HindawiPublishingPerusahaanJournalofOncologyVolume2015,IDArtikel571.

739,14halaman
http://dx.doi.org/10.1155/2015/571739

ReviewPasalPengobatanGigipadaPasiendengan
Leukemia
CarolineZimmermann,1MariaInsMeurer,2,3LilianeJaneteGrando,2,3Joanita
AngelaGonzagaDelMoral,4InsBeatrizdaSilvaRath,5danSilviaSchaeferTavares6
1GraduateProgramKedokteranGigi,UniversitasfederalSantaCatarina,88040900Florianpolis,SC,Brasil2Department
Patologi,UniversitasfederalSantaCatarina,88040900Florianpolis,SC,Brasil3StomatologyKlinik,RumahSakit
Universitas,UniversitasfederalSantaCatarina,88040900Florianpolis,SC,Brasil4HematologyService,RumahSakit
Universitas,UniversitasfederalSantaCatarina,88040900Florianpolis,SC,Brasil5DepartmentKedokteranGigi,
UniversitasfederalSantaCatarina,88040900Florianpolis,SC,Brasil6IntegratedMultidisiplinKesehatan,Universitas
federalSantaCatarina,88040900Florianpolis,SC,Brasil
CorrespondenceharusditujukankepadaMariaInsMeurer;meurer.mi@ufsc.br
DiterimaOktober20142;Revisi23Desember2014;Diterima11Januari2015
AkademikEditor:BruceC.Baguley
Copyright2015CarolineZimmermannetal.IniadalahsebuahartikelaksesterbukadidistribusikandibawahlisensiCreative
CommonsAtribusi,yangmemungkinkanpenggunaantakterbatas,distribusi,danreproduksidalammediaapapun,asalkankarya
aslibenardikutip.
Perawatangigipasiendenganleukemiaharusdirencanakanatasdasarterapiantineoplastikyangdapatkemoterapidenganatau
tanparadioterapidantulangtransplantasisumsum.Banyakadalahmanifestasioralyangdisajikanolehpasienpasienini,yang
timbuldarileukemiadan/atauperawatan. Selain itu, melakukanprosedurgigipadaberbagaitahappengobatan(sebelum,
selama,atausetelah)harusmengikutiprotokoltertentudalamkaitannyadenganindekshematologispasien,yangbertujuanuntuk
menjagakesehatandanmemberikankontribusiterhadapefektivitashasilterapiantineoplastik.Melaluitinjauanliteratur,tujuan
dari penelitian ini adalah untuk melaporkan kelainan hematologi hadir pada pasien dengan leukemia, mencoba untuk
menghubungkanmerekadengankelayakanperawatangigipadaberbagaitahappenyakitini.Halinidisimpulkandalamtulisan
inibahwaperawatangigidalamkaitannyadenganindekshematologisdisajikanolehpasiendenganleukemiaharusmengikuti
protokol tertentu, terutama yang berhubungan dengan neutrofil dan jumlah trombosit, dan kehadiran dokter gigi di tim
multidisiplindiperlukanuntukperawatankesehataninisabar.

1.Pendahuluan
penyisipan kedokteran gigi dalam konteks multidisiplin hematologionkologi adalah bagian penting dari
keberhasilanpengobatankanker.Komplikasioraldapatmembahayakanprotokolkemoterapi,mungkinmembuat
perlu untuk mengurangi dosis yang diberikan, perubahan protokol pengobatan, atau bahkan penghentian terapi
antineoplastik,langsungmempengaruhikelangsunganhiduppasien[1,2].
Kelayakanuntukmelakukanprosedurgigitertentupadapasienleukemiatergantungpadakeadaankeseluruhan
kesehatanpasien,sertatahappenyakitdan/atauterapiantineoplastikatauselindukhematopoietiktransplantasi.
Meskipunharapan menemukan literatur pada leukemia/ hubungan gigi,survei bibliografi dilakukan (PubMed,
BIREME,JurnalPortaljubah,danSciELO)mengakibatkanbeberapaartikelyangmelibatkanamplitudo
hubunganini.Menghadapikebutuhanuntukmenetapkanprotokoluntukperawatangigipasienoncohematological
diRumahSakitUniversity,UniversitasFederalSantaCatarina,panduandisederhanakanuntukbimbinganwarga
dalam kedokteran gigi di tion dan pengobatan pasien evaluasi dikembangkan. Panduan ini terdiri dari tabel
menghubungkanfasekemoterapidantransplantasiselindukhematopoietikkeprosedurgigiyangpalingumum
(klasifikasidiadaptasidariSonisetal.[3]).
2.PertimbanganUmumtentangLeukemia
Leukemiaadalahpenyakityangganasdaridarah,dimanaproliferasitidakterkendaliseldarahyangbelummatang
yangoriginatedarimutasiselhematopoietikstemterjadi.Eventusekutuselselmenyimpangbersaingdengansel
normaluntukruangdisumsumtulang,menyebabkankegagalansumsumtulangdankematian[4].
2JournalofOncology
2.1.Klasifikasi.Theleukemiayangpalingumumpadaumumnyadiklasifikasikansebagai(1)limfositikakut,(2)
myeloidakut,(3)limfositikkronis,dan(4)myeloidkronis.Kriteriaklasifikasinyaleukemiaadalahhistologisdan
didasarkanpada(a)kesamaanantaraselselleukemiadanselnormal(myeloidvslimfoid)dan(b)perjalananklinis
penyakit(akutdankronis)[4].
Bentukakuthasilleukemiadariakumulasiselselyangbelummatangdantakberfungsidisumsumtulang,
denganperkembanganpesat[5],cepatfatalpadapasienyangtidakdiobati[6].Leukemiakronis,padagilirannya,
mulailambatdenganproliferasiyangtidakterkontroldariselselyanglebihmatangdanterdiferensiasi[5].
2.2. Pengobatan. Pengobatan leukemia tergantung pada faktorfaktor seperti jenis dan subtipe penyakit, risiko
faktorfaktor,danusiapasien.Secaraumum,pengobatanyangdianjurkanadalahkemoterapidenganatautanpa
KASIHmengobatiadjuvant.Hematopoietiktransplantasiselinduk(HSCT)dilakukan,secaraumum,dalambentuk
akutpenyakitdanbeberapakasusleukemiamyeloidkronis:
(i) akut lymphoblastic leukemia (ALL): profase (pengurangan inisial dari selsel leukemia), induksi (mencapai
remisilengkap),konsolidasi(meningkatkankualitasremisi),intensifikasi(postremissionpenguranganlebihlanjut),
danterapipemeliharaan(maintenancekonsolidasi);profilaksisnerpusatsistemvous(CNS)iradiasiterapiatau
iradiasijikaSSPterlibat;yangHSCTdapatdilakukandalambeberapakasus[7];
(ii)myeloidakutleukemia(AML):induksi(sampairemisilengkap),konsolidasi,danintensifikasi[8];
(iii)leukemiamyeloidkronis(CML):remisiselmicleukedankromosomPhiladelphiapositifdengankemoterapi
dosistinggi,pemantauanterapi,danHSCT[9];
(iv)limfositikkronisleukemia(CLL):pengobatankonvensionaltidakkuratif;kemoterapidilakukansebagaikontrol
[10].
2.2.1.PertimbangankhusustentangHSCT.PengobatandenganHSCTbertujuanuntukterisikembalisumsum,yang
sebelumnyadihancurkandengankemoterapidosistinggidenganatautanparadiasi,untukselselsehatyangnormal.
TheHSCTdapatdarijenisautologus(sendiriselindukhematopoietikpasien)ataualogenik(selhematopoietikyang
diperolehdari donor)[4,11]dansistscondarilimafase: (1)penyesuaianawal,(2)AC faseneutropenia,(3)
engraftment pemulihan hematopoietik, (4) pemulihan kekebalan / pemulihan dari toksisitas sistemik, dan (5)
kelangsunganhidupjangkapanjang[1].
KomplikasiutamaHSCTadalahpenolakangraft(kegagalandiimunosupresipasien)dangraftpenyakitversus
host(GVHD),dimanaselseldonorimunokompetenmenyerangantigenpasien,yangdapatmenyebabkanpenipisan
limfositT.Berpotensifatal,GVHDdapatterjadisegerasetelahHSCT(GVHDakut)atausetelahbeberapabulan
(GVHDkronisataucGVHD).Denganimunosupresidalamdanpanjang,pasienmenjadirentanterhadapinfeksi
jamurdanvirus[4].
2.3.Manifestasi Oral Leukemia. Padaleukemiaakut,hiperplasiagingivaumumnyadiamati, lokal atauumum,
terutamayangmempengaruhipapilainterdentaldanmarginalgingivadisebabkanolehperadangan,atauinfiltrasi
leukemia,danmungkindilokalisasiatauumum,yangterlatmenjadibentukyangpalingsering[3,5].Infiltrasisel
selleukemiajugadapatmelibatkanjaringanperiapikaldanmensimulasikan,baiksecaraklinisdanradiografi,lesi
inflamasiperiapikal[6].Padaleukemiakronis,infiltratleukemiadijaringanmulutkurangseringdandapatdiamati:
pucatmukosa,infeksijaringanlunak,danlimfadenopatigeneralisata[5].
Manifestasidaritrombositopeniamonlebihcomketikajumlahtrombositdibawah50.000sel/
mm3

[12]dandapatbermanifestasisebagaimemar,petechiaedi
langitlangitkerasdanlunak,danjugaspontanperdarahangusi,terutamajikajumlahtrombositdibawah20.000
sel/mm
3

[6].InfeksioportunistikdenganCandidaalbicansdanHermanpesvirus
yangumumdandapatmelibatkansetiapareamukosa.Ulkusjugabisaterjadiakibatgangguanpertahanankekebalan
tubuhdalammemerangifloranormal[6].
2.4.ManifestasiOralTerkaitdenganHSCT.Manifestasioralyangpalingumumyangterkaitdenganpra,segera
pasca,danakhirpascaHSCTdirangkumdalamTabel
6.manifestasioralyangmungkinadayangberkorelasidenganfaseHSCT[1]:(1)pengkondisian:infeksimulut,
ulserasi,perdarahan,dandisfungsisendilartemporomandibu;(2)neutropeniapenyejukfase:mucositis,dysgeusia,
xerostomia, perdarahan, nyeri mulut, infeksi patan tunistic, neurotoksisitas, dan disfungsi temporomandibular,
biasanya memanifestasikan dengan prevalensi tinggi dan bentuk parah; pada tahap ini, pasien dapat
mengembangkan GVHD akut hipertensi dengan komplikasi oral yang lebih parah; (3) engraftment pemulihan
hematopoietik:tionsinfeksioportunistikyangumumdanGVHDakutmenjadiperhatian;Perdarahandapathadir,
xerostomia, neurotoksisitas, ulomas gran / papillomas, dan disfungsi temporomandibular; (4) kekebalan
pemulihan / pemulihan dari toksisitas sistemik: disfungsi saliva, infeksi virus akhir, kelainan pertumbuhan
kraniofasial,cGVHD,dankarsinomaselskuamosa;dan(5)kelangsunganhidupjangkapanjang:padapasienanak,
terutamaanakanakdibawah6tahun,seseorangdapatmengamatikomplikasidalamperkembangantulangdangigi;
padatahapini,kekambuhandanneoplasmaganasdapatdiamati.
DalamterjadinyaGVHD,mucositis,gingivitis,eritema,dannyeribiasanyadiamati.DalamcGVHD,manifestasi
oralyangpalingumumadalahlumutjenisfitur,hiperplakkeratotik,Mucocele,mukosaatrofi,ulserasi[13,14],
fibrosis dengan pembukaan terbatas mulut, hiposalivasi, dan xerostomia [1316]. Selain itu, sekunder untuk
cGVHD,pasienmemilikikecenderunganlebihbesaruntukmengembangkankanker[14,17,18].
JournalofOncology3

3.PertimbanganUmummengenai
PengobatanGigi
Manajemengigipasiendenganleukemiaidensarilytertanamdalamkonteksmultidisiplin,karenakompleksitas
medisyangmenyajikanpasieninidapatmengganggudalampenentuanprioritasdanwaktuyangtersediauntuk
perawatangigi.UntukUSNationalCancerInstitute[2],timmultidisiplinharusmemilikiahlionkologi,perawat,
doktergigi(umumdanpraktisistomatologi),pekerjasosial,ahligizi,danprofesionalkesehatanlainnya,yangdapat
berkontribusiuntukpencegahandanpengobatankomplikasioralpadainipasien.
Sonisetal.[3]mengusulkanklasifikasipasiendalamkategoririsikotinggi,sedang,danrendahuntukperawatan
gigi,berdasarkanjenisleukemia(akut ataukronis)dankemoterapi.Pasienyangberisikotinggiadalahmereka
denganleukemiaaktif,yangmemilikisejumlahbesarselneoplastikdisumsumtulangdandarahperifer;karenaini,
mereka thrombocytopenic dan neutropenia. Kelompok risiko ini juga termasuk pasien antileukemic dalam
perawatan,dansebagaiakibatdariterapi,penekanansumsumtulangini.Dianggappasienrisikosedangadalah
merekayangberhasilmenyelesaikantahappertamapengobatan(induksi)dansedangmenjalanitahappemeliharaan,
sehinggatidakmenunjukkantandatandakeganasanpadasumsumtulangataudarahperifer;Namun,merekahadir
mielosupresikarenaAPYchemother.Dalamkategoririsikorendahadalahpasienyangberhasilmenyelesaikan
pengobatandanmenyajikanbuktikeganasanataumyelosupresi.
PerawatankesehatandasarharusmenjadibagiandarirutinitaspasienselamaterapiantineoplastikdanHSCT
untukmenjagakesehatanmulut yangbaik danmengurangi risikoinfeksi sistemikasal oral.Tujuanperawatan
termasukpencegahaninfeksi,mengontrolrasasakit,pemeliharaanfungsimulut,danpengelolaankomplikasiterapi
antineoplastik,yangbertujuanuntukmeningkatkankualitashiduppasien[19].
Sedikitetal.[5]danEladetal.[19]menguatkanbahwaperandoktergigiharusterjadipadatigamomenyang
berbeda:
(1)praantineoplastikevaluasipengobatandan
persiapannyapasienuntukini,
(2)pedomandanperawatankesehatanmulutselamapengobatan,
(3)perawatanpascaperawatan.
3.1.PreantineoplastikPenilaianPengobatandanPersiapanPasien.Perawatangigipadatahapinididasarkanpada
tanggungpriordanharusdiarahkanpadakebutuhanakut;elektifperlakuandapatditundakewaktuketikapasien
yangsepatutnyauntukkondisiklinisdanlaboratorium[1,2,5,19,20].
Pemeriksaan gigi, jika memungkinkan, harus terjadi imme segera setelah proses diagnosis dan sebelum
memulai kemoterapi sehingga memungkinkan penghapusan sumber infeksi asal gigi [3, 5, 20, 21], karena
neutropeniadiharapkanselamakemoterapipredisposisipasienuntukpenyebaraninfeksi[5].
Tujuandaripraantineoplastikperawatanevaluasigigiadalahsebagaiberikut[1,3,5,2022]:
(1)mengidentifikasidanmenghilangkansumberinfeksiyangadaataupotensial,tanpa,bagaimanapun,
mempromosikankomplikasiataumenundaterapikanker;(2)mendidikpasien(ataukeluargamereka)tentang
pentingnyamenjagakesehatangigidanmulutdalammengurangimasalahdanketidaknyamananmulutsebelum,
selama,dansetelahpengobatankanker;(3)memperingatkantentangkemungkinanefekantineoplastik
terapidironggamulut,sepertimucositis;(4)mengidentifikasiisuisuspesifikdiagnosisleukemia,
sepertileukemiainfiltratdijaringanmulut.Pencegahancederadaninfeksimulutadalahfokusdariperawatan
gigipadapasienleukemiadanperawatandengankebersihanmulut(menyikatgigi,penggunaanfluoride,dandiet
noncariogenic)harusditekankandiseluruhpengobatan[1,5,19].
DatadariUSNationalCancerInstitute[2]menyatakanbahwabeberapapusatkankermendorongmenyikatgigi
dan flossing, sementara yang lain menunjukkan gangguan menyikat gigi dan flossing ketika komponen darah
memilikidropdibawahbatasyangditentukan(misalnya,trombosit<30.000sel/mm
3)

. Namun, menurut lembaga itu sendiri, tidak ada bukti dalam

literaturmengenaipendekatanyangterbaik.Pusatpusatmenyediakanstrategiberpendapatbahwamanfaattepat
menyikatgigidanflossingtepatlebihbesardaripadarisiko,karenagangguankesehatanmulutrutinmeningkatkan
risikoinfeksi,daninibisamempromosikanperdarahansertameningkatkanrisikoinfeksilokaldansistemik.Eladet
al.[23]sepakatbahwaperawatangigisebelumHSCTdisukaiuntuktidakintervensigigi.
3.2.KesehatanmulutselamaantineoplastikTreatment.Pasienyangmenjalanikemoterapitelahmenjadiimmuno
ditekandankarenaiturentanterhadapinfeksisistemik.Merekadiklasifikasikansebagaipasienberisikotinggi,tidak
hanyaolehkemungkinanmengembangkaninfeksi,tetapisejauhdankeparahanpotensiini,yangdapatmemiliki
kursuscepatdanmenjadifatal[24].
Tujuandariperawatangigiselamakemoterapiadalahsebagaiberikut[1]:
(1)menjagakesehatanmulutyangoptimal;(2)mengobatiefeksampingdariterapiantineoplastik;(3)memperkuat
kepadapasienpentingnyakesehatanmulutdalammengurangimasalah/ketidaknyamananyangtimbuldari
kemoterapi.Terlepasdarimucositislisan,komplikasilisanutamakemoterapi,perubahanlaindapatterjadi,seperti
ingbleed,peningkatantingkatkaries,infeksi(bakteri,virus,ataujamur),absesgingiva,berulangherpesstomatitis,
kandidiasis,disfungsikelenjarludah,xerostomia,geusiadisfungsi,dannyeri[2,3,20,24].Adalahpentinguntuk
menyadaribahwainfeksidironggamulutdapatberkembangmenjadiinfeksisistemik,memburuknyastatus
kesehatanpasien,dankehadirandoktergigidan/ataustomatologistmemberikandukunganpentingbagistafmedis
[2,3,21,25,26].
4JournalofOncology
3.3.PostantineoplastikPengobatanOralHealthCare.Padatahapperawatanpascaantineoplastik,pasiendianggap
sembuhdarileukemiadantidakmemilikimanifestasioralkarenasakitataukemoterapi,denganpengecualianorang
orangdengangejalasisadariradioterapiatauanakanakyangmenerimakemoterapidalamtahappembentukangigi
[3],yangdapathadirdaerahhipoplasiaemailgigi(gangguanmineralisasi)danperubahandalamperkembanganakar
gigi(yangdisajikanpendekdanberbentukV)[27].
3.4.PertimbangankhusustentangKesehatanOraldiHSCTPasien.Pertimbanganmengenaikesehatanmulutpada
pasienHSCTdipra,pascalangsung,danakhirpascaHSCTdirangkumdalamTabel6.
PrinsipprinsipperawatangigisebelumHSCTsangatmiripdenganyangdibahasdalamBagian3.1danharus
mempertimbangkan fol melenguh fitur: (1) dalam HSCT, dosis total kemoterapi dan / atau radiasi dari tubuh
dilakukanbeberapaharisebelumtransplantasidan(2)imunosupresiakanjangkapanjangsetelahtransplantasi[1].
Meskipun penyakit mulut yang umum seperti penyakit periodontal dapat berdampak sistemik pada pasien
HSCT, penilaian HSCT pra oleh seorang dokter gigi diperlukan, dan harus mencakup pemeliharaan pedoman
kesehatanmulut.
SemuapasienyangmenjalaniHSCTharusmenerimaperawatankhusus,terutamamerekayangmengembangkan
cGVHD.Evaluasigigiyanglengkapharusterjadisecarateratur,danperhatianyangkhususharusdifokuskanpada
deteksidinikankerdanprekursorlesioral[14,17,18,28];diagnosisdanpengobatanlesimukosa[14,28]dan
eritemaataulumutjenisfiturdengansimtomatologi[18];kariespencegahan[14,28,29];reestablishmentkesehatan
mulutdalamkasuskariesmerajalela[14,30],dengankemungkinanpenggunaanaplikasifluoride[14]atauperak
diaminafluorideuntukpengendalianpenyakitdanbantuandarihipersensitivitas[30];danterapifarmakologi[14,
28,31]ataupengobatannonfarmakologi[14,28,29]darihiposalivasidanxerostomia.
DiagnosiscGVHDlisantergantungpadariwayatpasien,temuanklinis,dantandatandaawaldangejala[14]dan
umumnyatidakperlumelakukanbiopsi[28].
Bahkansetelahterapiimunosupresif,pasienyangmengembangkancGVHDmemerlukanperawatanintensif
jangkapanjang.Dalamperawatanadalahpengurangangejala,resolusilukayangmenyakitkan,danpencegahandan
pengelolaankomplikasisekunder,sertapedomanuntukpemeliharaankebersihanmulutyangbaik[14].

4.ProsedurGigidiTahapanyangberbedadari
PenyakitdanPengobatan
pengobatanGigiharusdirencanakansesuaidenganterapiantineoplastik[3]danHSCT[19].Pelaksanaanbeberapa
prosedurterutamagigimerekadarikarakterinvasiftergantungpadastatuskesehatankeseluruhandaripasiendan
tahapperawatanantineoplastikyangterletak.Mengingatrisikoperdarahandaninfeksiseriusyangberhubungan
dengan prosedur invasif dalam rongga mulut, sudah ada beberapa protokol yang menekankan pentingnya
mengevaluasiindekshematologicaltertentu,terutamaneutrofildantrombosit.Variasi
yangdiamatiantarapenulismengenaijumlahpertimbanganeredminimaluntukprosedurgigiinvasifdalampra
dantranschemotherapyfase.Tabel1dan2menunjukkanvariasisertamemenuhirekomendasimengenaikebutuhan
untuktransfusi,profilaksisantibiotik,danpenundaanperawatangigi[13,5,22,3234].
InivariasimenjelaskanakandisajikandandidiskusikandalamTabel3,4,dan5,dibangununtuksetiaptahap
pengobatan.
4.1. Pengobatan Gigi di Tahap Prechemotherapy. Tabel 3 (prechemotherapy) merangkum prosedur gigi dan
keterbatasanmerekadalamliteratur,mengenaiindekshematologidandiutamakanyangdiperlukanuntukprosedur
inipertimbangankenaiinisiasikemoterapi.
 Awalnya, perawatan gigi harus diarahkan untukkebutuhan akut [5]. Perawatan elektif harus ditundauntuk
waktuyangtepatketikapasiendalamkondisiklinisdanhematologiyangbaik[1,2,19,20].
The US National Cancer Institute [2] berpendapat bahwa intervensi pada tahap ini harus diarahkan untuk
pengobatan lesi pada mukosa mulut, lesi karies dan endodontik, penyakit periodontal, buruk gigi palsu pas,
peralatanortodontik,perubahansenditemporomandibular,dansalivapenyelewenganfungsi.
Elad et al. [19] menyarankan dokter gigi harus menghilangkan potensi sumber trauma di mukosa, seperti
peralatanortodontik,gigipalsuyangtidakpas,restorasitidakmemuaskan,gigitrauma,dankalkulusgigi.Mereka
jugamengklaimbahwanonrestorablegigi(denganpaparanakar,keterlibatanperiodontalparahdanberdampak
dengansinyalperikoronitis)harusdiekstrak.Dalamkasusgigirestorable,harusditentukanjikaadacukupwaktu
untukpengobatanyangtepat.Beberapaekstraksiharusdipertimbangkanjikagigidiabaikanolehpasien.
MenurutSonisetal.[3],gigimembusukharusdikembalikanketikatidakadarisikoketerlibatanpulpa;jika
risikoiniada,merekaharusdihapusataudiperlakukanendodontik.Merekajugamenyatakanbahwasetiapgigi
denganprognosisdipertanyakanharusdihapus,sertagigidenganketerlibatanperiodontaldanerupsisebagiangigi
molartigayangmungkinterbuktimenjadifokusdariperikoronitis.
TheAmericanAcademyofPediatricDentistry[1]berpendapatbahwaketikasemuakebutuhangigitidakdapat
diatasisebelummemulaiterapikanker,prioritasharussumbermenghilangkaninfeksidantrauma,sertaekstraksi
dan perawatan periodontal. Perawatan endodontik gigi nonvital gejala harus dilakukan setidaknya seminggu
sebelumdimulainyaAPYchemotheruntukmemilikiwaktuyangcukupuntukmenilaikeberhasilanpengobatan;
jikahalinitidakmungkin,ekstraksiditunjukkan.Gigiyangtidakdapatmenerimaperawatanendodontikdalamsatu
sesijugamemilikiekstraksisebagaipengobatanpilihan,denganprofilaksisantibiotik(penisilinatauklindamisin)
selamasekitarsatuminggu.Padagigitanpagejala,perawatanendodontikharusditundasampaiindekshematologis
pasienmenstabilkan(initermasukendodontikdiperlakukangigidenganlesiperiapikal,tanpatandatandadangejala
infeksi).Gigitidakdapatdikembalikandengankantongperiodontallebihbesardari6mm,dengangejalainfeksi
akut,kehilangantulangyangsignifikan,pencabangan
JournalofOncology5
Tabel1:nilaihematologiminimumuntukkinerjaprosedurgigiinvasifpadapasienpengobatanprechemotherapymenurut
penulisyangberbeda.
Penulistrombositneutrofilmenghitung
Eversoleetal,2001[33]mm3.
<50.000sel/Tidakmelakukanoperasigigiatauperiodontaldalampengaturankantor.

.Sedikitetal,2007[5]
<50.000sel/mm3:menghindariprosedurinvasif.<40.000sel/mm3:melakukantransfusidalamprosedurinvasif.
<500sel/mm3:profilaksisantimikroba(ataudenganleukosit<2000sel/mm3).
AmericanAcademyofPediatricDentistry,2013
[1]>1000sel/mm3:tidakperluuntukprofilaksisantibiotik.Beberapapenulisberpendapatbahwaprofilaksisdilakukandengan
nilaiantara1.000dan2,000cell/mm3(mengikutirekomendasidariAmericanHeartAssociation).Jikainfeksihadiratauada
keraguan,profilaksisantibiotikyanglebihagresifdapatdiindikasikandanharusdidiskusikandengantimmedis.<1.000sel/
mm3:Menundaperawatangigi.Dalamkasuskasusdarurat,membahasantibiotikcakupandanendokarditisprofilaksissebelum
pengobatandengantimmedis.Rawatinapmungkindiperlukan.
USNationalCancerInstitute,2011
[2]>75.000sel/mm3:tanpadukungantambahan.40.000untuk75.000sel/mm3:transfusitrombositdapatdipertimbangkan
dalampraoperasidanpascaoperasi(24jam).<40.000sel/mm3:Menundaperawatangigi.Dalamkasusdaruratgigi,hubungi
dokterpasiensebelumperawatangigiuntukmembahaslangkahlangkahmendukung,sepertitransfusitrombosit,kontrol
perdarahan,danperluuntukrawatinap.Teskoagulasilainnyamungkindiperlukandalambeberapakasus.
>60.000sel/mm3:tanpadukungantambahan.30.000sampai60.000sel/mm3:transfusiopsionaluntukprosedurnoninvasif.
<30.000sel/mm3:Trombositharusditransfusi1jamsebelumprosedur.Mendapatkanjumlahpostinfusionplateletlangsung;
transfusisecarateraturuntukmenjagajumlah>30.00040.000sel/mm3sampaiawalpenyembuhan.
>2000sel/mm3:tanpaperluprofilaksisantibiotik.1.000sampai2.000sel/mm3:profilaksisantibiotik(risikorendah).<1.000
sel/mm3:profilaksisantibiotikdenganAmikacin150mg/m21jamsebelumoperasidantikarsilin75mg/KgIV1jam
sebelumoperasi.Ulangikedua6jampascaoperasi.
Tabel2:NilainilaihematologiMinimumuntukmelakukanprosedurgigiinvasifpadapasienyangmenjalanikemoterapi,
menurutpenulisyangberbeda.
Penulistrombositneutrofilmenghitung
Sonisetal,1995[3]mm3.
<100.000sel/Perawatangigielektifharusditunda.
<3.500sel/mm3(leukosit):perawatangigielektifharusditunda.
.Haytacetal,2004[32]
<40.000sel/mm3:periodontalekstraksimenyelidikdangigikontraindikasi.
<1.500sel/mm3:periodontalekstraksimenyelidikdangigikontraindikasi.
.Brennanetal,2008[22]
<50.000sel/mm3:kontraindikasiuntukmelakukanprosedurinvasif.
<1.000sel/mm3:kontraindikasiuntukmelakukanprosedurinvasif.Koulocheris[34]
etal,mm3.
2009>60.000sel/Diterimauntukbedahmulut.>1000sel/mm3:diterimauntukbedahmulut.
paparan,mobilitas,danakaryangterkenadampakdansisaharusdihapus.Idealnya,ekstraksiharusterjadidua
minggu sebelum dimulainya pengobatan antineoplastik atau setidaknya 7 sampai 10 hari sebelum. Akhirnya,
akademimerekomendasikanbahwaprosedurbedahharussebagaiatraumaticmungkin,tanpameninggalkantepi
tulangsisadandenganjahitanmemuaskanluka.Jikaadainfeksiberhubungandengangigi,antibiotikprofilaksis
harusdilakukanselamaseminggudandenganobatidealnyadipiliholehantibiogram.
MenurutSedikitetal.[5],ekstraksiharusdilakukan,sebaiknyatigaminggusebelumkemoterapiatauradioterapi
dansetidaknya10sampai14harisebelumnya.Jikajumlahtrombositkurangdari50,000cells/mm
2.000sel/mm
3

ataukurangdari500sel/mm
3.

Erupsi sebagian gigi molar dapat menjadi sumber infeksi karena

perikoronitis.Jikajaringangingivayangmenutupisebagiangigimerupakanfaktorpotensialuntukinfeksi,jaringan
harusdipotong,jikatingkathematologimengizinkan.
Toljanicetal.[35]melakukanstudiprospektifyangditujukanuntukmenilaiprotokolminimumuntukperawatan
gigiprechemotherapymelibatkan48pasiendenganneoplasmapadatatauhematologi,secaraempiris
mengklasifikasikanperubahankronisasalodontogeniksebagairingan,sedang,atauberat,pertimbangankenai
kemungkinanmerekamengembangkandalamprosesprosesakutselamakemoterapi.Dalamakutdidiagnosis
perubahan3,harusdihindari;bilakurangdari40,000cells/mm
prosedurinvasif
3,

ini
berdasarkantandatanda(edema,drainasepurulen,dancompatiperubahanradiografible)dangejala(nyeri,nyeri
tekan,menunjukkanmelakukantransfusi.profilaksisantimikroba
dandemam),sumberinfeksidihapussebelumlaxis
dianjurkanketikaleukositmenghitungkurangdari
kemoterapi.Sebaliknya,perubahankronis,sumber
6JournalofOncology
Tabel3:Kemungkinanprosedurgigidifaseprechemotherapy.
ProsedurPertimbangandanpembatasan
waktusebelumdimulainyaCTTipeI
Ujian
ClinicalradiografiHygienepetunjuk
adapembatasan.
Moldingprosedurelektif,menundaTipeII
restorasiSederhana(ART)Profilaksisdanskalasupragingiva
Tidakadabatasan.
Ortodonti
PengobatanPilihan,menunda.Mempertimbangkanmenghapusperalatanortodontik.

TipeIII
restorasiyanglebihkompleks
Sematamatauntukkecukupanlingkunganmulut.Pertimbangkanpenggunaanbahanrestoratifsementara(misalnya,kaca
ionomer).

Scalingdanperencanaanroot(subgingival)
prosedurinvasifdaririsikotinggidilakukandenganhatihati.Untukmengevaluasiindekshematologitrombositdanneutrofil.
Perluuntukprofilaksisantibiotik.

Endodontik
simtomatikgigi
Evaluasiindekshematologitrombositdanneutrofil.Perluuntukprofilaksisantibiotik.Pertimbangkanekstraksijikaendodontik
gagal.
Minimal1minggu[1]
gigiasimtomatik
Tunda(tricresolformalin)ATAUEvaluasiindekshematologitrombositdanneutrofil.Perluuntukprofilaksisantibiotik.
Minimal1minggu[1]
KetikIV
ekstraksiSimple
3minggu;minimum1014hari[5]2minggu;minimum710hari[1]
Kuret(gingivoplasty)
prosedurinvasifberisikotinggi.Mengevaluasiindekshematologitrombositdanneutrofil.Perluuntukprofilaksisantibiotik.
Prosedurelektif,invasifdanberisikotinggi.Menunda.

TipeV
Beberapapencabutan
Jikauntukkecukupanlingkunganmulut,mengevaluasiindekshematologitrombositdanneutrofil.Perluuntukprofilaksis
antibiotik.Jikaelektif,menunda.
3minggu;minimum1014hari[5]2minggu;minimum710hari[1]operasiFlap/gingivectomyEkstraksiberdampakgigi
ApicoectomyimplanLajangpenempatan
prosedurelektif,invasifdanberisikotinggi.Menunda.

JenisVI
Ekstraksiseluruhlengkunganataukedua
Jikakecukupanlingkunganmulut,mengevaluasiindekshematologitrombositdanneutrofil.Perluuntukprofilaksisantibiotik.
Jikaelektif,menunda.
3minggu;minimum1014hari[5]2minggu;minimum710hari[1]EkstraksibeberapagigiyangterkenadampakoperasiFlap
OrthognathicoperasiPenempatanbeberapaimplan
prosedurelektif,invasifdanberisikotinggi.Menunda.

JournalofOncology7
Tabel4:Kemungkinanprosedurgigidifasetranschemotherapy.
ProsedurPertimbanganataupembatasan
waktuantarasiklusTipeI
Ujian
ClinicalradiografiHygienepetunjuk
adapembatasan.
Moldingprosedurelektif.Menunda.TipeII
restorasiSederhana(ART)Profilaksisdanskalasupragingiva
Tidakadabatasan.
Ortodonti
PengobatanPilihan.Mempertimbangkanmenghapusperalatanortodontik.

TipeIII
restorasiyanglebihkompleks
Sematamatauntukkecukupanlingkunganmulut.Pertimbangkanpenggunaanbahanrestoratifsementara(misalnya.,Kaca
ionomer).

Scalingdanakarperencanaan(subgingival)
pengobataninvasif,berisikotinggi,melakukandenganhatihati.Mengevaluasiindekshematologitrombositdanneutrofil.Perlu
untukprofilaksisantibiotik.

Endodontik
simtomatikgigi
Evaluasiindekshematologitrombositdanneutrofil.Perluuntukprofilaksisantibiotik.Pertimbangkanekstraksijikaendodontik
gagal.
Minimal1minggu[1]
gigiasimtomatik
Tunda(tricresolformalin).OREvaluasiindekshematologitrombositdanneutrofil.Perluuntukprofilaksisantibiotik.
Minimal1minggu[1]
KetikIV
ekstraksiSimple
3minggu;minimum1014hari[5]2minggu;minimum710hari[1]Kuret(gingivoplasty)perawatanelektif,invasifdan
berisikotinggi.Menunda.TipeV
Beberapaekstraksi
pengobataninvasifberisikotinggi.Evaluatehematologicalindicesofplateletsandneutrophils.Needforantibioticprophylaxis.
Ifadequacyoftheoralenvironment,evaluatehematologicalindicesofplateletsandneutrophils.Needforantibioticprophylaxis.
Ifelective,postpone.
 3weeks;minimum1014days[5]2weeks;minimum710days[1]Flapsurgery/gingivectomyExtractionofimpactedtooth
ApicoectomySingleimplantplacement
Electiveprocedure,invasiveandhighrisk.Postpone.

TypeVI
Extractionofanentirearchorboth
Ifadequacyoftheoralenvironment,evaluatehematologicalindicesofplateletsandneutrophils.Needforantibioticprophylaxis.
Ifelective,postpone.
3weeks;minimum1014days[5]2weeks;minimum710days[1]ExtractionofmultipleimpactedteethFlapsurgery
OrthognathicsurgeryPlacementofmultipleimplants
Electiveprocedure,invasiveandhighrisk.Postpone.

8JournalofOncology
Table5:Possibilityofdentalproceduresinpostchemotherapyphase.
InterventioninpostchemotherapyConsiderationsandrestrictionsTypeI
Exam
ClinicRadiographicHygieneinstructions
Norestrictions.
MoldingTypeII
Simplerestorations(ART)
Norestrictions.Prophylaxisandsupragingivalcellscaling
Orthodontics
Completedchemotherapyandaftertwoyearsfreeofdisease,onecanrestarttheorthodontictreatmentTypeIII
MorecomplexrestorationsScalingandrootplanningcell(subgingival)Endodontics
Norestrictions.SymptomatictoothAsymptomatictoothTypeIV
SimpleextractionsCurettage(gingivoplasty)
Needforantibioticprophylaxisuntilsixmonthsaftercompletionofchemotherapy.
TypeV
MultipleextractionsFlapsurgery/gingivectomyExtractionofimpactedtooth
Needforantibioticprophylaxisuntilsixmonthsaftercompletionof
chemotherapy.ApicoectomySingleimplantplacementTypeVI
ExtractionofanentirearchorbothExtractionofmultipleimpactedcellteethFlapsurgery
Needforantibioticprophylaxisuntilsixmonthsaftercompletionof
chemotherapy.OrthognathicsurgeryPlacementofmultipleimplants

ofinfectionwasnotremoved.Chroniclesionsofodontogenicoriginwereidentifiedin79%ofpatients,where
44%wereconsideredseriouschronicillness;ofthese,only4%hadepisodesoffeverdiagnosedasodontogenicin
origin,whichweretreatedwithantibioticswithoutinterruptionofchemotherapy.Fortheauthors,theseresults
demonstrated that patients with chronic odontogenic lesions can safely undergo chemotherapy without dental
procedures,sincetheconversionofchronicprocessesinacutecaseswasuncommonandwhensharpeningoccurred
itwaseffectivelytreatedwithoutinterruptionoftherapyandwithoutadverselyaffectingtheoncologicaltreatment.
This strategy would significantly change the established protocols, which recom mend a more aggressive
prechemotherapydentaltreatment.Theauthorsreasonedthat,dependingontheseverityofthecancer,theremaybe
aneedtoquicklystartchemotherapytomaximizeitstherapeuticeffectsandinthatnarrowwindowoftime,the
extractionofteethwithoutpotentialrecoverymay
betheonlyviabletreatmentoptionandstillthepossibilityofinfectionaftertoothextractionwoulddelaytherepair
ofthewound.Itisconcludedthatthetreatmentofchronicodontogeniclesionscanbesafelypostponeduntiltheend
ofchemotherapy,consideringthetherapeuticbenefits.
AccordingtoHaytacetal.[32]aneutrophilcountof1,500/mm
3

andplateletsof40,000cells/mm
3
 are required for performing periodontal probing or extractions. The
proceduresmustbeperformedunderantibioticcoverandatleastthreedaysbeforethestartofchemotherapy
(approximately10daysbeforethegranulocytecountfallsbelow500cells/mm
3

); when not possible, dental treatment should be

postponeduntilthehaematologicalindicesincrease.
TheAmericanAcademyofPediatricDentistry[1]arguesthatorthodonticappliancesshouldberemovedifthe
patienthasdeficientoralhygieneand/orincaseswheretheprotocolofantineoplastictreatmentconfersriskfor
developingmoderateorsevereoralmucositis;simpledevicesthatdonot
JournalofOncology9
10JournalofOncology
irritatethesofttissues,removableappliances,orretainerswelladaptedmaybemaintainedprovidedthatthepatient
hasgoodoralhygiene.ShellerandWilliams[36]defendthatorthodonticappliancesshouldberemoved.
Itisimportantthatthedentistisawareofthesignsandsymptomsofperiodontaldisease,sincethesecanbe
subtlewhenthepatientisimmunosuppressed[1,37].
After treatment of acute needs, other procedures such as smoothing of rough restorations, rounding, or
restorationoftoothfracturesmaybeperformed,inadditiontotheassessmentofdentures.Scalingproceduresand
rootplanningshouldbeperformedtopreventperiodontalinfections,aswellasenhancingoralhygieneinstruction
andtheuseofmouthwashwithfluorideinpreventingdentalcaries[3,5].
4.2.DentalTreatmentintheTranschemotherapyPhase.Table4referstothestagewherethepatientisundergoing
chemotherapyandliststhedentalproceduresandrestrictionsassignedtoit,referringtohaematologicalindicesand
consideringtheperiodbetweencyclesofchemotherapy.
Inhighriskpatients(activeorunderleukemiabonemarrowsuppression)dentalinterventionislimitedtoemer
gencycare.However,oralhygienemustbemaintainedbytheuseofmouthwashesandmildantimicrobialand
antisepticsolutions,inordertopromoteulcerhealingandminimizecomplicationsfrominfection.Whenthereis
evidence oforal infection,highriskpatientsshouldreceivebroadspectrum antibioticsintravenously[3,5].In
UH/UFSC0.12%,solutionbasednonalcoholicchlorhexidinegluconateisusedintheformofdailymouthwashor
appliedwithgauzeorswab.
Inpatientsatmoderaterisk(maintenancephase),themyelosuppressionpeakismostevident,usuallyafter14
daysofdrugadministration,andatthistime,dentaltreatmentshouldbeavoided;beforeor21daysafterthestartof
chemotherapythetreatmentcanbeperformed;however,thedoctorshouldbeconsulted.Iftheleucocytecountis
below3,500cells/mm
greaterthan1000cells/mm
3

andplateletcountofatleast60,000cells/mm3areacceptableratesfororalsurgeries.
Whenthereisspontaneousbleedingresultingfromminortrauma,thedentistshouldstrivetoimprovetheoral
hygieneofthepatientanduselocalmeasurestocontrolthebleeding.Ifthesemeasuresarenotsufficient,platelet
transfusionmayberequired[5].
Themanagementforcontroloforalbleedingincludestheuseofvasoconstrictoragents,clots,andtissueguards.
Toreducetheflowofbloodfrombleedingvessels,onecanuseepinephrine;toorganizeandstabilizebloodclots,
topical thrombin and/or collagen hemostatic agents can be used; and to stanch the bleeding sites and protect
organizedclots,theapplicationofthemucosaadhesiveproducts,suchasthosebasedoncyanoacrylate,maybe
performed.Thetopicalaminocaproicacidcanbeusefulinpatientswithfriableclotsandintravenousadministration
maybeconsidered,insomecases,toimprovecoagulationandtheformationofstableclots[2].Topicaluseof
tranexamicacidisalsocitedasaneffectivehemostaticinreducingtheincidenceofpostoperativebleedingin
patientstakingcontinuoususeoforalanticoagulants[38,39].Coetzee[40]reportstheempiricaluseof500mg
crushedtabletsgroundinmoistcottonatthesiteofthesurgicalwoundaftertoothextraction,ordilutedinwater
formouthwash,suggestingitasanoption.
4.3. Dental Treatment after Chemotherapy. Table 5 relates the postchemotherapy period and summarizes the
considerationsandconstraintsintheliteratureforperformingdentalprocedures.
Patientswhowerecuredofleukemiaareconsideredtobeoflowriskandcanbemetwithnormal dental
treatmentregimens[3].Aftercompletionofcancertherapyandonlyaftertwoyearsfreeofdisease,theorthodontic
treatmentthatwasinterruptedcanberestarted[36].
3

ortheplateletcountislessthan100,000cells/mm
3

,electivedentaltreatmentshouldbepostponed[3].Accordingtotheseauthors,typeIprocedures
canbeperformedaccordingtostandardprotocols,sincein
Koulocherisetal.[34]suggestthatantibioticprophylaxisduringoralandmaxillofacialsurgicalproceduresshould
beperformedforatleastsixmonthsafterthecompletionofchemotherapy.typesII,III,andIVprocedures,
antimicrobialprophylaxisisrecommended.
TongandRothwell [24]donotrecommendroutineantibioticprophylaxisfordental proceduresinpatients
undergoingchemotherapy;however,forinvasiveproceduressuchastoothextractionsandotherdeepperiodontal
scalingproceduresthatcancausesignificantbleedingandpropagationofbacteriaintothebloodstream,antibiotic
coverageshouldbeperformed.
Koulocherisetal.[34],citingotherauthors,statethatinoralsurgicalproceduresduringchemotherapy,thebene
fit/risktothepatientmustbeconsidered,aswellastheconsequencesofchemotherapycycles;theseprocedures
shouldthereforebeplannedandagreedonaninterdisciplinarylevel.
4.4. Dental Treatment in Different Phases of Chemotherapy Treatment. Table 7 shows, insummary form, the
considerationsandlimitationsrelatedtodentalproceduresatdifferentstagesofantineoplastictreatment.
Noninvasiveproceduresdonotrequireadditionalcareandmaybeperformedatanystageofthediseaseor
chemotherapy.FitinthissituationthetypeI(clinicalexamination,radiographs,andoralhygieneinstruction)and
typeIIprocedures(simplerestorations,atraumaticrestorativetreatmentART,supragingivalscalingand
prophylaxis)[3].Sincethepriorityisthetreatmentofleukemiabeforethediagnosis(prechemotherapyphase)or
duringantineoplastictreatment,somedentalprocedures,classifiedastypeI(moldFurthermore,thesurgical
procedureshouldbethemost
ing)andtypeII(orthodontictreatment),are
consideredconservativepossible,withtransandpostantibioticprophy
electiveforthesepatients,andeveninthe
postchemotherapylaxisandpostoperativeplatelettransfusionifnecessary.It
phase,somerestrictionsmustbeconsideredwhen
relatedtoisclaimed,inaddition,thatanabsoluteneutrophilcount
orthodontictreatment.
JournalofOncology11
Thereareprocedures,however,thatareconsiderednonsurgical(typeIII)suchastherealizationofmore
complexrestorations,scaling,rootplanning(subgingival),andendodontictreatmentbuttheyrequirespecialcare
intheprechemotherapyandtranschemotherapyphases,consideringthegeneralstateofhealthandtheriskversus
benefittothepatient.Someauthorssuggestthatperiodontalproceduressuchasprobingandperiodontalscaling
couldcausebacteremia[4144].Inaddition,theendodontictreatmentprotocolforasymptomaticteeth,accordingto
theliterature,isnotwellestablished.Thus,therealizationofendodonticshastojustifytheremovalofinfectious
foci;however,someprofessionalsprefer,insuchsituations,toadoptaradicalbehavior,performingtheextractionof
thedentalelementinquestioninordertoavoidfuturecomplications.Inthepostchemotherapyperiod,thesedental
procedurescanbeperformedwithoutrestrictions.
Invasiveproceduressuchassimpleextractions(typeIV),multipleextractions(typeV),orthoseofanentirearch
orentiremouth(typeVI)canbeperformed,butitsexecutionisdependentonthepatient'sriskandshouldtherefore
the risk versus the benefit should be considered in specific situa tions [3]. We believe that gingivoplasty
procedures,multipleextractions(noinfectiousfoci)flapsurgery(gingivectomy),extractionofsingleormultiple
impactedteeth,apicoectomy,placingimplants,andorthognathicsurgeryareconsideredelectivetreatmentsbefore
thediagnosisand/ortreatmentofleukemiaandshouldnotbeperformeduntilthepatientcompletesandmaintains
theirantineoplastictreatmentsuccessfully.
4.5.SpecialConsiderationsaboutDentalTreatmentinHSCTPatients.Theconsiderationsofthedentaltreatmentin
thepre,immediatepost,andlatepostHSCTaresummarizedinTable6.
TheAmericanAcademyofPediatricDentistry[1]recommendsthatdentaltreatmentismadedependenton
eachphaseofHSCT.Inthepreconditioningphase,alldentaltreatmentshouldbecompletedbeforethepatient
becomesimmunosuppressive.Electivetreatmentshouldbedelayeduntilthereestablishmentofimmunity(atleast
100 days after transplant, or more in the case of oral complications or other cGVHDs). In the neutropenic
conditioning phase, the focus is the monitoring and management of oral complications, with reinforcement of
maintenanceguidelinesofgoodoralhygiene.Dentalproceduresshouldnotbeperformedatthisstage;inthecaseof
emergencies,dentalapproachshouldbedevelopedwiththeparticipationofthemedicalstaff.Intheengraftment
phasetohematopoieticrecovery,adentalassessmentshouldbeperformed,withspecialattentiontoxerostomiaand
GVHD.Invasiveproceduresshouldbemadeonlywiththeapprovalofthemedicalstaff;thepatientshouldbe
encouragedtomaintaingoodhygienewithanoncariogenicdiet.Intheimmunereconstitution/recoveryphasefrom
systemictoxicity,aperiodicevaluationwithdentalradiographycanbeperformed;however,invasiveprocedures
shouldstillbeavoided; clarifyingtherisksandbenefitsoftheuseoforthodonticappliancesisrecommended.
Finally,inthelongtermsurvivalphase,aroutinedentalevaluation
Table7:Possibilityofdentalproceduresatvariousstagesofchemotherapy.
InterventionPreTransPostTypeI
Exam
ClinicalNRNRNRRadiographicNRNRNROralhygieneinstructionNRNRNRMoldingEENRTypeII
Simplerestorations(ARTs)NRNRNRProphylaxisandsupragingivalscaling
NRNRNR
OrthodonticsEERTypeIII
MorecomplexrestorationsRRNRScalingandrootplanning(subgingival)
RHI,AP
RHI,AP
NR
Endodontics
Symptomaticteeth
RHI,AP
RHI,AP
NR
Asymptomaticteeth
E,RHI,AP
E,RHI,AP
NR
TypeIV
Simpleextractions
R,HI,AP
R,HI,AP
R
Curettage(gingivoplasty)EIHREIHRRTypeV
Multipleextractions
R,HI,AP
R,HI,AP
R
Flapsurgery/gingivectomyEIHREIHRRExtractionofimpactedtoothEIHREIHRRApicoectomyEIHREIHRRSingle
implantplacementEIHREIHRRTypeVI
Extractionofanentirearchorboth
R,HI,AP
R,HI,AP
R
Extractionofmultipleimpactedteeth
EIHREIHRR
FlapsurgeryEIHREIHRROrthognathicsurgeryEIHREIHRRPlacementofmultipleimplantsEIHREIHRRNR:no
restriction,R:withrestriction,E:elective,EIHR:elective,invasive,andhighrisk,HI:needforevaluationofhematological
indices,andAP:antibioticprophylaxis.

withinterdisciplinaryandmultidisciplinaryinvolvementisnecessary.
TheauthorsdiffersomewhatastothebestapproachforabetterdentalprotocolinHSCTpatients,butare
unanimousinstatingthattheassessmentanddentalcareareneeded.
RaberDurlacheretal.[37]investigatedthecorrelationbetweengingivitis/periodontitisandthedevelopmentof
bacteremiaduringtheperiodofneutropeniaafterHSCT.Eighteenpatientswereexaminedandclassifiedintotwo
groups:(1)periodontallyhealthy(probingpocketdepth:PPD
12JournalofOncology
4mmandbleedingonprobing:BOP10%)and(2)thepresenceofgingivitis(PPD4mmandBOP>10%)or
periodontitis(PPD>4mmandBOP10%).Only28%ofthepatientswereconsideredperiodontallyhealthy.Of
thetotal,67%ofthepatientsdevelopedbacteremia(diagnosedbybloodsamplescollected2timesperweek),and
group2hadmorefrequentepisodesduringtheneutropeniaphasethangroup1.Theauthorssuggestedthatgingivitis
andperiodontitismayrepresentariskfactorforthedevelopmentofbacteremia,whichhasalsobeenshownin
other studies [43,44].They furtherstated that theexacerbationofgingivitisand chronic periodontitisisrare,
probably due to the institution of prophylactic therapy; on the other hand, common illnesses should not be
overlooked,suchaspotentialunderdiagnosedofbacteremiasource,particularlyduringperiodsofneutropenia.
Melkosetal.[45]conductedaprospectivestudyof58patientsundergoingHSCTandevaluatedthepreexisting
odontogeniclesions,dentalcare,andtheeffectofbothonthemedicalprocedure.Allpatientswerereferredfora
dentalevaluationbeforetheHSCT,beingexaminedbytwoexperienceddentiststhroughclinicalexamination(soft
andhardtissues)andradiographic(panoramicandoccasionallyforsymptomaticperiapicalteeth).Infectiousfoci
teethwereconsideredwithperiapicalandperiodontalinfectionandthosesemiimpacted.Thetypeofpretransplant
dentalworkandtheoccurrenceofposttransplantcomplications(mucositis,infections,graftversushostdisease
(GVHD),andrelapseofdisease)wereevaluatedforanaverageof50.45weeksafterthedateoftransplantation.The
protocolfordentaltreatmentincludedrestorationofactivecariesandextractionofnonrestorableteethandthose
withadvancedperiodontaldisease;nonvitalteethwereendodonticallytreatedorextracted,whereasperiapical
lesionsweretreatedendodontically,performingapicoectomyorextraction.Patientsweredividedintotwogroups:
(I)noinfectiousfociorcompletedentaltreatmentbeforetransplantation(n=36)and(II)withinfectiousfoci,
submittedtotransplantationwithoutdentalintervention(n=22).Posttransplantcomplicationswereobservedin
75% of patients in group I and 95.4% in group II. The impact of infectious outbreaks in the occurrence of
posttransplantinfectionswasnotstatisticallysignificant,aswellascorrelationsbetweendecayed,impacted,and
semierupted teeth, fever of unknown origin, mucositis, and the survival rate of patients with preexisting foci;
however, the infectious foci were significant when associated with acute GVHD, mainly impacted teeth and
periapicallesions.AhigherrateofcomplicationswasfoundingroupII,indicatingtheimportanceofevaluationand
pretransplantdentalwork.ItwasconcludedthatdentaltreatmentbeforeHSCTshouldnotberadical.Restorative
andpreventativetechniques,however,mustbeindividuallyadjustedforeachpatient.
Yamagataetal.[46]alsoconductedaprospectivestudyof41patientswhowereundergoingHSCTusinga
conservativedentalprotocol.Allpatientswereevaluatedbyclinicalexaminationoftheoralsoftandhardtissues
and,ifnecessary,radiographswererequested.Ofthe41patients,36requiredoneormoredentalinterventions.The
followingdiagnoses
andprocedureswereperformed:101cariouslesions:40wererestoredand61wereuntreated;5pulpitistreatedwith
endodontics;10teethwithapicalperiodontitisgreaterthan5mmand33withlessthan5mm:7lesionswere
surgicallyremoved,5teethwereendodonticallytreated(includingtwowithsymptomatology),and31teethwith
lesionssmallerthan5mmandasymptomaticreceivednotreatment;94teethwithperiodontitis:6wereextracted
and88preserved,withsurveymonitoringandhygieneeducation;21partiallyeruptedwisdomteeth:3presenting
symptomatologywereremoved,therestwereuntreated.Alldentalprocedureswereperformedupto10daysbefore
HSCT,withoutchangeinterruptionordelayintheplanningofthetransplant.Nopatienthadsignsorsymptomsof
odontogenicinfectionduringtheimmunosuppressionperiod.Theauthorsconcludedthattheconservativeprotocol
appearedtobesuitableforpreHSCTpatients.
AbdullahandAhmad[47]conductedastudyof44pediatricpatients.Dentalconditionswereevaluatedbyclin
icalexaminationbeforeHSCT.Inthecaseofsymptomatictoothperiapicalradiographswereperformed.Decayed
teethconsideredunviablewereextracted,andtheotherswererestored.Inpatientsathighriskofcaries,sealantwas
applied.Allpatientsreceivedoralhygieneguidelines.Thepatientswereevaluatedafter1,3,and6monthsafter
HSCT.Mostpatients(65.9%)neededsometypeofpreHSCTdentaltreatment,havingperformed101restorations,
13extractions,and19sealants.Within6monthsofmonitoring,10%ofthepatientswhodidnotreceivepreHSCT
dental treatment had odontogenic infection. No cases of odontogenic infection were observed in patients who
previously received dental care. The authors concluded that the preHSCT dental treat ment can reduce the
occurrenceofinfectionofdentalorigin,anditisimportanttopreventseriousinfections.
The US National Cancer Institute [48] points out that the time ofreconstitutionof the immune system in
transplantpatientscanrangefrom6to12monthsandthatthedentalcareroutineshouldnotbedoneinthisperiod,
includingscalingandperiodontalplanning.Proceduresthatproduceaerosol,suchasultrasoundequipmentandhigh
speed,canalsopresentariskofaspirationofdebrisandbacteriaandcausepneumoniainthesepatients[19,48].If
emergencytreatmentisrequired,strategiesforreducingaerosolaspirationandantibioticprophylaxisshouldbe
used.Finally,itisrecommendedthattheuseofIgG,antibiotics,corticosteroids,and/orplatelettransfusionshould
beconsideredbeforeimplementinginvasiveprocedures[48].

5.FinalConsiderations
Fromtheliteraturereviewconducted,severaloralmanifestationsinleukemicpatientsarose.Thesemanifestations
areoftenthefirstsignofleukemiaandmaypresentclinicallyasleukemicinfiltrationinoraltissuesaswellas
simulatingaperiapicallesion.Othersymptomsmayoccursuchaspalemucosa,poorwoundhealing,bleeding
(petechiaeandecchymoses),atypicalorrecurrentcandidiasis,recurrentherpesinfections,andulcerationsintheoral
mucosa.Duringantineoplastictreatment(chemotherapy,mostly),themaincomplicationismucositis.
JournalofOncology13
Other conditions that may also occur include bleeding, increase the rate of decay, infection, gum abscess,
recurrent herpetic stomatitis, candidiasis, salivary gland dysfunction, xerostomia, dysgeusia, and pain. In the
posttherapyperiod,patientsareconsideredcuredandusuallypresentnosequelaeoftreatment.
OralmanifestationsaresimilarinpatientsundergoingHSCT;however,generallythesecasesareduetolong
termimmunosuppressionofthepatientevenafterthetransplantation.Specialfeaturesareobservedinpatients
undergoingallogeneicHSCT,suchascGVHD,whichtypicallymanifestsaslichentypefeatures,hyperkeratotic
plaques,mucocele,andfibrosiswithlimitedmouthopening,andaremorelikelytodevelopmalignanciessuchas
squamouscellcarcinoma.
Performingdentalprocedurescanofferrisktothepatient,dependingonhisstateofhealthandphaseoftherapy.
Furthermore,someproceduresoffergreaterriskthanothers.Thus,noninvasiveprocedures(typeIandtypeII)can
beperformedatanystageofthediseaseortreatment.TypeIIIproceduresmayrequirespecialcare.Finally,invasive
procedures(typesIV,V,andVI)offerhigherrisk.Inemergencysituationsofriskconsidered,particularlythose
involvingpain(acutecases),thepatientshouldbeassisted,ifnecessary,inahospitalsetting,withtheinstitutionof
measurestoincreasethehematologicalindices(transfusions)and,ifapplicable,withantibioticcoverage.
Inassessingpatientsfordentalprocedures,twohematologicalindicesareparticularlyimportant:neutrophiland
plateletcounts.Atlowlevelsofneutrophilcounts,andwhentheprocedurecannotbedelayed,prophylacticantibi
otictherapyprotocolsshouldbeconsidered,beingvariableaccordingtothedegreeofneutropenia;thereisnostrict
consensusamongauthors,butmostrecommendedantibioticprophylaxiswithvalueslessthan1,000cells/mm
[2]USNationalCancerInstitute,OralComplicationsofChemotherapyandHead/NeckRadiation,USNationalCancerInstitute,
2011,http://www.cancer.gov/cancertopics/pdq/supportivecare/oralcomplications/HealthProfessional.[3]STSonis,RCFazio,
andL.Fang,PrinciplesandPracticeof
OralMedicine,WBSaunders,1995.[4]MRHowardandPJHamilton,Leukaemia,inHaematology,
pp.3366,Elsevier,Philadelphia,Pa,USA,3rdedition,2008.[5]JWLittle,DAFalace,CSMiller,andNLRhodus,
Disordersofwhitebloodcells,inDentalMagenementoftheMedicallyCompromisedPatient,pp.373395,2007.[6]B.
Neville,D.Damm,C.Allem,andJ.Bouquot,Hematologicdisorders,inOralandMaxillofacialPathology,pp.573613,
Elsevier,3rdedition,2009.[7]R.Wsch,W.Digel,andM.L ubbert,Acutelymphoblasticleukemia(ALL),inConcise
ManualofHematologyandOncology,M.Andreeff,B.Koziner,H.Messner,andN.Thatcher,Eds.,pp.400414,Springer,
Berlin,Germany,2008.[8]K.HeiningMikeschandM.L ubbert,Acutemyeloidleukemia(AML),inConciseManualof
HematologyandOncology,M.Andreeff,B.Koziner,H.Messner,andN.Thatcher,Eds.,pp.415420,Springer,Berlin,
Germany,2008.[9]W.LangeandC.Waller,Chronicmyeloidleukemia(CML),inConciseManualofHematologyand
Oncology,pp.432438,Springer,Berlin,Germany,2008.[10]J.BurgerandJ.Finke,Chroniclymphocyticleukemia(CLL),
inConciseManualofHematologyandOncology,pp.470476,Springer,Berlin,Germany,2008.[11]K.Durey,H.Patterson,
andK.Gordon,Dentalassessmentpriortostemcelltransplant:treatmentneedandbarrierstocare,BritishDentalJournal,vol.
206,no.9,articleE19,2009.[12]JBEpstein,L.Vickars,J.Spinelli,andD.Reece,Efficacyofchlorhexidineandnystatin
rinsesinpreventionoforalcomplicationsinleukemiaandbonemarrowtransplantation,OralSurgeryOralMedicineandOral
Pathology,vol.73,no.6,
3

.Inthecase
pp.682689,1992.[13]AHFilipovich,D.Weisdorf,S.Pavleticetal.,NationalInstioftheplateletcount,theauthorsconsider
theneedfortrans
tutesofHealthconsensusdevelopmentprojecton
criteriaforfusionfromindicesbetween40,000and60,000cells/mm
3
.
clinicaltrialsinchronicgraftversushostdisease:I.
DiagnosisThus,weconclude,basedontheliteraturereviewpresentedhere,thatthedentaltreatmentinrelationto
haematologicalindicespresentedbypatientswithleukemiashouldfollowsomejudiciousprotocols,mainlyrelated
toneutrophilandplateletcounts.However,itisnoteworthythatmanyofthesestudiesarebasedonexpertopinion.
Thepresenceofthedentistinamultidisciplinaryteamisessential,sinceweunderstandthatmaintainingoralhealth
contributessignificantlytotheoverallhealthandimprovedqualityoflifefor
andstagingworkinggroupreport,BiologyofBloodandMarrowTransplantation,vol.11,no.12,pp.945956,2005.[14]N.
Treister,C.Duncan,C.Cutler,andL.Lehmann,Howwetreatoralchronicgraftversushostdisease,Blood,vol.120,no.17,
pp.34073418,2012.[15]KMHull,I.Kerridge,andM.Schifter,Longtermoralcomplicationsofallogeneichaematopoietic
SCT,BoneMarrowTransplantation,vol.47,no.2,pp.265270,2012.[16]HSBrand,CPBots,andJERaberDurlacher,
Xerostomiaandchronicoralcomplicationsamongpatientstreatedwithpatientsthroughtheuseofdentalapproachesbasedon
scien

haematopoieticstemcelltransplantation,
BritishDentalJourtificevidence,preventive,curative,andpalliativeinnature.
nal,vol.207,no.9,articleE17,2009.

ConflictofInterests
[17]RAAbdelsayed,T.Sumner,CMAllen,A.Treadway,GMNess,andSLPenza,Oralprecancerousandmalignantlesions
Theauthorsdeclarethatthereisnoconflictofinterestsregardingthepublicationofthispaper.
associatedwithgraftversushostdisease:reportof2cases,OralSurgery,OralMedicine,OralPathology,OralRadiology,and
Endodontology,vol.93,no.1,pp.7580,2002.[18]F.Demarosi,D.Soligo,G.Lodi,L.Moneghini,A.Sardella,References
andA.Carrassi,Squamouscellcarcinomaoftheoralcavityassociatedwithgraftversushostdisease:reportofacaseand[1]
AmericanAcademyofPediatricDentistry,Guidelineondental
reviewoftheliterature,OralSurgery,OralMedicine,
Oralmanagementofpediatricpatientsreceivingchemotherapy,
Pathology,OralRadiologyandEndodontology,vol.100,
no.1,pp.hematopoieticcelltransplantation,and/orradiation,Journal
6369,2005.ofPediatricDentistry,vol.35,no.5,pp.
E185E193,2013,
[19]S.Elad,JERaberDurlacher,MTBrennanetal.,Basic
http://www.ncbi.nlm.nih.gov/pubmed/24290549.
oralcareforhematologyoncologypatientsandhematopoietic
14JournalofOncology
stemcelltransplantationrecipients:apositionpaperfromthejointtaskforceoftheMultinationalAssociationofSupportive
CareinCancer/InternationalSocietyofOralOncology(MASCC/ISOO)andtheEuropeanSocietyforBloodandMarrow
Transplantation(EBMT),SupportiveCareinCancer,vol.23,no.1,pp.223236,2015.[20]R.Albuquerque,V.Morais,andA.
Sobral,Protocolodeatendimentoodontol ogicoapacientesoncol ogicospeditricosrevis aodeliteratura,Revistade
OdontologiadaUNESP,vol.36,no.3,pp.275280,2007.[21]D.Martins,MAMartins,andL.Sneda,Suporteodontol
ogicoaopacienteoncol ogico:preven ao,diagn ostico,tratamentoereabilita aodassequelasbucais,PratHosp,vol.7,no.
41,pp.166169,2005.[22]MTBrennan,S.B.Woo,andPBLockhart,Dentaltreatmentplanningandmanagementinthe
patientwhohascancer,DentalClinicsofNorthAmerica,vol.52,tidakada.1,pp.1937,2008.[23]S.Elad,T.Thierer,M.
Bitan,MYShapira,andC.Meyerowitz,Adecisionanalysis:thedentalmanagementofpatientspriortohematologycytotoxic
therapyorhematopoieticstemcelltransplantation,OralOncology,vol.44,no.1,pp.3742,2008.[24]DCTongandBR
Rothwell,Antibioticprophylaxisindentistry:areviewandpracticerecommendations,JournaloftheAmericanDental
Association,vol.131,no.3,pp.366374,2000.[25]M.Paiva,J.Moraes,R.DeBiase,O.Batista,andM.Honorato,Estudo
retrospectivodascomplica oesoraisdecorrentesdaterapiaantineoplsicaempacientesdoHospitalNapole aoLaureanoPB,
OdontologiaCl nicoCient fica,vol.6,no.1,pp.5155,2007,http://www.scielo.br/scielo.php?script=scinlinks
&ref=000139&pid=S1414462X20130001000020002&lng=pt.[26]C.PadminiandKYBai,Oralanddentalconsiderationsin
pediatricleukemicpatient,ISRNHematology,vol.2014,ArticleID895721,11pages,2014.[27]A.Avsar,M.Elli,
[34]P.Koulocheris,MCMetzger,MRKesting,andB.HohlwegMajert,Lifethreateningcomplicationsassociatedwithacute
monocyticleukaemiaafterdentaltreatment,AustralianDentalJournal,vol.54,no.1,pp.4548,2009.[35]JAToljanic,JF
Bedard,RALarson,andJPFox,Aprospectivepilotstudytoevaluateanewdentalassessmentandtreatmentparadigmfor
patientsscheduledtoundergointensivechemotherapyforcancer,Cancer,vol.85,no.8,pp.18431848,1999.[36]B.Sheller
andB.Williams,Orthodonticmanagementofpatientswithhematologicmalignancies,AmericanJournalofOrthodonticsand
DentofacialOrthopedics,vol.109,no.6,pp.575580,1996.[37]JERaberDurlacher,AMGALaheij,JBEpsteinetal.,
Periodontalstatusandbacteremiawithoralviridansstreptococciandcoagulasenegativestaphylococciinallogeneic
hematopoieticstemcelltransplantationrecipients:aprospectiveobservationalstudy,SupportiveCareinCancer,vol.21,no.6,
pp.16211627,2013.[38]FWGCosta,RRRodrigues,LHTdeSousaetal.,Localhemostaticmeasuresinanticoagulated
patientsundergoingoralsurgery.Asystematizedliteraturereview,ActaCirurgicaBrasileira,vol.28,no.1,pp.7883,2013.
[39]G.Ramstrom,S.SindetPedersen,G.Hall,M.Blomback,andU.Alander,Preventionofpostsurgicalbleedinginoral
surgeryusingtranexamicacidwithoutdosemodificationoforalanticoagulants,JournalofOralandMaxillofacialSurgery,vol.
51,no.11,pp.12111216,1993.[40]MJCoetzee,Theuseoftopicalcrushedtranexamicacidtabletstocontrolbleedingafter
dentalsurgeryandfromskinulcersinhaemophilia,Haemophilia,vol.13,no.4,pp.443444,2007.[41]ACRTHorliana,L.
Chambrone,AMFozetal.,Dis
O.
Darka,andG.Pinarli,Longtermeffectsofchemotherapyoncariesformation,dentaldevelopment,and
salivaryfactorsinchildhoodcancersurvivors,OralSurgery,OralMedicine,OralPathology,OralRadiologyandEndodontol
ogy,vol.104,no.6,pp.781789,2007.[28]S.Elad,SBJensen,JERaberDurlacheretal.,Clinicalapproachinthe
managementoforalchronicgraftversushostdisease(cGVHD)inaseriesofspecializedmedicalcenters,SupportCare
Cancer,2014,http://www.ncbi.nlm.nih.gov/pubmed/25417041.[29]JBEpstein,JERaberDurlacher,A.Wilkins,M.G.Chavar
ria,andH.Myint,Advancesinhematologicstemcelltransplant:anupdatefororalhealthcareproviders,OralSurgery,Oral
Medicine,OralPathology,OralRadiology,andEndodontology,vol.107,no.3,pp.301312,2009.[30]C.Chu,AHLee,L.
Zheng,MLMei,andGCChan,Arrestingrampantdentalcarieswithsilverdiaminefluorideinayoungteenagersufferingfrom
chronicoralgraftversushostdiseasepostbonemarrowtransplantation:acasereport,BMCResearchNotes,vol.7,article3,
2014.[31]JCAtkinson,M.Grisius,andW.Massey,Salivaryhypofunctionandxerostomia:diagnosisandtreatment,Dental
ClinicsofNorthAmerica,vol.49,no.2,pp.309326,2005.[32]MCHaytac,MCDogan,andB.Antmen,Theresultsofa
preventivedentalprogramforpediatricpatientswithhematologicmalignancies,OralHealth&PreventiveDentistry,vol.2,no.
1,pp.5965,2004.[33]L.Eversole,Bleedingdisorders,inEssentialsofOralMedicine,S.Silverman,LREversole,andEL
Truelove,Eds.,pp.6166,
seminationofperiodontalpathogensinthebloodstreamafterperiodontalprocedures:asystematicreview,PLoSONE,vol.9,
no.5,ArticleIDe98271,2014.[42]CGDaly,DHMitchell,JEHighfield,DEGrossberg,andD.Stewart,Bacteremiadueto
periodontalprobing:aclinicalandmicrobiologicalinvestigation,JournalofPeriodontology,vol.72,no.2,pp.210214,2001.
[43]DFKinane,MPRiggio,KFWalker,D.MacKenzie,andB.Shearer,Bacteraemiafollowingperiodontalprocedures,
JournalofClinicalPeriodontology,vol.32,no.7,pp.708713,2005.[44]C.Daly,D.Mitchell,D.Grossberg,J.Highfield,and
D.Stewart,Bacteraemiacausedbyperiodontalprobing,AustralianDentalJournal,vol.42,no.2,pp.7780,1997.[45]AB
Melkos,G.Massenkeil,R.Arnold,andPAReichart,Dentaltreatmentpriortostemcelltransplantationanditsinfluenceonthe
posttransplantationoutcome.,Clinicaloralinvestigations,vol.7,no.2,pp.113115,2003.[46]K.Yamagata,K.Onizawa,H.
Yoshidaetal.,Dentalmanagementofpediatricpatientsundergoinghematopoieticstemcelltransplant,PediatricHematology
andOncology,vol.23,no.7,pp.541548,2006.[47]S.AbdullahandZ.Ahmad,Protocolfordentaltreatmentbeforebone
marrowtransplantation(BMT)inpaediatricpatient,PakistanOral&DentalJournal,vol.34,no.3,pp.399405,2014.[48]
NationalCancerInstitute(US),PosttransplantationDentalTreatment,http://www.cancer.gov/cancertopics/pdq/suppor
tivecare/oralcomplications/HealthProfessional/page11.
BCDecker,London,UK,2ndedition,2001.
TheScientificWorldJournal
HindawiPublishingCorporationhttp://www.hindawi.comVolume2014
JournalImmunologyof
Research
HindawiPublishingCorporationhttp://www.hindawi.comVolume2014

PPARResearch
HindawiPublishingCorporationhttp://www.hindawi.comVolume2014
ComputationalandMathematicalMethodsinMedicine
HindawiPublishingCorporationhttp://www.hindawi.comVolume2014

JournalOphthalmology
of
HindawiPublishingCorporationhttp://www.hindawi.comVolume2014

BehaviouralNeurology
HindawiPublishingCorporationhttp://www.hindawi.comVolume2014

GastroenterologyResearchandPractice
HindawiPublishingCorporationhttp://www.hindawi.comVolume2014

StemCellsInternational
HindawiPublishingCorporationhttp://www.hindawi.comVolume2014

Submityourmanuscriptsathttp://www.hindawi.com
Parkinson'sDisease
HindawiPublishingCorporationhttp://www.hindawi.comVolume2014

EvidenceBasedComplementaryandAlternativeMedicine
HindawiPublishingCorporationhttp://www.hindawi.com
Volume2014
MEDIATORSINFLAMMATIONof
HindawiPublishingCorporationhttp://www.hindawi.comVolume2014
JournalDiabetesof

Research
HindawiPublishingCorporationhttp://www.hindawi.comVolume2014
AIDSResearchandTreatment
HindawiPublishingCorporationhttp://www.hindawi.comVolume2014
JournalObesity
of
HindawiPublishingCorporationhttp://www.hindawi.comVolume2014
InternationalEndocrinology
Journalof
HindawiPublishingCorporationhttp://www.hindawi.comVolume2014

DiseaseMarkers
HindawiPublishingCorporationhttp://www.hindawi.comVolume2014
JournalOncologyof
HindawiPublishingCorporationhttp://www.hindawi.comVolume2014

BioMedResearchInternational
HindawiPublishingCorporationhttp://www.hindawi.comVolume2014
OxidativeMedicineandCellularLongevity
HindawiPublishingCorporationhttp://www.hindawi.comVolume2014