Reconstruction of upper limb soft-tissue defects after sarcoma resection with free flaps: A systematic review

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JournalofPlastic,Reconstructive&AestheticSurgery(2020)000,1–13

Review

Reconstruction

of

upper

limb

soft-tissue

defects

after

sarcoma

resection

with

free

flaps:

A

systematic

review

Elena

Lucattelli

a ,∗

,

Irene

Laura

Lusetti

b

,

Federico

Cipriani

a

,

Alessandro

Innocenti

a

,

Giorgio

De

Santis

b

,

Marco

Innocenti

a

a_{PlasticandReconstructiveMicrosurgery,CareggiUniversityHospital,Florence,Italy} b_{PlasticandReconstructiveSurgery,PoliclinicodiModena,Modena,Italy}

Received 3January2020;accepted20October2020 Availableonlinexxx KEYWORDS Microsurgery; Upperextremity; Soft-tissuesarcoma; Limbsalvage; Functional reconstruction; Microsurgical reconstruction

Summary Background and Objectives: Upper limb preservation after softtissue sarcoma (STS)surgicalexcisionisnowtheacceptedgoldstandardanditoftenrequiresreconstruction withfreeflaps.Thepurposeofthisreviewistosummarize currentliteratureonupperlimb reconstructionwithfreeflapsafterSTSresection.

Methods: A systematic review was performed in July 2019 in PubMed and MedLine Ovid databasesaccordingtothePRISMAguidelines.

Results: Atotalof17studieswereincludedinthefinalanalysis,with132patients.Themost commondiagnosiswasMalignantFibrousHistiocytoma.Themostfrequenttimingofflap cov-eragewasimmediate.Thesuccessratewasalmostalways100%.Thelengthoffollow-upwas reportedin11studieswitharangeof2–187 months.Themostcommonlyreported patient-centeredoutcomewastheMSTSScore.Basedontheevidenceoftheliteraturecollected,we dividedtheupperlimbintofourparts(shoulder,elbowandarm,forearmandwrist,andhand) anddescribedthemostcommon andfunctionalfree flapsusedforreconstructionafter STS resection.

Conclusions: Free flapsinthetreatmentofSTSoftheupperextremityhaveagoodoverall outcome,withalowpostoperativecomplicationrate.Awidearrayoffreeflapsisavailable forreconstruction, andthechoiceofflap isbasedondefectsize, typesoftissuerequired, postoperativefunctionalgoal,andsurgeonpreference.Agreaterdegreeofstandardizationis neededinthereportingofpatient-centeredoutcomestofacilitatefuturecomparativestudies.

∗_{Correspondingauthor.}

E-mail address: elena.lucattelli@gmail.com(E.Lucattelli).

https://doi.org/10.1016/j.bjps.2020.10.065

1748-6815/© 2020BritishAssociationofPlastic,ReconstructiveandAestheticSurgeons.PublishedbyElsevierLtd.Allrightsreserved.

Pleasecitethisarticleas:E.Lucattelli,I.L.LusettiandF.Ciprianietal.,Reconstructionofupperlimbsoft-tissuedefectsaftersarcoma resectionwithfreeflaps:Asystematicreview,JournalofPlastic,Reconstructive&AestheticSurgery,https://doi.org/10.1016/j.bjps. 2020.10.065

2 E.Lucattelli,I.L.LusettiandF.Ciprianietal.

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© 2020BritishAssociationofPlastic,ReconstructiveandAestheticSurgeons.Publishedby El-sevierLtd.Allrightsreserved.

Contents

Introduction... 2

Methods... 2

Results... 3

Shoulder... 6

Elbowandarm... 6

Forearmandwrist... 9

Hand...10

Discussion...11

Conclusion...12

DeclarationofCompetingInterest...12

Acknowledgements...12

References...12

Introduction

In2018,theAmericanCancerSocietyestimatedthat13,040 newsoft tissuesarcomas(STS)would bediagnosed inthe United States with an associated mortality of 5,150 pa-tients.Approximately50%ofSTSoccursintheextremities, and30%ofthesearelocatedintheupperlimbs.1

Overall survival following treatment for extremity STS has improved over the past decades, with5-year survival rateapproaching80%.2_{Limbpreservationsurgeryisnowthe}

acceptedgoldstandardtreatmentforpatientswithSTSwith less than5% necessitating amputation.A multidisciplinary approachthat integrates surgerywith neoadjuvantor ad-juvantchemoand/orradiotherapyprovideslocalcontrolin morethan90%ofcasesandhashadasignificantimpacton disease-freesurvival.3,4

Asuccessfulmultidisciplinary managementof STSmust take into account the quality of the oncological resec-tion,thesoft-tissuecoverageandthefunctionaloutcome. Hence, the surgical pathwayin the treatment of patients affectedbySTSoftheextremitiesincludestumorresection withadequate margins,functionally andaesthetically ac-ceptablereconstruction,andapplicationofadjuvant ther-apyprotocols.5

Resection of STSin the extremityfrequently results in largecomplexsoft-tissuedefectswhicharenotsuitablefor primaryintentionorskingraftclosure.Inthesecases, pedi-cledorfreeflapreconstructionismandatorytoachievethe limbsalvage,providingastableandlong-lastingsoft-tissue coverage.

Intheupperlimb,effortsmustbemadetopreservehand functionasmuchaspossible.Therefore,nerve reconstruc-tionandtendontransfers areproceduresoftenassociated withmicrosurgicalsoft-tissuereconstruction.Thechoiceof the idealflap must becustomized in each single case in-cluding,whenneeded,chimeraflapsincorporatingtendons whichmayrestorethefunctionlostafteroncological exci-sion.

The purposeofthisreview istosummarizecurrent lit-erature onupperlimb reconstructionafter STSresection. This mayhelp sarcomateams toimprove selectionof the

mostappropriateflapforsuchreconstructionsbeforeinitial treatment.

Methods

A systematic search was performed in both PubMed and MedLineOviddatabasesaccordingtothePRISMA(Preferred ReportingItemsforSystematicReviewsandMeta-Analysis) guidelines.Thesearchtermsincluded“ freeflap”, “micro-surgical”,“reconstruction”,“sarcoma”,and“upperlimb”. The inclusion criteria were the use of free flap transfer inreconstructionofthehand,wrist,forearm,elbow,arm, andshoulderandthepossibilityofgatheringseparateddata for free flaptransfer of the upper extremity if thestudy described multiple procedures.The references of the ar-ticlesthat metinclusion criteriaafter screening were re-viewed to identify potential studies not captured by the initialdatabasequeries.Weexcludednon-Englishlanguage studies.Theinitialreviewwasconductedbytwo indepen-dent authors(E.L.and I.L.L.).Disagreementswere solved throughdiscussion,in whichoneadditionalauthorwas in-volved(M.I.).

Thepatientcharacteristicsrecordedfromeachstudy in-cludednumberofpatients whometinclusion criteria,sex (male/female),age(mean),presentingstatus(primary, lo-calrecurrence),typeofneoplasm, anatomicalregion, tu-morstage,sizeofdefect,timeofflapcoverage(immediate ordelayed),andtypeoffreeflap.Wealsorecordedtheuse ofpre-and/orpost-operativechemotherapyand/or radio-therapy.The postoperative results gatheredincluded suc-cessrate,complications(minorormajor),numberof reop-erations,lengthof follow-up,andoutcomemeasure(TESS score,MSTSorotherscales).

Patientswithbonesarcomasornon-upperlimbsitewere excludedfromqualitativesynthesis,aswellaspatientswith post-traumaticreconstructionorreconstructionwith tech-niquesdifferentthanfreeflaps(pedicledflaps,direct clo-sure,or split-thickness skin graft).Case reportsdescribed particularcasesofreconstructionwithchimericflapswhich included a bony component, so were excluded. On the

Pleasecitethisarticleas:E.Lucattelli,I.L.LusettiandF.Ciprianietal.,Reconstructionofupperlimbsoft-tissuedefectsaftersarcoma resectionwithfreeflaps:Asystematicreview,JournalofPlastic,Reconstructive&AestheticSurgery,https://doi.org/10.1016/j.bjps. 2020.10.065

Reconstructionofupperlimbsoft-tissuedefectsaftersarcomaresectionwithfreeflaps 3

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Fig.1 Flowchartoftheselectionprocessforinclusionofarticlesinthesystematicreview.

other hand, the articles with 1-3 cases we included in the review, contained longer case series which were re-ducedaftertheapplicationoftheaforementionedselection criteria.

Results

After removalofduplicates, atotal of147 citations were identified. Fifty-six potentially relevant articles were se-lectedthroughtitle/abstractscreening,ofwhich17studies remainedforqualitativesynthesisafterfull-textscreening (Fig.1).Duringthe full-textreview we hadtoremovean article of the same authorof one of the included article becausethecasesdescribedwerethesame.2

The 17included studiesencompassed132 patientswho met inclusion criteria(Table 1). Studies data are summa-rized in Table 2.Patients agewas reportedin 15studies, andtheaverageagewas49.25(Fig.2).Thirteenstudies re-ported the sexof patients, amongwhich 53% were male.

Ninety-threetypes of neoplasmwere specified ofthe 132 patients, and the most common diagnosis was Malignant FibrousHistiocytoma(MFH) with the30% of diagnosis fol-lowedbyleiomyosarcomain10cases.Thetimeofflap cov-eragewasimmediateinallcases,asitwasspecifiedin10 articles.Thirteenstudies reportedthe useof pre- and/or post-operative radiotherapy, while only seven studies re-ported the use of pre- and/or post-operative chemother-apy. In those studies that reportedradiotherapy use, 57% ofpatientsreceivedneoadjuvantradiotherapywhereas31% ofpatientsreceivedadjuvantradiotherapy.Incomparison, 20% of patients received neoadjuvant chemotherapy, and 14%ofpatientsreceivedadjuvantchemotherapy.

Success rate wasreportedin 16 articles and was100% in all except three. Of all the132 patients that received a free flap, only in three cases a flap loss was reported. Follow-uplengthwasreportedin11studies,ranging2–187 months. Outcome resultsare summarized in Table 3. The mostcommonlyreportedpatient-centeredoutcomewasthe MSTSScore,whichwascalculatedin6studies.

Pleasecitethisarticleas:E.Lucattelli,I.L.LusettiandF.Ciprianietal.,Reconstructionofupperlimbsoft-tissuedefectsaftersarcoma resectionwithfreeflaps:Asystematicreview,JournalofPlastic,Reconstructive&AestheticSurgery,https://doi.org/10.1016/j.bjps. 2020.10.065

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Table1 ResultsofliteratureanalysisforfreeflapreconstructionofupperextremityafterSTSexcision. N° Author (year) N° Sex male/female Age(years) (mean+SD) Presenting status (primary/local recurrence) Typeof neoplasm Anatomical region

Tumorstage Sizeofdefect Timeofflap coverage (immediate,≤ 72h,>72h) Typeoffree flap RT(neoo adjuvant) CT(neoo adjuvant)

Successrate Major complications Minor complications N° of reoperations FU Outcome measures 1 Slump (2018) 26 15/11 53.5± 15.2 24/2 NA 14proximal,12 distal I:5(19.2%),II: 11(42.3%),III: 8(30.8%),IV:2 (7.7%)

9cm3 26Immediate LD,radial,RAM, ALT,gracilis, parascapular 21neo,2 adjuvant 0neo NA 12(14.1%)∗ 10(11,8%)∗ NA NA Difference betweenthe mean preoperative and postoperative functional score:TESS:5.5 MSTS87:-1.5 MSTS93:-3.3 2 Stranix (2017) 1 F 53 NA 1Spindlecell sarcoma 1Distaldorsal forearm NA 12× 10 1Immediate 1 ALT+VL+ mo-tor nerve+LFCN+IL band+TFL RTadjuvant 0 100,00% 0 0 0 22months MSTS:24/30 3 Weichman (2015) 3 2/1 22,29,46 NA 2Epithelioid sarcomas,1 leiomyosar-coma 1Dorsalthumb, 1thumb,1 dorsalthenar eminence

NA 24,27,40cm2 3Immediate 3aALT 1RTneo,1RT adjuvant NA 100,00% 0 1Wound dehiscence 1 6,94,99monthsNA 4 Grinsell (2014) 2 1/1 58,74 1/1 1Synovial sarcoma,1 fibrosarcoma (recurrence) 1Deltoid,1 bicepsbrachii NA NA 2Immediate Myocutaneous medial gastroc-nemius+motor nerve(from sci-atic)+sensory nerve(from sural) NA NA 100,00% 0 0 0 12,24months MRC:5/5 abductionand flexionof shoulderjoint; 5/5armflexion (elbowrange 30–120degrees) 5 Mundinger (2014) 2 1/1 26,33 2local recurrences 1Epithelioid sarcoma,1 ded-iferrentiated osteosarcoma 1Forearm extensor compartment, 1biceps 3 NA 2Immediate 1 Non-innervated LD,1 innervated gracilis 1RTneoe adjuvant NA 100,00% 0 1Inferiorflap epidermolysis 1Widelocal excisionoflocal recurrence (ulnar reconstruction withfibulafree flap);1flap debulking 43.3months (7-85)∗ TESS:NA;35.3 6 Payne (2013) 36 18/18 56.9(17-78) NA 12MFH,3 liposarcomas,6 fibrosarcomas, 5MPNST,3 DFSP,5 leiomyosarco-mas,2 others 14Shoulder,13 elbow,9 wrist/hand I:7(19%),II:5 (14%),3:24 (67%) 7× 5× 4 NA ALT,LD,RAM, gracilis NA NA 97,00% 1Flaploss (partial),1DVT 5Wound infections,2 delayedhealing 1Surgical excision NA TESS:87.68% MSTS87: 28.78/35MSTS 93:81.38% 7 Grinsell (2012) 3 NA NA NA 2Pleiomorphic sarcomas,1 liposarcoma 2 Bi-ceps+brachialis, 1 rhom-boid+trapezius NA NA 3Immediate 2Innervated gracilis,1 innervatedLD

3RTneo NA 66,00% 1Flaploss (complete) 0 1Surgical excisionand substitution withpedicled LD 14,15,15 months MSTS:25,30,13 MRC:4/5,4/5, 5/5DASH:31, 0,14 Please cite this article as: E. Lucattelli, I.L. Lusetti and F. Cipriani et al., R e construction of upper limb soft-tissue defects after sarcoma resection with free flaps: A systematic review , Journal of Plastic, R e constructive & Aesthetic Surgery , https://doi.org/10.1016/j.bjps. 2020.10.065

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JID: PRAS [m6+; Decemb e r 1, 2020;20:24 ] Table1 (Continued) 8 Chao (2012) 15 NA NA NA 2MFH 2arm,3elbow, 9forearm,1 hand NA NA NA NA 12RTneo,3RT adjuvant NA 93,00% 1Flaploss (complete,due tovenous thrombosis) NA 1shoulder disarticulation duetolocal recurrence3 monthsafter reconstruction NA NA 9 Marré (2012)

1 NA 52 NA 1Angiosarcoma1Arm NA NA NA 1ALT 1RTneo NA 100,00% 0 0 0 NA NA

10 Momeni (2011) 6 3/3 36-84(mean 63.5) NA 1 Myxofibrosar-coma,2 Pleomorphic sarcomas,1 rhabdomyosar-coma,1synovial sarcoma,1 myxoinflamma-tory sarcoma 1Elbow,4 forearm,1hand NA 36,9-96cm2 (mean65)

6Immediate 6ALT 6RTadjuvant NA 100,00% 0 0 1re-excision forR1resection 6-47months (36)∗ NA 11 Barner-Rasmussen (2010) 12 NA 61∗ NA 7MFH,2 fibrosarcomas, 1synovial sarcomas,1 epithelioid sarcoma,1 MPNST NA II:1(8,3%),III: 5(41.7%),IV:6 (49,8%) NA NA 5LD,1ALT,3 radialforearm, 2TFL,1 antebrachial replantation 10RTadjuvant, 1RT neoadjuvant∗ 1CT adju-vant+neoadjuvant ∗ 100,00% 1Vein reanastomose, 1hematoma 2Minorwound complications NA 2-187months(5 DOD,2DUC,5 NED) NA 12 Muramatsu (2009) 4 1/3 17-65(mean 45.25) 3Primary/1 local recurrence 1MFH,1 angiosarcoma, 2synovial sarcomas 2Dorsalarm,1 dorsalhand,1 thenar eminence IIA:3(75%),IV: 1(25%) NA 4Immediate 2Gracilis,1 Groin,1 Peroneal

2RTadjuvant 2CTneo 100,00% 0 0 0 38-173months (108.5),3NED, 1DOD

Enneking scoringsystem: 30,30,23,20 13 Lee(2007)1 M 32 NA 1MyxofibromaForearm NA 12× 7cm NA 1TDAP

(transverse) NA NA 100,00% 1Subflap haematoma 0 0 NA 14 Mehrara (2008) 2 1/1 28–46 NA 1Epithelioid sarcoma,1 leiomyosar-coma

2Thumbs NA 5× 6cm NA ALT None None 100,00% 1Stichabscess withexposition ofbonegraft, neededafirst dorsal metacarpal arteryflap 0 0 22monthsfree fromdisease MSTS:28,29 15 Dabernig (2007) 1 M 60 1Local recurrence

1Sarcoma 1Upperarm NA 16× 6cm 1Immediate 1CSAP NA NA 100,00% 0 0 NA NA NA 16 KimJY (2004) 15 8/7 56.8(12-75) 3Primary,12 recurrence 6MFH,3 leiomyosarco-mas,2synovial sarcomas,2 liposarcomas,1 epithelioid sarcoma,1 unclassified sarcoma 1Armand elbow,1elbow andforearm,1 elbow,10 forearm,2arm I:1(6.7%),II:5 (33.3%),III:7 (46.7%),IV:2 (13.3%) >5cmin8 patients,<5cm in9patients NA 7RAM,3LD,2 gracilis,1 scapular,1 lateralarm,1 radialforearm 12RTneo,2RT adjuvant,4 adjuvant brachytherapy 9CTneo,8CT adjuvant 100,00% 2Vessel thrombosis

1hematoma 1Resectionand gracilisflapfor local recurrence 2-119months,4 DOD,3NED,6 AWD,2DOC Ennekingscore: range14-30 17 Ihara (2003) 2 2M 65(60-70) 2recurrences 1Liposarcoma, 1DFSP

2Shoulder IA:2(100%) NA 4Immediate 2TFL 0 1CT 100,00% 0 0 0 62-67months MSTS:97%, 100% aALT:adipofascialanterolateralthigh;ALT:anterolateralthigh;AWD:alivewithdisease;CSAP:circumflexscapulararteryperforator;CT:chemotherapy;DASH: DisabilityoftheArm, Shoulder,andHand;DFSP:dermatofibrosarcomaprotuberans;DOD:deadofdisease;DUC:deathfromunrelatedcause;DVT:deepvenousthrombosis;IL:ileotibial;LD:latissimusdorsi; LFCN:lateral femoralcutaneousnerve;MFH:malignantfibroushistiocytoma;MPNST:malignantperipheralnervesheathtumor;MRC:MedicalResearchCouncil;MSTS:Musculoskeletal TumorSociety;NA:notapplicable;NED:noevidenceofdisease;RAM:rectusabdominismuscle;RT:radiotherapy;TDAP:thoracodorsalarteryperforator;TESS:TorontoExtremitySalvage Score;TFL:tensorfascialata;VL:vastuslateralis.∗datanotdividedforthegroupofpatientsofourinterestamongtheotherresultsdescribedinthestudy

Please cite this article as: E. Lucattelli, I.L. Lusetti and F. Cipriani et al., R e construction of upper limb soft-tissue defects after sarcoma resection with free flaps: A systematic review , Journal of Plastic, R e constructive & Aesthetic Surgery , https://doi.org/10.1016/j.bjps. 2020.10.065

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Fig.2 Bargraphshowingthenumberoftotalarticles(n=17)reportingeachvariable.Numbersinblackwithinthebarsrepresent thenumberofarticlesdescribingeachvariable.

Table2 Overallstudy characteristicsoffree flap recon-structioninupperextremitySTStreatment.

Includedpapers 17

Numberofpatients 132

Averageage(years) 49.25

Percentmale 53%

Lengthoffollow-up(rangeinmonths) 2–187

Shoulder

Extirpationofsarcomasoftheshoulderanditsgirdlewith adequatemarginsoftenresultsinextensivedefectsofthe overlying skin and functionallyimportant muscles such as thedeltoidandthetrapezius.6_{Accordingly,notonlywound}

coveragebutalsocosmeticandfunctionalproblemsmustbe solvedtoobtain satisfactoryresultsoflimbsalvageinthis region. Soft-tissue reconstruction is usually accomplished usingcutaneous,muscular,andmusculocutaneouspedicled flapsaroundtheshoulder asadonorsource(Table4).The latissimusdorsi(LD)pedicledflapistheprocedureofchoice for extensive defects after oncological resection as it is usuallyavailable,easytoharvest,andcanprovidealarge amountoftissuecoverage.Moreover,thisflapcanbea reli-ablesourceforfunctionalreconstruction.7,8_Insomecases,

suchaspreviousthoracicsurgeryoraxillarylymphnode dis-section, LDelevation maycarrya risk of failure:inthese cases,a tensorfascialata ora medialgastrocnemiusfree flapcanbeharvested.

Thetensorfascialatamuscleincludesastrongfascialata that providesan appropriate suspendingstructure for the shoulder.9_{Simultaneousharvestoftheflapisfeasiblein}

ei-therthesupineorlateralpositionsduringshouldersurgery. Inaddition,theflapcanalsobeusedasafunctioning

mus-clewithneurorrhaphyofthemotornerve.10 _Theanatomic

uniformityandthe large diameterofthe vascular pedicle minimizethedrawbacksofthisfreeflap.Theflapcouldbe a donorof first choice for shoulder reconstruction, espe-ciallyfor deltoidreplacement,becauseitsmusclebellyis morecompactandis nearlyequivalenttothatofthe del-toid,whereastheLDcanbetoolarge.Functionalusemay alsobefeasibleinthecaseofanentiredefectofthe trapez-iusbyaccomplishinganeurorrhaphyofthemotornervewith thespinalaccessorynerve.

Thefunctionalmedialgastrocnemiusfreeflaphasbeen describedfordeltoidreconstructionasgoodoptioninview ofitsstrength,musclebulk,length,andlimiteddonor-site morbidity.11

Elbowandarm

ALTflapistheflapofchoiceincaseofSTSinvolvingthis re-gionforitslongandsizeablepedicle,predictableanatomy, minimal donor-site morbidity,andits provision ofthe op-portunitytoimplementatwo-teamapproach.12,13 _Valuable

alternativesarethethincircumflexscapularartery perfo-ratorflap(CSAP) anda rectus abdominismuscle (RAM)or myocutaneous(RAMC)freeflap(Table5).

The thin CSAP has been described as a valid alterna-tivepossessingeasilydefinedsurfacemarkings,good pedi-clelength,andlarge-diametervessels. Moreover,thisflap avoidsintramusculardissectionwhile retainingall the po-tentialforthinning.Thecharacterofthedermiscanbe ad-justedby varying the orientation of the skin paddle, and multiplechimericoptionsarepossible.14_{However,thisflap}

requireslargeranatomical,radiological,andclinicalstudies toclearlydefineitspotentialdimensions,safety,anduse.

SelectionofaRAMor RAMCfreeflapcanbeassociated withlargedefectsizes.15_{Whilethebulkynatureoftheflap}

Pleasecitethisarticleas:E.Lucattelli,I.L.LusettiandF.Ciprianietal.,Reconstructionofupperlimbsoft-tissuedefectsaftersarcoma resectionwithfreeflaps:Asystematicreview,JournalofPlastic,Reconstructive&AestheticSurgery,https://doi.org/10.1016/j.bjps. 2020.10.065

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Table3 OutcomeresultsforanatomicalregionafterfreeflapreconstructionofupperextremityafterSTSexcision.

Anatomical region

Study Flap Major

complica-tions

Minor com-plications

FU(months) Reoperations

Shoulder Grinselletal. (2014)

1Myocutaneous medial gastrocne-mius+motornerve (from

sciatic)₊sensory nerve(fromsural)

/ / 12 /

Payneetal.(2013) 11ALT,3LD,1 rectusabdominis

∗ ∗ _NA ∗

Grinselletal. (2012)

1innervatedLD / / 14 /

Iharaetal.(2003) 1innervatedTFL,1 TFL.

/ / 62,78 /

Arm Grinselletal. (2014)

1Myocutaneous medial gastrocne-mius+motornerve (from

sciatic)+sensory nerve(fromsural)

/ / 24 / Mundingeretal. (2014) 1innervated myocutaneous gracilis / 1inferior flap epider-molysis ∗ _1flap debulking Grinselletal. (2012)

2innervatedgracilis 1failed / 15 1Substituted withLD

Chaoetal.(2012) 2 ∗ ∗ NA ∗

Marrè etal.(2012) 1ALT / / NA /

Daberingetal. (2007) 1CSAP / / NA / KimJYetal. (2004) 1scapularmuscle,1 RAM,1RAMC ∗ ∗ ∗ ∗

Elbow Payneetal.(2013) 9ALT,4LD ∗ ∗ NA ∗

Chaoetal.(2012) 3 ∗ ∗ NA ∗ Momenietal. (2011) 1ALT / / ∗ ∗ KimJYetal. (2004) 1RAMC,1 LDM+STSG ∗ ∗ ∗ ∗

Forearm Stranixetal. (2017) 1ALT₊VL₊motor nerve₊LFCN₊IL band₊TFL / / 22 / Mundingeretal. (2014) 1LD / / ∗ Local recurrence (ulnar reconstruction withfreefibula flap)

Chaoetal.(2012) 9 ∗ ∗ NA ∗

Momenietal. (2011)

4ALT / / ∗ ∗

Leeetal.(2007) 1TDAP 1sub-flap hematoma / NA KimJYetal. (2004) 1gracilis₊STSG,4 RAM+STSG,1LDMC, 1LDM₊STSG,1 lateralarmmuscle, 1myocutaneous gracilis,1radial forearm

∗ ∗ ∗ ∗

(continued on next page ) Pleasecitethisarticleas:E.Lucattelli,I.L.LusettiandF.Ciprianietal.,Reconstructionofupperlimbsoft-tissuedefectsaftersarcoma resectionwithfreeflaps:Asystematicreview,JournalofPlastic,Reconstructive&AestheticSurgery,https://doi.org/10.1016/j.bjps. 2020.10.065

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Table3 (continued)

Anatomical region

Study Flap Major

complica-tions

Minor com-plications

FU(months) Reoperations

Hand/wrist Weichmanetal. (2015)

3ALT 1wound

dehis-cence

/ 94,99,6 1

Payneetal.(2013) 6ALT,2rectus abdominis,1gracilis ∗ ∗ _NA ∗ Chaoetal.(2012) 1 ∗ ∗ NA ∗ Momenietal. (2011) 1ALT / / ∗ ∗ Muramatsuetal. (2009) 2innervatedgracilis, 1groin,1peroneal / / 173,86,38, 137 / Mehraraetal. (2008) 2ALT 1Stich abscess with exposition ofbone graft / 22 1firstdorsal metacarpal arteryflap

aALT:adipofascialanterolateralthigh;ALT:anterolateralthigh;CSAP:circumflexscapulararteryperforator;FU:follow-up;IL:ileotibial; LD:latissimusdorsi;LDM:latissimusdorsimuscle;LDMC:latissimusdorsimyocutaneous;LFCN:lateralfemoralcutaneousnerve;NA:not applicable,RAM:rectusabdominismuscle;RAMC:rectusabdominismyocutaneous;STSG:split-thicknessskingraft; TFL:tensorfascia lata;TDAP:thoracodorsalarteryperforator;VL:vastuslateralis.∗:datanotdividedforanatomicalregion

Table4 Surgicaloptionsforshoulderreconstruction.

Flap Advantages Indications Functional

outcome Limitations LDpedicled flap Easytoharvest, lowdonor-site morbidity,large amountoftissue, lowoperativetime

Firstchoicefor deltoid reconstruction; allowsfunctional reconstruction Goodfunctional recovery Previousthoracic surgeryoraxillary lymphnode dissection (Innervated) tensorfascia latafreeflap

Simultaneous harvestbothin supineorlateral position,large diameterof vascularpedicle, limiteddonor-site morbidity,useful fordeltoid replacementfor itscompact musclebelly

Secondchoicefor deltoid reconstructionor completetrapezius replacement;allows functional reconstruction accomplishinga neurorrhaphyofthe motornervewith respectivelyaxillary orspinalaccessory nerve MSTS:97%for functional reconstruction Previousthigh surgeryinvolving tensorfascialata muscle (Innervated) medial gastrocnemius freeflap Easytoharvest, limiteddonor-site morbidity,allows two-team approach

Thirdchoicefor deltoid reconstruction;allows functional reconstruction accomplishinga neurorrhaphyofthe motornervewith axillarynerve

Complete abductionand flexionofthe shoulderjointfor functional reconstruction

Previouslegupper thirdsurgery involvingmedial gastrocnemius muscle,short pedicle

LD:LatissimusDorsi;MSTS:MusculoskeletalTumorSociety

Pleasecitethisarticleas:E.Lucattelli,I.L.LusettiandF.Ciprianietal.,Reconstructionofupperlimbsoft-tissuedefectsaftersarcoma resectionwithfreeflaps:Asystematicreview,JournalofPlastic,Reconstructive&AestheticSurgery,https://doi.org/10.1016/j.bjps. 2020.10.065

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Table5 Surgicaloptionsforarmandelbowreconstruction.

Flap Advantages Indications Functional

outcome

Limitations (Thin)ALTfree

flap

Longandsizeable pedicle,predictable anatomy,minimal donor-sitemorbidity, allowstwo-teams approach;thelateral femoralcutaneous nervecanbeincluded forpossiblesensory reinnervation.

Firstchoicefor soft-tissue reconstruction, especiallyforlarge defects;iliotibialband canbeharvestedalong withVLmuscletoanchor theresectedtendon remnantsandestablish staticmusculoskeletal stabilizationofjoints

N/A Previousthigh surgery,rarely smallcutaneous perforatorvessels

CSAPfreeflap Thin,easydefined surfacemarking,good pediclelength,large diametervessels, avoidsintramuscular dissection

Secondchoicefor soft-tissue

reconstruction;idealfor theelbowjoint

N/A Requireslager anatomical, radiological,and clinicalstudiesto clearlydefineits potential dimensions, safety,anduse RAMorRAMCfree

flap

Easytoharvest, predictableanatomy, allowstwo-team approach

Thirdchoicefor soft-tissue reconstruction, especiallyforlarge defects

N/A Bulky,possible abdominalhernia andbulges

(Innervated) myocutaneous gracilisfreeflap

Limiteddonor-site morbidity,allows two-teamapproach

Firstchoiceforbiceps reconstruction;allows functional

reconstruction accomplishinga neurorrhaphyofthe motornervewith musculocutaneousnerve forelbowflexion

Goodfunctional recovery

Shortpedicleand small-diameter vessels (Innervated) medial gastrocnemius freeflap Easytoharvest, limiteddonor-site morbidity,allows two-teamapproach

Secondchoiceforbiceps reconstruction;allows functional

reconstruction accomplishinga neurorrhaphyofthe motornervewith musculocutaneousnerve forelbowflexion

Grade5/5arm flexionand abduction;elbow range30-120 degrees

Previouslegupper thirdsurgery involvingmedial gastrocnemius muscle,short pedicle

ALT:AnterolateralThigh;CSAP:CircumflexScapularArteryPerforator;RAM:RectusAbdominisMuscle;RAMC:RectusAbdominis Myocutaneous;VL:VastusLateralis

at initial inset may be worrisome,over a time period of months, theflapatrophies, becomingmoreflush withthe surroundingtissue.Disadvantagesofitsuserelatemostlyto donorsitemorbidity,withabdominalherniaandbulge for-mationbeingseeninfrequently.

Incaseofmassiveresectionofthebicepsmuscle,a my-ocutaneousgracilisfreeflapwithaneurorrhaphywith mus-culocutaneous nerve can besuccessfully usedin order to restoretheelbowflexion.8,16,17_{Functionalmedial}

gastroc-nemiusfreeflapcanbeanotheroptionafterbicepsmuscle resection.11

Forearmandwrist

Forsmalldefects, propellerflapsbasedeitheron perfora-torsraisingfromthevascularnetworkoftheelboworfrom radialand ulnar arteriesare thefirst choice.18 _{In case of}

largerdefects,thinALTflapisroutinelyused(Table6).13,19

The thoracodorsalarteryperforatorflap(TDAP) canbe usedforitsminimaldonor-sitemorbidityandrelatively hid-den scarthat canbe cosmeticallyimproved by harvesting theflapinatransversefashion.20 _{RAM,RAMC,andgracilis}

muscleflapsarealsodescribedasotheralternatives.15

Pleasecitethisarticleas:E.Lucattelli,I.L.LusettiandF.Ciprianietal.,Reconstructionofupperlimbsoft-tissuedefectsaftersarcoma resectionwithfreeflaps:Asystematicreview,JournalofPlastic,Reconstructive&AestheticSurgery,https://doi.org/10.1016/j.bjps. 2020.10.065

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Table6 Surgicaloptionsforforearmandwristreconstruction.

Flap Advantages Indications Functional

outcome

Limitations Propellerflaps Limiteddonor-site

morbidity,low operativetime, reconstruction“like withlike”

Firstchoicefor soft-tissue reconstruction, especiallyforsmall defects

N/A Notsuitablefor verylargedefects

ThinALTfreeflap Longandsizeable pedicle,predictable anatomy,minimal donor-sitemorbidity, allowstwo-teams approach;thelateral femoralcutaneous nervecanbeincluded forpossiblesensory reinnervation

Secondchoicefor soft-tissue reconstruction, especiallyforlarge defects;iliotibial bandcanbe harvestedalongwith VLmuscletoanchor theresectedtendon remnantsand establishstatic musculoskeletal stabilizationofjoints MSTS:24/30.Near normalfinger extension,active wristextension achievableto neutral Previousthigh surgery,rarely smallcutaneous perforatorvessels

TDAPfreeflap Minimaldonor-site morbiditywith relativelyhiddenscar

Thirdchoicefor soft-tissue reconstruction, especiallyfor small-medium defects

N/A Doesnotallow two-team approach

(Innervated) gracilisfreeflap

Limiteddonor-site morbidity,allows two-teamapproach

Firstchoicefor extensororflexor forearmmuscles reconstruction

Ennekingscoring system:30/30

Shortpedicleand small-diameter vessels (Innervated)LD

freeflap.

Easytoharvest,low donor-sitemorbidity, largeamountof tissue

Secondchoicefor extensororflexor forearmmuscles reconstruction Goodfunctional recovery Bulky (Innervated)RAM orRAMCfreeflap

Easytoharvest, predictableanatomy, allowstwo-team approach

Thirdchoicefor extensororflexor forearmmuscles reconstruction Goodfunctional recovery Bulky,possible abdominalhernia andbulges

ALT:AnterolateralThigh;LD:LatissimusDorsi;RAM:RectusAbdominisMuscle;RAMC:RectusAbdominisMyocutaneous;TDAP: ThoracodorsalArteryPerforator;MSTS:MusculoskeletalTumorSociety;VL:VastusLateralis

ThemyocutaneousALTflapcanbeusedincaseof com-positesoft-tissueandmusculardefects,whiletheiliotibial (IT) band canbeharvested alongwiththevastus lateralis (VL) muscleto anchorthe resected tendon remnants and establishstaticmusculoskeletalstabilizationofjoints.The lateral femoral cutaneous nerve can beincluded for pos-sible sensoryreinnervation.21 _{LD muscle or myocutaneous}

freeflapisavaluableoptionfor functionalreconstruction afterextensororflexorcompartmentsresection.16,40

Hand

Thehandpresentsspecificchallengesbecauseofitsunique anatomic structure. There is little soft tissue, and each compartment is narrow sothat importantstructuresexist incloseproximity.Anatomicconstraintsmakeitdifficultto achievewidesurgicalmargins.17

Forhandpalmreconstruction,themedialplantarflapis theonlyavailableoptioninordertoreconstructthedefect witha specializedskin.22 _{If notsuitable, thinALT, lateral}

arm,orSCIPfreeflapsmaybeused,althoughthequalityof theskinisnotcomparabletothatharvestedfromthefoot sole(Table7).16,23,24

Incaseofhanddorsumreconstruction,thinandpliable skinisrequired:ultrathinALTorSCIPfreeflapsarethefirst choices(Table8).23,24_{Peronealfreeflaphasbeendescribed}

asavaluablealternative.17_{Indeed,itcanprovidesufficient,}

healthytissuewithoutcompromisingthefunctionoftheleg, astheanatomyoftheperonealperforatorisrelatively con-stantandthereisnoneedtosacrificeanymainarteriesin thelowerleg. Moreover,theflapisthinandmatcheswell withtheupperlimbskinintextureandcontour,anditcan beharvestedassensoryflapifsuralnerveisincluded.

Thethumbposesaparticulardilemmainthatlossofthe thumbseriouslyimpairstheuseofthehandandtheentire

Pleasecitethisarticleas:E.Lucattelli,I.L.LusettiandF.Ciprianietal.,Reconstructionofupperlimbsoft-tissuedefectsaftersarcoma resectionwithfreeflaps:Asystematicreview,JournalofPlastic,Reconstructive&AestheticSurgery,https://doi.org/10.1016/j.bjps. 2020.10.065

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Table7 Surgicaloptionsforhandpalmreconstruction.

Flap Advantages Indications Limitations

Medialplantarfree flap

Lowdonor-sitemorbidity, reconstruction“likewithlike”, allowstwo-teamapproach

Firstchoiceforsoft-tissue reconstruction,especially forsmalldefects

Previousfootsurgery, shortpedicle,and small-diametervessels ThinALTfreeflap Longandsizeablepedicle,

predictableanatomy,minimal donor-sitemorbidity,allows two-teamsapproach;the lateralfemoralcutaneous nervecanbeincludedfor possiblesensoryreinnervation

Secondchoicefor soft-tissuereconstruction, especiallyforlargedefects

Previousthighsurgery, rarelysmallcutaneous perforatorvessels

Lateralarmfreeflap Allowstwo-teamapproach Thirdchoiceforsoft-tissue reconstruction,especially forsmall-mediumdefects

Previousarmsurgery, importantdonor-site morbidity,bulky SCIPfreeflap Minimaldonor-sitemorbidity,

allowstwo-teamapproach

Fourthchoiceforsoft-tissue reconstruction,especially forsmall-mediumdefects

Previousinguinalsurgery, unreliableanatomy, shortpedicle,and small-diametervessels

ALT:AnterolateralThigh;SCIP:SuperficialCircumflexIliacPerforator

Table8 Surgicaloptionsforhanddorsumreconstruction.

Advantages Indications Limitations

UltrathinALTfree flap

Longandsizeablepedicle, predictableanatomy,minimal donor-sitemorbidity,allows two-teamsapproach;the lateralfemoralcutaneous nervecanbeincludedfor possiblesensoryreinnervation

Firstchoiceforsoft-tissue reconstruction,especiallyfor largedefects

Previousthighsurgery, rarelysmallcutaneous perforatorvessels

SCIPfreeflap Minimaldonor-sitemorbidity, allowstwo-teamapproach

Secondchoiceforsoft-tissue reconstruction,especiallyfor small-mediumdefects

Previousinguinalsurgery, notreliableanatomy, shortpedicle,and small-diametervessels Peronealfreeflap Relativelyconstantanatomy,

longandsizeablepedicle, minimaldonor-sitemorbidity, allowstwo-teamapproach;the suralnervecanbeincludedfor possiblesensoryreinnervation

Thirdchoiceforsoft-tissue reconstruction,especiallyfor small-mediumdefects

Previouslegsurgery, presenceofperonea magnaartery

ALT:AnterolateralThigh;SCIP:SuperficialCircumflexIliacPerforator

upperlimb.ThetemporoparietalfascialandALTfascialfree flapshavebeendescribedforthinpliableflapcoveragewith aglidingsurface.25

Discussion

STS are rare malignant mesenchyme-derived tumors that commonlyinvolvetheextremities.Historically,thesecases were treated by amputation, but improvements in surgi-cal techniques, radiological imaging, and adjuvant thera-pies havenowmadelimb preservationpossibleinthe ma-jorityofcases.3,26_{Multidisciplinarymanagementofpatients}

with extremity STS frequently involves both wide

resec-tiontoachieve clear marginsand(neo)adjuvant radiation tominimizelocalrecurrence.Inmanycases,thisresultsin extensive soft-tissue defectsthat cannot be managed us-ing simple wound closure or skin grafting techniques. Re-constructionusingpedicledor freeflapsisthereforeoften necessarytoprovidecoverageofvitalstructuresor prosthe-sesandfacilitatelimbpreservation.27_{Particularly,freeflap}

reconstructionis neededin 11–18%of patientsundergoing limb-sparingsurgeryforupperextremitySTS.15,28,29

As free flaps require microvascular anastomosis, they may be perceived to be more complicated and therefore associated with higher complication risk.30 _{On the other}

hand,pedicledflapsofteninvolveextensivesurgical dissec-tionadjacent tothezone of tumorablation, which might

Pleasecitethisarticleas:E.Lucattelli,I.L.LusettiandF.Ciprianietal.,Reconstructionofupperlimbsoft-tissuedefectsaftersarcoma resectionwithfreeflaps:Asystematicreview,JournalofPlastic,Reconstructive&AestheticSurgery,https://doi.org/10.1016/j.bjps. 2020.10.065

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adversely affect functional outcome. Free flaps, indeed, maybepreferablewhenadjacentpedicledflapsarelocated withinthefieldofpreoperativeradiation.31,32 _Slumpetal.

demonstratedthatthetypeofflapusedwasnotan indepen-dent predictorofcomplications inpatientswithupper ex-tremityreconstruction,andfreeandpedicledflapswere as-sociatedwithsimilarpostoperativefunctionaloutcomesin upperlimbreconstruction.33_{Patientswhoexperienced}

com-plicationsexhibitedlowerpostoperativefunctionalscores. However,thefunctionalscoresusedinthestudyonly con-sider thesiteof tumorablation whileflapreconstructions mayalsoresultinsomedegreeofimpairmentatthedonor site,whichwasnotevaluated.

The need for coverage with a well-vascularized tissue responds not only to the nature of the lesion itself, but also tothe impaired healingof irradiated and sometimes scarredtissuefrequentlyencounteredafterSTSresection. Patientswithmultipleinterventionsduetoaffectedmargins andinwhomradiotherapyhasbeenrepeatedlyappliedfor localrecurrencearemuchmorepronetodevelop complica-tions followingreconstruction, withsubsequentworsening offunctionaloutcomesandpoorqualityoflife.Asirradiated andscarredtissuewithimpairedbloodsupplywilloftenfail tohealevenwithmicrosurgicaltransfers,asdemonstrated by Marré et al., the reconstructive surgeonshould be in-volved in the management of STS patients from day 1.34

Somestudiessuggestthatacuteirradiationmaypredispose tomicrovascular thrombosis,yet free flaps, if successful, may potentially protect against complications related to damagecausedbyneoadjuvantradiationtherapyby replac-ing irradiated tissue with well-vascularized nonirradiated tissuefromdistantsites.35–37_{ThefindingsofChaoetal.}

sug-gestthatthetimingofirradiationhasnosignificantbearing onthedevelopmentofperioperativerecipient-site compli-cations,butlong-termrecipientsitecomplicationsoccurred significantlymore oftenwithadjuvantthan with neoadju-vantradiotherapy,with"probablybecauseofsmaller radia-tiondosesandfieldsizeswiththesecondoption.Moreover, incaseofneoadjuvantradiotherapy,irradiatedtissuesare replacedbywell-vascularized,non-irradiatedfreeflap tis-sues,andpostoperativecomplicationsarelessfrequent to occur.32

The main goal of reconstructive surgery has tradition-ally been soft-tissue coverage becausein the majority of the cases,theremaining musclesare abletohypertrophy andpartiallyreplacethefunctionoftheresectedmuscles. Theindicationforafunctionalreconstructionhasbeen lim-itedthereforetotheforearmandtheposteriorleg,38_butin

somecasesthishasbeen extendedtothethigh,the ante-riorlowerleg,theshoulder,andthebuttock,withoverall satisfactory results.39 _{In their study, Grinsell et al. found}

that theuse ofinnervated freeflaps didnotincrease the severityof postoperative complications comparedto non-innervatedflaps,whileprovidingamuchbetterfunctional outcome.Despitethecomplexityofincludingmultiple ves-sel and nerve repairs and the tensioning of muscle and tendonunits makingitamore complextask,theysuggest that the excellent functional outcome for these patients justifiesthepotentially higherflaplossrate.Several stud-iesreported theuse of reinnervated free flapsfor recon-structionofshoulder,bicepsbrachii,andforearmextensor compartment,11,16,33_{withanoverallsatisfactoryfunctional}

outcome.However,asthestudiesuseddifferentfunctional scores(MSTS, MRC,and TESS),itwasdifficult tocompare functionaloutcomesbetweenthem.

Ourstudydemonstratedalackofhomogeneousreporting ofoutcomesfollowing upperlimb reconstructionafterSTS excision.Severalstudiescombinedresults forpatients un-dergoingdifferentproceduresorforindicationsotherthan malignancy,suchasinfectionortrauma.Thisledtoseveral papersbeingexcludedfromthisstudyandalsomadedata extractionmoredifficultinsomepapersthatdidnotmeet inclusioncriteria. Additionally,some studiescombined re-sultsforupperandlowerextremityreconstruction. Strati-fyingdatabasedonspecificdiagnosis,graftsite,andpatient demographicswouldfacilitatetheabilityofinvestigatorsto applyevidence-basedconclusionstopatientcare.

Thisstudywassubjecttoseverallimitations.Thestudies comprising our review were primarily retrospective, non-randomized,anduncontrolled andthus pronetoselection andobserverbias.Additionally,somestudiesreported out-comes for their entire cohort, making it difficult to con-trol for confounding factors. It was not possible to per-formatruemeta-analysistocalculateoutcomesand stan-darddeviationsbecauseestimatesofvariabilitywithineach studywere notavailable. Studies employeddifferent sur-gicaltechniques,postoperativemanagement,andphysical therapy regimens, furtherconfoundingthe outcomes. De-spitetheselimitations,thisreview providesan initial out-lookonthegenerallysuccessfuluseoffreeflapsforupper extremitySTS.

Conclusion

Limb salvage does not adversely affect oncological out-come,andthefunctionalbenefitsoflimbsalvagewith soft-tissuereconstructionin sarcomasurgeryhavebeen estab-lished.Freeflapsprovidewell-vascularizedtissue facilitat-ingwound healing andalsotolerate radiotherapy well. In addition,nofurthermorbidityiscausedtotheextremity.A widearrayof freeflapsis availableforreconstruction fol-lowingupperextremitytumorresection,andthechoiceof flapisbasedondefectsize,typesoftissuerequired, post-operativefunctional goal,andsurgeonpreference.Future studies should attempt to correlate patient demograph-ics,specificoncologic diagnosis,flaptype,and theuseof chemotherapy/radiotherapy with postoperativefunctional outcome,rateofreoperationsandcomplications.

Declaration

of

Competing

Interest

Nonedeclared.

Acknowledgements

None.

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