DrAdrianLimMBBSFACDFACPRoyalNorthShoreHospital,uRepublicCosmeticDermatologyandVeinsNSWAustralia

Cryolipolysiswithadouble-applicator3-dimensionalcoolingcupdeviceIntroductionThereisastrongconsumerdemandfornon-invasivebodycontouringthroughlocalisedfatreduction.Lasers,radiofrequency,acousticwaveandfocusedultrasoundarecurrentlyavailableoptionsforthispurpose.Since2005,suction-assistedcryolipolysis(fatfreezing)hasbecomeoneofthemostpopulartechniquesforbodycontouringwithmanystudiessupportingitssafety,efficacyandreliability.Asaresult,consumersandpractitionersgloballyhaveembracedthismethodoffocalbodycontouring.Inlate2015,theAustralianTherapeuticGoodsAdministration(TGA)approvedanewcryolipolysisdevicewithtwoapplicatorswith3-dimentionalsurroundcoolingcup(CLATUU)forbodycontouring.TheprimaryobjectiveofthisstudyistoassessefficacyandsafetyoflocalisedfatreductionwithCLATUU.Thesecondaryobjectiveistocompareandevaluatethedifferentbodycontourmeasuringtechniques–standardisedphotography,callipermeasurement,circumferencetapemeasurement,ultrasoundmeasurementandpatientself-assessment–intheirvalidityandreliabilityinmonitoringpatientprogressfollowingcryolipolysis.Methods8consecutivetreatment-eligiblepatientswereenrolledintothecryolipolysisstudyforprospectiveevaluationovera4-monthfollow-upperiod.Patientswithlocalisedfataccumulationonthetrunkandproximallimbswereincludedinthestudy.Patientswithglobalobesity,coldintolerancesuchasRaynaud’s,andconnectivetissuediseasessuchasmorpheaorlupuspanniculitis,andpatientswithpreviouspreviousinvasive(liposuction)ornon-invasivemethodsoflocalisedfatreductionprocedureswereexcludedfromthestudy.Patientswererequestedtomaintainaconstantweightoverthestudyperiod(keepingwithin3kgofbaselineweight)andtomaintaintheircurrentlevelofphysicalactivity.Thetargetsiteswerepatientinitiatedtoreflectreal-lifeclinicalsettingandthelocationrecordedwithXandYaxisusingtheumbilicusasthefixedreferencepoint.Alltrialpatientshadtheoptionoftreatingeithersingle-siteor2-sitessimultaneously(e.g.lateralabdomenandoneinnerthigh).Baselineassessmentinvolved6-viewbodyphotography(anterior,posterior,rightanterolateral,leftposterolateral,rightlateral,leftlateral),weight,circumferencetapemeasurements,callipermeasurementsandM-modeultrasoundmeasureofadiposetissuethickness(meanof12differentmeasurementspointstakenwithinthetreatmentarea).Alltrialpatientswerefollowed-upat2monthsand4monthsforsimilarmeasurements.In2patientswithsymmetricalbilateralfataccumulation,thecontralateralsiteservedasinternalcontrol.Thetrialpatientshadtheoptionoftreating2–sitesattheonetimee.g.lateralabdomenandinnerthigh.Trialpatientswerealsoofferedtheoptionofarepeattreatmenttothesameareawithaminimumintervalof2monthsbetweentreatments.Theclinicalmeasurementswereundertakenbythesamenursepractitionerandtheultrasoundmeasurementswereperformedbythesamesonographer(Toshiba)

Alltrialpatientsweretreatedwithastandardprotocolatthenominated‘problem’site(s).Thetreatmentprotocolinvolvedinitialpriorapplicationofamatrixgelpadfollowedbyapplicationofeitheraflatorwing(curved)suctioncupdependingonthebodylocationandcontour.Theparametersweresuction(step4),cooling(step4)anddurationofonehour.Twomonthsafterthefinaltreatment,patientsweresurveyedabouttheirexperienceandsatisfactionoftheprocedure,includingself-ratingofperceiveddegreeoffatreductionpost-treatment.Attheendofthestudy,twoblindeddermatologistsratedthebaseline,2-monthsand4-monthsphotographsforallthetrialpatientsaccordingtoa4-pointscale:nochange(0%),mildreduction(<25%),moderatereduction(25-50%)andmarkedreduction(>50%).ResultsThesubjectdemographicswere:6femalesand2males,agerange:36–60yearsold(mean:46.8yearsold).Onesubjectwasexcludedfromthestudybecauseofanunrelatedtraumaticinjurytotheshoulderrequiringsurgery.Ofthe7subjects,atotalof13sitesweretreated:3subjectsrequestedtreatmentat2bodysites,2subjectshad1sitetreated,and1subjecthad4sitestreated.Thelateralabdomenwasthemostcommonlynominatedsite(figure1).Thespecifiedmeasurementsweredoneatbaseline,2-monthsand4-monthspost-treatment(table1).

Figure1.Leftlateralabdominalbefore(upperleftimage)and4-monthsafter1treatmentsession(upperrightimage).Rightlateralabdomenisthecontrolside(untreated).Upperabdomen:right(4-monthspostfirsttreatment)andleft(2-monthspostsecondtreatment).Themostconsistentrecordofbodycontouringchangewasphotographicassessmentandultrasonicfatmeasurements,wherethemeanglobalultrasonicfatreductionacrossallsubjectswas-19.44%(control:+0.62%)(table1).Fatreductionacrossthe3treatmentgroups(control,singletreatment,doubletreatment)appeartocorrelatewiththeultrasoundmeasurementsof+0.62%,-16.43%and-19.44%respectively.Thecalliperandcircumferencemeasurementscorrelatedpoorlywiththeclinicalchanges,withmeanglobal

reductionof-5.54%and-0.31%respectivelyfortheenrolledsubjects.Independentblindedphysician(dermatologists)assessmentoflocalisedfatreductionwas-30.0%after1treatmentand-39.5%after2treatments,basedonamean4-pointratingscale(table1).Therewascloseconcordancebetweentheblindeddermatologistsglobalscore:1.45and1.36(mean1.41),representingameanglobalreductionof-35.2%onthe4-pointratingscale(control:-12.5%).

Table1:Summaryoffatmeasurementsandpatientandphysicianratings.

Table2:PatientsatisfactionsurveyThepatientsatisfactionsurveyat2-monthspost-treatmentrevealed71.4%(5outof7patients)either‘agreed’or‘stronglyagreed’thattheoutcomewassatisfactory(table2).Fivepatientselectedtohavearepeattreatmentonthesamearea2monthsaftertheinitial

treatment.Ofthe2dissatisfiedpatents,onefeltthattherewas‘nochange’post-procedurebutrevisedherself-assessmentto‘markedreduction’uponreviewingthebefore-afterphotos(figure2).Theoverallpatientself-assessmentshowedconcordancewithblindedphysicianassessment:-36.4%and-35.2%respectivelyonthe4-pointratingscale(Rating:0[nochange],1[mild<25%],2[moderate25-50%],3[marked>50%]).

Figure2.Lowerabdomenbefore(leftimage)and2-monthsafterthe2treatmentsessions(rightimage).DiscussionInthelastfewyearstherehasbeenamarkedincreaseininterestanduptakeofcryolipolysisforlocalisedfatreduction.Onestudyshowedan823%increaseincryolipolysisproceduresovera3-yearperiod:201patientstreatedinthefirstyear,671patientsinthesecondyearand1857patientsinthethirdyear,highlightingthebusinesscaseforofferingtheservice.1Othernon-surgicaloptionsforlocalisedfatreductionincludehighintensityfocusedultrasound,unipolarradiofrequency,acousticwavetherapyandandlasertherapy,butthesedonotcompareasfavourablyascryolipolysisintermsofefficacy,safetyandtolerability.2Inonestudywith42patients,79%noticedfatreductiononthemselvesat2-4months.3Anotherstudywith50patients,89%showedanoticeableimprovementonphotographywithasimilarproportion(80%)beinghappywiththeresultsat6months.4.5Moststudiesindicateafatreductionofapproximately20-25%-eitheroncalliperorultrasonicmeasurements-3to6monthsafterasingletreatmentsession.6.7Twotreatmentsappeartoresultingreaterfatreductionthanasingletreatmentsession:28.5%versus19.7%.8Boeyetaldemonstrateda44%increaseinfatlosswith2minutesofmassagingimmediatelypostcryolipolysis,andthismanoeuvrehasbecomestandardpracticeinmostcentres.9Carruthersetalspeculatedonpossibleskintighteningeffectspostcryolipolysisbasedonaseriesof14patients.10Thesafetyofcryolipolysishasbeenwellestablished.Cryolipolysisisnotassociatedwithanyalterationsinserumlipidsandliverfunction.11Dysaesthesia(numbness)hasbeenreportedtooccurinupto73%ofpatientslasting3weeksalthough18%ofcasesmaypersistupto3

months.12Thedysaesthesiaisself-limitingandperipheralnervebiopsyandconfocalmicroscopydidnotshowanyalterationintheneuralnetwork.13Therewasasinglereportedcaseofparadoxicalfathypertrophythatstartedat3monthsandstabilisedat5monthsandtheincidenceofthiseventhasbeenestimatedtobe1:20,000.14OurstudyshowednoadverseeffectsassociatedwithCLATUUcryolipolysis.Oursubjectsexperiencedaninitial‘suction’discomfortlasting5-10minutesfollowedbycold-inducednumbnessfortherestoftheprocedure.Themostcommonpost-treatmenteffectwasnumbnesslastingfrom1to3weeks.Onepatientwithatopicdermatitisexperiencedmilditchingoverthetreatedsiteforafewdayspost-cryolipolysis.Onepatienthadserialskinbiopsiesatbaseline,1-week,1-monthand2-monthspostcryolipolysisrevealinganinflammatoryresponsethatwasmildat1week,markedat1monthandfullyresolvedat2months(figure3a,b)withcorrespondingultrasoundmeasurementimagesoftheleftupperpostero-lateralflank(figure3c).Patientswilltypicallynoticelocalisedfatlossoverthetreatedareaat2months,butasearlyas1-monthpost-procedure.

Baseline 1-week 1-month 2-months

Figure3a,b,c.Bilateralupperpostero-lateralflanksbefore(lefttopimage)andafter(righttopimage)cryolipolysis.Rightflank:2-monthsafter2treatmentsessionsandleftflank:2-monthsafter1treatmentsession(righttopimage).Histologyatbaseline,1week,1-monthand2-monthspost-treatment(middleimage,lefttoright).Post-treatmentinflammatorycellularinfiltrateisvisibleat1-week,prominentlyvisible

at1-month,andnormalisesat2-months.Correspondingultrasoundmeasurementsofleftflank2-monthsafter1treatmentsessiondemonstratingareductioninfatthickness(bottomimage)Ourpilotstudyonvariousmethodsoftrackingfatreductionfavourstandardisedphotographyandultrasoundovercallipersandcircumferentialtapemeasure.Circumferentialtapemeasurementofabdominalgirthisunlikelytobereliablegiventhelimitedtargetareainthecontextofthemuchlargertruncalgirth,whichexpandsandcontractswiththebreathingcycle.Wewereunabletodemonstrateconsistencywithcallipermeasurementsofskinfoldthickness,whichcanbepinch-andpressure-sensitiveandpronetoearlyuser-error.Photographyperformswellonreliability,familiarityandaccessibility,andfurthermore,allowsmeaningfulbefore-aftercomparisonforpatients.Theanterior(front-on)andside(lateral)profileviewsareparticularlyusefultodemonstratecontourchanges.Obliqueviewsmaynothighlightcontourchangesadequatelyandthiswashighlightedbyonepatientwhowasuncertainabouttheoutcomeandremainedunconvincedonreviewofpost-treatmentobliquephotosdespitea26.9%fatthicknessreductiononultrasound(figure4).Thiscaseillustrateshowimproperpatientselection(highbodymassindex)andsiteselection(non-obviousfatbulge)canleadtopatientdissatisfaction.

Figure4.Rightlowerlateralobliqueabdomenbefore(leftimage)and2-monthsafter1treatmentsession(rightimage).Ultrasonicmeasurementoffatlossisessentiallyaresearchtoolwithsignificantaccessibilityandtechnicalissuesformostclinicians.Fatthicknessmeasurementwiththeultrasoundprobeissusceptibletoprobe-pressureandpatient-posturevariations(lying/sitting/standing)andthesearelikelyexplanationsfortheapparentunderestimateoftheglobalfatreduction(19.44%)relativetophotographicassessment.Photographicrepresentationofbodycontourcanalsobeinfluencedbyseveralfactorsincludingcameraangle,lighting,patientstance,postureandbreathingcycle.Nevertheless,standardisedphotographyremainsavaluabletoolformonitoringpost-cryolipolysisprogressandprovidedonesubjectwithvaluablephoto-documentationofvisiblefatreduction(figure2).

Thelimitationsofthisstudyarearelativelysmallsamplesize,apredominanceoftorso(abdominal)treatmentsitesandpotentialinvestigatorbiasfromusinganindustry-sponsoreddevice(CryomedAustralia).ConclusionCryolipolysiswithCLATUUisasafeeffectiveprocedureforlocalisedfatreductionwithahighpatientsatisfactionrate.Standardisedphotographyisrecommendedasaneffectivemonitoringtoolanddocumentationofpost-cryolipolysisprogress.References1.StevensWG,PietrzakLK,SpringMA.BroadoverviewofaclinicalandcommercialexperiencewithCoolSculpting.AesthetSurgJ.2013Aug1;33(6):835-462.KruegerN,MaiSV,LuebberdingS,SadickNS.Cryolipolysisfornoninvasivebodycontouring:clinicalefficacyandpatientsatisfaction.ClinCosmetInvestigDermatol.2014Jun26;7:201-5.3.Rosales-BerberIA,Diliz-PerezE.Controlledcoolingofsub-cutaneousfatforbodyreshaping.Presentedatthe15thWorldCongressoftheInternationalConfederationforPlastic,ReconstructiveandAestheticSurgery,2009,NewDelhi,India.4.KaminerMW,NewmanJ,AllisonJ.Visiblecosmeticimprovementwithcryolipolysis:Photographicevidence.Paperpresentedat:2009AnnualMeetingoftheAmericanSocietyforDermatologicSurgery:October1-4,2009;Phoenix,Ariz.5.DoverJ,KaminerM,TeahanM,BarrettL.Patientsatisfactionat2and6monthsafterasinglenon-invasivecryolipolysistreatmentforsubcutaneousfatlayerreduction.LasersSurgMed.2011;43:968.6.SasakiGH,AbelevN,Tevez-OrtizA.Noninvasiveselectivecryolipolysisandreperfusionrecoveryforlocalizednaturalfatreductionandcontouring.AesthetSurgJ.2014;34:420–431.7.DierickxCC,MazerJM,SandM,KoenigS,ArigonV.Safety,tolerance,andpatientsatisfactionwithnoninvasivecryolipolysis.DermatolSurg.2013Aug;39(8):1209-16.8.PintoHR,Garcia-CruzE,MelamedGE.Astudytoevaluatetheactionoflipocryolysis.CryoLetters2012;33:177–181.9.BoeyGE,WasilenchukJL.Enhancedclinicaloutcomewithmanualmassagefollowingcryolipolysistreatment:a4-monthstudyofsafetyandefficacy.LasersSurgMed.2014Jan;46(1):20-6.2013.10.CarruthersJ,StevensWG,CarruthersA,HumphreyS.Cryolipolysisandskintightening.DermatolSurg.2014Dec;40Suppl12:S184-9.

11.RiopelleJT,KovachB.Lipidandliverfunctioneffectsofthecryolipolysisprocedureinastudyofmalelovehandlereduction.LasersSurgMed.2009:82.12.GaribyanL,SipprellWHIII,JalianHR,SakamotoFH,AvramM,AndersonRR.Three-dimensionalvolumetricquantificationoffatlossfollowingcryolipolysis.LasersSurgMed.2014;46:75–80.13.ColemanSR,SachdevaK,EgbertBM,PreciadoJ,AllisonJ.Clinicalefficacyofnoninvasivecryolipolysisanditseffectsonperipheralnerves.AestheticPlastSurg.2009Jul;33(4):482-8.14.JalianHR,AvramMM,GaribyanL,MihmMC,AndersonRR.Paradoxicaladiposehyperplasiaaftercryolipolysis.JAMADermatol.2014Mar;150(3):317-9.