CASE REPORT – OPEN ACCESS

(1)

CASE REPORT – OPEN ACCESS

InternationalJournalofSurgeryCaseReports81(2021)105824

ContentslistsavailableatScienceDirect

International Journal of Surgery Case Reports

j o ur na l h o m e p a g e :w w w . c a s e r e p o r t s . c o m

Forequarter amputation post transarterial chemoembolization and radiation in synovial sarcoma: A case report

Erwin Danil Yulian

^a,∗

, Jacub Pandelaki

^b

, Evelina Kodrat

^c

, I. Gusti Ngurah Gunawan Wibisana

^a

aSurgicalOncologyDivision,DepartmentofSurgery,Dr.CiptoMangunkusumoGeneralHospital,FacultyofMedicineUniversitasIndonesia,Indonesia

bInterventionalRadiologyDivision,DepartmentofRadiology,Dr.CiptoMangunkusumoGeneralHospital,FacultyofMedicineUniversitasIndonesia, Indonesia

cDepartmentofAnatomicalPathology,Dr.CiptoMangunkusumoGeneralHospital,FacultyofMedicineUniversitasIndonesia,Indonesia

a rt i c l e i nf o

Articlehistory:

Received1February2021

Receivedinrevisedform21March2021 Accepted21March2021

Availableonline23March2021

Keywords:

Forequarteramputation Transarterialchemoembolization Radiation

Synovialsarcoma Casereport

a b s t ra c t

INTRODUCTIONANDIMPORTANCE:Forequarteramputationorinterscapulathoracalisamputationisa majoramputationprocedurethatinvolvestheentireupperextremity,scapula,andawholeorpart oftheclavicula.Forequarteramputationiscommonlyusedtocontrolbleedinginmalignanttumorcases inwhichnotreatmentisavailablefortheextremities.

CASEPRESENTATION:Wereportacaseofforequarteramputationina25-year-oldpatientwithsynovial sarcoma.Transarterialchemoembolization(TACE)andradiationsynovialsarcomawereperformedinthe patienttoreducebleeding.Thistechniquemayalsobeusedfortreatingsynovialsarcomawithmassive bleeding.

CLINICALDISCUSSION:Despiteforequarteramputationindicationsinmalignanttumorcasesandrecurrent cancercases,theeffectivenessofthistechniqueremainsunclear.Thepatientwasreadmittedwitha recurrentmassthreemonthsaftersurgery.

CONCLUSION:Inthisstudy,TACEandradiotherapyareeffectiveincontrollingbleedingpreoperatively andintraoperativelyinpatientswithsynovialsarcoma.

1. Introduction

Synovialsarcoma (SS) isa malignant soft tissue tumorwith highrecurrenceanddistantmetastases.SSaccountsfor5–10%of allformsofsofttissuetumors,whichusuallyaffectsadolescents andyoungadults[1,2].Sarcomaofthistypeoccursmostlyinthe upperpartofthekneeandintheparapharyngealregionofthehead andneck[1–3].Ithasoftenbeenidentiﬁedinperiarticularregions, closetotendonsheaths,bursae,andjointcapsules.Ingeneral,SS iscircumscribed,butitmayalsobeentangledwithmuscles,ten- dons,andneurovascularstructuresarounditinafewinstances.The lungs,lymphnodes,liver,andbonesarethemostcommonsitesof metastasis.SShasa poorprognosis,whichliesbetween36and 76percentand20and63percentfor5-and10-yearsurvivalrates, respectively.Widesurgicalresection,withorwithoutradiotherapy, is thepreferredtreatmentforSS. Limb-sparingsurgery iscom-

Abbreviations: TACE,transarterialchemoembolization;SS,synovialsarcoma;

EMA,epithelialmembraneantigen;SMA,smoothmuscleactin.

∗ Correspondingauthorat:DepartmentofSurgery,Dr.CiptoMangunkusumo NationalCentralGeneralHospitalBuildingA,4thFloor,PangeranDiponegoroStreet No.71,Kenari,Senen,CentralJakarta,10430,Indonesia.

E-mailaddress:[email protected](E.D.Yulian).

monlyperformedinsofttissuesarcoma,butextremityamputation maybeusedasacurativeandpalliativetreatmentformalignant tumors[4–7].Forequarteramputationisasupportivetreatmentin theshouldergirdleofpatientswithsofttissuesarcoma[6].Only afewcasesofmalignanttumorswithnerveandveininﬁltration intheshouldergirdlehavebeenreportedthatrequirethis type ofamputationtocuratively andpalliativelyachieve oncological margins[6,8].

Forequarteramputationwasﬁrstperformedin1808fortreating abulletwoundandﬁrstusedtotreatupperextremitymalignancy in1836[9].Itisaradicalablativesurgicaloperationinvolvingthe fullupperextremityoftheshouldergirdle[10].Theindicationsof thistreatmentarepersistentseverepain,neurovascularinvolve- ment,majorprimarytumordevelopment,failuretomaintainlimb functionwithfulltumormarginresection,inadequatechemother- apy,andradiotherapy,high-gradesarcomapathologicalfracture, severelymphedema,bleeding,andpalliativetherapy[9–11].

Preoperativeembolization forcontrollingblood lossinintra- operativeand postoperative settings hasbeenreported foruse in conjunction with sarcoma resection. However, its use in preoperative amputation has not been described. Transarterial chemoembolization(TACE)isperformedbeforesurgerytocontrol thehemorrhage[10,11].Embolizationintheprimarysoft tissue

https://doi.org/10.1016/j.ijscr.2021.105824

org/licenses/by/4.0/).

(2)

Fig.1.MRIresultsshowingrecurrenttumor.

tumorormetastaticembolizationintheextremitiesisindicatedto reducehemorrhageriskduringandaftersurgery.Theprimarypur- poseofembolizationistoachievethrombusformationandarterial occlusionbyadministeringembolizingagentsusingaselectiveor super-selectivecatheterinsertedintothefeedingarteriesofthe tumor.Thiscasereportpresentsapatientwithrecurrentsynovial sarcomaoftheupperextremitywhowastreatedwithradiother- apytocontrolhemorrhage,followedbypreoperativeembolization beforeforequarteramputation.Theworkhasbeenreportedinline withtheSCARE2020criteria[12].

2. Casepresentation

A24-year-oldmanwasadmittedtotheERwithalarge,painful (VAS8),andrecurrentbleedingmassintherightupperchestquad- rant,increasinginsizefortwomonthsbeforeadmission.Beforethe surgery,themassdimensionwas14cm×9cm×6cm,withthe pathologicalresultofagradeIImyxoﬁbrosarcoma.Thepatientdid notsufferfromcough,dyspnea,orfever.Therewasnofamilyhis- toryofmalignancyinthefamily.MRI(Fig.1)andCTScan(Fig.4) showedthatthepatienthadarecurrenttumor.

The histology slides wereexamined, and the morphological features showedspindle cellsarcoma reminiscentof low-grade fibromyxoidsarcomawithextensivenecrosis.Immunohistochem- icalstainingwasnotentirelyspecificdue toextensivenecrosis, but asa low-gradefibromyxoidsarcoma,themorphologycould stillbesupported[13].Weperformedwidesurgicalexcisionwith removal ofthepectoralis majormuscleand obtaineda primary tumormeasuring22×13×18cmwithanon-tumor-freemargin.A high-gradesarcomaofthespindlecellwasthepostoperativepatho-

logicaloutcome.Immunohistochemicalstainingrevealedepithelial membrane antigen(EMA) focalpositivity, and CD99,BCL2, and CD56positive,smoothmuscleactin(SMA)negative,anddesmin andS100protein-positiveresults.Thisstainingpatternwasmostly associatedwithmonophasicsynovialsarcomaalongwiththemor- phology[13].WethenperformedaPETscanwithnotumorcells.

Thereafter,thepatientrefusedtoreceiveradiationandchemother- apyfor2monthsandchosetobetreatedbyamedicinemanfor twomonthsratherthanreceivingchemotherapy.Meanwhile,the massreappearedintherightupperquadrantofthechestandinthe rightupperextremity,whichhadbeengrowinginsizeaslargeas anadulthead.Thepatientssufferedfromaswollenrighthandand activehemorrhageinthemasses(Fig.1).Multiplebloodtransfu- sionswereneeded,andseveraltreatments,includingcorticosteroid injections,betadinedressing,ﬂamazine,andcauterization,were consideredtostopthebleeding.Hemostasiswasachievedonlyby compressionbandage,andbandageremovalinducedrebleeding.

Weperformedexternalradiationforhemostaticpurposessixtimes, whichresultedinreducedhemorrhage.However,aftertheexter- nalradiationprocedure, bleedingofthemasswasstill ongoing.

Becauseofthelargetumorsizeandextensivevascularandsofttis- sueinvolved,weplannedasalvagesurgeryrescueprocedure.PET didnotrevealanyothermetastaticlesions.

Afterextensiveconsultations,amultidisciplinarymeetingcon- sistingofoncologysurgeons,cardiothoracicandvascularsurgeons, pathologists, and radiation oncologists agreed that amputation wasthebestalternativetotreatpain,bleeding,lymphedema,and compromisedpatientfunction.Ateamofoncologysurgeonsand cardiothoracicand vascular surgeons performedthe procedure.

Basedonadiscussionwiththepatientandhisfamilyaboutthepro-

(3)

CASE REPORT – OPEN ACCESS

E.D.Yulian,J.Pandelaki,E.Kodratetal. InternationalJournalofSurgeryCaseReports81(2021)105824

Fig.2.Digitalsubtractionangiographyofaxillaryartery;pre-embolization(left)andpost-embolization(right).

cedure’sradicalnature,beneﬁt,andpotentialcomplications,they agreedtoundergotheoperation.Hehadrestrictedarmmobility duetomassimpact,chronicintractablepain,andlymphedema.

Preoperativeembolizationwasadvisedbyinterventionalradi- ologistsduringpreoperativeconsultation.Duetothelargetumor sizeattheproximalareaandapreviouslyirradiatedbedmassposi- tion,wepreservedthevascularfunction(subclavianandaxillary vessels)andreduced woundbleeding duringsurgery.TACEwas performedinthetumorartery,andthepatientunderwentright subclavianandaxillaryarteryangiographywithembolization of therightsubclavianartery(Fig.2).TheTACEprocedureaimedto controlbleeding,strengthenlocalsurgicalcontrol,anddecreasethe morbidityofwideexcisions.

Vascularaccessfromtherightfemoralarterywasachievedwith introducersheath6Fr,andadiagnosticcatheter5Frwasinserted untilthetipreachedtherightsubclavianartery.Thiswascontinued withthemappingarteriography.Hypervascularizationofthefeed- ingarteryoriginatingfromthesuperolateralrightaxillaryartery neovascularization branch and theproximal inferomedial right brachialisarteryneovascularizationbranchwasdemonstratedby thisprocedure.Then,microcatheter2,4Frwasinserteduntilthetip wasselectivelylocatedintheneovascularizationofthesebranches, and a chemoembolizationagent wasinserted. GS particlesand microcoilswereusedinthisprocedure.Thechemoembolization agentusedinthisprocedurewasdoxorubicin(50mg)andLipiodol (10mL),includingtheembolizationagent,PVA(500–700microns), andgelfoamcombination.Theoperationwasperformedfromthe neovascularizationbranchofthesuperolateralrightaxillaarteryin thefeedingarteryandtheproximalinferomedialrightbrachialis arteryintheneovascularizationbranch.

Six days after the TACEprocedure, we performed extensive surgeryontheentirerightupperextremity,scapula,andwhole claviculawith235mLbleedingduringthesurgery,andthesizeof themasswas30×24×10.5cmfromtherightupperquadrantof thechestandshouldergirdle(Fig.3).

3. Surgicalprocedure

Under general anesthesia, surgery was performed with the patient in the full lateral position. Several surgical techniques havebeendescribedforperformingaforequarteramputation.We usedasemi-lateralapproach,andthemajorityofthesurgerywas

performed anteriorly.The patient was in a left lateral decubi- tuspositiontorevealthethorax,withtherightupperextremity positionedtorotatefreely.Wemadeanellipticalincisiononthe superiorapexabovetheclavicleatoneendandproceededinferio- laterally.Skinﬂapswereelevatedtotheanteriormidline,superior totheclavicle,inferiortothecostalarch,andmedialtothemidline.

Thelatissimusdorsiandthesuperomedialborderofthemasswere thelateralbordersoftheskinﬂaps.Attheoriginofthesternum,we dissectedthepectoralismajormusclefromthemedialastheinser- tion,whichwasalsoinvadedbythemass.Ontheanteriorside,the pectoralismusclewasinﬁltratedbythetumormass,separatingthe pectoralismajorandminor.

Thebrachialplexusandaxillaryvesselswereexposedanteriorly.

Thesurgicaltechniqueinvolved anincisiononthepreoperative markingsatadistanceof2cmfromtheedgeoftheinduration.

Wethenperformedanteriorvascularexplorationbyseparatingthe majorpectoralismusclefromtheclavicle.Theseweredeepened intothemusculofasciallayers.Theplatysmaandsupraclavicular nerveswereexcised.Toallowcontrolof thesubclavianvessels, clavicularosteotomywasperformedbyexposingtheclavicleand cuttinglaterallytothesternocleidomastoidwithaGiglisaw.The tendonsof thepectoralismajor,coracobrachialis,and theshort headofthebicepswerecut.Dissectionwascontinuedtothetho- racicwallinordertoexcisethepectoralmuscles,softtissues,and theribs’periosteum.First,ligationofthesubclavianarterywasper- formed,andthearterywascut.Thereafter,thesubclavianveinwas ligatedandcut.Thiswasperformedtoavoidanybleedingfromthe shoulder’scollateralbloodsupply.Thebrachialplexuswasproxi- mallyligatedanddivided.

Aposteriorincisionwasmade,allperiscapularmuscleswere released,andfasciocutaneousskinﬂapsweredeveloped.Themajor andminorrhomboid,trapezius,omohyodeusventerinferior,and levatorscapulaemuscleswerethensplitbyelectrocauteryasthey wereinsertedintothescapula.Moving caudally,we transected thelatissimusdorsiandresecteditfromthechestwall.Theexpo- surewascontinuedtotherhomboidmuscleinsertionsposteriorly andlaterally.Anaxillaryincisionwasmadetoconnecttheante- riorandposteriorincisions.Thisfreedtheshouldergirdleandthe entireextremityfromthetrunk.Finally,afterthesubclavianartery andbrachialplexusligationandtransection,theentireforequar- terwasremoved, alongwiththetumor material,includingthe scapula,inevitablyproducingalargetissuedefect.Posteriorskin

(4)

Fig.3.Preoperative,intraoperative,andpostoperativeofforequarteramputation.

Fig.4.ThoraxCTscanshowingthetumormass.

ﬂapswereusedtoclosethedefect.Thedog-earskinexcesswas excised.Finally,drainswereusedtopreventthedevelopmentof hematomaandwoundcomplications.

No signiﬁcantcomplicationsofforequarter amputationwere observed,suchasthedevelopmentofapneumothoraxwithconsec- utiverespiratoryinsufﬁciency.Ourpatientcomplainedoftheminor complicationofdelayedwoundhealing,whichrequiredlocalsur-

gicaldebridement.Healsosufferedfrompostoperativephantom painorlocalpainwithmoderateVASscoresof5–6thatcouldbe overcomewithoralanalgesics.Whenthewoundhealedaftertwo weeks,hewasreleasedfromthehospital.

Thepathologyﬁndingswereconsistentwiththepreviousdiag- nosisofmonophasicsynovialsarcoma[15].Threeweeksafterthe forequarteramputation,thepatientunderwent30roundsofradia-

(5)

CASE REPORT – OPEN ACCESS

tiontherapy.Threemonthsafterthesurgery,PETshowednotumor mass.TwoweeksafterthelastPETscan,twomassesreappearedon therighthemithoraxneartheamputationwound.Surgicalexcision of1.2×0.8×0.8cmmasswithpathologicaloutcomeofmonopha- sicgradeIIIIsynovialsarcomawasperformed.Oneweekafterthe last surgicalexcision,thepatienthadtoundergochemotherapy withregimenofdoxorubicin,mesna,andholoxan.

Thepatientseldomexperiencedphantomlimbpain.Thisisa commonsequelaofforequarteramputations.Thepatientreceived 4outof6cyclesofchemotherapy,whichwassafe.DuetotheCovid- 19pandemic,thepatientwasafraidtogotothehospital.Eleven monthsaftertheprocedure,thepatientdiedofrespiratoryfailure inhishome.

4. Discussion

Forequarteramputationis anablativeand radicalsurgeryto remove the entireupper extremity, includingtheshoulder girdle[10].Amputationhasbeenconsideredasthestandardofcare for patientswithsoft tissueor bone sarcomaof thelimbs.The generalaimof this procedureistoradically remove softtissue and bones,includingthescapula.Eventhoughtheresultisdis- ﬁguring, as observed with ourpatient, forequarter amputation is able to effectively palliate the upper extremity tumor [10].

The indications of forequarter amputation are for limb-sparing resection, unresectable sarcoma, recurrent soft tissue sarcomas following an ineffective limb-sparing operation, several shoulder girdle radiation-induced sarcomas, pathological high-grade sarcoma fractures (particularly for poor response to induction chemotherapy),andpalliativeamputation(duetofungatingtumor, infection,orbleeding)[14,15].Amputationintheforequartershas abeneﬁcialimpactonthepatient’spsychologicalandfunctional integrity.Elsner etal.[16]revealedthatforequarteramputation remained a reasonably safe and effective technique for upper extremitymalignancycurativeorpalliativecare,especiallyinthe absenceofotherlessradicalalternatives[10,16].Daigeleretal.[17]

foundthatpatientstreatedwithproximalmajoramputationhad anincreasedqualityoflifeandpost-amputationpainrelief.The studyalsoreportedacorrelationbetweenfullresectionandpro- longedsurvival,consideredtolocalizethediseasewithcurative purpose[17].Inpatientswhohadrecurrenttumorsafteramputa- tion,remoteandoccultmetastaseswereusuallypresent.However, therewasnosigniﬁcantdifferenceinpatientsurvivaltimebetween thedisseminateddiseaseandthelocalizeddiseaseatthetimeof theamputation[17]. Wittigetal.[18] foundthatpostoperative survival rangedfrom3 to12 monthsin patientswithpalliative forearmamputation.Wereportachallengingcaseofalargeand localizedshouldersynovialsarcoma.Withtherecentavailabilityof chemotherapyandradiotherapy,theprimaryaimofourtreatment waslimb-sparingresectionasoneoftheindicationsofforequar- ter amputation [14]. Thetumormust becompletely excisedto retainlimbfunctionwhilethebrachialplexusismaintainedfor thepatient[14].Therefore,weperformedforequarteramputation surgeryonthispatient.Webelievethatthisprocedurewasbest toleratedbyourpatient,whosufferedintractablepainandadys- functionallimb.

Forequarteramputationisacomplicatedprocedurewithphys- icalandmentaleffectsduetototalfunctionallossofthelimbsand signiﬁcantopticaldisﬁgurement.Locallyadvancedtumorsspread- ingtotheaxillarepresentindicationsforforequarteramputation andbecomeirresectablewithalimb-sparingprocedure[19].Byeti- ology,afterafailedlimb-sparingoperation,thesetumorsaremost commonlyhigh-gradeshouldersofttissuesarcomas,axillarysoft tissuesarcomasaffectingrecurrentbone,brachialplexus,andsoft- tissuesarcomas[20].Severeuntreatedpain,totalfunctionalfailure oftheaffectedleg,andnotinfrequentlypronouncedlymphedema,

arethemajorcandidatesforsequentialamputation.Palliation,even thoughonlybrieﬂyaccomplished,becomesanevenmorecritical featureinthiscase[20].

In thepresent case, thepatient experienced active bleeding fromthetumor mass. Bleedingcomplications typically arise in patientswith advanced cancer, with10% experiencing at least oneepisode of bleeding [21,22]. Bleedingfrom cancer, suchas localtumorinvasion, irregularvasculatureof thetumor,tumor regression,orsystemiccoagulopathy,isinducedbyparaneoplastic syndrome[22,23].Bleedingincancerpatientsmaybeworsenedby theuseofimmunotherapy,nonsteroidalanti-inﬂammatorydrugs (NSAIDs),andanticoagulants.Toavoidbleedingatthetumorsite, anti-inﬂammatorymedicationforpaininadvancedcancerneedsto bereconsidered[22].Localalternativetherapies,includingdress- ing,pressureapplication,packing,radiationtherapy,percutaneous embolization,andsurgeryrecommended[22].

In neurosurgery, urology, general surgery, head and neck surgery,orthopedics,andoralsurgery,preoperativeembolization hasbeenidentiﬁedasessentialtoreducingintraoperativebleed- ing.Despitepotentialcomplications,includingarterialinfarction, ischemicevent,nerveinjury,andlocalhemorrhage,mosthavebeen successfullyperformed[9].Inpatientswithrenalcellcarcinomas, atumorembolizationtechniquehasbeendeveloped[19].Mini- malinvasionoftranscatheterarterialembolizationwashelpfulin achievinghemostasiswhensurgicalligationwasdifﬁcult[24].

Reducingtheriskofbleedingpostoperativelyforhypervascu- larized tumors, simplifying tumormanipulation, increasing the chemotherapyresponseandradiotherapy,and palliativecareof painarethemainindicationsforembolization.Whensurgeryis inappropriateorassociatedwithahigherrisk,embolizationcan alsobeatherapeuticoptionforsurgery[25].Moreover,thedistinc- tionsbetweenthetumorandthesurroundingtissuearebecoming clearer,makingiteasierforoperationalmanipulationandexcision.

Tumor-feedingarteriesmustbesuper-selectivelycatheterized,and themosteffectiveembolizingagentsshouldbeusedtopreservethe hemodynamicsofthenormalsurroundingtissues[25].

Whenperformedbyanexperiencedteamwithproperemboliz- ing agents, preoperative selective/superselective transarterial embolizationofhypervascularmalignantsofttissuetumorsofthe extremitiesisanefficientandsafeprocedure.Toavoidcomplica- tions,achievesuccessfuldevascularization,andcompleteresection ofatumor,super-selectionandflowcontrolareessential[25].A relatedstudybyIwamotoetal.[24]revealedanidealindication forarterialembolizationpriortomusculoskeletaltumorexcision topreventsignificantintraoperativebleeding,casesoflowriskof seriouscomplicationfollowingembolization,andcasesoftrunk, pelvic,and proximallimb hypervasculartumors,except forthe peripheraland spinal areas. In a study conducted by Iwamoto etal.,theuseofselectivetranscatheterarterialembolizationfor musculoskeletalbonetumorssignificantlyreducedintraoperative bleedingafter arterialembolization.A retrospectiveanalysisby Jiangetal.[26,27]foundthatcancerpain(asmeasuredbyVAS) wasdecreasedaftertheTACEprocedureinpatientswithadvanced soft tissue sarcoma,but cancerpain wasmore commonin the chemoembolizationgroupthaninthechemoinfusiongroup.Jiang etal.[26]alsoreportedthatpatientswithsofttissuesarcomahada 32.5%overall3-yearsurvival,butthisdidnotmeanthattheoverall survivalofthechemoembolizationgroupwashigherthanthatof thechemotherapyinfusiongroup.However,inpatientswhounder- wentactivechemoembolization,themeanrelapsetimewaslonger thaninpatientswhoonlyunderwentchemo-infusion.Jiangetal.

alsofoundthattheefﬁcacywasaffectedbythePVAdiameter.In patientswitha PVAcommunitydiameterof100␮m,themean relapseperiodwaslongerthan300␮m[26].

Synovialsarcoma(SS)isanactivetumorofsofttissuewitha propensityforlocalrecurrenceandahighriskofdistantmetasta-

(6)

sis.Unlikemanyothersarcomas,inonly10–20percentofcases,it mayinvadetheadjacentbone.With5-and10-yearsurvivalrates of36–76percentand20–63percent,respectively,theprognosisfor SSisusuallypoor.Under20yearsofage,lowertumorstage,tumor size<5cm,sufﬁcientexcision,andamoredistalpositionofthe extremitiesarefactorsassociatedwithbetterprognosis.Poorprog- nosispredictorsincludeless-differentiatedtumorregions,necrosis, and highmitoticactivity[28].Bleedingisacommonconcernin patientswithadvancedcancerandcanoccurin6–10%ofadvanced cancer cases; a few of these cases may be thedirect cause of deathforatleastoneepisode.Patientsandtheirfamiliesaredis- tressed; bleedingis alsolikely tohave anegative effectonthe qualityoflifeofthepatient(QoL)[29].Inpatientswithadvanced malignancy,multiplemodalitiesareconventionallyusedtocontrol hemorrhage,asreviewedbyPereiraandPhan,includinghemostatic agents,endoscopy,vesselligation,cauterization,tissueresection, transcutaneous arterialembolization, balloons placements, and radiotherapy.Bloodproducts,vasopressin,antiﬁbrinolyticagents, andsomatostatinanalogsarealsosystemictherapies[23].

Fordecades,radiotherapy(RT)hasbeenusedasanon-invasive treatmentfor bleedingassociated withcancer. Afteronlyafew fractionsofRT,thehemostaticefficacyofradiotherapyisnormally visibleandiscommonlyclarifiedbyincreasedplateletadhesion to the vascular endothelium. By inducing vessel fibrosis com- binedwithtumorremission,thelong-termeffectcouldbeclarified [29].Althoughtheprecisemechanismtomanagemalignantbleed- ingremains unclear,radiotherapyisusedtocontrolbleeding in sometypesofcancer.RTdestroysthemalignantbloodvessels.By causingmalignantendothelialcelldamage,radiationcaninduce thepathophysiologicalprocessesofmalignantvessels.Thesignal transduction pathway,whichleadstocellcyclearrest, canalso beaffected.Tumorbleedingcanalsobecausedbyvasculardam- ageduetolocaltumorinvasionorsystemiccoagulopathydueto paraneoplastic syndrome. RTmay not,however,preventbleed- ingofnormalvesselsthatareinvadedbycancers,suchascarotid blowoutsinprogressivemalignancyoftheheadandneck[23].

Thepathophysiologyofthecancerradiationeffectcausessignif- icantdamagetoDNAbyinducingmalignantdamagetoendothelial cells,causingsignaltransductionpathwayactivationandleading tocellapoptosis[23].Radiotherapywasshowntohaveaneffect within24−48hoursoftheﬁrstdose.Therewereseveralpalliative careregimensavailableforpatientswithcancerbleeding,including single8–10Gray(Gy)procedures,intermediate4–8Gyimplemen- tation3–5times,orlonger30–45Gyimplementation10–15times [22].Theimprovedconvenienceandreducedcostapproachwas reportedbyVan denHout etal.in91 percentofadvancedand metastaticcancerpatientswithshorterradiationtreatments[30].

Aretrospectiveanalysisof62patientswithadvancedcancerfound malignantbleedingcouldbereducedbyhemostaticradiotherapy [29]. Sapienzaindicated that radiotherapy couldtreatbleeding, resultinginan89percentoverallprimarybleedingcontrolrate.By position,88percent(14/16forheadandneck),93percent(13/14 forthoracic),100percent(9/9extremity),and100percent(6/6), and gynecologicsites were theprimary bleeding control rates.

While theeffectofhemostaticradiotherapy hasnot beensufﬁ- cientlyevidentinsynovialsarcoma,ithasthepotentialtocontrol bleedinginothermalignancies[31].

Research by Sapienzaet al. hasshownthat palliative radio- therapyisefﬁcientinprimarybleedingcontrol[31].Nevertheless, longerradiotherapyregimens,whichweremorethan5fractions, resultedinanincreasedlengthofhospitalstayandsideeffects.

Hence,inthispalliativesetting,shorterhemostaticregimensare preferredtominimizethecareburdenforpatients.Administering a higherdoseshouldconsiderthebalancebetweenthepossible beneﬁts and potential toxicity. In the event of life-threatening bleeding, hypofractionationwithalargesingledosecaninduce

rapidhemostasis,buteveninthispalliativeend-of-lifeenviron- ment,therisksofextremetoxicitiesmustbeconsidered[29].

5. Conclusions

Forpatientswithsofttissuemalignanciessuchassynovialsar- coma,particularlytumorrecurrencewithbleedingmanifestation, forequarter amputationis a safeand reliable treatmentoption.

TACEandradiotherapycanbetreatmentoptionsforpatientswith malignantbleedingandareeffectiveincontrollingpreoperative andintraoperativebleedingduringforequarteramputation.

DeclarationofCompetingInterest

Theauthorsreportnodeclarationsofinterest.

Sourcesoffunding Nonedeclared.

Ethicalapproval Notapplicable.

Consent

Writteninformedconsentwasobtainedfromthepatientfor publicationofthiscasereportandaccompanyingimages.Acopy ofthewrittenconsentisavailableforreviewbytheEditor-in-Chief ofthisjournalonrequest.

Authorscontribution

ErwinDanilYulian:Conceptanddesignofcase report,data collection,drafting,revision,approvalofﬁnalmanuscript.

JacubPandelaki: Data collection,revision, approval of ﬁnal manuscript.

Evelina Kodrat: Data collection, revision, approval of ﬁnal manuscript.

IGustiNgurahGunawanWibisana:Datacollection,revision, approvalofﬁnalmanuscript.

Registrationofresearchstudies Notapplicable.

Guarantor

ErwinDanilYulian.

Provenanceandpeerreview

Notcommissioned,externallypeer-reviewed.

Presentationatameeting Nonedeclared.

Acknowledgements

Theauthorsaregratefultothefollowingindividualsfortheir generoushelp:Thepatientandhisfamily.KevinVarianMarce- viantoand HaryodiSarmana Putrafor assisting thepublication processofthiscasereport.

(7)

CASE REPORT – OPEN ACCESS

References

[1]J.R.Goldblum,A.L.Folpe,S.W.Weiss,SoftTissueTumors,2019,pp.

1200–1218.

[2]A.H.Krieg,F.Hefti,B.M.Speth,G.Jundt,L.Guillou,U.G.Exner,etal.,Synovial sarcomasusuallymetastasizeafter&5years:amulticenterretrospective analysiswithaminimumfollow-upof10yearsforsurvivors,Ann.Oncol.22 (2)(2011)458–467.

[3]S.K.Machen,K.A.Easley,J.R.Goldblum,Synovialsarcomaoftheextremities:a clinicopathologicstudyof34cases,includingsemi-quantitativeanalysisof spindled,epithelial,andpoorlydifferentiatedareas,Am.J.Surg.Pathol.23 (March(3))(1999)268–275.

[4]M.Lehnhardt,C.Hirche,A.Daigeler,O.Goertz,A.Ring,T.Hirsch,etal.,Soft tissuesarcomaoftheupperextremities:analysisoffactorsrelevantfor prognosisin160patients,Chirurg83(2)(2012)143–152.

[5]R.S.Robert,G.Ottaviani,W.Huh,S.Palla,N.Jaffe,Psychosocialandfunctional outcomesinlong-termsurvivorsofosteosarcoma:acomparisonof limb-salvagesurgeryandamputation,Pediatr.BloodCancer54(7)(2010) 990–999.

[6]M.A.Clark,J.M.Thomas,Majoramputationforsoft-tissuesarcoma,Br.J.Surg.

90(1)(2003)102–107.

[7]G.Ottaviani,R.S.Robert,W.W.Huh,N.Jaffe,Functional,psychosocialand professionaloutcomesinlong-termsurvivorsoflower-extremity osteosarcomas:amputationversuslimbsalvage,Pediatr.Adolesc.

Osteosarcoma152(2009)421–436.

[8]M.E.Puhaindran,J.Chou,J.A.Forsberg,E.A.Athanasian,Majorupper-limb amputationsformalignanttumors,J.HandSurg.37(6)(2012)1235–1241.

[9]M.Taylor,D.Pichora,Forequarteramputationfollowingpre-operative embolizationtotreattwoupperextremitymalignanciesinapreviously irradiatedtissuebed:acasereport,Orthop.MuscularSyst.4(2)(2015)2–5.

[10]V.Dimas,J.Kargel,J.Bauer,P.Chang,Forequarteramputationformalignant tumoursoftheupperextremity:Casereport,techniquesandindications,Can.

J.Plast.Surg.15(2)(2007)83–85.

[11]R.Qadir,S.Sidhu,L.Romine,M.S.Meyer,S.F.M.Duncan,Interscapulothoracic (forequarter)amputationformalignanttumorsinvolvingtheupper extremity:surgicaltechniqueandcaseseries,J.ShoulderElb.Surg.23(6) (2014)127–133.

[12]R.A.Agha,T.Franchi,C.Sohrabi,G.Mathew,fortheSCAREGroup,TheSCARE 2020guideline:updatingconsensussurgicalCAseREport(SCARE)guidelines, Int.J.Surg.84(2020)226–230.

[13]A.Suurmeijer,M.Ladanyi,T.Ladanyl,SynovialsarcomainWHOclassiﬁcation oftumours,in:SoftTissueandBoneTumours,5thed.,2020.

[14]S.S.Al-Busaidi,S.N.Al-Hashmi,R.K.Jayachandran,Managementof longstandingsynovialsarcomaoftheshoulderregion–acasereport,JPRAS Open12(2017)39–43.

[15]M.Malawer,P.Sugarbaker,Forequarteramputation,in:Musculoskeletal CancerSurgery,2001,pp.289–298.

[16]U.Elsner,M.Henrichs,G.Gosheger,R.Dieckmann,M.Nottrott,J.Hardes, etal.,Forequarteramputation:asaferescueprocedureinacurativeand

palliativesettinginhigh-grademalignomaoftheshouldergirdle,WorldJ.

Surg.Oncol.14(1)(2016)4–11.

[17]A.Daigeler,M.Lehnhardt,A.Khadra,J.Hauser,L.Steinstraesser,S.Langer, etal.,Proximalmajorlimbamputations-aretrospectiveanalysisof45 oncologicalcases,WorldJ.Surg.Oncol.7(2009)1–10.

[18]J.C.Wittig,J.Bickels,Y.Kollender,K.L.Kellar-Graney,I.Meller,M.M.Malawer, Palliativeforequarteramputationformetastaticcarcinomatotheshoulder girdleregion:indications,pre-operativeevaluation,surgicaltechnique,and results,J.Surg.Oncol.77(2)(2001)105–113.

[19]L.E.Almgard,I.Fernstrom,M.Haverling,A.Ljungqvist,Treatmentofrenal adenocarcinomabyembolicocclusionoftherenalcirculation,Br.J.Urol.45 (October(5))(1973)474–479.

[20]P.Nierlich,P.Funovics,M.Dominkus,O.Aszmann,M.Frey,W.Klepetko, Forequarteramputationcombinedwithchestwallresection:asingle-center experience,Ann.Thorac.Surg.91(June(6))(2011)1702–1708.

[21]C.Cartoni,P.Niscola,M.Breccia,G.Brunetti,G.M.D’Elia,M.Giovannini,etal., Hemorrhagiccomplicationsinpatientswithadvancedhematological malignanciesfollowedathome:anItalianexperience,Leuk.Lymphoma50 (3)(2009)387–391.

[22]C.Johnstone,S.E.Rich,Bleedingincancerpatientsanditstreatment:areview, Ann.Palliat.Med.7(2)(2018)265–273.

[23]H.S.I.Jang,A.Spillane,F.Boyle,G.Fogarty,Radiotherapycancause haemostasisinbleedingskinmalignancies,CaseRep.Med.2012(2012)1–4.

[24]S.Iwamoto,S.Takao,H.Nose,Y.Otomi,M.Takahashi,T.Nishisho,etal., Usefulnessoftranscatheterarterialembolizationpriortoexcisionof hypervascularmusculoskeletaltumors,J.Med.Invest.59(3–4)(2012) 284–288.

[25]S.Exhibit,V.Kartsouni,M.Milatou,M.G.Gkeli,Pre-OperativeEmbolizationof MalignantSoftTissueTumorsoftheExtremities,2015,pp.1–19.

[26]C.Jiang,J.Wang,Y.Wang,J.Zhao,Y.Zhu,X.Ma,etal.,Treatmentoutcome followingtransarterialchemoembolizationinadvancedboneandsofttissue sarcomas,Cardiovasc.Intervent.Radiol.39(10)(2016)1420–1428.

[27]W.B.vandenHout,Y.M.vanderLinden,E.Steenland,R.G.J.Wiggenraad,J.

Kievit,H.deHaes,etal.,Single-versusmultiple-fractionradiotherapyin patientswithpainfulbonemetastases:cost-utilityanalysisbasedona randomizedtrial,JNCIJ.Natl.CancerInst.95(February(3))(2003)222–229.

[28]U.Yalc¸ınkaya,N.U˘gras¸,G.Özgün,G.Ocako˘glu,A.Deligönül,S.K.C¸etintas¸, etal.,Enhancerofzestehomologue2(EZH2)expressioninsynovialsarcomas asapromisingindicatorofprognosis,Bosn.J.BasicMed.Sci.(July)(2017).

[29]N.Cihoric,S.Crowe,S.Eychmüller,D.M.Aebersold,P.Ghadjar,Clinically signiﬁcantbleedinginincurablecancerpatients:effectivenessofhemostatic radiotherapy,Radiat.Oncol.7(1)(2012)1–9.

[30]J.A.Lee,D.H.Lim,W.Park,Y.C.Ahn,S.J.Huh,Radiationtherapyforgastric cancerbleeding,Tumori95(6)(2009)726–730.

[31]L.G.Sapienza,M.S.Ning,A.Jhingran,L.L.Lin,C.R.Leão,B.B.daSilva,etal., Short-coursepalliativeradiationtherapyleadstoexcellentbleedingcontrol:

asinglecentreretrospectivestudy,Clin.Transl.Radiat.Oncol.14(January) (2019)40–46.

OpenAccess

ThisarticleispublishedOpenAccessatsciencedirect.com.ItisdistributedundertheIJSCRSupplementaltermsandconditions,which permitsunrestrictednoncommercialuse,distribution,andreproductioninanymedium,providedtheoriginalauthorsandsourceare credited.