capusla video

REZUMATUL TEZEI DE DOCTORAT

Aportul diagnostic al videocapsulei endoscopice

Doctorand Ciobanu Lidia

C

onductor de doctorat Prof. Dr. Oliviu Pascu

CUPRINSINTRODUCERE 15

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STADIULACTUALALCUNOATERII 1.Teh icuvideocapsulaendoscopicnicaexaminri 19

1.1.Aspectetehnice1.2.Aspectepractice

1920

2.Apl picicaiiclinicealeexaminriicuvideocapsulaendoscoareacuvideocapsula

232.1.Semiologialeziuniloridentificatelaexaminendoscopic

hn23

2.2.LeziuninaltsugestivepentruboalaCro 292.3.Leziunispecificeenteropatieiglutenice

edeantiinflamatoarenonsteroidienelanivelulbire

292.4.Leziunideterminatmucoaseiintestinuluisu 302.5.Enteropatiaradic

irenvasculite31

2.6.Afectareaintestinuluisubeenterale

31322.7.Boliinfecioas

2.8.Patologiirare 333.Perendos

formanadiagnosticiimpactulclinicalvideocapsuleicopice 353.1.Performanadiagnosticiimpactulclinicalvideocapsuleiendoscopicelapacieniicuhemoragiedigestivobscur3.2.Performanadiagnosticiimpactulclinicalvideocapsuleiendoscopicela

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pacieniicuboalaCrohn 383.3.Performanadiagnosticavideocapsuleicolonice3.4.Performanadiagnosticavideocapsuleiesofagiene

4041

CONTRIBUIAPERSONAL 43

451.Ipotezadelucru/obiective2.Metodologiegeneral 463.Studiul1 Aportuldiagnosticalexaminrii cuvideocapsuleiendos ologiaenteralcopicenpat 48

3.1.Introducereiective

483.2.Ipotezadelucru/ob

metod49

3.3.Materialie

493.4.Rezultat 50

573.5.Discuii3.6.Concluzii 60

4. Studiul 2 Aportul diagnostic al examinrii cu videocapsulaendos ileinflamatoriiintestinalecopicnbol 61


614.2.Ipotezadelucru/ob4.3.Materialimetod

6262

3Aportuldiagnosticalvideocapsuleiendoscopice

4.4.Rezultate 654.5.Discuii4.6.Concluzii

7276

75. Studiul 3 Aportul diagnostic al examinrii cu videocapsulaendos laceliaccopicnboa 75.1.Introducere

iective77

5.2.Ipotezadelucru/obimetod

785.3.Material

e79

5.4.Rezultat 795.5.Discuii5.6.Concluzii

8486

6.Studiul4Aportuldiagnosticalexaminriicuvideocapsulaendos ieniicuhemoragiadigestivobscurcopiclapac 88



imetod90

6.3.Materiale


102109

7.Studiul5Efectulrifaximineiasupraenteropatieiindusdeindom aietacinlacob 110



imetod111

6.3.Materiale


118120

8.Studiul6 InterrelaiadintreantiinflamatorenonsteroidieneiCan lanivelultubuluidigestivalcobailordidaalbicans 121



imetod122

6.3.Materiale


129131

7.Concluziigenerale 1331378.Originalitateaicontribuiileinovativealetezei

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REFERINE 139

157ANEXECuvinte cheie: videocapsul endoscopic, hemoragie digestiv obscur, boliinflamatorii intestinale, boala celiac, enteropatia dat de antiinflamatorenonsteroidiene rifaximina,imunologiatubuluidigestiv,Introducere

Apariia n 2001 a videocapsulei endoscopice (VCE) a nsemnat un imensprogres n explorarea direct a intestinului subire (IS), ntrun mod fiziologic,noninvaziv,ageneratunvaldesperaneiacrescut interesulpentrupatologiaIS. ntimptehnicasaperfecionat,rspunzndnevoilorpractice,attpentruexplorareaIS,ctipentruinvestigareacolonuluiiaesofagului.

TezaactualipropunestudiereaperformaneidiagnosticeaVCEnpatologiaenteral pe un numr de 255 de examinri realizate n perioada noiembrie 2005 iunie 2013 n Clinica Medical III, ClujNapoca. Cea mai frecvent patologiediagnosticat a fost enteropatia indus de antiinflamatoarele nonsteroidiene (AINS)care a condus la realizarea a dou studii experimentale: primul investigheaz rolulrifaximineiasupraenteropatieidatdeAINSlacobai,iaraldoileadescrieinterrelaiadintreAINSiCandidaalbicanslanivelultubuluidigestivalcobailor.

nparteageneralesteprezentatexaminareacuVCE,estedescrissemiologialeziunilordetectate ndiferitepatologii (exemplificate n imaginile anexei1). Studiulbibliografic prezint succint i riguros performana diagnostic i impactul clinic alexaminriicuVCE,fiindbazatpe191dereferine.Ipotezadelucru/obiectiveNeamproendoscopic

pusevaluareaexperieneinoastreprivindexaminareacuvideocapsula(VCE)(255examinrila252pacieni)prinaprecierea:

a celor dou protocoale utilizate (pentru investigareatreguluiinte

fezabilitii tehniceintestinuluisubireipentruexaminarean stin)

aplicabilitiiclinicePerf fost cuantificat separat pentru

principalelormana diagnostic i impactul clinic a

eindicaiialeacesteiexaminri:

tudiul1 tudiul1

suspiciuneadetumorenteralns

durereabdominalnesistematizatns

studiul1

sindromdiareiccronicn

boliinflamatoriiintestinalenstudiul2boalceliacnstudiul3

hemoragiedigestivobscurstudiul4

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Aportuldiagnosticalvideocapsuleiendoscopice

Entestudiatcu

ropatia dat de consumul de antiinflamatoare nonsteroidiene a fostajutoruladoumodeleexperimentale:

- studiul 5 a analizat potenialul protector a diferite doze de rifaximinasupraenteropatieindusdeadministrareadeindometacinlacobai

- studiul 6 a cercetat interrelaia dintre Indometacin i Candida albicans lanivelultubuluidigestivalcobailor.

MetodologiegeneralStudiile clinice au fost efectuat ntrun singur centru teriar, Institutul de

Gastroenterologie i Hepatologie Cluj, Universitatea de Medicin i Farmacie IuliuHaieg 05 iunie 2013. Au fost luate n studiu 255examin

anu, n perioada noiembrie 20riIndi

consecutivela252pacieni.

caiiledeexaminarecuVCE:

hemoragiedigestivobscur(HDO)clinicmanifestactivsauoprit;anemieferiprivdeetiologieneprecizat(HDOocult);

ale: boal Crohn cunoscut sau suspect, boaleclasificabil(colitnedeterminat)

boli inflamatorii intestininflamatorieintestinaln

boalceliaccunoscut; renteral(intestinsubire,colon);suspiciuneadetumo diareecronic; Criteriideexcludere:

durereabdominal.

subirestenozcunoscutaintterioarecude

estinului bitmarefistulean tulburridedeglutiie Dou

sarcin

protocoalealeexaminriicuVCEaufostutilizate:examinareacuajutorulVCEpentruintestinsubirePillCamSB1i2;

examinareacuajutorulVCEpentrucolon:PillCamColon1si2,administratdupunprotocolmodificatcarespermitvizualizareaatta intestinuluisubire,ctiacolonului,dupopregtireprealabilcu4litrideFortrans.Acestprotocolafostefectuatdac:pacieniiprezentauhemoragiedigestivobscuricolonoscopiaanterioarafostefectuatcu36lunianteriorsaula colonoscopia anterioar pregtirea nu a fost satisfctoare, dac existasuspiciuneadetumorenteral(intestinsubireisaucolon)ilapacieniicuboalCrohnsaucolitnedeterminatpentruevaluarecompletatubuluidigestiv.

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Datele nregistrate au fost analizate de ctre doi examinatori independent, cuajutoru l 2 glsoftu uiRAPID, laovitezde1 14ima ini/secund.Citireasaefectuatntrunintervaldemaxim12oredelaterminareainvestigaiei.

Pentru modelele experimentale privind enteropatia dat de antiinflamatorenonsteroidienelacobaimetodologiaestedescrisncadrulstudiilorrespective.

Studiul1AportuldiagnosticalexaminriicuvideocapsulaendoscopicnpatologiaenteralIpotezdelucru

Neampropus evaluarea experienei noastre privind examinarea cuVCE (255examinrila252pacieni)prinapreciereafezabilitiitehniceacelordouprotocoaleutilizate i a aplicabilitii clinice (indicaiile de examinare). n acest studiuperformana diagnostic i impactul clinic au fost analizate pentru urmtoareleindicaii:tumorenteral(29examinri),dureriabdominale(17pacieni)isindromdiareiccronic(31pacieni).

RezultateAufostluatenstudiu255examinriconsecutivela252pacienicuurmtoarele

indicaii: hemoragiidigestiveobscure:93examinri(36,4

7%): boliinflamatoriiintestinale:65examinri(25,49%):

boalaceliaccunoscut:20examinri(7,84%); sau colon): 29 examinrisuspiciune de tumor enteral (intestin subire

(11,37%); sindromdiareiccronic:17examinri(6,66%); durereabdominal:31examinri(12,15%).Dintotalulde255deexaminri,178(69,8%)aufostefectuatedupprotocolul

pentru examinarea IS i 77 (30.19%) dup protocolul de explorare IS i colon cuajutorul capsulei de colon. Din 255 de examinri retenia capsulei care a necesitatintervenie chirurgical sa nregistrat la 5 pacieni (1,96%). De asemenea sanregis ttratreteniacapsuleisub48orela6pacieni(2,35%)din recaretreicuboalCrohnlanivelulintestinuluisubirei3pacienicuenteropatiegluteniccomplicat.

Examinri complete lanivelul intestinului subire au fost233 (91,37%) cuuntimpmediudetranzitlanivelulintestinuluisubirede261deminute.Avndnvederecamutilizatcaiprokineticfosfatdesodiupentruprotocoluldeexaminareintestinsubie i colon, am exclus aceti pacieni, obinnd un timp mediu de examinare aintestinuluisubirede287minute.

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Ratadedetecieaformaiunilortumoralesituatelanivelulintestinuluisubiredintotalitatea examinrilor efectuate cuVCEa fost n studiulnostrude5,49%, celemaifrecventefiindadenocarcinoameleiGISTurile.

PerformanadiagnosticaVCElapacieniicusindromdiareiccronic,franemiesau modificri inflamatorii a fost de 35,29%, iar la cei cu dureri abdominalenesistematizatenabsenamarkerilorinflamatoriafostde38,7%.

Studiul2AportuldiagnosticalvideocapsuleiendoscopicenbolileinflamatoriiintestinaleIpotezdelucru/obiective

Avndnvederecategoriilediferitedepacienicuboliinflamatoriiintestinale,sau identificat trei grupuri de pacieni, la care performana diagnostic a VCE a fostcuantifi .cat separat

LotulAPrin analiza retrospectiv a 23 de pacieni suspectai de boal Crohn i

examinai cu VCE neam propus determinarea performanei diagnostice a acesteiexaminri, determinarea parametrilor predictivi clinici i paraclinici pentru oexaminarepozitivievaluareaconsecinelorclinicealeexaminrii.

LotulBLasublotulde36depacieni cunoscuicuboalCrohnamurmritdetectarea

leziunilor sugestive de activitate a bolii n vederea explicrii simptomelor, respectivvindecareamucozal,urmrindimpactulterapeuticdupexaminareacuVCE.

LotulCLasublotulde6pacienicucolitnedeterminatamanalizatperformanaVCE

dencadrarenozologicnboalCrohn,respectivcolitulcerativ.

MetodologieLezi stinterunileaufo nfelulurmtor

rezultatepozitive fostnaltsugestivedeboalCrohn te3ulceraiisauafte,

pretate dacau

rezultateposibilpozitivedacaufostprezentepesposibileboliCrohnincipiente;

corespunzndunui formulareaaltordiagnosticepebazaleziunilorgsite

rezultatenegativepentruboalaCrohndacnuaufostdepistateleziunisauaufostprezenteariiminoredeeritem,micizonededenudrialemucoasei,limfangiectazii, aspect micropolipid al ileonului terminal (hiperplazieinodularelimfoide).

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DiagnosticulfinaldeboalCrohnsapuslaunandeevoluie,princoroborareadatelorclinice,biologice,endoscopice,histologiceiimagistice.

RezultatePerformana diagnostic a examinrii cu VCE la pacienii cu suspiciunea de

boal Crohn este de 47.22%, dac se consider totalitatea examinrilor care relevleziuniulcerative(rezultatepozitiveiposibilpozitive).

IdentificarealeziunilornaltsugestivedeboalCrohn(ulcereserpinginoase,ariiinflamatoriimarcate,aspectdepiatrdepavaj)cuajutorulVCEareospecificitatede88.88% i o valoare predictiv pozitiv de 75% pentru diagnosticul final de boalCrohn.DacnanalizarezultatelorVCEseiaunconsiderareiprezenamodificrilorulcerativeminimespecificitateaestede70.34%ivaloareapredictivpozitiv52.94%,valoar t n nu e te u ilizat n practica cli ic, care poat constitui un argumen pentru undiagnosticpozitivioterapiespecific.

La pacienii suspectai de boal Crohn, prezena parametrilor inflamatoriasociaimanifestrilorclinicepledeaznfavoareaunuirezultatpozitivlaexaminareacu VCE. Prezena simptomelor extraintestinale (artralgii, boal perianal, eritemnodos, colangit sclerozant primitiv) este predictiv pentru un rezultat pozitiv deboalCrohnlanivelulintestinuluisubire.

La pacienii cu boal Crohn cunoscut, utilizarea protocolului adaptat pentruvizualizareaintestinuluisubireiacolonuluiconducelaoperformandiagnosticde78% d xac se consider toate leziunile ulcerative i de 65,21% dac se e cludexaminrilecarerelevnumaiprezenaulceraiilorisauaaftelor.

La pacienii cunoscui cu boal Crohn nu se documenteaz o corelaie ntremanifestrileclinice,biologiceiimagistice.

Examinarea cu VCE la pacieni cu boal Crohn cunoscut a condus la oschimbare terapeutic la 70% din cazuri i a schimbat diagnosticul la 4 pacieni(17.39%)(enteropatiegluteniccujejunoileitulcerativ).

Studiul3Aportuldiagnosticalvideocapsuleiendoscopicenenteropatiaglutenic Ipotezdelucru/obiective

Un prim obiectiv a fost caracterizarea leziunilor depistate de VCE la 20 depacien u s al m ei c no cui cu bo celiac, la care si ptomel au persistat, n vedereadepistriieventualelorcomplicaii.

Un alt obiectiv a fost definirea rolului VCE n diagnosticul de novo alenteropatiei glutenice la toi pacienii examinai cu manifestri clinice tipice sau

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atipice prin identificarea atrofiei vilozitare clasice i a reducerii dimensiunilormarginiinperie.

Meto gdolo ieLotulAestealctuitdin20depacienidiagnosticai anterior cuboal celiac.

Indicaia dezvoltrii complicaiilor, ncontex

pentru examinarea cu VCE a fost suspiciuneatulpDin

ersisteneisimptomelori/sauaanemiei.dateleexaminriicuVCEaufostconsemnate:

prezenasemnelorclasicedeatrofievilozitar:aspectulfestonatalpliurilornale,mucoasei, prezena fisurilor, pierderea pliurilor circulare duode

aspectulmozaicatsaunodulariextinderealorprezenareduceriiparialeamarginiinperiesaumodificriparcelare;

prezenaulceraiiloriaulcerelor,aformaiunilortumorale,astricturilorialeziunilortumoralesuspecte(bulgingmass).

SeleciapentrulotulBsaefectuatastfel:dintretoipacieniiinvestigaicuVCEaufostexcluiceicunoscuicuboalceliaciulterioraufostselectateexaminrilelacare sa descris reducereamarginii n perie saumodificri nalt sugestive de atrofievilozitar.

RezultateLaunnumrde15pacieni(75%)sadescrisaspecttipicdeatrofievilozitar,

modificrimucozalefiindcontinuela14pacieniiparcelarelanivelulduodenuluiijejunuluilaunpacient.Ladoipacieni(10%)sadescrisunaspectdereducereparialamarginiinperieilatreipacieni(15%)examinareacuVCEafostnlimitenormale.La toi pacienii care prezentau modificri tipice de atrofie vilozitar rezultatulanatomopatologic a demonstrat gradul sever al atrofiei (gradul III Marsh). Atrofievilozitarsemnificativafostdocumentatla64,28%(9/14)dinpacieniicomplianila regimul fr gluten, acetia fiind diagnosticai cu boal celiac refractar. Toipacieniinoncomplianilatratamentprezentauatrofievilozitarextins(la4pacienila nive llul jejunului i la 2 pacieni la nive ul ileonului). Noncompliana la regim sensoetedeatrofiesemnificativmaiextins(p=0,026testulPearsonChisquare).

La jumtate din pacienii lotului A examinarea cu VCE a depistat modificrisugestive pentru complicaii ale bolii celiace: jejunoileit ulcerativ 35%, suspiciunenaltde limfomla15%.Extinderea leziunilordeatrofieestecorelatcudezvoltareacomplicaiilor(p=0.039,testulPearsonChisquare).

Lotu 45 cien a datrofievilo

lB (tabelul6) a cuprins pa i la care u fost escrisemodificridezitardin235deexaminrilapacieninecunoscuicuboalceliac:

10 examinri cu leziuni nalt sugestive de atrofie vilozitar, confirmatebiopticcafiindenteropatieglutenicMarshIII;

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m 35exa inricureducereamarginiinperie,dincareunpacientaprezentatmodificrimixteMarshIIiIIIa.

Diagnosticul final de boal celiac a fost formulat la 4,68% pacieni (11/235),dintre care peste jumtate (54,54%) prezentau complicaii de tipul jejunoileiteiulcerative.ImaginiledepistatelaVCEiinterpretatecaireducereamarginiinperieau o specificitate redus pentru boala celiac 2,85%, impunnduse efectuareabiopsiilorduodenale.

Studiul4AportuldiagnosticalexaminriicuvideocapsulaendoscopiclapacieniicuhemoragiedigestivobscurIpotezdelucru

Prinanalizaretrospectiva93depacienicuhemoragiedigestivexaminaicuVCEneampropusdeterminareaperformanei diagnostice, identificareaunor factoriclinic predictivi pentru un rezultat pozitiv i studierea consecinelor clinice aleexaminriicuVCE.

MetodologieAnalizaperformaneidiagno ticeAvnd n vedere necesitile clinice practice, propunem o alt clasificare a

hemorag

s

iilordigestiveobscuren:1. emH oragiidigestiveobscure,active(lotulA)a. detectarealeziunilorresponsabiledesngerareaactiv

enia o leziune (sunt necesarentrudiagnosticitratament

b. detectarea sngelui luminal, fr a se evidalteexplorriinvazivesauchirurgicale)pe

ec. rezultat negative(examinriincomplete)H oragiidigestiveobscure,oprite(lotulB)a. Leziuni cu potenial hemoragic cert (vasculare, ulcerative, neoplazice,

m

2. em

ischemie ezenteric, fistule enterale, fistule enterovasculare,hemosuccuspancreaticus)

ial hemoragic incert (bulging mass, limfangiectazii,b. Leziuni cu potenflebectazii)

c. Rezultatenegative3. neA miiferiprivedecauzneprecizat(HDOoculte)(lotulC)a. Leziuni cu potenial de a explica anemia feripriv (leziuni vasculare,

ulcerative,neoplazice, inflamatorii, ischemiemezenteric,modificricarepotmpiedicaabsorbiafierului)

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lincertdeaexplicaanemiaferiprivb. Leziunicupotenia

c. Perf

Rezultatenegativeormanadiagnosticafostcalculatdiferit:

- pentru HDO activ, procentul examinrilor care au identificat loculuisngerriisaualeziunilorrspunztoaredehemoragie

pentruHDOmanifestclinic,opritprocentulexaminrilorcareaudepistaleziunicupotenialhemoragiccert.

pentruanemiaferiprivprocentulexaminrilorcareaudepistat leziunicupotenialcertdeaexplicaanemiaferipriv.

RezultatePerformana diagnostic la pacienii cu HD obscur activ este de 96,62%, la

pacienii cu HD manifest clinic, oprit este de 71,79%, iar la pacienii cu anemieferipriv de cauz neprecizat este de 45,16%. Aceast nou clasificare reflectimpactul examinrii cu VCE asupra investigaiilor ulterioare: scade numrulenteroscopiilordela39,13%nHDactive,la28,25%nHDoprite,respectivla16,12%n anemii feriprive. De asemenea scade necesarul interveniilor chirurgicale de la21,73%nHDactive,la15,38%nHDinactive,respectivla6,45%nanemiileferiprive.Proporionalseconstatcretereaconduiteiconservativelaceletreiloturi.

UtilizareaVCE lapacieniicuHDactivacondus laoperformandiagnosticcrescut de 95,62%, iar n sublotul de pacieni cu instabilitate hemodinamicperformana diagnostic a fost de 88,88%. O particularitate a studiului o reprezintprocentul mare de ulcere Dieulafoy identificate pe intestinul subire i un ulcerDieulafoycolonic.

PerformanadiagnosticaVCEdeadetecta leziuniresponsabiledehemoragielapacienicuHDobscur,opritestede71,79%.EfectuareaVCEnprimeleaptezilede la oprirea hemoragiei se asociaz semnificativ cu identificarea leziunilor cupotenial hemoragic cert (p=0.022). Consumul de AINS este un parametru predictivindependentpentruundepistareauneileziunicupotenialhemoragiccert(p=0,037)lapacieniicuhemoragiedigestivmanifestclinic,inactiv.

Performana diagnostic a VCE de a detecta leziuni cauzatoare de anemieferiprivestede45,16%.

Enteropatia indusdeantiinflamatoarenonsteroidieneesteprincipala cauzaHDobscureopriteiaanemiilorferiprivedecauzneprecizat.

Analiza univariat a artat c utilizarea de AINS i efectuarea VCE n primeleapteziledelaoprireahemoragieiseasociazsemnificativcuidentificarealeziunilorcupotenialhemoragiccert la lotulB.Vrstapeste70deani,ceamaimicvaloareahemoglobinei, utilizarea antiagregantelor, utilizarea anticoagulantelor, patologiacardiovascular nu se asociaz cu depistarea leziunilor cu potenial hemoragic.Protocolul de examinare cu VCE pentru intestin subire a condus la rezultate

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concludente n66,6%dincazuri, iarprotocolulpentru intestin subire i colon launprocentmultmaimarede87,5%(fraatingepraguldesemnificaiestatistic).

La ntreaga populaie de studiu, VCE a identificat 11,82% leziuni la nivelulstomaculuisicolonului,responsabilepentruhemoragiadigestivsauanemiaferiprivcareiniialnuaufostevideniatedeendoscopiileclasice

LaunandelaexaminareacuVCEevoluiaafostfavorabilla61%dinpacieniilotuluiAila87%dinpacieniilotuluiB,respectivC.

Studiul5EfectulrifaximineiasupraenteropatieiindusedeindometacinlacobaiIntroducereTranslocarea bacterian la nivelul intestinului subire este prima modificareresponsabildeactivareastresuluioxidative(iNOS/NO)ianeutrofilelor,implicatenpatogenezaleziunilorindusedeindometacinlanivelulintestinluisubire.Ipotezdelucru/obiectiveeampropusstudiereaefectelorrifaximineiasupraleziunilorindusedeindometacinanivelulintestinuluisubirelacobai.NlMaterialimetode.Animaleleaufostmpritenpatruloturiintervenionalecareaucuprinsaseanimalefiecare (notate de la A la D) i un lot martor de trei animale. Lotul A a primitindometacin administrat oral o dat pe zi (30mg/Kg), timp de trei zile consecutiv.Aceeidozdeindometacinafostasociatcudozediferitederifaximin:50mg/kgla

olotul B, 100mg/kg la lotul C i 200mg/kg la lotul D. Animalele din l tulmartor auprimitserfiziologicfrmedicamente(vehicul).Dup 72 de ore animalele au fost sacrificate i intestinal subire a fost investigatmacroscopicpentrudecelareaariilordeinflamaie,respectivedeulceraie,careaufostulterior examinate microscopic. Am gradat rspunsul inflamator (prin cuantificareaneutrofileloriaeozinofilelordelanivelulmucoasei),leziuniledegenerative(necrozafocal sau a extremitii superioare a vilozitilor, necroza mai mare de 1/3 dinmucoasa, necroza transmural), modificrile endoteliului vascular (congestie,tromboz, inflamaieperivascular).Amcuantificatsemicantitativ imunopozitivitateaiNOS la nivelul epiteliului de suprafa, a epiteliului glandular i la nivelul lamineipropria.RezultateAnaliza statistic nu a gsit diferene semnificative ntre grupurile A i B n ceea ceprivete leziunile macroscopice, leziunile degenerative microscopice, afectareaendoteliului i imunopozitivitatea iNOS. Semnificativmaipuine leziunidegenerativemacroscopice (U=3, p=0.015) i microscopice (U=2, p=0.008) au fost depistate lagrupul C comparative cu grupul A; de asemenea grade semnificativ mai reduse ale

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imunopozitivitiiiNOSaufostdepistatengrupulC(U=0,p=0.002).ngrupulDsauobinut grade ale imunopozitivitii iNOS semnificativ mai reduse fa de grupul A(U=0, p=0.002) i leziuni degenerative mai puine, dar fr a se atinge pragulsemnificaieistatistice(U=4,p=0.026).Concluzii:Rifaximina ndozde100mg/kgsadovediteficient nprevenirea leziunilor indusede AINS la nivelul intestinului subire al cobailor, imunopozitivitatea iNOS fiindsemnificativredus.Efectulprotectivparesfiedependentdedoz,fiindnecesarealtecercetri privind interaciune acomplex dintre AINS, populaia bacterian irifaximinpentruadocumentaaceastobservaie.

Studiul6InterrelaiadintreAINSiCandidaalbicanslanivelultubuluidigestivalcobailorIntroducereStudiirecenteausugeratccolonizareacuCandidaalbicansesteasociatcuafeciuniinflamatorii gastrointestinale, fiind responsabile pentru ncetinirea proceselor devindecare a ulcerelor peptice. Nu sunt raportate date n literatur privind efectulcolonizrii cu Candida albicans a leziunilor degenerative induse de indometacin lanivelul tubului digestive. Alte cercetri argumenteaz efectele benefice aleantiinflamatoarelor nonsteroidiene privind scderea potenialului de colonizare aCandideialbicans.Ipotezdelucru/obiectiveeampropusstudiereainterrelaieidintreindometaciniCandidaalbicanslanivelulractuluidigestivea obailor.Nt lcMaterialimetode.Animalele au fost mprite n trei loturi intervenionale care au cuprins11 animalefiecareiunlotmartordetreianimale.Unlotaprimitindometacinadministratoralodatpezi(30mg/Kg),timpdecincizileconsecutiv.Aceeidozdeindometacinafostadministrat i celui de al doilea lot, care a primit ulterior i colonii de Candidaalbicans. Un lot a fost colonizat cu Candida albicans. Animalele au fost sacrificate iintestinalsubireafost investigatmacroscopicpentrudecelareaariilordeinflamaie,respective de ulceraie, care au fost ulterior examinate microscopic. Am gradatrspunsul inflamator (prin cuantificarea neutrofilelor i a eozinofilelor de la nivelulmucoasei), leziunile degenerative i modificrile endoteliului vascular (congestie,tromboz,inflamaieperivascular).RezultateAdministrarea indometacinului nu scade semnificativ capacitatea de colonizare aCandidei albicans. Administrarea indometacinului i ulterior a Candidei albicans a

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determinat leziuni semnificativmai importante dect la grupul care a primit numaiCandidaalbicansileziuniasemntoarecugrupulcareaprimitnumaiindometacin.Concluzii:IndometacinulnureducesemnificativcapacitateadecolonizareaCandideialbicanslanivelul mucoasei tubului digestiv al cobailor. Asocierea Candidei albicans laindometacinnuaconduslaleziunidegenerativemaiimportantedectceleprodusedeindometacin.

ConcluziigeneraleExaminri complete la nivelul IS au fost 233 (91,37%) cu un timpmediu de

tranzit la nivelul intestinului subire de 261 de minute. Retenia capsulei care anecesitatinterveniechirurgicalsanregistratla5pacieni(1,96%).

Rata de detecie a formaiunilor tumorale situate la nivelul IS din totalitateaexamin c crilorefectuateafostde5,49%, elemaifrecventefiindadenocar inoameleiGISTurile.

Performana diagnostic a VCE la pacienii cu sindrom diareic cronic, franemi i alee saumodificri inflamatorii a fostde35,29%, ar la cei cudureri abdominnesistematizatenabsenamarkerilorinflamatoriafostde38,7%.

Performana diagnostic a examinrii cu VCE la pacienii cu suspiciunea deboal Crohn este de 47.22%, dac se consider totalitatea examinrilor care relevleziuniulcerative (rezultatepozitiveiposibilpozitive). Identificarea leziunilor naltsugestive de boal Crohn (ulcere serpinginoase, arii inflamatorii marcate, aspect depiatr p a E e ede avaj)cu jutorulVC areospecificitat de88.88%iovaloar predictivpozitivde75%pentrudiagnosticulfinaldeboalCrohn.

La pacienii suspectai de boal Crohn, prezena parametrilor inflamatoriasociaimanifestrilorclinicepledeaznfavoareaunuirezultatpozitivlaexaminareacu VCE. Prezena simptomelor extraintestinale (artralgii, boal perianal, eritemnodos, colangit sclerozant primitiv) este predictiv pentru un rezultat pozitiv deboalCrohnlanivelulintestinuluisubire.

La pacienii cu boal Crohn cunoscut, utilizarea protocolului adaptat pentruvizualizareaISiacolonuluiconduce laoperformandiagnosticde78%.Laacetipacieni nu se documenteaz o corelaie ntre manifestrile clinice, biologice iimagistice. Examinarea cu VCE la pacieni cu boal Crohn cunoscut a condus la oschimbare terapeutic la 70% din cazuri i a schimbat diagnosticul la 4 pacieni(17.39%)(enteropatiegluteniccujejunoileitulcerativ).

Aspectul tipic de atrofie vilozitar depistat de VCE, nalt sugestiv de boalceliac are o sensibilitate i o specificitate de 100% pentru diagnosticul de boal

15


celiac Marsh III att la pacien ii cunoscui cu boal celiac, ct i la cei noudiagnosticai.

n studiulnostru, jumtatedinpacienii cunoscui cuboal celiac care aveaupersistenta simptomelor au prezentat complicaii (jejunoileit ulcerativ, strictur,limfom),cumeniuneacotreimedinpacieninuerauaderenilaregimulfrgluten.

Procentul mare de complicaii depistat la lotul nostru de pacieni cu boalceliac 5 de a simptomatici ( 0%), in pendent de vrst, valoarea hemoglobinei s ucomplianalaregimulfrglutenimpuneefectuareaexaminriicuVCE.

Noua clasificare propus pentru cuantificarea rezultatelor VCE adaptat lasituaiiclinicespecificeHDOaduceinformaiiutileprivindperformanadiagnosticiconduita terapeutic. Performana diagnostic la pacienii cu HDO activ este de96,62%,lapacieniicuHDOmanifestclinic,opritestede71,79%,iarlapacieniicuanemie feripriv de cauz neprecizat este de 45,16%. Aceast clasificare reflectimpactul examinrii cu VCE asupra investigaiilor ulterioare: scade numrulenteroscopiilordela39,13%nHDactive,la28,25%nHDoprite,respectivla16,12%n anemii feriprive. De asemenea scade necesarul interveniilor chirurgicale de la21,73% nact nnHDactive,la15,38%nHDi ive,respectivla6,45% anemiileferiprive.Proporionalseconstatcretereaconduiteiconservativelaceletreiloturi.

Performaa diagnostic a VCE la pacienii cu hemoragie digestiv activ cuinstabilitate hemodinamic performana diagnostic a fost de 88,88%. Oparticu t olaritateas udiului reprezintprocentulmaredeulcereDieulafoyidentificatepeintestinulsubireiunulcerDieulafoycolonic.

Efectuarea VCE n primele apte zile de la oprirea hemoragiei se asociazsemnificativ cu identificarea leziunilor cu potenial hemoragic cert (p=0.022).ConsumuldeAINSesteunparametrupredictivindependentpentruundepistareauneileziuni cu potenial hemoragic cert (p=0,037) la pacienii cu hemoragie digestivmanifestclinic,inactiv.

Enteropatia indusdeantiinflamatoarenonsteroidieneesteprincipala cauzaHDOopriteiaanemiilorferiprivedecauzneprecizat.

La ntreaga populaie de studiu, VCE a identificat 11,82% leziuni la nivelulstomaculuisicolonului,responsabilepentruhemoragiadigestivsauanemiaferiprivcareiniialnuaufostevideniatedeendoscopiileclasice.

Rifaximina n dozde100mg/kg sa dovedit eficient n prevenirea leziunilorindusedeAINSlanivelulintestinuluisubirealcobailor,imunopozitivitateaiNOSfiindsemnificativredus.Efectulprotectivparesfiedependentdedoz,fiindnecesarealtecercetri privind interaciune acomplex dintre AINS, populaia bacterian irifaximinpentruadocumentaaceastobservaie.

Datele nostre pe modele experimentale nu au adus argumente pentrucapacitatea AINS de a scdea potenialul Candidei albicans de a coloniza mucoasatubului digestiv al cobailor. Asocierea dintre AINS i Candida albicans a determinatsemnificativ mai multe leziuni degenerative dect cele produse de ctre Candidaalbicans, dar nu a augmentat potenialul necroinflamator al AINS asupra mucoaseigastriceienteraleacobailor.

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PhD Thesis - abstract

Diagnostic yield of capsule endoscopy

PhD Candidate Ciobanu Lidia

P

hD Advisor MD PhD Oliviu Pascu

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TableofcontentsINTRODUCTION 15

CURRENTSTATEOFKNOWLEDGE1.Exa ueminationtechniq

19

1.1.Technicalaspects1.2.Practicalaspects

1920

2.ClinicalaspectsofVCEexaminationmination

232.1.SemiologyofidentifiedlesionsonVCEexa

lesions23292.2.HighlysuggestiveCrohnsdisease

2.3.Specificlesionsforceliacdiseasecausedbynonsteroidalantiinflammatorydrugs

292.4.SmallbowellesionsNSAIDsenteropathy 302.5.Radiationenteritis

invasculitis31

2.6.Smallbowellesionss

312.7.Infectionsenteriti2.8.Rarepathologies

3233

3.DiagnosticyieldandclinicalimpactofVCEtestinal

353.1.DiagnosticyieldandclinicalimpactofVCEinobscuregastroinbleeding

Crohnsdisease35

3.2.DiagnosticyieldandclinicalimpactofVCEin 383.3.Diagnosticyieldofcoloncapsuleendoscopy3.4.Diagnosticyieldofesophagealcapsuleendoscopy

4041

Personalcontribution 43

451.Aims2.Methodology 463. 1st study Diagnostic yield ofVCE in small and large bowelpathology

round48

3.1.Backg 483.2.Aims

logy49

3.3.Methodo 493.4.Results 50

573.5.Discussions3.6.Conclusions 60

4. 2nd study Diagnostic yield of VCE in inflammatory boweldisorders

round61

4.1.Backg4.2.Aims

6162

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4.3.Methodology 624.4.Results 654.5.Discussions4.6.Conclusions

7276

5.3rd osticyieldofVCEinceliacdiseasestudyDiagnround


ology78

5.3.Method 795.4.Results 795.5.Discussions5.6.Conclusions

8486

6.4thstudyDiagnosticyieldofVCE]nobscuregastrointestinalbleeding

round


logy90

6.3.Methodo 906.4.Results 936.5.Discussions6.6.Conclusions

102109

7.5thstudyEffectsofrifaximinonindomethacininduceintest inguineapigsinaldamage

round110


ology111


118120

8.6thstudyTheinterplaybetweenNSAIDsandCandidaalbicansonthe inaltractofguineapigsgastrointest

round121


ology122


129131

7.Generalconclusions 1331378.Originalityandinnovativecontributionofthethesis

19


References 139

157AppendixKey words: videocapsule endoscopy, obscure gastrointestinal bleeding,inflammatory bowel diseases, celiac disease, nonsteroidal antiinflammatorydrugsenteropathy(NSAIDsenteropathy),rifaximin,gutimmunologyIntroduction

The development of VCE in 2001 represented a major progress for directexploration of small bowel, generated tremendous hope and challenged thedevelopmentofnoninvasiveendoscopyforahighaccuracyexaminationoftheentiredigestivetract.Theexperienceacquiredinthelast10yearswasfollowedbynumerousstudies regarding diagnosis yield of esophageal, small bowel and colon capsule invariousdisorders.

ThisPhDthesisstudiedthediagnosticyieldofVCEinentericpathologyon255examinationperformedbetweenNovember2005andJune2013in3rdMedicalClinic,ClujNapoca. The most frequent identified pathology was NSAIDs enteropathy, thatpromotes two experimental studies. First experimental model investigated thepotentialprotectiveroleofrifaximinonindomethacininducedenteropathyinguineapigs. T he second experimental model describes the interplay between NSAIDs andCandidaalbicansonguineapigsdigestivetract.

In theoretical part the technique of VCE examination is presented. Thesemiological appearance of different lesions is described, being illustrated in firstappendix. The bibliographic study present in a rigorous and concessivemanner thediagnosticyieldandclinicalimpactofVCE,basedon191references.AimsOur generexaminatio

al objectives were the assessment of our experience with VCE (255nson252consecutivepatients)regarding:

- fthetwoprotocolused(oneforsmallbowelandonetechnicalfeasibilityofortheentiregut)

- clinicalapplicability.The eseparatelyquantifiedforthe

maininddiagnosticyieldandclinical impactwer

- in1ststudyications:

l-

smallandlargebowe tumorst

- abdominalpainin1 study

dy- nd

chronicdiarrheain1ststu

- inflammatoryboweldisordersin2 studyceliacdiseasein3rdstudy

- obscuregastrointestinalbleedingin4thstudy

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NSAIDsenteropathywasstudiedintwoexperimentalstudies:- thstu the5 dyanalyzedthe potentialroleofdifferentdosesofrifaximin

forpreventingindomethacininducedintestinaldamageinguineapigs.- the 6th research studied the interplay between NSAIDs and Candida

albicansinguineapigsdigestivetract.Methodology

Clinical studies were done in a single tertiary center: Regional Institute ofGastroenterology and Hepatology, Cluj, University of Medicine and Pharmacy IuliuHatie numberof255examinationswere ere:

ganu,betweenNovember2005and June2013.A

- analyzedon252consecutivepatients.TheVCEreferralreasonsw

- obscuregastrointestinalbleeding,activeorstoppedirondeficiencyanemia(occultobscuregastrointestinalbleeding)

- bowel disease: suspected Crohns disease, knownCrohns diseaseinflammatory

- andundeterminedcolitis

- rlargeboweltumorceliacdisease

o

suspectedsmallea- chronicdiarrh

- Excl

abdominalpain.

- usioncriteria

bowel- easedflow

knownstrictureofsmalltulawithincrpreviousfis

- deglutitionimpairments- pTwop

regnancy

- rotocolsofVCEexaminationwereused:ExaminationforsmallbowelwithPillCamSB1and2

- ExaminationforentiregutwithPillCamColon1and2afteramodifiedprotocolforacompletegutexamination.Thebowelcleannesswasachievedafter4 literingestionofFortrans.WeusedthisprotocolifthepatientspresentedOGIBandthepreviouscolonoscopywasdoneinthelast36monthsorthecleannesswasinadequate,ifaenterictumorwassuspectedorinpatientswithCrohnsdiseaseorundeterminedcolitisinordertoachieveacompletegutevaluation.Therecordeddatawereanalyzed independentlybytwophysicians,withRapid

d s o nfre

softwerewithame ium peedof1214images/sec nd.Thereadi gwasdoneinlessthan12hoursfromtheendo cording. Methodology used in experimental model is described separately, beingdifferentforthetwostudies.

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1stStudyDiagnosticyieldofvideocapsuleexaminationinentericpathologyAimsOurobjectivesweretheassessmentofourexperiencewithVCE(255examinationson252consecutivepatients)regardingtechnicalfeasibilityofthetwoprotocolused(oneforsmallbowelandonefortheentiregut)andclinicalapplicability.Inthisstudythediagnostic yield and clinical impact were quantified separately for: suspected gutumor (29 examinations), abdominal pain (17 patients) and chronic diarrhea (31atients).

tpResultsThereferralreasonsforVCEexaminationswere:

ions(36.5- - %)Obscuregastrointestinalbleeding:93examinat

- Inflammatoryboweldiseases:65examinations(25.5%)

%)- el):29examinations(11.4%)

Knownceliacdisease:20examinations(7.8

- Suspectedenterictumor(smallorlargebowChronicdiarrhea:17examinations(6.7%)

- Abdominalpain:31examinations(12.1%)From255examinations,178(69.8%)weredoneusingsmallbowelprotocoland

77(30.2%)usingamodifiedprotocolinordertoexaminetheentiregutmucosawithcoloncapsule.Capsuleretentionrequiringsurgerywasobservedin5patients(1.96%).Capsuleretentionforlessthan48hourswasrecordedin6patients(2.35%),threeofthemwithCrohnsdiseaseandthreewithcomplicatedceliacdisease.Completesmallbowel examination were achieved in 233 patients (91.37%) with a medium smallboweltransittimeof261minutes.Afterexclusionofpatientsthatweregivensodiumphosphateboostwecalculatedamediumsmallboweltransittimeof287minutes.

Thedetectionrateoftumormasseslocalizedinthesmallbowelwas5.5%,mostfrequenttumorsbeingadenocarcinomaandGISTs.

hediagnosticyieldofVCE inpatientswithchronicdiarrhea,withoutanemiaorinflammatorysignswas35.3%andinpatientswithabdominalpain38.7%.

T

2nd Study Diagnostic yield of VCE in inflammatory

boweldiseasesAimsThediagnosticyieldwasquantifiedseparatelyforspecifictypesofpatients:

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- GroupA:23suspectedCrohnsdiseasepatientsthediagnosticyieldofVCE,clinicalandparaclinicalpredictiveparametersforapositiveexaminationandclinicalconsequences

- GroupB:36patientswithknownwithCrohnsdiseasedetectionofactivesuggestivelesionsinordertoexplainsymptoms,detectionofmucosalhealing

6patientswithundeterminedcolitisdiagnosticyieldforcorrectlyorulcerativecolitis.

- GroupC:

MidentificationofCrohnsdisease

ethoLesi

dology

- onswere quantifiedasfollow:PositiveresultsiftherearehighlysuggestiveforCrohnsdisease

- re more than three ulcerations of aphtae,Possible results if there we

- correspondingtopossibleearlyCrohnsdiseaseAnothersignificantdiagnosis

- Negativeresults forCrohnsdisease ifno lesionsweredetectedor ifsmallmucosal lesionswere identified: smallareasoferythema,mucosalbreaks,lymphangiectasia, micropolyps of terminal ileum (nodular lymphatichyperplasia)

hefinaldiagnosisofCrohnsdiseasewasmadeafteroneyearofevolutionbyakingincountclinical,biological,endoscopic,histologicalandimagisticresults.TtResultsThe diagnostic yield of capsule endoscopy in patients suspected by Crohns

diseaseis47.22%ifallexaminationthatidentifiedulcerativelesionswereconsidered(positiveandpossibleresults).

Highly suggestive lesions for Crohns disease (linear, deep ulcers, markedinflammatoryareas, cobble stoneappearance) identifiedbyVCEhavea specificityof88.8%andpositivepredictivevalueof75%forthefinaldiagnosisofCrohnsdisease.Ifsmallulcerativelesionsweretakenincount,thespecificitywas70.3%andapositivepredic e d in l d etiv value:52.9%;these ata areused clinica practicean cannotbeus dforpositivediagnosticandspecifictherapy.

In patients suspected of Crohns disease, biological inflammatory signsassociatedwith clinicalmanifestation argue for positive results on VCE. Presence ofextraintestinalsymptoms is independentlyassociatedwithapositiveresult forsmallbowelCrohnsdisease.

In patients known with Crohns disease, the protocol for the entire gutvisualization provide a diagnosis in 78%of patients if all degenerative lesionswerecountered and 65.21% if only highly suggestive lesions are considered. In thesepatien its there is no correlation between clinic, biology, endoscopy and magisticstudies.

After VCE examination, in 70%of patients a therapeutically changewas doneandacompletelychangeofdiagnosisin17.4%(complicatedceliacdisease).

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3rd Study Diagnostic yield of videocapsuleendoscopyinceliacdiseaseAims

Our first objectivewas lesion characterizationdepictedbyVCE in 20patientsknown with celiac disease, with persisting symptoms in order to detect decomplications.AnotheraimwastodefinetheroleofVCEindiagnosisceliacdiseaseinsymptomatic patients through identification of villous atrophy or reduced villouslength.Methodology

In the groupAwe have 20 patients previously diagnosedwith celiac disease.Thereferra ti atientssymptomso

lreasonforVCEwasdepic onofcomplication,asthesep presentedranemia.RecordeddataonVCEwere

- circular folds,The presence of classical signs of villous atrophy: loss of

- fissures,mosaicornodularpatternandtheirextensionThepresenceofreducevillouslengthorpatchydistribution

o i- Thepresence fulcerat velesions,tumormasses,stricturesandsuspectedmasslesionscalledbulgingmass

The selection for group B was from all patients investigated with capsuleendoscopy,withoutthosealreadyknownwithceliacdiseaseinwhichareducedvilloussizeorclassicalpatternofatrophywasdetected.

Results

In 15 patients (75%) of group A, classical villous pattern was depicted,continuous distributed in 14 patients and patchy in one patient at duodenum andjejunum. In twopatients (10%)a reducedvillous lengthwasdescribedand in threepatients the examination did not find lesions. In all patients with typical atrophiclesions,thehistologicalexaminationdemonstratedtheseveregradeofvillousatrophy(grade III Marsh). Significant villous atrophy was documented in 64.28% (9/14)patientswhowerecomplianttoglutenfreediet.Allpatientsnoncompliantonglutenfreediethadextendedvillousatrophy:4patientsatthejejunumand2patientsattheileum. Noncompliance to glten free diet was significantly associatedwith extendedvillousatrophy(p=0.026,PersonChisquare).

VCEdepictedlesionssuggestiveforcomplicatedceliacdiseaseinhalfofpatientsfrom group A: ulcerative jejunoileitis: 35%, highly suspected neoplasia in 15%.Extensionofvillousatrophywascorrelatedwithcomplicationdevelopment(p=0.039,PearsonChisquaretest).

GroupBcomprised45patientsinwhichthetotalorsuspectedvillousatrophywas depicted from a total number of 235 examinations in patients not knownwith

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celiac disease: 10 patientswith tipical atrophyc lesions, confirmedMarsh III and 35patientswithreducedvilloussize,buthistologyconfirmedatrophyonlyinonepatient.

The finaldiagnosisof celiacdiseasewasmade in4.68%patients (11/235), inwhom alfhad jejunoilietis. Imageswhichdepictedreducedvillousatrophyhaveaverylowspecificityforceliacdisease:2.85%,duodenalbiopsybeingrequired.

h

4th Study The diagnostic yield of capsule endoscopy in

obscuregastrointestinalbleeding

AimsWeaimedtodeterminethediagnosisyieldofVCEin93patientswithobscure

gastrointestinal bleeding, to predictive parameters for a positive result and clinicalconsequencesofVCEexamination.Methology

lrequirementswithproposedanotherclassificationofobscur

Consideringthepracticae1.gastrointestinalbleeding(OGIB):OGIBactive(groupA)a.Detectionoflesionsresponsibleforactivebleeding

out identification of lesion (areent

b. Detection of intraluminal bleeding withnecessaryotherinvasiveexaminationorsurgeryfordiagnosticandtreatmc.negativeresults(incompleteexamination)

2.OGIB,clinicallymanifest,stoppedattheVCEtimeexamination(groupB)a. Lesions responsible for bleeding (vascular lesions, ulcerative, neoplasic

lesions ischemia fist ic fis, mesenteric , enteric ula, enter vascular tula, hemosucccuspancreaticus)

rtain potential bleeding (bulging mass,lymph

b.Lesions with unceangiectasia,flebectasia)c.Negativeexamination3.Irondeficiencyanemia(occultOGIB)(groupC)

re ibl ef lar lceuc ns irs

a.Lesions spons eforirond iciencyanemia(vascu lesions,u rative,neoplasiclesions,mesentericischemia,m osallesio thatimpa ironabsorption)

ertain potential bleeding (bulging mass,lymph

b.Lesions with uncangiectasia,flebectasia)c.Diag

Negativeexaminationnosticyieldwascalculatedseparately:

- tfor activeOGIB, thepercentage of examinations tha identifies the site ofbleedingorthesourceofbleeding

- for stopped OGIB, the percentage of examinations that depicted lesionsresponsibleforbleeding

25


- for irondeficiency anemia, the percentage of examination that identifiedlesion responsible for bleeding or mucosal changes that impair ironabsorption

ResultsThe diagnostic yield in patients with active OGIB is 96.62%, in patients with

stoppedOGIB is 71.8% and in patientswith iron deficiency anemia is 45.16%. Thisnew classification corresponds with clinical impact of VCE for the need of furtherinvestigations: thenecessaryofenteroscopydropsfromfrom39.13%inactiveOGIBto28.25%instoppedOGIBto16.12%inirondeficiencyanemia.Theneedforsurgeryalsodrops from21.73% in activeOGIB to15.38% in inactiveOGIB to6.45% in irondeficiencyanemia.Theconservativemanagementproportionallyincreasesinthethreegroups.

VCEexaminationinactiveOGIBhadaveryhighdiagnostic:95.62%.Inpatientshemodynamicallyunstablethediagnosticyieldwas88.9%.Anoriginalobservationofour study is thehighpercentageofDieulafoys like lesions identifieson smallbowelandacolonicDieulafoylikelesion.

ThediagnosticyieldofVCEinstoppedOGIBis71.79%.IftheVCEexaminationisdoneinthefirstsevendaysfromthestoppingbleedingmomentsignificantlyincreasesthe chance to detect thebleeding source (p=0.022).NSAIDs used is an independentparameter to detect a lesions responsible for bleeding (p=0.037) in patients withstopped OGIB. Elderly age (more than 70 years), the hemoglobine level less than7g/dl,theusedofantiaggregatesandanticoagulants,cardiovascularpathologyarenotindependentpredictivefactorsforpositiveresults.Theprotocolexaminationforsmallbowel reveals conclusive results in66.6%of examination, compared to87.5%usingtheprotocol for thewholegutexaminationwithcoloncapsule,without reaching thestatisticalsignificance.

NSAIDs enteropathy is the main cause of bleeding in patients with stoppedOGIBandinpatientswithirondeficiencyanemia.

TheVCEidentifiedasourceofbleedinginsuperiororinferiordigestivetractin11.82%notrevealedatstandardendoscopies.

Afteroneyearfollowup,theclinicalstatuswasfavorablein61%ofpatientsingroupAand87%ingroupBandC.

5thstudyEffectsofrifaximinonindomethacininducedintestinaldamageinguineapigsAIM: Enterobacterial translocation into the gutmucosa is the first step required foractivation of neutrophils and inducible nitric oxide synthase (iNOS), involved in thepathogenesisof indomethacininduced intestinal lesions.Rifaximinmay limitNSAID

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associatedintestinaldamagebydecreasingthebacterial load.Weaimedtostudytheeffectofrifaximinonindomethacininducedintestinaldamageinguineapigs.MATERIALS AND METHODS: Twentyfour guinea pigs, equally divided in fourinterventional groups (AD), received indomethacin, given orally once daily (30mg/kg) for threeconsecutivedays. IngroupsB,C,Ddifferentdosesof rifaximin (50mg/kg,100mg/kgand200mg/kg)weregivenorallytwohoursbeforeindometachinadministration. Semiquantitative grades were measure for gross findings,degenerativelesions,neutrophilsandeosinophilsinfiltratesandiNOSimunopositivity.Statistical comparisons used Mann Whitney Test, with a Bonferroni correction foralpha(p0.016).RESULTS: Statistical analysis of graded gross findings, microscopic degenerativelesions,endotheliumdamageandiNOSimmunopositivityfoundnodifferencebetweenA and B groups. Significant fewer gross findings (U = 3, p = 0.015), microscopicdegenerativelesions(U=2,p=0.008)andlowergradesforiNOSimmunopositivity(U=0,p=0.002)werefoundingroupCcomparedwithgroupA.IngroupD,significantlowergrades for iNOS immunopositivitywereobtained (U=0,p=0.002)comparedwithgroupAand iv w re t tfewerdegenerat e lesions ithout achings atis icalsignificance(U=4,p=0.026).CONCLUSIONS: 100 mg/kg of rifaximin proved efficient in preventing gutdegenerativelesionsinducedbyindomethacininaguineapigmodel,theiNOSactivitybeingsignificantlydecreased.6thStudyTheinterplaybetweenNSAIDsandCandidaalbicansinuineapigsdigestivetractg

BackgroundRecent studies suggested that Candida albicans colonization is associated withinflammatory degenerative lesions of digestive tract, being responsible for slowinghealing processes. There are not literature dates regarding Candida albicanscolonization of lesions induced by indometachin of digestive tract. Other researcherargue for the beneficial effects of NSAIDs to reduce the colonization potential ofCandidaalbicans,AimsOurobjectivewastodefinetheinterplaybetweenindomethacinandCandidaalbicansonguineapigsdigestivetract.MethodologyWeworkedwiththreeinterventionalgroupswith11guineapigseachandacontrolgroupofthreeanimals.Onegroupreceivedorallyindomethacinoncedaily(30mg/kg)forfiveconsecutivedays.ThesamedoseofindomethacinwasassociatedwithCandidaalbicans (109 UFC/ml). Another group received only Candida albicans. Semi

27


quantitativegradesweremeasureforgrossfindings,degenerativelesions,neutrophilsandeosinophils. Statistical comparisonsusedMannWhitneyTest,with aBonferronicorrectionforalpha.ResultsIndomethacinadministrationdidnotsignificantlydecreasethecolonizationpotentialofCandidaalbicansonguineapigsdigestivetract.TheadministrationofindomethacinandCandidaalbicansproducedsignificantlymoredegenerativelesionsthanthegroupthat receive only Candida albicans, but the same pattern as group that receive onlyindomethacin.ConclusionsIndomethacin did not significantly reduce the colonization potential of Candidaalbicans on guinea pigs digestive tract. Association of Candida albicans tondomethacin did not increase the grade of degenerative lesions on guinea pigsigestivetract.

idGeneralconclusion

Complete small bowel examination were achieved in 233 patients (91.37%)withamediumsmallboweltransittimeof261minutes.Capsuleretentionthatneededsurgerywasobservedin5patients(1.96%).

Thedetectionrateoftumormasseslocalizedinthesmallbowelwas5.5%,mostfrequenttumorsbeingadenocarcinomaandGISTs.

ThediagnosticyieldofVCEinpatientswithchronicdiarrhea,withoutanemiaorinflammatorysignswas35.3%andinpatientswithabdominalpain38.7%.

The diagnostic yield of capsule endoscopy in patients suspected by Crohnsdiseaseis47.22%ifallexaminationthatidentifiedulcerativelesionswereconsidered(positive and possible results). Highly suggestive lesions for Crohns disease (linear,deepulcers,markedinflammatoryareas,cobblestoneappearance) identifiedbyVCEhaveaspecificityof88.8%andpositivepredictivevalueof75%forthefinaldiagnosisofCrohnsdisease. Ifsmallulcerativelesionsweretakenincount, thespecificitywas70.3% l d eandapositivepredictiveva ue:52.9%;these ataareus dinclinicalpracticeandcannotbeusedforpositivediagnosticandspecifictherapy.

In patients suspected of Crohns disease, biological inflammatory signsassociatedwith clinicalmanifestation argue for positive results on VCE. Presence ofextraintestinalsymptoms is independentlyassociatedwithapositiveresult forsmallbowelCrohnsdisease.

In patients known with Crohns disease, the protocol for the entire gutvisualization provide a diagnosis in 78%of patients if all degenerative lesionswerecountered and 65.21% if only highly suggestive lesions are considered. In thesepatients there is no correlation between clinic, biology, endoscopy and imagisticstudies.

28

CiobanuLidia

After VCE examination, in 70% of Crohns disease patients a therapeuticallychange i (wasdoneandacompletely changeofdiagnos s in17.4% complicatedceliacdisease).

Typically aspect of villous atrophy depicted by capsule endoscopy, highlysuggestive for celiac disease has a sensitivity and specificity of 100% for Marsh IIIceliacdiseaseinalreadyknownornewlydiagnosedwithceliacdisease.

In our study half of the patients with celiac disease presented complications(ulcerative jejunoileitis andneoplasia),onlyone thirdbeingnoncompliant toglutenfreediet.

The diagnostic yield in patients with active OGIB is 96.62%, in patients withstoppedOGIB is 71.8% and in patientswith iron deficiency anemia is 45.16%. Thisnew classification corresponds with clinical impact of VCE for the need of furtherinvestigations: thenecessaryofenteroscopydropsfromfrom39.13%inactiveOGIBto28.25%instoppedOGIBto16.12%inirondeficiencyanemia.Theneedforsurgeryalsodrops from21.73% in activeOGIB to15.38% in inactiveOGIB to6.45% in irondeficiencyanemia.Theconservativemanagementproportionallyincreasesinthethreegroups.

VCEexaminationinactiveOGIBhadaveryhighdiagnostic:95.62%.Inpatientshemodynamicallyunstablethediagnosticyieldwas88.9%.Anoriginalobservationofour study is thehighpercentageofDieulafoys like lesions identifieson smallbowelandacolonicDieulafoylikelesion.

ThediagnosticyieldofVCEinstoppedOGIBis71.79%.IftheVCEexaminationisdoneinthefirstsevendaysfromthestoppingbleedingmomentsignificantlyincreasesthe chance to detect thebleeding source (p=0.022).NSAIDs used is an independentparameter to detect a lesions responsible for bleeding (p=0.037) in patients withstopped OGIB. Elderly age (more than 70 years), the hemoglobine level less than7g/dl,theusedofantiaggregatesandanticoagulants,cardiovascularpathologyarenotindependentpredictivefactorsforpositiveresults.Theprotocolexaminationforsmallbowel reveals conclusive results in66.6%of examination, compared to87.5%usingthepr mina hiotocol for thewholegutexa tionwithcoloncapsule,without reac ng thestatisticalsignificance.

NSAIDs enteropathy is the main cause of bleeding in patients with stoppedOGIBandinpatientswithirondeficiencyanemia.

V i a b cThe CEident fied source of leedingin superiororinferiordigestivetra tin11.82%notrevealedatstandardendoscopies.

The dose of 100 mg/kg of rifaximin proved efficient in preventing gutd tdegenerativelesionsin ucedbyindome hacininaguineapigmodel,theiNOSactivity

beingsignificantlydecreased.Indomethacin did not significantly reduce the colonization potential of Candidaalbicans on guinea pigs digestive tract. Association of Candida albicans toindomethacin did not increase the grade of degenerative lesions on guinea pigsdigestivetract.

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