J. Coloproctol. (Rio J.) vol.36 número4

w w w . j c o l . o r g . b r

Journal

of

Coloproctology

Original

Article

Colorectal

cancer:

comparative

analysis

of

clinical

and

pathological

characteristics

in

patients

aged

above

and

below

45

years

of

age

and

impact

on

prognosis

Joana

Sofia

Gomes

Pestana

_,

_Sandra

_Fátima

_Fernandes

_Martins

a_{UniversidadedoMinho,FaculdadedeCiênciasdaSaúde,LifeandHealthSciencesResearchInstitute(ICVS),Braga,Portugal}

b_{PTGovernmentAssociateLaboratory,LifeandHealthSciencesResearchInstitute/3B’s(ICVS/3B’s),Braga/Guimarães,Portugal}

c_{CentroHospitalardeTrás-os-MonteseAltoDouro,DepartamentodeCirurgia,Braga,Portugal}

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received23January2015 Accepted23April2016 Availableonline22June2016

Keywords:

Colorectalcancer Age

Clinicopathologicalfeatures Survival

a

b

s

t

r

a

c

t

Introduction:Colorectalcancer,inPortugal,presentsasthesecondmostcommoncancerand

ofcancerdeathcause.CRCisadiseaseoftheelderly;however,therehasbeenanincreaseof incidenceinyoungerpatientsanddoubtshaveemergedaboutitsbehavior,characteristics andprognosisinthisgroup.

Methods:Inthisstudy,wehaveevaluatedasampleof512patientsdiagnosedwithcolorectal

cancersubmittedtosurgicaltreatmentintheperiodbetweenJanuary1st,2005and Jan-uary1st,2010,throughacomparativeclinical,pathologicalandsurvivalanalysisofpatients underandover45yearsold(GroupsIandIIrespectively).

Results:GroupIpatientsaccountedfor5.5%ofthesample.Therewasapredominanceof

malesandthemostcommonsitewastheleftcoloninbothagegroups.Intheyoungergroup, thehistologicaltypepresentswithapredominanceoftumorswithamucinouscomponent andwithsignetringcells(p=0.001),however,therewasnodifferenceintermsofoverall survivalanddisease-freesurvival.

Conclusion:Inthisstudy,colorectalcanceratyoungeragesshowssimilarcharacteristicsto

thoseofolderpatients.

©2016SociedadeBrasileiradeColoproctologia.PublishedbyElsevierEditoraLtda.This isanopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/

licenses/by-nc-nd/4.0/).

∗ _{Correspondingauthor.}

E-mail:sandramartins@ecsaude.uminho.pt(S.F.Martins).

http://dx.doi.org/10.1016/j.jcol.2016.04.010

Câncer

colorretal:

análise

comparativa

das

características

clínicas

e

anatomopatológicas

em

doentes

com

idade

superior

e

inferior

a

45

anos

de

idade

e

impacto

no

prognóstico

Palavras-chave:

Câncercolorretal Idade

Característicasclínicase anatomopatológicas Sobrevida

r

e

s

u

m

o

Introduc¸ão: OCâncerColorectal(CCR),emPortugal,constituiosegundocâncermais

fre-quenteem termosdeincidênciaedemortalidade.Éumadoenc¸adoidoso,noentanto, tem-seobservado umaumentoda incidênciaem pacientesmaisjovens,tendosurgido dúvidasacercadoseucomportamento,característicaseprognósticonestegrupoetário.

Métodos: 512pacientescomdiagnósticodeCCRoperadosentreJaneirode2005eJaneiro

de2010foramavaliadosatravésdaanálisecomparativadascaracterísticasclínicas, anato-mopatológicasesobrevidaemindivíduoscomidadeinferioresuperiora45anos(GrupoIe IIrespetivamente).

Resultados: OspacientesdoGrupoIrepresentaram5,5%daamostra.Houvepredomínio

dogêneromasculinoeolocalmaisfrequentefoiocólonesquerdoemambososgrupos. Nogrupomaisjovem,relativamenteaotipohistológicoocorreupredomíniosignificativo detumorescomcomponentemucinosoecélulasemaneldesinete(p=0,001),massem diferenc¸aaoníveldasobrevidaglobalesobrevidalivrededoenc¸a.

Conclusão: Nesteestudo,oCCRemidadesmaisjovensreveloucaracterísticassemelhantes

àsdospacientesmaisidosos.

©2016SociedadeBrasileiradeColoproctologia.PublicadoporElsevierEditoraLtda.Este ´eumartigoOpenAccesssobumalicenc¸aCCBY-NC-ND(http://creativecommons.org/

licenses/by-nc-nd/4.0/).

Introduction

Inrecentdecades,therehasbeenanincreasingprevalence ofcancersintheworld.1,2_{Colorectalcancer(CRC)isthemost}

commonmalignancyofthegastrointestinaltract3,4_anddueto

theincreasedincidenceandmortalitythatoccurredinrecent decades,andalsotothecoststhatareassociatedwith diag-nosisandtreatment,thiscancerhasbecomeamajorpublic healthproblemworldwide.5

Worldwide,CRCisthe3rdmostcommoncancerandthe 4thleadingcauseofdeathsbycancer;in2008,609,051deaths occurred,223,268oftheminEurope.3

About95%ofallCRCsarisefromadenomatouspolypsof the intestinalmucosa, with increasingincidencewith age; however,only10%ofadenomaswillresultinaCRC.6–9

Theknowledgeofthenaturalhistoryofthediseaseandthe possibilityofinterveningatanearlierstageledtothe imple-mentationofscreeningprograms,whichcurrentlycoverthe populationover50yearswithnoriskfactorsforCRC.10,11

There are several risk factors that are associated with the developmentofCRC, and someofthem implyan ear-lierscreening.12–14_{Ageisoneofthemainriskfactorsforthe}

developmentofCRC,withover90%ofcasesoccurringin indi-vidualsagedover50years,withameanageofdiagnosisof65 years.14–16_{Forthisreason,CRCisconsideredadiseaseofthe}

elderly.

Thepopulationunder50yearsandwithoutriskfactorsis excludedfrom the screening groupand istherefore some-whatneglected,andthisrequiresahighindexofsuspicion bythephysicianfortheestablishmentofadiagnosisofCRC. Althoughoccurringlessfrequently,CRCisalsodiagnosedin thisage group,and there hasbeenan increasedincidence

amongthesepeople,afactthatcannotbeignored.17–19

Pre-viousstudiesdescribeawidevariationofthisfrequency,with valuesfrom1.3%to37%,andthehighestvaluesarefoundin theAsianpopulation.19–27_{Thisissuehasarousedgreat}

inter-estinthemedicalliterature,thoughwithcontroversialresults, and many studies havebeen conducted inorder to evalu-atepossibledifferencesinbehaviorandprognosisofCRCin youngpeoplecomparedwiththegeneralpopulationwiththis cancer.Mostauthorsarguethatyoungageisassociatedwith moreadvancedstagesofthe diseaseatdiagnosis andwith moreaggressivehistopathologiccharacteristics,forexample, alowerdegreeofdifferentiationandmucinsecretion.19,23,24

Someauthorsstilldescribeaworseprognosisinthisgroup.26

However,otherstudiescontradictthesefindings,describing resultssimilartothoseofpatientswithalaterdiagnosis,or evenwithimprovementintheirsurvival.21,22,27

Takingintoaccountthecontroversyonthissubjectandthe lackofstudiesinPortugal,thisprojectwascarriedoutinorder tomakeacomparativeanalysisoftheclinicalandpathological characteristicsofpatientswithCRCdiagnosedwithagesover andunder45years,andtoevaluatethepossibleimpactofthe agefactorinitsprognosis.

Methods

Exclusioncriteriawere:patientswithinflammatorybowel disease(IBD),namelyCrohn’sdiseaseandulcerativecolitis; patientswithhereditarysyndromessuchasfamilial adeno-matouspolyposis(FAP)andhereditarycolorectalcancernot associatedwithpolyposis(HCCNP);patientswithnoprimary diseaseofthecolonorrectum;patientsdiagnosedwithCRC butwhodidnotundergosurgery,andpatientswithCRC under-goingnon-curativesurgicaltreatment.

Theexclusionofpatientswithhereditarysyndromeswas performedafterconfirmedbygeneticstudiesinpatientsfor whomtherewasaclinicalsuspicion.

Tocollectinformation,aprospectivedatabaseofCRCwas surveyed,andthefollowingdatawerecollected:

Clinicaldataandpreoperativetests

Informationconcerningtheage,gender,clinicalpresentation, tumorlocationandthepresenceofmetastasiswasevaluated. Regardingage,thepatientsweregroupedintoageunderor equalto45years(GroupI)andmorethan45years(GroupII).

Pathologicaldata

Theparametersevaluatedincludedtumorsize,macroscopic appearance ofthe tumor, histologic type,tumor extension (pT), tálusdegreeofdifferentiation, the presenceoflymph nodemetastases(pN),presenceofvenousandlymphatic inva-sion,andstaging.

ThestagingwascarriedoutaccordingtotheTNM classi-ficationoftheAmericanJointCommitteeonCancer(AJCC), SixthEdition.28

Follow-up

Thepatientsweremonitoredregularly.

Thefollow-upofpatientswithCRCissubdividedintothree periods:1stand2ndyear,3rdto5thyear,andfrom6thyear postoperatively.Thus,inthe1stand2ndyears,thepatients areevaluatedinquarterlyconsultations;from3rdto5thyear, the assessment becomes biannual, and after 5 years, the patientisevaluatedannually.Intheseconsultations,besides patientobservation,tumormarkers(CEAandCA19-9)arealso accessed,andanannualchestX-rayisobtained.

Regardingcolonoscopy,theprocedureisperformedwithin oneyearaftersurgicalresection(or3–6monthsaftersurgery, if the colonoscopywas notperformed pre- or transopera-tively dueto anobstructive lesion) with repetition3years aftersurgery;subsequently,acolonoscopyisobtainedevery 5years,unlessafollow-upcolonoscopyrevealsevidenceofan advancedadenoma(villouspolyp,polyp>1cm,orhigh-grade dysplasia).Inthiscase,thecolonoscopyshouldberepeated1 yearafterpolypectomy.

Regardingtherealizationofcomputerizedaxial tomogra-phy,thisprocedureisperformedannuallyinthefirst three yearsaftersurgery,orwheneversymptomsoranincreaseof tumormarkerswarrantthisprocedure.Inthecaseofrectal cancer,apelvicNMRisalsoperformed6months postopera-tively,whichwillremainasreferenceNMR.

Themomentofdiagnosiswasusedasstartingpointfor survival analysis. In the case ofoverall survival, this was

calculated until the patient’s death for any reason, and disease-freesurvivalwasconsideredasthetimeelapseduntil the occurrenceofarelapse. Bothindicatorswereevaluated untilAugust31,2012.

Statisticalanalysis

TheStatisticalPackageforSocialSciencesforWindows(SPSS version19.0.0,SPSSInc.)wasusedinthedatabaseanalysis.

Statistical comparisonsbetweengroupswere performed usingthePearson’schi-squaredtest(X2_{)wheneverpossible,}

andtheFisher’sexacttest(values<5).

Overallsurvivalanddisease-freesurvivalcurveswere cal-culatedusingtheKaplan–Meiermethod,andthecomparison betweenthe twogroupswas performedusingthe log-rank test.

p-values<0.05wereconsideredstatisticallysignificant. Thisstudywassubmittedto,andapprovedby,theBraga HospitalEthicsCommittee.

Results

IntheperiodbetweenJanuary1,2005,andJanuary1,2010,672 patientswithCRCwerediagnosedinBH;512patientsmetthe criteriapreviouslydescribed.

GroupIaccountedfor5.5%(n=28)ofthesampleandGroup IIfor94.5%(n=484).Inbothgroupsapredominanceofmales wasnoted:67.86%(n=19)forGroupIand61.98%(n=300)for GroupII,withnostatisticallysignificantdifference(p=0.533). Mostpatientsinbothgroupshadsymptomsatthemomentof diagnosis(92.86%,n=26and81.2%,n=393,respectively).The mostcommonsitewastheleftcolon,withatotalof48.44% ofcases(n=248)followedbytherectumwith28.13%(n=144) andtherightcolonwith23.44%(n=120).Comparingthesite byagegroup,wefoundsimilarresults.

At diagnosis, we found that 32.19% (n=9) and 20.04% (n=97),respectively,hadmetastases.Astothevariables stud-ied,nosignificantdifferenceswereobservedbetweengroups

(Table1).

Table1–Distributionofvariablesrelatedtoclinicaland preoperativetestdata,accordingtotheagegroup,inthe sampleunderstudy.

GroupI GroupII pa %(n) %(n)

Age 5.5%(28) 94.5%(484)

Gender

Male 67.86%(19) 61.98%(300) 0.533

Female 32.14%(9) 38.02%(184)

Clinicalpresentation

Symptomatic 92.86%(26) 81.2%(393) 0.137

Asymptomatic 7.14%(2) 18.8%(91)

Location

Rightcolon 28.57%(8) 23.14%(112)

Leftcolon 46.43%(13) 48.55%(235) 0.794

Rectum 25%(7) 28.31%(137)

Metastases

Absent 67.86%(19) 79.96(387) 0.124

Present 32.19%(9) 20.04%(97)

a _{CalculatedbyFisher’sexacttest.}

in43.95%(n=225)ofcases.Thesmaller thedifferentiation, thelowerthefrequency.However,inGroupI,themost fre-quentcategorywasthatof“moderatelydifferentiated”tumor, occurringin42.86%(n=12)ofcases.Itwasalsofoundinthis groupthatwell-differentiatedgradewaslessfrequent;poorly differentiatedgradewasmoreoftenseen,with32.14%(n=9) and18%(n=5),respectively,comparedtoGroupII,with44.63% (n=216)and9.09%(n=44),respectively.

Inthisgroup,wealsofoundalowerfrequencyofwell dif-ferentiatedgradetumorsand ahigher frequencyofpoorly differentiatedgradetumors,with32.14%(n=9)and18%(n=5), respectively,comparedtogroupII,with44.63%(n=216)and 9.09%(n=44),respectively.

InGroupI, therewere morepatients withthe presence (53.57%)versusabsence(42.86%)ofnodalmetastases;Onthe otherhand,the oppositeoccurred inGroupII, with40.29% and56.61%,respectively.Thevenousinvasionoccurredmore ofteninGroupI,50%ofcases,asopposedtoGroupII,41.32%. Inbothagegroups,thepresenceoflymphaticinvasion pre-vailed,57.14% and 52.45% respectively. As for staging, the stagesII,III and IVwerethe mostfrequentinthe sample, with28.57%(n=8)35.71%(n=10)and28.57%(n=8)patients, respectively, inGroup Iand 36.98% (n=179), 35.71% (n=10) and30.99%(n=150),respectively,inGroupII.Comparingthe twoagegroups,ahigherfrequencyofstagesIIIandIVwas notedin GroupI. For the several variables studied, signifi-cantdifferences betweengroupswere notobserved,except forhistologicaltype(Table2).

Thefollow-uptimerangedfrom2to7years.Overall sur-vivalwas63%,withamediansurvivalofapproximately63±2 months(Fig.1).

Group I showed a 5-year overall survival of61% and a mediansurvivalofapproximately58±6months.InGroupII, 5-yearoverallsurvivalwas63%andthemediansurvivalwas approximately63±2months(Fig.2).Therewasnostatistically significantdifferencebetweengroupswithrespecttosurvival (p=0.738).

Table2–Distributionofvariablesrelatedtopathological data,accordingtotheagegroup,inthesampleunder study.

GroupI %(n)

GroupII %(n)

pa

Measurement

≤45mm 50%(14) 58.06%(281) 0.963

>45mm 32.14(9) 36.57%(177)

Macroscopicaspect

Polypoid 60.71%(17) 50.41%(244)

Ulcerative 14.29%(4) 23.97%(116) 0.588

Infiltrative 3.57%(1) 8.68%(42)

Exophytic 10.71%(3) 8.06%(39)

Villous 0.0%(0) 0.41%(2)

Histologicaltype

Adenocarcinoma 78.57(22) 88.26(432)

Mucinous 14.29(4) 10.33(50) 0.001

Signetringcells 7.14(2) 0.41(2)

Differentiation

Welldifferentiated 32.14%(9) 44.63%(216)

Moderatelydifferentiated 42.86%(12) 41.53%(201) 0.337 Poorlydifferentiated 18%(5) 9.09%(44)

Undifferentiated 0.0(0) 0.83%(4)

Ganglionicmetastases

Absent 42.86%(12) 56.61%(274) 0.153

Present 53.57%(15) 40.29%(195)

Venousinvasion

Absent 46.43%(13) 53.72%(260) 0.394

Present 50.0%(14) 41.32%(200)

Lymphaticinvasion

Absent 39.29%(11) 41.32%(200) 0.699

Present 57.14%(16) 51.45%(249)

Stage

I 7.14%(2) 15.5%(75)

II 28.57%(8) 36.98%(179) 0.224

III 35.71%(10) 30.99%(150)

IV 28.57%(8) 14.05%(68)

a _{CalculatedbyFisher’sexacttest.}

1.0 Survival

function Censored

0.8

0.6

0.4

0.2

0.0

0 20 40 60

Time (months) Overall survival

Cum

ulativ

e sur

viv

al

80 100

1.0

0.8

0.6

0.4

0.2

0.0

0 20 40

Time (months) Overall survival

Age group

≤45

≤45-censored

>45

>45-censored

Cum

ulativ

e sur

viv

al

60 80 100

Fig.2–Cumulativeoverallsurvivalbyagegroupinthe sampleunderstudy.CalculatedbyLog-Ranktest.p=0.738.

SurvivalcurveswereestimatedbytheTNMstagingsystem; itwasfoundthatthemoreadvancedthestageatdiagnosis, thelowerthe5-yearoverallsurvival,with91%instageI,70%in stageII,56%instageIIIand33%instageIV.Five-yearsurvival onstageIwas100%inGroupIand91%inGroupII;onstageII, 88%and69%,respectively;onstageIII,70%and55%, respec-tively;andonstageIV,13%and36%,respectively.Comparing thetwoagegroups,wefoundabettersurvivalinGroupIfor thosecasesinwhichthediagnosiswasestablishedinstages I,IIandIII,andaworsesurvivalinstageIV.However,these differenceswerenotstatisticallysignificant,despitethetrend observedforstageIV(stageI:p=0.659,stageII:p=0.252;stage III:p=0.504;stageIV:p=0.061).Inthestudysample,the5-year disease-freesurvivalwasapproximately86%,withameanof 83±1month(Fig.3).InGroupItherewasa5-yeardisease-free survivalof81%,withameanof82±3months,aslightlylower resultversusGroupII,inwhichthisparameterwas86%with ameanof83±1months,butwithoutstatisticallysignificant difference(p=0.578)(Fig.4).

1.0

0.8

0.6

0.4

0.2

0.0

0 20 40

Time (months) Disease-free survival

Cum

ulativ

e sur

viv

al

60 80 100

Survival function Censored

Fig.3–Disease-freesurvivalinthesampleunderstudy.

1.0

0.8

0.6

0.4

0.2

0.0

0 20 40

Time (months) Disease-free survival

Age group

≤45

≤45-censored

>45

>45-censored

Cum

ulativ

e sur

viv

al

60 80 100

*P=.578

Fig.4–Disease-freesurvivalbyagegroupinthesample understudy.*CalculatedbyLog-Ranktest.

Discussion

CRC is a disease of the elderly, occurringmore frequently in the sixth and seventh decades of life, although it was observedincreasedincidenceinyoungerindividualsinrecent decades.17–19_{Intheliterature,theimpactof“age”inthe}

prog-nosis ofpatientswithCRC isanobject ofcontroversy and hasbeen thesubject ofmuchinterest andresearch. Taken intoaccountthattherearenodataonthePortuguesereality, thisstudysoughttobetterunderstandthisissueinpatients treatedattheBragaHospital,throughananalysisofclinical andpathologicalcharacteristicsofCRCinpatientsdividedinto twoagegroups,andtheassessmentoftheimpactofthisfactor onsurvival.

Itwasfoundthat5.5%ofpatientswereaged45yearsor younger(GroupI),whichisconsistentwiththevaluesfound intheliterature.Malegenderwasthemostfrequentinthis study,bothinthetotalsampleandinagegroups,whichis inlinewiththegeneraldistributionofgenderinthosecases ofCRCdescribedbyGLOBOCAN2008,3_{andinsomestudies}

basedonyoungpopulations,21,23_{withnostatisticaldifference}

regardingthisparameter.Otherstudiesbasedonyoungpeople describeanequaldistributionbetweengenders.19,24,26

Inbothgroups,thepresenceofsymptomsprevailedat diag-nosis,indicatingthatthecorrectvaluationandassessmentof symptomsthroughadditionalteststoanaccurate establish-mentofthediagnosisisessentialforthediagnosisofCRC, regardlessofage.Theseresultsareinagreementwiththose foundbyotherstudies.27

The sites most commonly affected by CRC are sigmoid colonandrectum,19,21,27_{whichisinlinewithourresults,in}

whichleftcolonpredominancewasnotedinbothgroups. Tumorswithsize≤45mmoccurredingreaternumbersand themacroscopicappearancemoreoftenseenwasthe poly-poidtypeinbothgroups;theseparametersarenosubjectof differencebetweenagegroups.

mucinousandsignetringcell/mucinousareatypes,a statisti-callysignificantdifferencewasnoted;theselattertypeswere moreoftenseeninGroupI(p=0.001),asalreadymentioned byotherauthors.19,24,26_{Despitethedescriptionofthese}

histo-logicaltypesinassociationwithaworseprognosis,30_thiswas

notthecaseinthisstudy,andtheoverallsurvivalwassimilar inbothgroups.

Severalstudieshavereportedlowerdifferentiationgrades inyounger patients, whichwould characterize CRC inthis groupasamoreaggressivetumor;19,24_{however,otherstudies}

contradictingthesefindingswerepublished.21,27_Inourstudy,

the degreefoundmorefrequently was the moderately dif-ferentiated;inGroupI,awell-differentiatedgradewasfound lessfrequently,andpoorlydifferentiatedgradewasthemost prevalent, although without statistical difference between groups.ThisfindingshowsthatCRCinyoungerpatientsdoes notshowmoreaggressiveness.

Thepresenceofvenousandlymphaticinvasionwassimilar inbothgroups.Thevenousinvasionoccurredinabouthalfthe cases,andlymphaticinvasionoccurredingreaterproportion, contributingtoamoreadvancedstageinthesample,which agreeswithresultsfromotherstudies.21,27

Severalauthorsdescribethepresenceofamoreadvanced diseaseatdiagnosisinyoungerpatients.24,26 _{Inthissample,}

advancedstagesweremorefrequent,reflectingtheinsidious andusuallysilent(orwithfewsymptoms)natureofthis dis-ease,whichresultsindelayeddiagnoses.Despite theslight predominanceofstagesIIIandIVinGroupI,therewasno statisticaldifference;andtheresultswereequivalenttothose ofGroupII.MostCRCswereseeninstageT3,nodalmetastases werepresentinabout41%ofthesample,andmetastasesat diagnosiswereuncommon,butfornoneofthesevariablesa statisticaldifferencewasobserved,confirmingthatthestage issimilarinbothagegroups.Somestudieshaveconfirmedthe resultsofthisstudywithrespecttothestage.19,21,27,29

Someauthors reporta lower survivalrate26 _inyounger

patients;however,mostoftherecentlypublishedstudieshave foundopposite results.19,21,22,24,27 _{In this study, there were}

nosignificantdifferencesinoverallsurvivalanddisease-free survival.IngroupI,inpatientsaged45yearsorlessthe over-allsurvivalwas61%and thedisease-freesurvivalwas81% –valuessimilar tothosefoundinGroup II.These findings demonstratethatadiagnosisinyoungerpatientsisnot asso-ciatedwithaworseprognosis.

Survivaldependslargelyonthestageatdiagnosis:themore advancedthestage,theworsethesurvival,withvaluesof91%, 70%,56%and33%forstagesI,II,IIIandIV,respectively,which agreeswiththevaluesfoundintheliterature.

Conclusion

Inthis study,it wasfound thatseveral clinical and patho-logicalparameters evaluatedwere verysimilar inbothage groupsanalyzed,andanincreasedincidenceoftumorswith mucinousandsignetringcomponentswerefoundinGroupI; however,thesefindingsdidnotimpactonthelevelofsurvival. Itisessentialthathealthprofessionalsareawareofthis diagnosis,eveninpatientsatyoungerages;Itshouldalsobe emphasizedtheimportanceofhealthpromotioncampaigns

tochangehabitsandlifestyles,andtodiseasepreventionwith screening programs,inorder toachieve areductionin the incidenceandmortalityassociatedwiththisdisease.

Webelievethatthisstudyisonlyapreliminaryassessment oftheimpactoftheagefactoronthesurvivalofpatientswith CRC.Takingintoaccountthatthisisastudyofpatientsfrom onlyonehospital,itwouldbeimportanttoextendittoother centersaswellastoincreasethefollow-upperiod,tobetter knowthePortuguesereality.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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e

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r

e

n

c

e

s

1.BoyleP,LevinB,editors.Worldcancerreport2008.Lyon,

France:WorldHealthOrganization,InternationalAgencyfor

ResearchonCancer;2008.

2.JemalA,BrayF,CenterMM,FerlayJ,WardE,FormanD.Global

cancerstatistics.CACancerJClin.2011;61:69–90.

3.FerlayJ,ShinHR,BrayF,FormanD,MathersC,ParkinDM. GLOBOCAN2008v2.0,cancerincidenceandmortality worldwide:IARCCancerBaseNo.10[Internet].Lyon,France: InternationalAgencyforResearchonCancer;2010.Available from:http://globocan.iarc.fr/[accessed12.07.12].

4.PimentelJ.;2009.Cancrocolo-rectal[Internet].PROCTOS– CentrodeColoproctologiadeCoimbra.Availablefrom:

http://www.proctos.pt/[accessed06.11.12].

5.Teliarova-FoucherE,O’CallaghanM,FerlayJ,MasuyerE, FormanD,ComberH,etal.Europeancancerobservatory: cancerincidence,mortality,prevalenceandsurvivalin Europe[Internet].EuropeanNetworkofCancerRegistries, InternationalAgencyforResearchonCancer;2012.Available from:http://eco.iarc.fr[accessed20.08.12].

6.MendesV.PreveniroCancrodoCóloneRecto.JPortGastr.

2008;15:153–5.

7.TeixeiraAV.PóliposeCancrodoCóloneRecto.ArquiMed.

2009;23:209–16.

8.JohnsHopkinsColonCancerCenter;2012.Colorectalcancer overview[Internet].Availablefrom:http://www.

hopkinscoloncancercenter.org[accessed20.11.12].

9.TownsendCM,BeauchampRD,EversBM,MattoxKL.Sabiston

textbookofsurgery.18thed.Elsevier;2009.p.1393.

10.MinistériodaSaúdeAltoComissariadodaSaúde

Coordenac¸ãoNacionalparaasDoenc¸asOncológicas.Plano NacionaldePrevenc¸ãoeControlodasDoenc¸asOncológicas 2007/2010(PNPCDO):Orientac¸õesProgramáticas.

11.PlanoOncológicoNacional2001–2005.DiáriodaRepública,Ia

Série-B(no.199).2001:5241–7.

12.AmericanCancerSociety;2012.Colorectalcancer[Internet]. Availablefrom:http://www.cancer.org/[accessed20.09.12].

13.HaggarFA,BousheyRP.Colorectalcancerepidemiology:

incidence,mortality,survival,andriskfactors.ClinColon

RectSurg.2009;22:191–7.

14.NationalCancerInstitute.Whatyouneedtoknowabout

cancerofthecolonandrectum.Bethesda,MD:National

InstitutesofHealth;2006.

15.HowladerN,NooneA,KrapchoM,NeymanN,AminouR, AltekruseS,etal.SEERcancerstatisticsreview1975–2009 [Internet].Bethesda,MD:NationalCancerInstitute.Available from:http://seer.cancer.gov/csr/19752009pops09/results

SEERdatasubmission,postedtotheSEERwebsite2012 [accessed20.09.12].

16.ParramoreJ,WeiJ,YehK.Colorectalcancerinpatientsunder

forty:presentationandoutcome.AmSurg.1998;64:563–7.

17.SiegelRL,JemalA,WardEM.Increaseinincidenceof

colorectalcanceramongyoungmenandwomeninthe

UnitedStates.CancerEpidemiolBiomarkPrev.

2009;18:1695–8.

18.MeyerJE,NarangT,Schnoll-SussmanFH,PochapinMB,

ChristosPJ,SherrDL.Increasingincidenceofrectalcancerin

patientsagedyoungerthan40years:ananalysisofthe

surveillance,epidemiology,andendresultsdatabase.Cancer.

2010;116:4354–9.

19.GanapathiS,KumarD,KatsoulasN,MelvilleD,HodgsonS,

FinlaysonC,etal.Colorectalcancerintheyoung:trends,

characteristicsandoutcome.IntJColorectalDis.

2011;26:927–34.

20.SvendsenLB,SorensenC,KjersgaardP,MeisnerS,Kjærgaard

J.Theinfluenceofageuponthesurvivalaftercurative

operationforcolorectalcancer.IntJColorectalDis.

1989;4:123–7.

21.SheK,WangH,ChenJ,MarH,ChenC,ChiangF,etal.

Colorectalcancerinyoungerthan30yearsoldgroupisnot

associatedwithpoorprognosis.JSocColonRectalSurgeon

(Taiwan).2011;22:93–8.

22.WangL,HollenbeakCS,StewartDB.Nodeyieldandnode

involvementinyoungcoloncancerpatients:istherea

differenceincancersurvivalbasedonage?JGastrointest

Surg.2010;14:1355–61.

23.DrumondCA,FerroRAF,NogueiraAMF,LuzMMP,Conceic¸ão

SA,SilvaRG,etal.Câncercolorretalempacientescomidade

inferiora30anos.RevBrasColoproctol.2003;23:147–54.

24.O’ConnellJB,MaggardMA,LiuJH,EtzioniDA,LivingstonEH,

KoCY.Doyoungcoloncancerpatientshaveworseoutcomes?

WorldJSurg.2004;28:558–62.

25.VanLangenbergA.Carcinomaofthelargebowelinthe

young.BrMedJ.1972;3:374–6.

26.DomergueJ,IsmailM,AstreC,Saint-AubertB,JoyeuxH,

SolassolC,etal.Colorectalcarcinomainpatientsyounger

than40yearsofage.Cancer.1988;61:835–40.

27.QuahHM,JosephR,SchragD,ShiaJ,GuillemJG,PatyPB,etal.

Youngageinfluencestreatmentbutnotoutcomeofcolon

cancer.AnnSurgOncol.2007;14:2759–65.

28.GreeneFL,ComptonCC,FritzAG,ShahJ,WinchesterDP.AJCC

cancerstagingatlas.NewYork,NY:Springer;2006.p.352.

29.NurdjanahS,TaroenoS,BayupurnamaP,MadusenoS,

RatnasariN.Colorectalcancerinyoungpatient:a

distinguisheddiseaseentity?IndonesianJGastroenterol

HepatolDigestEndosc.2005;6:37–41.

30.NumataM,ShiozawaM,WatanabeT,TamagawaH,

YamamotoN,MorinagaS,etal.Theclinicopathological

featuresofcolorectalmucinousadenocarcinomaanda

therapeuticstrategyforthedisease.WorldJSurgOncol.