarcinogenesis癌发生

andtumorgrowth.Treatmentofmetastaticlesion

radiotherapyforbrainmetastasisintrapleuralinjection胸腔注射of

chemotherapeuticagentsformalignantpleuraleffusion.

TreatmentSCLCChemotherapybasedcomprehensivetreatmentandtoimprovelong-termsurvival.Chemotherapy

Withouttreatment,SCLCisarapidlyfataldisease.Radiotherapy

ForlimitedSCLC,radicalradiotherapyisrecommended.

ProphylacticcranialirradiationPCI

预防性颅脑放射CombinedtherapyTreatmentBiologicalresponsemodifier，BRM

生物反应调节剂

（Interferon干扰素,transferfactor转移因子,Colonystimulatingfactor，CSF集落刺激因子etc.）Increasethetolerance耐受性ofthebodytochemotherapyandradiotherapy.ChinesetraditionalmedicinePreventionAwayfromthecarcinogenicfactorsStopsmokingOccupationalprotectionImprovementofenvironmentalpollutionPrognosisTheoutcomeoflungcancerisdepe