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Multi-detectorspiralCTstudyoftherelationshipsbetweenpulmonaryground-glassnodulesandbloodvessels,EurRadiol(2013)23:32713277,1,.,2019/11/26,Abstract,Objective:Toinvestigatetherelationshipsbetweenpulmo-naryground-glassnodules(GGN)andbloodvesselsandtheirdiagnosticvaluesindifferentiatingGGNs.Conclusion:DifferentGGNshavedifferentrelationshipswithvessels.UnderstandingandrecognisingcharacteristicGGN-vesselrelationshipsmayhelpidentifywhichGGNsaremorelikelytobemalignant.,2,.,2019/12/19,KeyPoints,Multi-detectorCToffersnewinformationaboutground-glassnodules.Differenttypesofground-glassnoduleshavedifferentrelationshipswithvessels.Thismayhelpidentifywhichground-glassnodulesarelikelytobemalignant.,3,.,2019/12/19,Introduction,Withtheextensiveacceptanceoflow-dosemulti-detectorspiralCTinlungcancerscreening,thenumberofdetectedGGNsorfocalground-glassopacities(fGGOs)hasdramaticallyincreased.GGNscanresultfromneoplasms,suchaspulmonaryadenocarcinoma,orbenigndiseases,suchasfocalfibrosis,inflammationoralveolarhaemorrhage.,4,.,2019/11/26,Inaddition,pre-invasiveabnormalities,includingatypicaladenomatoushyperplasia(AAH)andadenocarcinomainsitu(AIS).IthasbeenreportedthattheproportionofmalignancyinGGNsishigherthaninsolidpulmonarynodules(SPNs)andthemajorityofmalignantGGNsareadenocarcinoma.Duetoimagingresemblance,however,itisextremelychallengingtodifferentiatemalignantGGNsfromtheaforementionedbenigncounterparts.,5,.,2019/12/19,AccuratedifferentialdiagnosisofGGNswillassistphysicianstomaketreatmentdecisionsandimprovetreatmentoutcomesandprognosis.SeveralinvestigatorshavesuggestedthatanalysisofrelationshipsbetweenSPNsandsurroundingvesselscanhelppredictthelikelihoodofmalignancyinsuchnodules.TherelationshipbetweenGGNsandbloodvesselsremainsunknown.WhetherthisrelationshipcanbeutilisedtofacilitatethediagnosisofmalignantGGNsisaworthyofinvestigation.,6,.,2019/11/26,Materialsandmethods,PatientsTheimagingdataofpatientswithpulmonaryGGNsreceivingthin-sectionmulti-detectorCTexaminationatourhospitalinJanuary2011throughNovember2012wereretrospectivelyreviewed.Alllesionsweresolitaryandmostofthem(104/108)surgicallyresectedwithin2weeksafterCTscanning.,7,.,2019/12/19,InclusioncriteriaTheGGNsizewaslessthan3cminthelargestdimension.ground-glassopacity(GGO)comprisedmorethan50%oftheareaofthelesiononCT.-Anareaofover50%GGOwassetasthecutoffvaluetoexcludesolid/semi-solidlesions.-AlthoughsolidnodulesfrequentlyhadGGOcomponentsaroundtheirmargin,probablyrepresentingsurroundingoedemaormerelypooraerationofthesurroundinglungtissuesduetocompressionorretractionbynodules,thesenoduleshadalreadybeenwellinvestigatedusingCTandthereforewerenotthestudyobjects,8,.,2019/12/19,Ultimately,108patientswereenrolledintothisstudy,including38malesand70femaleswithmeanageof58.1812.89years(range,22to79years).43patientswereasymptomatic,28hadrespiratorysymptoms,and37hadlungcancerriskfactors,suchassmokingandfamilyhistory.,9,.,2019/12/19,Accordingtopathologicalfindings,GGNsweredividedintothreegroups:Benigndiseasegroup(10cases),includingfournodulesdiagnosedwithacombinationofclinicalsymptomsandimagingpresentations(nodulesdisappearedorgraduallyreducedinsizeonmultiplefollow-upCTimaging)andsixnodulesconfirmedbypathologicalexamination(1caseofsclerosinghaemangiomaand5casesofchronicinflammation).(2)Preinvasivediseasegroup(24cases),including7AAHsand17AISs.,10,.,2019/12/19,(3)theinvasiveadenocarcinomagroup(74cases),confirmedpathologically,therewere39non-mucinousminimallyinvasiveadenocarcinomas(MIA)and35invasiveadenocarcinomas(IAC;specifically,13lepidicpredominantadenocarcinomas;19acinus-predominantadenocarcinomas;2papillary-predominantadenocarcinomasand1solidpredominantwithmucin粘蛋白production).,11,.,2019/12/19,CTimaginganalysis,protocolparameters:0.625-mmsectionwidthwitha0.625-mmreconstructioninterval,pitchof0.984,120kVand250mA.Allimageswerereviewedwithahigh-resolution,2,0481,560pixel,standardlungwindow(ww,1,500HU;wl,-500HU)andmediastinalwindow(ww,350HU;wl,50HU)GGNscanbefurthersubdividedintomixedground-glassnodules(mGGNs)andpureground-glassnodules(pGGNs).ThepercentageoftheGGOcomponentwascalculatedasfollows:(DGGO-D)/DGGO100,whereDGGOisthelargestdiameteroftheentirelesionandDisthelargestdiameterofthesolidcomponentwithinthelesion.,12,.,2019/12/19,BloodvesselanalysiswasperformedintermsofvascularmorphologyandvascularrelationshipswithGGNlesions.thediameterofpulmonaryvesselsgraduallydecreasesfromthehilumtowardtheperiphery.Ifthediameterofthevascularsegmentwithinlesionswaslargerthantheproximalsegmentorlesionvesselswereapparentlywiderthanothervesselsatthesamebranchlevel,thevesselwasdeemedasabnormalvascularbroadening.Thevesselswereconsideredtobedistortedorrigidiftravelingastrayfromtheexpectednormalcourse.,13,.,2019/12/19,Multiplesupplyingvessels,withdifferentoriginatingsources,convergingtowardalesion,wereprobablyindicativeofanincreasedbloodcirculationwithin.Tofurtherclarifyaffiliationsofsupplyingvessels,wetracedvascularcoursesslice-wisebackwardtomajorvesselsinthehilum.TherelationshipsbetweentheGGNsandsupplyingbloodvesselswereanalysedinaxialimages,MPRimagesCPRimages.,14,.,2019/12/19,theGGN-vesselrelationshipswerecategorizedintofourtypesaccordingtoimagingfeatures:typeI(pass-by),vesselspassedbyGGNswithoutdetectablesupplyingbranchestolesions.,typeI,15,.,2019/12/19,typeII(pass-through),vesselspassedthroughthelesionswithoutobviousmorphologicalchangesintravelingpathorsize.,16,.,2019/12/19,typeIII(distorted/dilated),vesselswithinlesionsweretortuousorrigidwithoutanincreaseinamount,17,.,2019/12/19,typeIV(complicated),morecomplicatedvasculatureotherthandescribedintheaforementionedtypeswithinGGNs,forinstance,coexistenceofirregularvasculardilationandvascularconvergencefrommultiplesupplyingvessels.,18,.,2019/12/19,Pathologicalanalysis,ThepathologicaldiagnosisandcategorisationofAAH,AIS,MIAandIACweremadebasedonthenewpulmonaryadenocarcinomaclassification,2011edition.GGNswereresectedbyvideo-assistedthoracoscopyorthoracotomysurgery.Allhistologicalpreparationsandanalyseswereperformedbytwoseniorpathologists.Inthecaseofdisagreements,aconsensuswasreachedaftermutualdiscussionand/orconsultationwithathirdpathologist.,19,.,2019/12/19,Statisticalanalysis,SPSS16.0forWindows,SPSS,Chicago,IllIndependentttestwasusedtocomparedifferentpathologicalgroups(benigndiseases,preinvasivediseasesandinvasiveadenocarcinoma)ofGGN.CorrelationsbetweenpathologicalfindingsofGGNsandGGN-vesselrelationshipswereexaminedusingSpearmansranktest.GGN-vesselrelationshipsbetweenMIAandIACdiseaseswerecomparedusingPearsonschi-squaredtest.Whentherewasanexpectedvalue1orapretestprobabilityclosetothetestlevel,Fishersexacttestwasusedinstead.StatisticalresultswereconsideredsignificantwhenthePvaluewaslessthan0.05.,20,.,2019/12/19,Results,SizevariationofGGNlesionsTheaverageGGNsizeinthebenigngroup,preinvasivegroupandadenocarcinomasgroupwas8.12.5mm,9.35.6mmand14.86.0mm,respectively.Nosignificantdifferencesexistedbetweenthepreinvasivegroupandthebenigngroup(t=0.64,p=0.53).However,thereweresignificantdifferencesbetweenbenignandpreinvasivegroupsandtheinvasiveadenocarcinomagroup(t=6.31,p=0.00;t=3.98,p=0.00).,21,.,2019/12/19,CorrelationsbetweenGGN-vesselrelationshipsandpathologicalfindingsOf108GGNs,typeI,II,IIIandIVGGNvessellrelationshipswereobservedin9,58,21and20cases,respectively.thetypeIIGGN-vesselrelationshipwasthedominantrelationshipineachpathologicalgroup,seenin9benign(90.0%),16preinvasive(66.7%)and33invasive(44.6%)GGNcases.,22,.,2019/12/19,comparedwiththelowincidenceoftypeIIIandIVrelationshipsinbenignandpreinvasivegroupsthecombinedincidenceoftypeIII(25.7%)andIV(25.7%)relationshipsintheinvasiveadenocarcinomagroupreached51.3%.,23,.,2019/12/19,MIAcouldpresentfourtypes,withtypeIIasthemajortype(48.7%).ThecombinationoftypeIIandIVcomprisedabout80%oftheMIAsubgroup;forIAC,typeIIandIIIhadthesameproportionof40%,hencethecombinationof80%.StatisticalstudiesshowednodifferenceintypeIIbutasignificantdifferencewasfoundintypeIIIandIVbetweenMIAandIAClesions(p=0.02).,24,.,2019/12/19,Thevessel(s)travelingthroughGGNcouldbeartery(ies)(categoryA),vein(s)(categoryB),orartery(ies)andvein(s)(categoryC).TherewerenosignificantdifferencesandcorrelationsbetweenvascularcategoriesandGGNgroups(p=0.50and0.96,respectively).,25,.,2019/12/19,AfurtherexaminationofthecorrelationbetweenvascularcategoriesandGGNswithtypeIIIandIVrelationshipsdidnotgenerateanysignificantresults(p=0.70).,26,.,2019/12/19,Discussion,Solitarypulmonarynodules(SPNs)arecommonfindingsinCTexaminationsandcanbedividedintotwogroupsbasedondensityvariation:solidnodulesandGGNs.In2011,theInternationalAssociationfortheStudyofLungCancer,theAmericanThoracicSocietyandtheEuropeanRespiratorySocietyproposedanewclassificationforlungadenocarcinomas.Inthenewclassificationsystem,thetermbronchioloalveolarcarcinoma(BAC)isnolongerused.TheformerBACconceptapplicabletomultiplecategoriesinthenewclassificationsystem,suchasAIS,MIAandthemucinoussubtypeofadenocarcinoma.BothAISandAAHlesionsareclassifiedaspreinvasiveadenocarcinomaunderthenewclassificationsystem,27,.,2019/12/19,EarlystagelungcancersoftenpresentasGGNsinCTimages;thus,itisimportanttobefamiliarwiththecharacteristicsofGGNswithmalignantpotential,astimelysurgicalresectionwillimprovepatientsurvivalandqualityoflife,andforpatientswithbenignGGNs,unnecessarysurgicalprocedurescanbeavoided.,28,.,2019/12/19,Clinicaldatahaveshownthatnodulesizeisanindependentpredictivefactorofmalignancy,withsizeincreasingthelikelihoodofmalignancyincreasing,consistentwithourresultsthatthemeansizesofGGNsinbenign,preinvasiveandadenocarcinomagroupswere8.1mm,9.3mmand14.7mm.Clinicalexperiencehasdemonstratedthatsomecommonimagingfeaturesofmalignantnodules,suchaspleuralindentation,spiculationandlobulation,areseldomseeninveryearlystagemalignantGGNs.,29,.,2019/12/19,Thisdemandsfurtherinvestigationofthisparticularabnormalimagingfindingtominimisemisdiagnosis.InthemanagementofGGNsinourpatients,clinicalguidelinesfromtheFleischnerSocietyandNationalComprehensiveCancerNetwork(NCCN)werereferenced.Eachindividualcasewasdiscussedbyamultidisciplinaryteam,includingdiagnosticradiologists,thoracicsurgeonsandpathologists,togenerateconsequentmanagementstrategies.Allpatientsreceivedadequatefollow-upobservationwith/withoutsupportiveorantiinflammatorytreatment,whichexplainedthefactthatfourGGNsdisappearedpriortothenextscheduledCTexamination.,30,.,2019/12/19,Exceptforthesefourcaseswithoutbiopsy,nodularlesionsintheremaining104patientsweresurgicallyremovedbecauseofthecontinuousincreaseinsizeand/ormassonfollow-upimagingstudies.ConsideringthedramaticallyincreasingincidenceoflungcancerinChina,patientsandphysiciansareveryalerttoitandthetreatmentmightbemoreaggressivethaninWesterncountries.,31,.,2019/12/19,Tumourbiologystudieshaverevealedthatvasculatureremodellingorneoangiogenesisisoneoftheinitiatingeventsoccurringintheearlystageoftumourdevelopment.Therefore,analysisofGGNsandrelatedbloodsupplyingvesselscouldprovideinformationonGGNdifferentiation.SmallbloodvesselsandtherelationshipsbetweenvesselsandlesionscanbereadilyrevealedandevaluatedinCTimagesacquiredwithmodernmulti-detectorscanners,especiallywhenimagingdataarepost-processedusingadvancedcomputertechniques,includingMPRandCPR.ManystudieshavedemonstratedthatrelationshipsbetweenSPNsandvessels,especiallythevascularconvergencesign(VCS),arevaluableforestimationofthemalignancypotentialofSPNs,32,.,2019/12/19,SomestudiesindicatedthatdiseaseprogressionfromAAH,AIS,MIAtoIACisacomplicated,polygene-involveddynamicprocess.MIAorIACmaygraduallydevelopfromAAHandAIS.InterstitialfibrehyperplasiawithinlesionsisthemaincontributingfactortotypeIIIandIVvascularmorphologicalchanges.theformationmechanismofVCS,leadingtotheconclusionthatthecourseofadjacentvesselsissubjecttolesions,especiallywhendiseasesinfiltratethebronchiovascularbundleandinterlobularsepta,33,.,2019/12/19,Asaresult,involvedvesselsmightappeardistorted,rigidorconcentratedtowardsthelesion.Thus,itisreasonabletopostulate假设thatthevascularconvergencesigncommonlyseeninSPNs.Actually,thetypeIVGGN-vesselrelationshipresemblesVCStosomedegree.Theinvasiveadenocarcinomagroupiscomposedoftwosubgroups,MIAandIAC.SubgroupanalysisshowedMIAandIAChaddifferentpatternsofGGN-vesselrelationships.,34,.,2019/12/19,TypeIIIvascularmorphologicalchangeswereobservedmoreoftenintheIACthanMIAsubgroup,indicatingthatwithincreasingmalignancy,fibrehyperplasiastimulatedbymalignanttissuesmaybecomemoresevere,andsubsequentlyimpactsonvasculaturebecomeaggravated.Furthermore,tumourmetabolismisfasterthaninnormaltissues;therefore,thebloodsupplydemandedbytumoursismuchhigherthaninnormaltissues.Thesemechanismsindirectlyleadtovesselproliferationandirregularluminaldilation.,35,.,2019/12/19,Somestudieshaveshownthatendogenousand/orextrinsictumorangiogenesisandneovascularisationcouldbethedrivingfactorsofvascularabnormalitiesobservedinmalignantearlystage.AsaCTimagingsign,VCSdescribesarelation
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