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Multi-detectorspiralCTstudyoftherelationshipsbetweenpulmonaryground-glassnodulesandbloodvesselsEurRadiol(2022)23:32713277第一页,共四十页。AbstractObjective:Toinvestigatetherelationshipsbetweenpulmo-naryground-glassnodules(GGN)andbloodvesselsandtheirdiagnosticvaluesindifferentiatingGGNs.Conclusion:DifferentGGNshavedifferentrelationshipswithvessels.UnderstandingandrecognisingcharacteristicGGN-vesselrelationshipsmayhelpidentifywhichGGNsaremorelikelytobemalignant.第二页,共四十页。KeyPointsMulti-detectorCToffersnewinformationaboutground-glassnodules.Differenttypesofground-glassnoduleshavedifferentrelationshipswithvessels.Thismayhelpidentifywhichground-glassnodulesarelikelytobemalignant.第三页,共四十页。IntroductionWiththeextensiveacceptanceoflow-dosemulti-detectorspiralCTinlungcancerscreening,thenumberofdetectedGGNsorfocalground-glassopacities(fGGOs)hasdramaticallyincreased.GGNscanresultfromneoplasms,suchaspulmonaryadenocarcinoma,orbenigndiseases,suchasfocalfibrosis,inflammationoralveolarhaemorrhage.第四页,共四十页。Inaddition,pre-invasiveabnormalities,includingatypicaladenomatoushyperplasia(AAH)andadenocarcinomainsitu(AIS).IthasbeenreportedthattheproportionofmalignancyinGGNsishigherthaninsolidpulmonarynodules(SPNs)andthemajorityofmalignantGGNsareadenocarcinoma.Duetoimagingresemblance,however,itisextremelychallengingtodifferentiatemalignantGGNsfromtheaforementionedbenigncounterparts.第五页,共四十页。AccuratedifferentialdiagnosisofGGNswillassistphysicianstomaketreatmentdecisionsandimprovetreatmentoutcomesandprognosis.SeveralinvestigatorshavesuggestedthatanalysisofrelationshipsbetweenSPNsandsurroundingvesselscanhelppredictthelikelihoodofmalignancyinsuchnodules.TherelationshipbetweenGGNsandbloodvesselsremainsunknown.WhetherthisrelationshipcanbeutilisedtofacilitatethediagnosisofmalignantGGNsisaworthyofinvestigation.第六页,共四十页。MaterialsandmethodsPatientsTheimagingdataofpatientswithpulmonaryGGNsreceivingthin-sectionmulti-detectorCTexaminationatourhospitalinJanuary2022throughNovember2022wereretrospectivelyreviewed.Alllesionsweresolitaryandmostofthem(104/108)surgicallyresectedwithin2weeksafterCTscanning.第七页,共四十页。InclusioncriteriaTheGGNsizewaslessthan3cminthelargestdimension.ground-glassopacity(GGO)comprisedmorethan50%oftheareaofthelesiononCT.-Anareaofover50%GGOwassetasthecutoffvaluetoexcludesolid/semi-solidlesions.-AlthoughsolidnodulesfrequentlyhadGGOcomponentsaroundtheirmargin,probablyrepresentingsurroundingoedemaormerelypooraerationofthesurroundinglungtissuesduetocompressionorretractionbynodules,thesenoduleshadalreadybeenwellinvestigatedusingCTandthereforewerenotthestudyobjects第八页,共四十页。Ultimately,108patientswereenrolledintothisstudy,including38malesand70femaleswithmeanageof58.1812.89years(range,22to79years).43patientswereasymptomatic,28hadrespiratorysymptoms,and37hadlungcancerriskfactors,suchassmokingandfamilyhistory.第九页,共四十页。Accordingtopathologicalfindings,GGNsweredividedintothreegroups:(1)Benigndiseasegroup(10cases),includingfournodulesdiagnosedwithacombinationofclinicalsymptomsandimagingpresentations(nodulesdisappearedorgraduallyreducedinsizeonmultiplefollow-upCTimaging)andsixnodulesconfirmedbypathologicalexamination(1caseofsclerosinghaemangiomaand5casesofchronicinflammation).(2)Preinvasivediseasegroup(24cases),including7AAHsand17AISs.第十页,共四十页。(3)theinvasiveadenocarcinomagroup(74cases),confirmedpathologically,therewere39non-mucinousminimallyinvasiveadenocarcinomas(MIA)and35invasiveadenocarcinomas(IAC;specifically,13lepidicpredominantadenocarcinomas;19acinus-predominantadenocarcinomas;2papillary-predominantadenocarcinomasand1solidpredominantwithmucin粘蛋白production).第十一页,共四十页。CTimaginganalysisprotocolparameters: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.第十二页,共四十页。BloodvesselanalysiswasperformedintermsofvascularmorphologyandvascularrelationshipswithGGNlesions.thediameterofpulmonaryvesselsgraduallydecreasesfromthehilumtowardtheperiphery.Ifthediameterofthevascularsegmentwithinlesionswaslargerthantheproximalsegmentorlesionvesselswereapparentlywiderthanothervesselsatthesamebranchlevel,thevesselwasdeemedasabnormalvascularbroadening.Thevesselswereconsideredtobedistortedorrigidiftravelingastrayfromtheexpectednormalcourse.第十三页,共四十页。Multiplesupplyingvessels,withdifferentoriginatingsources,convergingtowardalesion,wereprobablyindicativeofanincreasedbloodcirculationwithin.Tofurtherclarifyaffiliationsofsupplyingvessels,wetracedvascularcoursesslice-wisebackwardtomajorvesselsinthehilum.TherelationshipsbetweentheGGNsandsupplyingbloodvesselswereanalysedinaxialimages,MPRimagesCPRimages.第十四页,共四十页。theGGN-vesselrelationshipswerecategorizedintofourtypesaccordingtoimagingfeatures:typeI(pass-by),vesselspassedbyGGNswithoutdetectablesupplyingbranchestolesions.typeI第十五页,共四十页。typeII(pass-through),vesselspassedthroughthelesionswithoutobviousmorphologicalchangesintravelingpathorsize.第十六页,共四十页。typeIII(distorted/dilated),vesselswithinlesionsweretortuousorrigidwithoutanincreaseinamount第十七页,共四十页。typeIV(complicated),morecomplicatedvasculatureotherthandescribedintheaforementionedtypeswithinGGNs,forinstance,coexistenceofirregularvasculardilationandvascularconvergencefrommultiplesupplyingvessels.第十八页,共四十页。PathologicalanalysisThepathologicaldiagnosisandcategorisationofAAH,AIS,MIAandIACweremadebasedonthenewpulmonaryadenocarcinomaclassification,2022edition.GGNswereresectedbyvideo-assistedthoracoscopyorthoracotomysurgery.Allhistologicalpreparationsandanalyseswereperformedbytwoseniorpathologists.Inthecaseofdisagreements,aconsensuswasreachedaftermutualdiscussionand/orconsultationwithathirdpathologist.第十九页,共四十页。StatisticalanalysisSPSS16.0forWindows,SPSS,Chicago,IllIndependentttestwasusedtocomparedifferentpathologicalgroups(benigndiseases,preinvasivediseasesandinvasiveadenocarcinoma)ofGGN.CorrelationsbetweenpathologicalfindingsofGGNsandGGN-vesselrelationshipswereexaminedusingSpearmansranktest.GGN-vesselrelationshipsbetweenMIAandIACdiseaseswerecomparedusingPearsonschi-squaredtest.Whentherewasanexpectedvalue1orapretestprobabilityclosetothetestlevel,Fishersexacttestwasusedinstead.StatisticalresultswereconsideredsignificantwhenthePvaluewaslessthan0.05.第二十页,共四十页。ResultsSize variation of GGN lesionsTheaverageGGNsizeinthebenigngroup,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).第二十一页,共四十页。Correlations between GGN-vessel relationships and pathological findingsOf108GGNs,typeI,II,IIIandIVGGNvessellrelationshipswereobservedin9,58,21and20cases,respectively.thetypeIIGGN-vesselrelationshipwasthedominantrelationshipineachpathologicalgroup,seenin9benign(90.0%),16preinvasive(66.7%)and33invasive(44.6%)GGNcases.第二十二页,共四十页。comparedwiththelowincidenceoftypeIIIandIVrelationshipsinbenignandpreinvasivegroupsthecombinedincidenceoftypeIII(25.7%)andIV(25.7%)relationshipsintheinvasiveadenocarcinomagroupreached51.3%.第二十三页,共四十页。MIA couldpresentfourtypes,withtypeIIasthemajortype(48.7%).ThecombinationoftypeIIandIVcomprised about80%oftheMIAsubgroup;forIAC,typeIIandIII hadthesameproportionof40%,hencethecombinationof 80%.StatisticalstudiesshowednodifferenceintypeIIbuta significantdifferencewasfoundintypeIIIandIVbetween MIAandIAClesions(p=0.02).第二十四页,共四十页。Thevessel(s)travelingthroughGGNcouldbeartery(ies)(categoryA),vein(s)(categoryB),orartery(ies)andvein(s)(categoryC).TherewerenosignificantdifferencesandcorrelationsbetweenvascularcategoriesandGGNgroups(p=0.50and0.96,respectively).第二十五页,共四十页。AfurtherexaminationofthecorrelationbetweenvascularcategoriesandGGNswithtypeIIIandIVrelationshipsdidnotgenerateanysignificantresults(p=0.70).第二十六页,共四十页。DiscussionSolitarypulmonarynodules(SPNs)arecommonfindingsinCTexaminationsandcanbedividedintotwogroupsbasedondensityvariation:solidnodulesandGGNs.In2022,theInternationalAssociationfortheStudyofLungCancer,theAmericanThoracicSocietyandtheEuropeanRespiratorySocietyproposedanewclassificationforlungadenocarcinomas.Inthenewclassificationsystem,thetermbronchioloalveolarcarcinoma(BAC)isnolongerused.TheformerBACconceptapplicabletomultiplecategoriesinthenewclassificationsystem,suchasAIS,MIAandthemucinoussubtypeofadenocarcinoma.BothAISandAAHlesionsareclassifiedaspreinvasiveadenocarcinomaunderthenewclassificationsystem第二十七页,共四十页。EarlystagelungcancersoftenpresentasGGNsinCTimages;thus,itisimportanttobefamiliarwiththecharacteristicsofGGNswithmalignantpotential,astimelysurgicalresectionwillimprovepatientsurvivalandqualityoflife,andforpatientswithbenignGGNs,unnecessarysurgicalprocedurescanbeavoided.第二十八页,共四十页。Clinicaldatahaveshownthatnodulesizeisanindependentpredictivefactorofmalignancy,withsizeincreasingthelikelihoodofmalignancyincreasing,consistentwithourresultsthatthemeansizesofGGNsinbenign,preinvasiveandadenocarcinomagroupswere8.1mm,9.3mmand14.7mm.Clinicalexperiencehasdemonstratedthatsomecommonimagingfeaturesofmalignantnodules,suchaspleuralindentation,spiculationandlobulation,areseldomseeninveryearlystagemalignantGGNs.第二十九页,共四十页。Thisdemandsfurtherinvestigationofthisparticularabnormalimagingfindingtominimisemisdiagnosis.InthemanagementofGGNsinourpatients,clinicalguidelinesfromtheFleischnerSocietyandNationalComprehensiveCancerNetwork(NCCN)werereferenced.Eachindividualcasewasdiscussedbyamultidisciplinaryteam,includingdiagnosticradiologists,thoracicsurgeonsandpathologists,togenerateconsequentmanagementstrategies.Allpatientsreceivedadequatefollow-upobservationwith/withoutsupportiveorantiinflammatorytreatment,whichexplainedthefactthatfourGGNsdisappearedpriortothenextscheduledCTexamination.第三十页,共四十页。Exceptforthesefourcaseswithoutbiopsy,nodularlesionsintheremaining104patientsweresurgicallyremovedbecauseofthecontinuousincreaseinsizeand/ormassonfollow-upimagingstudies.ConsideringthedramaticallyincreasingincidenceoflungcancerinChina,patientsandphysiciansareveryalerttoitandthetreatmentmightbemoreaggressivethaninWesterncountries.第三十一页,共四十页。Tumourbiologystudieshaverevealedthatvasculatureremodellingorneoangiogenesisisoneoftheinitiatingeventsoccurringintheearlystageoftumourdevelopment.Therefore,analysisofGGNsandrelatedbloodsupplyingvesselscouldprovideinformationonGGNdifferentiation.SmallbloodvesselsandtherelationshipsbetweenvesselsandlesionscanbereadilyrevealedandevaluatedinCTimagesacquiredwithmodernmulti-detectorscanners,especiallywhenimagingdataarepost-processedusingadvancedcomputertechniques,includingMPRandCPR.ManystudieshavedemonstratedthatrelationshipsbetweenSPNsandvessels,especiallythevascularconvergencesign(VCS),arevaluableforestimationofthemalignancypotentialofSPNs第三十二页,共四十页。SomestudiesindicatedthatdiseaseprogressionfromAAH,AIS,MIAtoIACisacomplicated,polygene-involveddynamicprocess.MIAorIACmaygraduallydevelopfromAAHandAIS.InterstitialfibrehyperplasiawithinlesionsisthemaincontributingfactortotypeIIIandIVvascularmorphologicalchanges.theformationmechanismofVCS,leadingtotheconclusionthatthecourseofadjacentvesselsissubjecttolesions,especiallywhendiseasesinfiltratethebronchiovascularbundleandinterlobularsepta第三十三页,共四十页。Asaresult,involvedvesselsmightappeardistorted,rigidorconcentratedtowardsthelesion.Thus,itisreasonabletopostulate假设thatthevascularconvergencesigncommonlyseeninSPNs.Actually,thetypeIVGGN-vesselrelationshipresemblesVCStosomedegree.Theinvasiveadenocarcinomagroupiscomposedoftwosubgroups,MIAandIAC.SubgroupanalysisshowedMIAandIAChaddifferentpatternsofGGN-vesselrelationships.第三十四页,共四十页。TypeIIIvascularmorphologicalchangeswereobservedmoreoftenintheIACthanMIAsubgroup,indicatingthatwithincreasingmalignancy,fibrehyperplasiastimulatedbymalignanttissuesmaybecomemoresevere,andsubsequentlyimpactsonvasculaturebecomeaggravated.Furthermore,tumourmetabolismisfasterthaninnormaltissues;therefore,thebloodsupplydemandedbytumoursismuchhigherthaninnormaltissues.Thesemechanismsindirectlyleadtovesselproliferationandirregularluminaldilation.第三十五页,共四十页。Somestudieshaveshownthatendogenousand/orextrinsictumorangiogenesisandneovascularisationcouldbethedrivingfactorsofvascularabnormalitiesobservedinmalignantearlystage.AsaCTimagingsign,VCSdescribesarelationshipbetweenSPNsandvessels,oneormultiplevesselsconcentratingtowardsandpassingthroughlesionsorbeingtruncatedattheedgeoflesions.第三十六页,共四十页。Involvedvesselsmayappeartortuous,rigidorirregularlywideningandlinktopulmonaryarteriesorpulmonaryveins.Inthisstudy,theGGN-vesselrelationshipswerecategorizedintofourtypes.StatisticalanalysisindicatedthatwhentherelationshipwastypeIIIorIV,especiallytypeIV,itwashighlylikelythatGGNsweremalignantinvasiveadenocarcinoma,withMIAmorethanIAC.Incontrast,themajorityofbenignandpreinvasivecaseswasseenintypeIortypeIIGGN-vesselrelationships.第三十七页,共四十页。Amajordrawbackofthisstudyisthelimitednumberofcases,especiallyinthebenigngroup,whichmaycompromisethediagnosticpower.Hence,aprospectiveclinicaltrialwithmoreGGNcasesiswarrantedtofurtherevaluateandvalidatethediagnosticvalueoffindingsinthisstudy.Additionally,thisstudycouldbestrengthenediftheanalysiswereconductedwithacombinationofvesseltypesandotherGGNfeatures,suchassizeandmass.Massmeasurementscanreflectlesiongrowthearlierwithlessvariabilitythandiametermeasurements.第三十八页,共四十页。Inconclusion,thisstudydemonstratesthatdifferentGGNsmighthavedifferentrelationshipswithvesselsduetovariationindevelopmentalbiologyandbehaviour.UnderstandingandrecognizingGGN-vesselrelationshipsinCTimagingandthestrongcorrelationbetweeninvasiveadenocarcinomaandtypeIIIandIVrelationshipsmayhelpidentifywhichGGNsaremorelikelytobemalignant.第三十九页,共四十页。内容总结Multi-detectorspiralCTstudyoftherelationshipsbetweenpulmonaryground-glassnodulesandbloodvessels。Discussion第四十页,共四十页。
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