结直肠癌（英文版）

Colorectalcancer12ColorectalcanceroccursinthecolonandtherectumRiskfactors

3Riskfactorsforcolorectalcancerincludelifestyle,olderage,andinheritedgeneticdisorders.Otherriskfactorsincludediet,smoking,alcohol,lackofphysicalactivity,familyhistoryofcoloncancerandcolonpolyps,presenceofcolonpolyps,race,exposuretoradiation,andevenotherdiabetes,obesity.4Physicalactivity5meat6Smokingalcohol7diabetes,obesity

AccordingtoWHO,Morethan30%Americanaretroublingwithobesityproblem.It’ssimilarinotherdevelopedcountrieswithhighrateofcolorectalcancer.8Otherriskfactors

suchasinflammatoryboweldisease,whichincludesCrohn'sdiseaseandulcerativecolitis,canincreasetheriskofcolorectalcancer.Someoftheinheritedconditionsthatcancausecolorectalcancerinclude:familialadenomatouspolyposisandhereditarynon-polyposiscoloncancer;however,theserepresentlessthan5%ofcases.Ittypicallystartsasabenigntumor,oftenintheformofapolyp,whichovertimebecomescancerous.Epidemiology910Age-standardizeddeathfromcolorectalcancerper100,000inhabitantsin2004.Globally,

Highest

incidenceratesintheAustralia,NewZealand,EuropeandtheUSandlowestratesinAfricaandSouth-CentralAsia.11Signsandsymptoms12abdominalpain,diarrhea….Thesymptomsandsignsofcolorectalcancerdependonthelocationofthetumorinthebowel,

andwhetherithasspreadelsewhereinthebody(metastasis).Signsandsymptoms1314RectumCheckingBecauseofhavingthesamesymptomwithbloodinthestoolandhavingnotclearlyrectumchecking,Inclinic,lotsofrectumcancerpatientsusuallymisdiagnosedashemorrhoids(痔疮）

andundergonesomeincorrecttreatments.15ThebodypostureforrectumcheckingLateralpostureKnee-chestpostureLithotomypostureCrouchpostureBendposture16AbdominaldistensionTumorwithbigmass,seriousascites,intestineobstruction…..17IntestinalObstruction1819CauseLocationandappearanceoftwoexamplecolorectaltumorsMorethan75-95%ofcoloncanceroccursinpeoplewithlittleornogeneticrisk.Otherriskfactorsincludeolderage,malegender,

highintakeoffat,alcohol

orredmeat,obesity,smoking,

andalackofphysicalexercise.20Inflammatoryboweldisease21Peoplewithinflammatoryboweldisease(ulcerativecolitis

andCrohn'sdisease)areatincreasedriskofcoloncancer.

Peoplewithinflammatoryboweldiseaseaccountforlessthan2%ofcoloncancercasesyearly.InthosewithCrohn'sdisease2%getcolorectalcancerafter10

years,8%after20

years,and18%after

30years.

Inthosewithulcerativecolitisabout16%developeitheracancerprecursororcancerofthecolonover30

years.

22ulcerativecolitisandCrohn'sdisease23Thosewithafamilyhistoryintwoormorefirst-degreerelatives(suchasaparentorsibling)haveariskofdiseaseandthisgroupaccountsforabout20%ofallcases.

Anumberofgeneticsyndromesarealsoassociatedwithhigherratesofcolorectalcancer.Themostcommonoftheseishereditarynonpolyposiscolorectalcancer(HNPCCorLynchsyndrome)whichispresentinabout3%ofpeoplewithcolorectalcancer.

24PathogenesisColorectalcancerisadiseaseoriginatingfromtheepithelialcellsliningthecolonorrectumofthegastrointestinaltract,mostfrequentlyasaresultofmutationsintheWntsignalingpathwaythatincreasesignalingactivity.Themutationscanbeinheritedoracquired,andmostprobablyoccurintheintestinalcryptstemcell(隐窝干细胞）.

25ThemostcommonlymutatedgeneinallcolorectalcanceristheAPCgene,whichproducestheAPCprotein.TheAPCproteinpreventstheaccumulationofβ-cateninprotein.WithoutAPC,β-cateninaccumulatestohighlevelsandtranslocates(moves)intothenucleus,bindstoDNA,andactivatesthetranscriptionofproto-oncogenes.Thesegenesarenormallyimportantforstemcellrenewal（重建、重生）

anddifferentiation,butwheninappropriatelyexpressedathighlevels,theycancausecancer.26P53proteinBeyondthedefectsintheWntsignalingpathway,othermutationsmustoccurforthecelltobecomecancerous.Thep53protein,producedbytheTP53gene,normallymonitorscelldivisionandkills

cellsiftheyhaveWntpathwaydefects.27DiagnosisSignsandsymptomsRadiologicaltechniquesEndoscopyTumormarkers(CEA,CA199…)Pathologicassessment28TheextentofthediseaseisusuallydeterminedbyaCTscanofthechest,abdomenandpelvis.ThereareotherpotentialimagingtestsuchasPETandMRIwhichmaybeusedincertaincases.ColoncancerstagingisdonenextandbasedontheTNMsystemwhichisdeterminedbyhowmuchtheinitialtumorhasspread,ifandwherelymphnodesareinvolved,andtheextentofmetastaticdisease.29Diagnosisofcolorectalcancerisviasamplingofareasofthecolonsuspiciousforpossibletumordevelopmenttypicallydoneduringcolonoscopyorsigmoidoscopy,dependingonthelocationofthelesion.30Pathologicassessmentmicroscopymacroscopy31Cancersontherightsideofthelargeintestine(ascendingcolonandcecum)tendtobeexophytic(外生的）,thatis,thetumorgrowsoutwardsfromonelocationinthebowelwall.Thisveryrarelycausesobstructionoffeces,andpresentswithsymptomssuchasanemia.Left-sidedtumorstendtobecircumferential（环周的）,andcanobstructthebowellumen

andresultsinthinnercaliberstools.

macroscopy32macroscopyAppearanceoftheinsideofthecolonshowingoneinvasivecolorectalcarcinoma(thecrater-like,reddish,irregularlyshapedtumor).Grossappearanceofacolectomyspecimencontainingtwoadenomatouspolyps(thebrownishovaltumorsabovethelabels,attachedtothenormalbeigeliningbyastalk)andoneinvasivecolorectalcarcinoma(thecrater-like,reddish,irregularlyshapedtumorlocatedabovethelabel).33macroscopyEndoscopicimageofcoloncanceridentifiedinsigmoidcolon

onscreeningcolonoscopyinthesettingofCrohn'sdisease.


PET/CTofastagingexamofcoloncarcinoma.Besidestheprimarytumoralotoflesionscanbeseen.Oncursorposition:lungnodule.

34Themicroscopecellularcharacteristicsofthetumorareusuallyreportedfromtheanalysisofthetissuetakenfromabiopsyorsurgery.Apathologyreportwillusuallycontainadescriptionofcelltypeandgrade.Themostcommoncoloncancercelltypeisadenocarcinomawhichaccountsfor98%ofcases.Other,rarertypesincludelymphomaandsquamouscellcarcinoma.microscopy35micrographsCancer—Invasiveadenocarcinoma(themostcommontypeofcolorectalcancer).Thecancerouscellsareseeninthecenterandatthebottomrightoftheimage(blue).Nearnormalcolon-liningcellsareseenatthetoprightoftheimage.Cancer—Histopathologicimageofcoloniccarcinoid.36micrographsPrecancer—Tubularadenoma（管状腺瘤）

(leftofimage),atypeofcolonicpolypandaprecursorofcolorectalcancer.Normalcolorectalmucosaisseenontheright.Precancer—Colorectalvillousadenoma(绒毛腺瘤）37ThecoloncancerstagingcanbemadeaccordingtotheTNMstagingsystemfromtheWHOorganization,theUICCandtheAJCC.TheAstler-Collerclassification(1954)ortheDukesclassification(1932)arenowlessused.Staging38TheTstagesofbowelcancerDukesstageAbowelcancer;thecancerisonlyintheinnerliningofthebowel.DukesstageBbowelcancer;thecancerhasinvadedthemuscleDukesstageCbowelcancer;thecancerhasinvadedthenearbylymphnodesDukesstageDbowelcancer;thecancerhasmetastasizedtheDukesclassification(1932)arenowlessused.39AJCC(TNM)StagingSystem:ThemostcommonlyusedstagingsystemforcolorectalcanceristhatoftheAmericanJointCommitteeonCancer(AJCC),sometimesalsoknownastheTNMsystem.40TheTNMsystemdescribes3keypiecesofinformation:T

describeshowfarthemain(primary)tumorhasgrownintothewalloftheintestineandwhetherithasgrownintonearbyareas.N

describestheextentofspreadtonearby(regional)lymphnodes.Lymphnodesaresmallbean-shapedcollectionsofimmunesystemcellsthatareimportantinfightinginfections.M

indicateswhetherthecancerhasspread(metastasized)tootherorgansofthebody.(Colorectalcancercanspreadalmostanywhereinthebody,butthemostcommonsitesofspreadaretheliverandlungs)41NumbersorlettersappearafterT,NandMtoprovidemoredetailsabouteachofthesefactors.Thenumbers0through4indicatedincreasingseverity.TheletterXmeans“cannotbeassessedbecausetheinformationisnotavailable.”42T

categories

for

colorectal

cancer

the

extent

of

spread

through

the

layers

thatform

the

wall

of

the

colon

and

rectum.

These

layers,

from

the

inner

to

the

outer,

include:

•The

inner

lining

(mucosa)

•A

thin

muscle

layer

(muscularis

mucosa)

•The

fibrous

tissue

beneath

this

muscle

layer

(submucosa)

•A

thick

muscle

layer

(muscularis

propria)

that

contracts

to

force

the

contents

of

the

intestines

along

•The

thin,

outermost

layers

of

connective

tissue

(subserosa

and

serosa)

that

cover

most

of

the

colon

but

not

the

rectum43Tx:No

description

of

the

tumor's

extent

is

possible

because

of

incomplete

information.

Tis:The

cancer

is

in

the

earliest

stage

(in

situ).

It

involves

only

the

mucosa.

It

has

not

grown

beyond

the

muscularis

mucosa

(inner

muscle

layer).

T1:The

cancer

has

grown

through

the

muscularis

mucosa

and

extends

into

the

submucosa.

T2:The

cancer

has

grown

through

the

submucosa

and

extends

into

the

muscularis

propria

(thick

outer

muscle

layer).

T3:The

cancer

has

grown

through

the

muscularis

propria

and

into

the

outermost

layers

of

the

colon

or

rectum

but

not

through

them.

It

has

not

reached

any

nearby

organs

or

tissues.

T4a:The

cancer

has

grown

through

the

serosa

(also

known

as

the

visceral

peritoneum),

the

outermost

lining

of

the

intestines.

T4b:The

cancer

has

grown

through

the

wall

of

the

colon

or

rectum

and

is

attached

to

or

invades

into

nearby

tissues

or

organs.

44N

categories

for

colorectal

cancer

N

categories

indicate

whether

or

not

the

cancer

has

spread

to

nearby

lymph

nodes

and,

if

so,

how

many

lymph

nodes

are

involved.

To

get

an

accurate

idea

about

lymph

node

involvement,

most

doctors

recommend

that

at

least

12

lymph

nodes

be

removed

during

surgery

and

looked

at

under

a

microscope.45Nx:No

description

of

lymph

node

involvement

is

possible

because

of

incomplete

information.

N0:

No

cancer

in

nearby

lymph

nodes.

N1a:

Cancer

cells

are

found

in

1

nearby

lymph

node.

N1b:Cancer

cells

are

found

in

2

to

3

nearby

lymph

nodes.

N1c:

Small

deposits

of

cancer

cells

are

found

in

areas

of

fat

near

lymph

nodes,

but

not

in

the

lymph

nodes

themselves.

N2a:Cancer

cells

are

found

in

4

to

6

nearby

lymph

nodes.

N2b:Cancer

cells

are

found

in

7

or

more

nearby

lymph

nodes.

46Mcategories

indicate

whether

or

not

the

cancer

has

spread

(metastasized)

to

distant

organs,

such

as

the

liver,

lungs,

or

distant

lymph

nodes.

M0:No

distant

spread

is

seen.

M1a:

The

cancer

has

spread

to

1

distant

organ

or

set

of

distant

lymph

nodes.

M1b:

The

cancer

has

spread

to

more

than

1

distant

organ

or

set

of

distant

lymph

nodes,

or

it

has

spread

to

distant

parts

of

the

peritoneum

(the

lining

of

the

abdominal

cavity).47Stage

0

:Tis,

N0,

M0Stage

I

:T1-T2,

N0,

M0Stage

IIA

:T3,

N0,

M0Stage

IIA

:T3,

N0,

M0Stage

IIC

:T4b,

N0,

M0Stage

IIIA

:T1-T2,

N1,

M0;T1,

N2a,

M0:Stage

IIIB

:T3-T4a,

N1,

M0;T2-T3,

N2a,

M0;T1-T2,

N2b,

M0Stage

IIIC

:T4a,

N2a,

M0;T3-T4a,

N2b,

M0;T4b,

N1-N2,

M0Stage

IVA

:Any

T,

Any

N,

M1aStage

IVB

:Any

T,

Any

N,

M1b:Stage

grouping

4849Mostcolorectalcancersshouldbepreventable,throughincreasedsurveillanceandlifestylechanges.Prevention50LifestyleCurrentdietaryrecommendationstopreventcolorectalcancerincludeincreasingtheconsumptionofwholegrains,fruitsandvegetables,andreducingtheintakeofredmeat.Theevidenceforfiberandfruitsandvegetableshoweverispoor.Physicalexerciseisassociatedwithamodestreductionincolonbutnotrectalcancerrisk.Sittingregularlyforprolongedperiodsisassociatedwithhighermortalityfromcoloncancer.Theriskisnotnegatedbyregularexercise,thoughitislowered.51MedicationAspirinandcelecoxib（希乐葆）

appeartodecreasetheriskofcolorectalcancerinthoseathighrisk.However,itisnotrecommendedinthoseataveragerisk.

Thereistentativeevidenceforcalciumsupplementationbutitisnotsufficienttomakearecommendation.VitaminDintakeandbloodlevelsareassociatedwithalowerriskofcoloncancer.52ScreeningAsmorethan80%ofcolorectalcancersarisefromadenomatouspolyps,screeningforthiscanceriseffectivenotonlyforearlydetectionbutalsoforprevention.

Diagnosisofcasesofcolorectalcancerthroughscreeningtendstooccur2–3yearsbeforediagnosisofcaseswithsymptoms.

Anypolypsthataredetectedcanberemoved,usuallybycolonoscopy,andthuspreventedfromturningcancerous.Screeninghasthepotentialtoreducecolorectalcancerdeathsby60%.53Thethreemainscreeningtestsarefecaloccultbloodtesting（大便潜血试验）,flexiblesigmoidoscopy,andcolonoscopy.

Ofthethree,onlysigmoidoscopycannotscreentherightsideofthecolonwhere42%ofmalignanciesarefound.

VirtualcolonoscopyviaaCTscanappearsasgoodasstandardcolonoscopyfordetectingcancersandlargeadenomasbutisexpensive,associatedwithradiationexposure,andcannotremoveanydetectedabnormalgrowthslikestandardcolonoscopycan.54Fecaloccultbloodtesting(FOBT)ofthestoolistypicallyrecommendedeverytwoyears.

IfabnormalFOBTresultsarefound,participantsaretypicallyreferredforafollow-upcolonoscopyexamination.AnnualtobiennialFOBTscreeningreducecolorectalcancermortalityby16%andamongthoseparticipatinginscreeningcolorectalcancermortalitycanbereducedupto23%,althoughithasnotbeenproventoreduceall-causemortality.

Immunochemicaltestsarehighlyaccurateanddonotrequiredietaryormedicationchangesbeforetesting.55SomecountrieshavenationalcolorectalscreeningprogramswhichofferFOBTscreeningforalladultswithinacertainagegroup,typicallystartingbetweenage50and60.ExamplesofcountrieswithorganizedscreeningincludetheUnitedKingdom,

AustraliaandtheNetherlands.56MedicalsocietiesintheUnitedStatestypicallyrecommendscreeningbetweentheageof50and75

yearswithsigmoidoscopyevery5yearsandcolonoscopyevery10years.Forthoseathighrisk,screeningsusuallybeginataround40.Itisunclearwhichofthesetwomethodsisbetter.

Colonoscopymayfindmorecancersinthefirstpartofthecolonbutisassociatedwithgreatercostandmorecomplications.Forpeoplewithaverageriskwhohavehadahigh-qualitycolonoscopywithnormalresults,theAmericanGastroenterologicalAssociationdoesnotrecommendanytypeofscreeninginthe10yearsfollowingthecolonoscopy.

Forpeopleover75orthosewithalifeexpectancyoflessthan10

years,screeningisnotrecommended.57Thetreatmentofcolorectalcancercanbeaimedatcureorpalliation.Thedecisiononwhichaimtoadoptdependsonvariousfactors,includingtheperson'shealthandpreferences,aswellasthestageofthetumor.

Whencolorectalcancerbefoundatearlystages,surgerycanbecurative.However,whenitisdetectedatadvancedstages(forwhichmetastasesarepresent),thisislesslikelyandtreatmentisoftendirectedatpalliation,torelievesymptomscausedbythetumourandkeepthepersonascomfortableaspossible.Treatment58SurgeryLaparotomyLaparoscopicoperationPalliativeoperation59SurgeryAdiagramofalocalresectionofearlystagecoloncancerAdiagramoflocalsurgeryforrectalcancer60D1,2,3DissectionCentralgroupMiddlegroupNearbygroup61CME

(completemesocolicexcision)forcoloncancerTME(totalmesorectalexcision)forrectumcancerTwoconceptsoftheoperationforcolorectalcancer:62TheprinciplesofCMEandTME:Withthevisualizingandthesharpdissection,totallyremovethemesocolicorthemesorectalbetweentheviscerallayerandwalllayeroffascia.Exposingandcuttingoffcentrallyatthemesentericvesselroot.Completelyremovetheregionallymphnodesandtopreventthespreadingandmetastasesofcancercells.63CME

(completemesocolicexcision)forcoloncancer64CME

(completemesocolicexcision)forcoloncancer65TME(totalmesorectalexcision)forrectumcancer----Coronalsection66-----sagittalsection----CoronalsectionTME(totalmesorectalexcision)forrectumcancer67ChemotherapyInbothcancerofthecolonandrectum,chemotherapymaybeusedinadditiontosurgeryincertaincases.Thedecisiontoaddchemotherapyintreatmentofcolonandrectalcancerdependsonthestageofthedisease.68InStageIcoloncancer,nochemotherapyisoffered,andsurgeryisthedefinitivetreatment.TheroleofchemotherapyinStageIIcoloncancerisdebatable,andisusuallynotofferedunlessriskfactorssuchasT4tumororinadequatelymphnodesamplingisidentified.Itisalsoknownthatthepatientswhocarryabnormalitiesofthemismatchrepairgenesdonotbenefitfromchemotherapy.ForstageIIIandStageIVcoloncancer,chemotherapyisanintegralpartoftreatment.69Ifcancerhasspreadtothelymphnodesordistantorgans,whichisthecasewithstageIIIandstageIVcoloncancerrespectively,addingchemotherapyagentsfluorouracil,capecitabineoroxaliplatinincreaseslifeexpectancy.

Ifthelymphnodesdonotcontaincancer,thebenefitsofchemotherapyarecontroversial.Ifthecanceriswidelymetastaticorunresectable,treatmentisthenpalliative.Typicallyinthissetting,anumberofdifferentchemotherapymedicationsmaybeused.Chemotherapydrugsforthisconditionmayincludecapecitabine,fluorouracil,irinotecan,oxaliplatinandUFT.70Antiangiogenicdrugssuchasbevacizumabareoftenaddedinfirstlinetherapy.Anotherclassofdrugsusedinthesecondlinesettingareepidermalgrowthfactorreceptor(EGFR)inhibitors,ofwhichthetwoFDAapprovedonesarecetuximabandpanitumumab.71Theprimarydifferenceintheapproachtolowstagerectalcanceristheincorporationofradiationtherapy.Often,itisusedinconjunctionwithchemotherapyinaneoadjuvantfashiontoenablesurgicalresection,sothatultimatelyascolostomyisnotrequired.However,itmaynotbepossibleinlowlyingtumors,inwhichcase,apermanentcolostomymayberequired.StageIVrectalcanceristreatedsimilartostageIVcoloncancer.72RadiationtherapyWhileacombinationofradiationandchemotherapymaybeusefulforrectalcancer,itsuseincoloncancerisnotroutineduetothesensitivityofthebowelstoradiation.

Justasforchemotherapy,radiotherapycanbeusedintheneoadjuvantandadjuvantsettingforsomestagesofrectalcancer.73PalliativecarePalliativecareismedicalcarewhichfocusesontreatmentofsymptomsfromseriousillness,likecancer,andimprovingqualityoflife.

Palliativecareisrecommendedforanypersonwhohasadvancedcoloncancerorhassignificantsymptoms.Involvementofpalliativecaremaybebeneficialtoimprovethequalityoflifeforboththepersonandhisorherfamily,byimprovingsymptoms,anxietyandpreventingadmissionstothehospital.74Palliativecarecanconsistofproceduresthatrelievesymptomsorcomplicationsfromthecancerbutdonotattempttocuretheunderlyingcancer,therebyimprovingqualityoflife.Surgicaloptionsmayincludenon-curativesurgicalremovalofsomeofthecancertissue,bypassingpartoftheintestines,orstentplacement.Theseprocedurescanbeconsideredtoimprovesymptomsandreducecomplicationssuchasbleedingfromthetumor,abdominalpainandintestinalobstruction.

Non-operativemethodsofsymptomatictreatmentincluderadiationtherapytodecreasetumorsizeaswellaspainmedications.Follow-up75Theaimsoffollow-uparetodiagnose,intheearliestpossiblestage,anymetastasisortumorsthatdeveloplater,butdidnotoriginatefromtheoriginalcancer.76TheU.S.NationalComprehensiveCancerNetwork(NCCN)andAmericanSocietyofClinicalOncology(ASCO)provideguidelinesforthefollow-upofcoloncancer.

Amedicalhistoryandphysicalexaminationarerecommendedevery3to6monthsfor2years,thenevery6monthsfor5years.

Carcinoembryonicantigenbloodlevelmeasurementsfollowthesametiming,butareonlyadvisedforpeoplewithT2orgreaterlesionswhoarecandidatesforintervention.77ACT-scanofthechest,abdomenandpelviscanbeconsideredannuallyforthefirst3yearsforpatientswhoareathighriskofrecurrence(forexample,thosewhohadpoorlydifferentiatedtumorsorvenousorlymphaticinvasion)andarecandidatesforcurativesurgery(withtheaimtocure).Acolonoscopycanbedoneafter1year,exceptifitcouldnotbedoneduringtheinitialstagingbecauseofanobstructingmass,inwhichcaseitshouldbeperformedafter3to6months.Ifavillouspolyp,apolyp>1centimeterorhighgradedysplasiaisfound,itcanberepeatedafter3years,thenevery5years.Forotherabnormalities,thecolonoscopycanberepeatedafter1year.78RoutinePETorultrasoundscanning,chestX-rays,completebloodcountorliverfunctiontestsarenotrecommended.

Theseguidelinesarebasedonrecentmeta-analysesshowingintensivesurveillanceandclosefollow-upcanreducethe5-yearmortalityratefrom37%to30%.79Exercisemayberecommendedinthefutureassecondarytherapytocancersurvivors.

Inepidemiologicalstudies,exercisemaydecreasecolorectalcancer-specificmortalityandall-causemortality.Resultsforthespecificamountsofexerciseneededtoobserveabenefitwereconflicting.Thesedifferencesmayreflectdifferencesintumourbiologyandexpressionofbiomarkers.Themechanismofhowexercisebenefitssurvivalmaybeinvolvedinimmunesurveillanceandinflammationpathways.Exercise80Inclinicalstudies,apro-inflammatoryresponsewasfoundinpatientswithstageII-IIIcolorectalcancerwhounderwent2weeksofmoderateexerciseaftercompletingtheirprimarytherapy.Oxidativebalancemaybeanotherpossiblemechanismforbenefitsobserved.Otherpossiblemechanismsmayinvolvemetabolichormoneandsex-steroidhormones,althoughthesepathwaysmaybeinvolvedinothertypesofcancers.81InEuropethefive-yearsurvivalrateforcolorectalcancerislessthan60%.Inthedevelopedworldaboutathirdofpeoplewhogetthediseasedie