imatinib and TAMIS A rectal gastrointestinal stromal tumor—a plea forneoadjuvant Coloproctology Journal of

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w w w . j c o l . o r g . b r

Journal of

Coloproctology

Case Report

A rectal gastrointestinal stromal tumor—a plea for neoadjuvant imatinib and TAMIS

Jagan Balu

^∗

, Sankar Subramanian, Suresh P, Shankar Narayanan AP, Amamndeep Sing Sandhu

DepartmentofSurgicalGastroenterology,SriRamachandraInstituteofHigherEducationandResearch,(SriRamachandraUniversity), Chennai,India

a r t i c l e i n f o

Articlehistory:

Received14May2019 Accepted29July2019

Availableonline13September2019

Keywords:

Rectalgastrointestinalstromal tumor

Neoadjuvantimatinib TAMIS

a bs t r a c t

Herewedescribeaninfrequentcaseofgastrointestinalstromaltumoroftherectumina57 year-oldmanwithspindlecellneoplasmprobablygastrointestinalstromaltumorandCT scanshowedtumorfromtheanteriorrectalwallandofferedabdominoperinealresectionfor thesame.Thepatientwasstartedonimatinibandhadasigniﬁcantreductioninsymptoms.

ThepatientwasreassessedwiththeCTscan,whichshowedareductionintumorsizeand Transanalminimallyinvasivesurgerywasplannedforthepatient.Useofimatinibpriorto surgicalresectiontoattainthereducedsizeofthetumorwithinthelimitofresectionisan attractiveapproach.Sincetumordevelopmentcanhappenrapidlyagainaftersubstantial tumorshrinkage,thebesttimetooperatedependingonresectabilityandthemaximum therapeuticoutcomeremainsdivisive.

licenses/by-nc-nd/4.0/).

Tumorestromalgastrointestinalnoreto—umcasodeusodeimatinibe neoadjuvanteeTAMIS

Palavras-chave:

Tumorestromalgastrointestinalno reto

Imatinibeneoadjuvante TAMIS

r e su m o

No presente estudo, os autores descrevem um casoraro de tumor estromalgastroin- testinalnoretoemumhomemde57anosqueseapresentoucomneoplasiadecélulas fusiformes,comprováveltumorestromalgastrointestinal.Atomografiacomputadorizada demonstroutumornaparedeanteriordoretoefoisugeridasuaressecçãoabdominoper- ineal.Opacienteinicioutratamentocomimatinibeeapresentouumareduçãosignificativa nossintomas.Opacientefoireavaliadoportomografiacomputadorizada,queevidenciou redução dotamanhodotumor; portanto,foiindicada cirurgiatransanal minimamente invasiva. Otumor era ressecável e foi necessário um extenso acompanhamento para romperoórgão,deformaaalcançararessecçãomáxima;casocontrário,otumorestromal

∗ Correspondingauthor.

E-mail:jaganbalu1988@gmail.com(J.Balu).

https://doi.org/10.1016/j.jcol.2019.07.003

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Introduction

Agastrointestinalstromaltumor(GIST)isaninfrequenttumor ofthegastrointestinaltractwhichisrareincaseofrectum origin.ThecommonestsiteofGISTisstomach,smallbowel,a colonfollowedbyesophagus.^1,2RectalGISTconstitutes0.1%

ofGItumors.TheoccurrenceofmesenchymaltumorintheGI tractislesscommonwithanincidenceof6.8millionannually accordingtoacurrentepidemiologicalstudyfromtheUSA.^3,4 GISTarisingfrom interstitialcellsofCajalexpressesCD117 (c-kitproto-oncogene),CD34andDOG1,whicharedetected immunohistochemicallyfordiagnosticconﬁrmation.⁵

ThemainstayoftreatmentinrectalGISTissurgerywith clear resection of margins as gold standard treatment.⁶ Neoadjuvant/adjuvantand/orImatinibtherapyareprescribed according to different situations.⁷ Imatinib plays a role in adjuvantsettingaswellasametastaticdisease;however,its functioninthe neoadjuvantsetting isnotestablishedwell.

HoweverinrectalGISTespeciallywhenitisbulkyneoadju- vanttherapywithimatinibwillbeusefulindownsizingand downstagingthediseaseforsphincterpreservation.Imatinib, atyrosinekinaseinhibitorinitiallyusedinchronicmyeloid leukemiatreatmentdeliveredwithgoodresultshasrevolu- tionizedthemanagementofGISTtreatmentalso.^8–12 Inthis report,wedescribeaninfrequentcaseofGISToftherectumin a57-year-oldmanwhounderwenttransanalminimallyinva- sivesurgeryaftertumorsizewasreducedwithneoadjuvant imatinib400mgODfor3months.

Case report

A57-year-oldmalepresentedwithcomplaintsofbleedingper rectum, constipation,and massdescendingper rectum for 6monthswithnootherconstitutionalsymptomsorcomor- bidillness.Onexamination,thepatientwasfoundtobepale andnomasswaspalpableonabdominalexamination.Rec- talexaminationrevealed apolypoidalmassintheanterior wallwhichwas3–4cmfromtheanalverge,whichwasmobile, ﬁrminconsistency,bledontouchanupperlimitcouldnotbe reached.

Atﬁrst,thepatientwasevaluatedinOPDclinic,oninvesti- gatinghishemoglobinwasfoundtobe7.9gms/dL,coagulation proﬁle, renal and liver function tests were within normal limits.Anearliercheckupinanother hospitalforthesame withColonoscopywithbiopsywhichshowedspindlecellneo- plasmprobablyGIST(Immunohistochemistrynotdone)and CT scan showed tumor from anterior rectal wall measur-

Fig.1–PreoperativeCTscanofrectalGIST.

ing 8.3×7×7.7cm (Figs. 1and 2).The patientwas offered abdominoperinealresectionforthesame.

Patient cameforthesecond opinion andwas desperate for sphincter preservation. Repeat colonoscopyand biopsy wasdoneinourinstitutionwhichshowedGISToflowmalig- nant potential, IHCbeing positiveforCD117(Fig.3),DOG1, Vimentin.Initially,itwasplannedfordownsizingtumor;the patientwasstartedonimatinib400mg0Dfor3months.The patientwasonregularfollow-upeverymonth,hehadasig- niﬁcantreductioninsymptomsafterstartingthetherapy,and hebecameasymptomaticafter3monthsoftherapy.

The patient was reassessed with the CT scan, which showedareductionintumorsizeto3.8×2.1×3.7cm(Fig.4).

Fig. 5a and 5b shows the coronal and sagittal section of CTshowingtumorafterneoadjuvanttherapy.Sincethesize decreased,weplannedforTAMIS(TransanalMinimallyInva- sive Surgery) for the patient. Thepatient was placedin a pronepositionduetothe anteriorplacementofthetumor;

Single-incisionlaparoscopicportwasusedforthesurgery.The harmonicscalpelwasusedforthedissection;afullthickness excisionoftheanteriorwallinvolvingGISTwithadequateneg- ativemarginwasperformed.Therawareaoftherectumwas closedwithV-Lockstitch.Thepostopperiodwasuneventful.

Enteralfeedingwasstartedontheﬁrstpost-opdayandthe patientwasdischargedonthefourthpost-opday.Finalbiopsy reportshowedypT2pNxcM0withGrade1GISTspindletype, withmarginsbeing freeoftumorandthe mitoticratewas 4/50HPF.ThepatientwasstartedonpostopImatinibtherapy;

heisonregularfollow-upevery3months.

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Fig.2–PreoperativeCTscanshowingrectalGISToccupyingtheentirerectum(beforeneoadjuvantimatinib).

Fig.3–IHCshowingCD117positivityinrectalGIST.

Discussion

GISTisaninfrequentmesenchymaltumorandincidenceof rectalGISTisarareoccurrence.GISTisconsideredtobeorig- inatingfrominterstitialcellsofCajal-likewhichhavebeen reportedfromseveralextraintestinalorgans.Thesymptoms ofGISTintherectumshowssimilarcharacteristictorectal tumorsandadiagnosticinvestigationisanalogoustoother rectalmass.ThefrequencyofrectalGISTisscantycompared toGISTofotherGIorganslikestomachorintestineandhence theclinical-pathologicaldetailsofrectalGISTarenotveriﬁed orestablishedcompletely.^2,5Withtheavailableliterature,itis nowconsideredthatrectalGISTpatientsusuallyhavebleed-

Fig.4–PreoperativeCTscanafterimatinibtherapy showingareductioninthesizeofrectalGISTcomparedto previousCTscan.

ingperrectum,constipation,tenesmustogetherwithpelvic pain.Apartfromthis,theymightalsohavemasspalpableper rectumduringexamination.^13,14

Variousradiologicalexaminationsareperformedtoestab- lishthediagnosisofGISTincludescolonoscopy,MRItoassess the tumorand sphinctercomplex and CT scanto lookfor metastasis.RoleofMRIorPETscaninGISTismainlytoassess themetastasisandresponsetotreatment.Colonoscopyalso provideswithsampleforbiopsytoknowthetypeoftumorand mitoticactivity.RectalGISThasaverysimilarclinicalprofile likeotherGIST,thereforethereisapredispositiontoauthen- ticatethesameprognosticfactorsforrectalGISTasforother GIST of different sites, particularly gastric GIST. Diagnosis includesdigitalassessmentoftherectum,colonoscopy,and transrectal ultrasoundtogether withpreoperativebiopsy.A definitediagnosisisdifficultwithoutthepresenceofmucosal invasionorextrinsicdeformity,andthusendoscopyprovides thediagnosticbiopsymaterialalone.^9,10,13,14

GISTcharacteristicallyexpressesCD117;oftenCD34and theirexpressionsvarydependingontheoriginofsites.GIST locatedallthroughthegastrointestinaltract,expressCD117, amostimportantGISTmarkerwhichalsoatarget fordrug therapy with imatinib, which isa tyrosine-kinase receptor inhibitor.Althoughimatinibisapromisingchemotherapeu- tic drug forhighly developed GIST,total surgical resection

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Fig.5–ThecoronalandsagittalsectionofCTshowingtumorafterneoadjuvanttherapy.

remainsthemostsuccessfultreatmentforsuchatumor.¹⁵ Duetorestrictedspaceinthepelvisarea,thetreatmentofGIST ofrectaloriginhaslimitedoptionfortreatmentandpatient mayrequireabdominoperinealresection.Sobeforeanysur- gicalprocedure,itisconsideredtodownsizetumor,preserve theanalsphincterusingimatinib.^16–18Inrandomized,trials 70%responserateforimatinibwasnotedinunresectableand metastaticGIST.Another study among161patients having locallyadvancedGISTsshowedagoodresponsetoneoadju- vantimatinibtreatmentwith80%responserate.¹⁹

TAMIS(Transanal MinimallyInvasive Surgery)isa min- imally invasive technique used in the treatment of rectal lesionsthatavoidsconventionalpelvicsurgeryorlaparotomy.

AdvantageofTAMISoverTEMS(TransanalEndoscopicMicro- surgery)istheavailabilityoflaparoscopicinstrumentsuniver- sally,noneedforspecialdedicatedinstruments.Ingeneral,in thepost-operativemanagementoftumorsathighriskand/or incasesofincompletesurgicalresection,therapywithima- tiniboradjuvantimatinibisalsosuggested.Althoughmoreor lessitisnowacceptedthatimatinibisasuitabletreatmentfor metastatictumorsevenatanadvancedstage,furtherin-depth analysis oftreatment efﬁciency with this drug is required in patients with high-risk tumors with the neoadjuvant therapy.^7,13,20,21

Use of imatinib prior to surgical resection to attain the reduced size of the tumor within the limit of resection is an attractive approach. In general, therapeutic schedule for a course of imatinib is 3–12 months, which require frequent imaging studies and a re-evaluation to decide the mostappropriatetime forsurgery. Sincetumor development can happen rapidly again after substantial tumor shrinkage, the best time to operate depending on resectabilityandthemaximumtherapeuticoutcomeremains divisive.

Inconclusion,rectalGISTalthoughitisextremelyrare,it canbetreatedbymeansofdifferentialdiagnosis.RectalGIST followstheverysimilardiagnosticwork-upasadvisedforany otherrectalneoplasia.Sincetheimmunohistochemicalchar- acterizationofCD117andCD34isalmostrequiredtoreach acertainpreoperativediagnosishence biopsyofthetumor isanecessarydiagnosticprocedure.Aseriesofpatientsfol- lowedforalongtimeunderobservationswouldmakeiteasyto assessthepost-surgicalresectionforrectalGISTwhichwould furtherhelptoascertainthemostefﬁcienttreatmentstrategy forrectalGIST.

Conﬂicts of interest

Theauthorsdeclarenoconﬂictsofinterest.

references

1.CorlessCL,FletcherJA,HeinrichMC.Biologyof

gastrointestinalstromaltumors.JClinOncol.2004;22:3813–25.

2.TranT,DavilaJA,El-SeragHB.Theepidemiologyofmalignant gastrointestinalstromaltumors:Ananalysisof1,458cases from1992to2000.AmJGastroenterol.2005;100:162–8.

3.GattaG,VanDerZwanJM,CasaliPG,SieslingS,DeiTosAP, KunklerI,etal.Rarecancersarenotsorare:therarecancer burdeninEurope.EurJCancer.2011;47:2493–511.

4.DemetriGD,VonMehrenM,AntonescuCR,DeMatteoRP, GanjooKN,MakiRG,etal.NCCNTaskForcereport:updateon themanagementofpatientswithgastrointestinalstromal tumors.JNatlComprCancNetw.2010;8Suppl2:S-1.

5.SteigenSE,EideTJ.Gastrointestinalstromaltumors(GISTs):a review.Apmis.2009;117:73–86.

6.JakobJ,MussiC,RonellenﬁtschU,WardelmannE,NegriT, GronchiA,etal.Gastrointestinalstromaltumorofthe rectum:resultsofsurgicalandmultimodalitytherapyinthe eraofimatinib.AnnSurgOncol.2013;20:586–92.

7.FranceNetoPR,RamosLA,SilvaLC,FernandesCK, Lacerda-FilhoA.Neoadjuvantuseofimatinibmesylatefor treatmentoflargerectalGIST:casereport.BrazJColoproctol.

2011;31:89–93.

8.HeinrichMC,CorlessCL,DemetriGD,BlankeCD,VonMehren M,JoensuuH,etal.Kinasemutationsandimatinibresponse inpatientswithmetastaticgastrointestinalstromaltumor.J ClinOncol.2003;21:4342–9.

9.MachlenkinS,PinskI,TulchinskyH,ZivY,SayfanJ,DuekD, etal.Theeffectofneoadjuvantimatinibtherapyonoutcome andsurvivalafterrectalgastrointestinalstromaltumour.

ColorectalDis.2011;13:1110–5.

10.NozawaH,KanazawaT,TanakaT,TakahashiM,IshiharaS, SunamiE,etal.Laparoscopicresectionofagastrointestinal stromaltumorofthelowerrectuminapatientwithcoronary arterydiseasefollowinglong-termneoadjuvantimatinib treatmentandanticoagulationtherapy.WorldJSurgOncol.

2014;12:211.

11.AkiyoshiT,UenoM,FukunagaY,NagayamaS,FujimotoY, KonishiT,etal.Laparoscopiclocalexcisionandrectoanal anastomosisforrectalgastrointestinalstromaltumor:

modiﬁedlaparoscopicintersphinctericresectiontechnique.

DisColonRectum.2014;57:900–4.

(5)

12.RutkowskiP,GronchiA,HohenbergerP,BonvalotS,Schöffski P,BauerS,etal.Neoadjuvantimatinibinlocallyadvanced GastrointestinalStromalTumors(GIST):theEORTCSTBSG experience.AnnSurgOncol.2013;20:2937–43.

13.EisenbergBL,TrentJC.Adjuvantandneoadjuvantimatinib therapy:currentroleinthemanagementofgastrointestinal stromaltumors.IntJCancer.2011;129:2533–42.

14.ArezzoA,VerraM,MorinoM.Transanalendoscopic microsurgeryafterneoadjuvanttherapyforrectalGIST.Dig LiverDis.2011;43:921–4.

15.SalazarM,BarataA,AndréS,VenâncioJ,FranciscoI,CravoM, etal.Firstreportofacompletepathologicalresponseofa pelvicGISTtreatedwithimatinibasneoadjuvanttherapy.

Gut.2006;55:585–6.

16.MachlenkinS,PinskI,TulchinskyH,ZivY,SayfanJ,DuekD, etal.Theeffectofneoadjuvantimatinibtherapyonoutcome andsurvivalafterrectalgastrointestinalstromaltumour.

ColorectalDis.2011;13:1110–5.

17.FioreM,PalassiniE,FumagalliE,PilottiS,TamboriniE, StacchiottiS,etal.Preoperativeimatinibmesylatefor

unresectableorlocallyadvancedprimarygastrointestinal stromaltumors(GIST).EurJSurgOncol.2009;35:739–45.

18.HamadaM,OzakiK,HorimiT,TsujiA,NasuY,IwataJ,etal.

RecurrentrectalGISTresectedsuccessfullyafterpreoperative chemotherapywithimatinibmesylate.IntJClinOncol.

2008;13:355–60.

19.LoSS,PapachristouGI,FinkelsteinSD,ConroyWP,Schraut WH,RamanathanRK.Neoadjuvantimatinibin

gastrointestinalstromaltumoroftherectum:reportofacase.

DisColonRectum.2005;48:1316–9.

20.RutkowskiP,GronchiA,HohenbergerP,BonvalotS,Schöffski P,BauerS,etal.Neoadjuvantimatinibinlocallyadvanced gastrointestinalstromaltumors(GIST):theEORTCSTBSG experience.AnnSurgOncol.2013;20:

2937–43.

21.NahasSC,NahasCS,MarquesCF,DiasAR,PollaraWM, CecconelloI.TransanalEndoscopicMicrosurgery(TEM):a minimallyinvasiveprocedurefortreatmentofselectedrectal neoplasms.ArqBrasCirDig.2010;23:35–9.