1Universitatea de Medicin\ [i Farmacie Iuliu Ha]ieganu

Cluj-Napoca

TRATAMENTUL CHIRURGICAL MINIM INVAZIV AL INCONTINEN}EI

URINARE DE EFORT LA FEMEIE

Rezumat tez\ de doctorat

Conduc\tor [tiin]ific: Doctorand:Prof. Dr. Nicolae Costin Dr. Nicolae Niculescu

CUPRINS

Parte General\I. Introducere ................................................................................................. 1

II. Date generale .......................................................................................... 2III. Date anatomo-topografice ....................................................................... 6

A. Vezica urinar\ [i uretra ................................................................... 6B. Elemente anatomice de sus]inere .................................................. 9

IV. Fiziopatologie ......................................................................................... 18A. Mecanismul continen]ei urinare .................................................... 18B. Fiziopatologia incontinen]ei urinare de efort ................................. 19

V. Etiologia incontinen]ei urinare de efort ................................................... 25VI. Diagnosticul incontinen]ei urinare de efort ............................................. 27

Parte special\I. Scopul lucr\rii ........................................................................................ 35

II. Obiective ................................................................................................ 36III. Material [i metod\ ................................................................................. 37

A. Caracteristicile lotului din studiul comparativ ................................ 37B. Caracteristicile lotului tratat prin colposuspensie laparoscopic\ ... 40C. Caracteristicile lotului tratat prin procedeu personal ..................... 44

2IV. Etapele diagnosticului [i recrutarea pacien]ilor ..................................... 48A. Selec]ia anamnestic\ ................................................................... 48B. Selec]ia clinic\ .............................................................................. 54C. Selec]ia paraclinic\ ....................................................................... 60

V. Principii ale chirurgiei minim invazive `n incontinen]a urinar\ de efort (considera]ii personale) .......................................................................... 64

A. Anatomia laparoscopic\ uroginecologic\ ..................................... 64B. Tehnici de acces `n laparoscopia uroginecologic\ ........................ 74C. Tehnici extraperitoneale ................................................................ 77

VI. Tehnologia laparoscopic\ `n uroginecologie .......................................... 79A. Aparatura laparoscopic\ standard ................................................ 79B. Instrumentar laparoscopic standard ............................................. 81C. Electrochirurgia `n laparoscopia uroginecologic\ ......................... 83D. Ultrasunetele `n laparoscopia uroginecologic\ ............................. 92

VII. Sutura laparoscopic\ `n incontinen]a urinar\ de efort ........................... 96A. Instrumente [i material de sutur\ [i protezare ............................. 96B. Tehnici de sutur\ ......................................................................... 107

VIII. Descrierea colposuspensiei Burch laparoscopic ................................. 114IX. Descrierea procedeului personal preperitoneal ................................... 129X. Rezultatele studiului comparativ .......................................................... 133XI. Analiza procedeelor laparoscopice ...................................................... 137

A. Analiza colposuspensiei laparoscopice ...................................... 137B. Analiza procedeului personal ...................................................... 146

XII. Dificult\]i tehnice ale tratamentului laparoscopic al incontinen]e urinare de efort ............................................................ 148

XIII. Complica]ii ............................................................................................ 150XIV. Discu]ii .................................................................................................. 152XV. Concluzii .............................................................................................. 168

Bibliografie

Anexe

Cuvinte cheie: incontinen]\ urinar\ de efort, chirurgie minim invaziv\,colposuspensie laparoscopic\, plase de protezare, investiga]ie urodinamic\, deficien]\ intrinsec\ sfincteruretral

3IntroducereIncontinen]a urinar\ de efort este definit\ ca o pierdere involuntar\ de urin\ prin uretra, `n afara

mic]iunilor, rezultat\ din deficien]a sistemului de `nchidere uretral\ sau dintr-o disfunc]ie vezical\. Esteo afec]iune privit\ `ntotdeauna ca un handicap important, cu consecin]e destul de grave asupra vie]ii co-tidiene a femeilor.

Tratamentul chirurgical al incontienen]ei urinare la femei nu este dect o secven]\ din problematicaterapeutic\ a unei patologii mult mai vaste, care se `ncadreaz\ sub termenul de tulbur\ri de static\pelvin\.

La ora actual\ exist\ peste 200 de tehnici chirurgicale descrise `n tratamentul incontinen]ei urinare,[i aceasta pentru c\ nici una, `n fond, nu este perfect\.

Ast\zi, chirurgia pelvi-perineal\ este dominat\ de noile tehnici laparoscopice [i/sau care utilizeaz\materialele sintetice [i protezele `n corec]ia incontinen]ei urinare la efort [i, mai nou, a prolapsului genital.Ea are la baz\ principiile teoriei integrale [i ale chirurgiei operatorii f\r\ tensiune, enun]ate de c\trePetros [i Ulmsten.

Conceptual lucrarea nu-[i propune s\ discute exhaustiv despre colposuspensia laparoscopic\ cide a acumula experien]\ `n aceast\ tehnic\ `ncercnd s\ eviden]ieze condi]iile care contribuie la reali -zarea cu succes a opera]iilor, la dep\[irea situa]iilor dificile [i la evitarea producerii complica]iilor.

Date anatomo-func]ionaleAparatul genital [i urinar sunt legate intim att anatomic ct [i embriologic din cele mai timpurii

etape ale ontogenezei. Vezica urinar\ [i uretra sunt situate direct deasupra peretelui vaginal anterior,avnd cu acesta interrela]ii anatomice, func]ionale hormonale [i ocazional patogenice. Termenul deuroginecologie reprezint\ subspecialitatea care se ocup\ cu partea din ginecologie care interfer\ cudezordini anatomice [i func]ionale ale tractului urinar inferior, ambele segmente anatomice fiind interco -nectate prin intermediul unor elemente comune cum ar fi, de exemplu, plan[eul pelvic, dar nu numai.

Fiecare organ pelvic (urinar, genital sau intestinal) traverseaz\ acest plan[eu fibromuscular [i comunic\ cu exteriorul printr-un orificiu specific. Musculatura striat\ a plan[eului pelvic `mpreun\ cuinterconexiunile fasciale ac]ioneaz\ unitar pentru a preveni deplasarea `n repaus [i la efort a acestor or-gane, pentru a le men]ine continen]a (anal\ [i urinar\) [i pentru a le controla activit\]ile de expulzie(defeca]ia [i mic]iunea).

Scopul lucr\rii ~n 1997 `n contextul preocup\rilor legate de incontinen]a urinar\ ale Clinicii de Ginecologie a

SCUMC a fost `nfiin]at\ Societatea de Uroginecologie din Romnia. ~n 1998 a fost introdus\ aparaturade investiga]ie urodinamic\, unicat la acel moment. Cu aceast\ ocazie am `nceput un studiu prospectivcu privire la analizarea procedurilor chirurgicale adresate incontinen]ei urinare de efort cu scopul de ademonstra [i confirma rezultatele superioare ale colposuspensiei Burch fa]\ de celelalte dou\ tehnicipracticate `n clinic\ [i anume plicatura suburetral\ Kelly [i suspensia suburetral\ retropubic\ cu acul.Dup\ achizi]ionarea aparaturii laparoscopice, `n anul 2002, am introdus [i adaptat tehnica antiinconti-nen]\ Burch `n varianta minim invaziv\ `ncercnd s\ demonstrez c\ tehnica este fezabil\ aducnd `nplus avantajele chirurgiei minim invazive. De asemenea din anul 2004 odat\ cu acumularea unei expe-rien]e `n tratamentul laparoscopic [i beneficiind de o solid\ experin]\ `n chirurgia vaginal\ am imaginatun procedeu personal de tratament al incontinen]ei urinare prin deficien]a intrinsec\ de sfincter uretral(DISU) aflat `n derulare.

Obiective Material [i metod\Primul obiectiv a constat `n a demonstra c\ procedeele retropubice sunt superioare pe termen

mediu [i lung plicaturii suburetrale [i suspensiei cu acul (286 cazuri urm\rite).~n momentul ini]ierii (ianuarie 2002) efectu\rii procedeului de colposuspensie laparoscopic\ tip

Burch era demarat din anul 1998 un studiu prospectiv privind compara]ia dintre eficien]a pe termenmediu [i lung a diverselor procedee de tratament chirurgical `n incontinen]a urinar\ de efort la femeie.Acest studiu `ncearc\ s\ confirme rezultatele unei metaanalize pe care au demarat-o cu un an `nainte.Practic la acea dat\ se efectuau trei tipuri de interven]ii chirurgicale [i anume plicatura suburetral\ Kelly,suspensia transvaginal\ cu acul sau variante ale acesteia [i colposuspesia Burch. La `nceput indica]iilepentru o procedur\ sau alta ]inea `n special de preferin]a chirurgului, procedeul plicaturii tip Kelly fiindpreponderent datorit\ simplit\]ii tehnice [i evolu]iei imediate simple `n majoritatea cazurilor. Pn\ ladotarea cu aparatura de investiga]ie urodinamic\ (1998) criteriul de selec]ie pentru celelalte dou\ pro-

4cedee era clinic `n exclusivitate [i se rezuma la forma recidivat\ `n special dup\ opera]ia Kelly sau la anumite forme considerate anamnestic [i la anumite teste clinice specifice ca fiind mai grave.Intro ducerea investiga]iei urodinamice a reu[it `n primul rnd s\ obiec tiveze tipul de incontinen]\ preoperator `n cazurile selec]ionate [i s\ analizeze obiectiv un segment, poate nu cel mai importantdintre pacientele operate. Multe paciente nu s-au reg\sit `ntr-o analiz\ ulterioar\ nici cel pu]in clinic\ aeficacit\]ii procedeului antiincontinen]\ la care fuseser\ supuse. Mai mult, un num\r mare de recidivenu s-au reg\sit `n statistica computerizat\ a aparaturii urodinamice.

Al doilea obiectiv a constat `n a demonstra c\ procedeul retropubic lapa roscopic aduce `n plusavantajele chirurgiei minim invazive (23 cazuri). Pornind de la rezultatele de etap\ a acestui studiu [i dela studierea rezultatelor diverselor metaana lize din literatur\ am ini]iat adaptarea pe cale laparoscopic\a acestei tehnici antiincontinen]\ considerat\ de trei decenii drept standard de aur. Am pornit de la cu-tuma cum c\ laparoscopia nu este o tehnic\ `n sine ci numai o cale de acces care aduce beneficiile binecunoscute numai atunci cnd tehnic este reprodus procedeul clasic, probat `n timp.

Al treilea obiectiv este analiza unui procedeu personal imaginat ca alternativ\ de tratament miniminvaziv `n hipermobilitate [i/sau deficien]a sfincterian\ intrinsec\ (8 cazuri) pe care l-am numit sling la-paroscopic asistat vaginal (SLAV). ~n derularea efectu\rii abordului laparoscopic [i beneficiind de aportulinvestiga]iei urodinamice am demarat un procedeu personal de tratament laparoscopic al incontinen]eiurinare. Acest procedeu `mbin\ colposuspensia tip Burch cu o tehnic\ de protezare foarte la mod\ [ieficace (TVT, TOT).

~n cele mai multe cazuri din cele 286, interven]iile chirurgicale au fost efectuate de aceea[i echip\operatorie.

Din ianuarie 2002 am ini]iat un studiu prospectiv paralel, `n curs de desf\[urare, referitor la rezul-tatele colposuspensiei laparoscopice transperitoneale Burch `n tratamentul incontinen]ei urinare primare[i recidivate. ~n perioada ianuarie 2002 martie 2007 am efectuat colposuspensie laparoscopic\transperitoneal\ Burch la un num\r de 23 paciente cu incontinen]\ urinar\ de efort. Criteriul de selec]iepentru interven]ie a fost diagnosticarea incontinen]ei urinare prin hipermobilitate a colului vezical

Slingul laparoscopic asistat vaginal (SLAV) l-am imaginat `n ideea c\ acest procedeu `mbin\ otehnic\ ce se adreseaz\ att incontinen]ei prin hipermobilitate ct [i formelor de incontinen]\ prin defi-cien]a intrinsec\ a sfincterului uretral cu o fixare solid\ (lig. Cooper) a protezei. Criteriile de selec]ie aufost similare cu cele ale colposuspensiei laparoscopice la care se adaug\ selec]ia prin investiga]ie uro-dinamic\ a cazurilor cu deficien]\ intrinsec\ de sfincter uretral.

Au fost selec]ionate paciente cu afec]iuni pelvice u[or de rezolvat laparoscopic pentru a nu interferasemnificativ ca timp complica]ii uzur\ fizic\ [i moral\ cu procedeul laparoscopic antiincontinen]\.Ra]iunea selec]iei pacientelor incontinen]e cu afec]iuni pelvine concomitente a fost acea de a avea `nplus o indica]ie a c\i laparoscopice transperitoneale mai ales `n perioada de reglare a tehnicii de colpo-suspensie.

Diagnosticul de patologie complementar\ a fost pus clinic [i ecografic.

Chirurgia minim invaziv\ `n uroginecologie principii de tehnic\ [i tehnologieLaparoscopia nu este o metod\ chirurgical\, ci o modalitate de acces.Consider\m c\ primul pas `n chirurgia laparoscopic\ `n general [i `n chirurgia uroginecologic\ la-

paroscopic\ `n particular trebuie s\ `nceap\ cu o corect\ [i exact\ cunoa[tere `n primul rnd a anatomieilaparoscopice de acces [i uroginecologice precum [i a aparaturii [i instrumentarului, foarte complexechiar `n cea mai simpl\ formul\.

Altfel, problemele care pot ap\rea `ngreuneaz\ sau compromit metoda, pot determina accidentegrave [i pot deteriora o tehnologie foarte scump\.

Odat\ ` n]eles acest prim pas, se poate ajunge la rezolvarea procedurilor laparoscopice din chirur-gia uroginecologic\ st\pnind trei elemente fundamentale:

A. Tehnici de creare a camerei de lucru: pneumoperitoneu sau preperitoneal\ (extraperi-toneal\).

B. Tehnici de hemostaz\ [i disec]ie.C. Tehnici de sutur\ laparoscopic\ indispensabile procedurilor de colposuspensie

~n uroginecologia laparoscopic\ se folosesc elemente de fizic\ particulare: sisteme sofisticate detransmisie a luminii, televiziune, instilarea de fluide sub presiune sau insuflarea cavit\]ilor cu gaz, curentulelectric sau ultrasunetele.

Pentru realizarea colposuspensiei directe nu exist\ alt\ alternativ\ de aproximare a ]esuturilordect prin sutur\ laparoscopic\ intra sau extra corporeal\.de aceea este obligatorie stapanirea acestortehnici.

5Am descris tehnica laparoscopic\ transperitoneal\ a[a cum am efectuat-o pentru colposus-pensia tip Burch. Calea transperitoneal\ mi-a fost mai familiar\ de la alte interven]ii, tocmai de aceeacazurile selectate au prezentat [i o patologie pelvin\ asociat\ care s\ justifice `n plus acest\ manier\de abord.

Ideea folosirii unei plase de protezare introdus\ transvaginal retropubic [i fixarea ei la ligamentuliliopectineu (Cooper) pe cale laparoscopic\ a ap\rut `n momentul unui e[ec de identificare a fasciei pubocervicale la o femeie programat\ pentru colposuspensie. Astfel disec]ia a fost abandonat\ [itransvaginal au fost introduse cu o pens\ lung\ capetele unei plase (ca `n procedeul TVT) de o parte [ide alta a jonc]iunii care a fost fixat\ apoi la ligamentul Cooper.

Rezultate~n studiul comparativ rata de continen]\ dup\ plicaturare suburetral\ a fost de 82% (43/52) din

pacientele cu incontinen]\ u[oar\ la efort, dar 49% (37/76) la pacientele cu incontinen]\ moderat\(P

62. Perioada medie de urm\rire din studiul nostru de 2-3 ani poate fi consi derat\ de asemeneamul]umitoare, fiind o perioad\ intermediar\ `ntre studiile care au publicat rezultate recente cuacest procedeu [i studiile care men]ioneaz\ perioade de follow-up mai mari de 3 ani.

3. Procentul nostru de e[ecuri a fost mic [i a fost corelat statistic cu rata complica]iilor intra- saupostoperatorii, ceea ce sugereaz\ c\ evitarea acestor complica]ii atrage dup\ sine o diminuarea riscului de recidiv\ postoperatorie a incontinen]ei.

4. Rezultatele noastre, `n termeni de eficacitate, sunt de asemenea compa rabile cu rezultatelemultiplelor studii analizate din literatur\ care folosesc `n tratamentul incontinen]ei opera]ia Burchclasic\ sau alte slinguri de suspensie uretral\.

5. ~n caz de incontinen]e urinare recidive, am ob]inut o rat\ de succes de 85%, u[or inferioar\ fa]\de cazurile cu incontinen]\ urinar\ primar\ [i absolut comparabil\ cu rezultatele altor publica]ii.

6. Am utilizat acest procedeu [i la pacientele cu prolaps genital de grad mic (I sau II), care `ns\nu au necesitat dect cel mult o opera]ie plastic\ minim\, anterioar\ sau posterioar\, excluzndcazurile care necesitau o histerectomie total\ pe cale vaginal\. {i `n aceste cazuri am ob]inuto rat\ global\ de succes subiectiv\ de 89%, care este aproape identic\ (chiar u[or mai mare)fa]\ de ratele de succes la opera]iile neasociate cu terapia chirurgical\ a prolapsului. Acestevalori sunt de asemenea comparabile [i cvasi-identice cu cele din literatur\, referitoare laaceast\ chestiune.

7. Procedeul nu se aplic\ la pacientele obeze la care tehnicile prin laparoscopie impun ctevariscuri operatorii suplimentare [i sunt grevate de complica]ii postoperatorii mult mai frecvente [imai grave.

8. Din studiul nostru reiese de asemenea o durat\ medie a opera]iei, similar\ cu cele publicatepn\ `n prezent. Men]ionez `ns\ c\ a existat o perioad\ de circa trei ani `n care am c\p\tat oexperien]\ pe mai mult de 1.000 de cazuri `n chirurgia laparoscopic\ pelvin\. De asemenea auexistat doi ani de experien]\ `n chirurgia laparoscopic\ urologic\ extraperitoneal\ [i antrenamentsus]inut a tehnicilor de sutur\ intra- [i extracoporeale.

9. Procentul global al complica]iilor din studiul nostru foarte mic, de asemenea comparabil cu mul-tiplele rezultate publicate anterior `n literatur\ [i aceasta se refer\ la toate complica]iile care aufost amplu tratate `n tez\.

10. Am avut: 1 perfora]ie vezical\, 1 serom al spa]iului Retzius. Procentele noastre `n raport cufiecare din aceste complica]ii sunt de cele mai multe ori inferioare sau identice cu cele ap\rute`n literatura de specialitate. Men]ion\m de asemenea, absen]a din cazuistica noastr\ a com-plica]iilor hemoragice intraoperatorii, a leziunii vasculare majore, a leziunilor nervoase sau aperfora]iilor intestinale accidentale.

11. ~n ce prive[te perfora]iile vezicale din lotul nostru de paciente. Aceste s-au produs la o bolnav\cu incontinen]\ recidivat\. Noi, ca [i al]i autori, consider\m c\ aceste antecedente chirurgicaleimprim\ un risc suplimentar de perfora]ie vezical\, dar ele nu trebuie considerate contrain -dica]ii absolute ale procedeului.

12. Expunem de asemenea `n teza noastr\, modalitatea prin care noi am rezolvat [i tratat fiecaredintre complica]iile noastre dar [i multiplele variante terapeutice de rezolvare care exist\ `n literatur\, cu argumentele pro [i contra pentru fiecare din posibilit\]ile existente. Nu exist\ unconsens general `n ce prive[te tratarea unui anumit tip de complica]ie, deoarece fiecare cazeste un caz individual care necesit\ analiz\ [i medita]ie am\nun]it\ pentru a g\si solu]ia ceamai bun\ de rezolvare.

13. Am demonstrat [i subliniat pe parcursul tezei `n repetate rnduri, necesitatea dobndirii uneiexperien]e chirurgicale cu acest procedeu. Este un element care intervine att `n rata com-plica]iilor, ct [i ca factor determinant ce influen]eaz\ procentele de succes global ale acesteiopera]ii.

Ambele procedee studiate necesit\ dotarea cu echipament specific: aparatur\ [i instrumentarstandard de chirurgie laparoscopic\ care a fost prezentat\ pe larg la capitolul de tehnologie operatorie.~n sine aparatura ca [i instrumentarul sunt scumpe necesitnd o investi]ie ini]ial\ costisitoare. ~ns\ prin folosirea responsabil\ a acestora, att `n ceea ce prive[te manipularea, sterilizarea, mentenan]a [ifolo sirea cu prioritate a tehnicilor conven]ionale (sutura, electrochirurgia monopolar\) per global costurilepot fi ameliorate.

Men]ion\m c\ aparatura, [i `n parte instrumentarul laparoscopic cu care s-au efectuat studiile pre zentate este `n uz de mai bine de 10 ani timp `n care s-au efectuat peste 3.000 de interven]iilaparoscopice.

7Tehnologia modern\: ultrasonic\, electrochirurgia bipolar\, aplicatoarele de clipuri pentru plasesunt scumpe dar reduc timpul operator, limiteaz\ complica]iile [i confer\ un confort benefic att ergo -nomic ct [i psihic echipei operatorii.

Ambele tehnici minim invazive la care ne referim `n aceast\ lucrare au fost posibil de realizat dup\ `ndelungi ani de c\p\tare a experien]ei `n chirurgia vaginal\ [i laparoscopic\ ct [i `n folosireamateria lelor de protezare. Am avut posibilitatea instruirii `n tehnologia modern\ (electrochirurgie, chirurgieultraso nic\) datorit\ dot\rii de excep]ie a clinicii `n care s-au efectuat studiile.

Tehnicile prezentate, att colposuspensia ct [i protezarea cu plase din cadrul procedeului per-sonal sunt dificile prin:

necesitatea st\pnirii tehnicilor de baz\ `n laparoscopia pelvic\ abilit\]i `n tehnica de sutur\ laparoscopic\ disec]ia unei regiuni anatomice f\r\ limite clare [i prezen]a unui plex venos fragil [i dezordonat

din jurul jonc]iunii cistouretrale pozi]ia particular\ dificil\ a operatorului att `n momentul disec]iei fasciei pubocervicale ct [i

`n timpul suturii acesteia la ligamentul Cooper experien]a `n aprecierea tensiunii firelor de sutur\ sau a plasei de protezare care trebuie s\ sta-

bilizeze jonc]iunea [i uretra medie [i nu s\ o suspende cooperarea permanent\ cu medicul anestezist `n contextul particularit\]ilor gazometrice [i de

pozi]ionare specifice st\pnirea tehnicilor de hemostaz\ laparoscopic\ abilit\]i [i experien]\ `n depistarea [i rezolvarea pe ct posibil tot pe aceea[i cale a complica]iilor cuno[tin]e `n cistoscopia diagnostic\Suspensia retropubic\ ofer\ rezultate mai bune pe termen mediu (2 ani) [i lung (5 ani) dect pro-

cedurile vaginale.Laparoscopia aduce avantaje fa]\ de tehnica clasic\ prin: avantajele c\ii de acces [i vizualiz\rii

magnificate a structurilor anatomiceEvaluare urodinamic\ este esen]ial\ `n cazurile recidivate .Principala problem\ a suturilor laparoscopice este necesitatea unui antrenament sus]inut, continuu

[i `ndelungat [i nicidecum doar un curs de o s\pt\mn\. {i acest lucru nu este cu nimic surprinz\tor,orice chirurg amintindu-[i orele zilnice petrecute luni de zile cu exersarea nodurilor clasice. Concluziaeste c\ efortul de `nv\]are prin practic\ sus]inut\ merit\, tehnicile de sutur\ asigurnd o versatilitatedeose bit\ `n toate interven]iile laparoscopice.

~n zilele noastre, laparoscopia se confrunt\ cu un aport tehnologic att `n ceea ce prive[te instru-mentarul, ct mai ales `n utilizarea unor aparaturi sofisticate de tipul tehnologiei laser, ultrasonice sau aroboticii, care [i-au g\sit numai `n parte justificarea. ~n aceast\ imens\ pia]\ de desfacere trebuie s\primeze ra]iunea chirurgului `n alegerea a ce este mai bun pentru pacient [i boala sa, `n func]ie deabilit\]i, experien]\ [i dotare.

CURRICULUM VITAE

Nume: NICULESCUPrenume: NICOLAEAdresa: Bucure[ti, Str. Apusului nr. 83, bl. M26, sc. 2, ap. 65, sector 6, RomniaAdresa serviciu: Sec]ia Ginecologie, Spitalul Clinic Militar Central Bucure[tiE-mail: nicniculescu@yahoo.comTelefon: 0722 232 602Data na[terii: 14.05.1963Locul na[terii: Ploie[tiSex: MasculinStarea civil\: C\s\torit, doi copiiStudii:

Liceul Militar Dimitrie Cantemir absolvit `n 1882 Institutul de Medicin\ Militar\ absolvit 1989 Medic specialist Obstetric\-Ginecologie 1994 Medic primar Obstetric\-Ginecologie 1999 Doctorand Universitatea de Medicin\ Cluj

Locul de munc\: Clinica Ginecologie a Spitalului Clinic de Urgen]\ Militar Central Carol Davila

Cursuri postuniversitare Curs clinic de chirurgie pelviscopic\ (prof. Kurt Semm) Timi[oara, 1993 Laparoscopia `n Obstetric\-Ginecologie Cluj, 1998 Histeroscopia diagnostic\ [i terapeutic\ Bucure[ti, 1998 Tratamentul chirurgical `n prolapsul utero-vaginal Bucure[ti, 1998 Tehnici avansate `n endoscopia ginecologic\ Clermont Ferrand, Fran]a, 1998 Curs de chirurgie laparoscopic\ Cluj, 1999 Curs de interven]ii celioscopice [i laparoscopico-vaginale Lyon, Fran]a, 2001 Curs de chirurgie laparoscopic\ [i histeroscopie Bucure[ti, 2002 Stagiu practic de coloposcopie Bucure[ti, 2002 Curs de colposcopie Bucure[ti, 2003

Competen]e Certificat de competen]\ `n Laparoscopie aprilie, 2002 Certificat de competen]\ `n Histeroscopie aprilie, 2002 Certificat de competen]\ `n Colposcopie aprilie, 2003 Certificat de supraspecializare `n Oncologie Ginecologic\ 2004 Certificat de competen]\ `n Ecografie 2006 Certificat de competen]\ `n Management Spitalicesc 2007 Atestat de studii complementare `n Managementul Serviciilor de S\n\tate 2009

Particip\ri la manifest\ri [tiin]ifice Participant cu lucrare prezentat\ oral Congres XVI Figo, Washington, 2000 Participant [i coautor poster COGI Congres II, Paris, 2001 Participant cu demonstra]ii operatorii `n Chirurgia Laparoscopic\ Chi[in\u, 2003 Organizator [i participant la demonstra]ii operatorii Laparoscopice sus]inute de:

prof. Harry Reich, 2001 prof. Goldenberg, 2002 prof. D. Dargent, 2002 prof. Harry Reich [i Koch, 2004

Participant [i coautor postere COGI, Congres IV, Berlin 2003 Participant Figo Congres VII, Chile, 2003 Participant cu lucr\ri prezentate oral la Congresele [i Conferin]ele SOGR Participant cu lucrare prezentat\ oral la Congresul de Medicin\ Militar\ Balcanic\ Atena,

2006 Participant cu lucrare prezentat\ oral la Simpozionul Intera]ional News of Infertility

Bra[ov, 2006

Participant cu lucrare prezentat\ oral la Congresul de Medicin\ Militar\ Balcanic\ PoianaBra[ov, 2007

Participant cu lucrare prezentat\ oral la Congresul de Medicin\ Militar\ Balcanic\ XIII Turcia, 2008

Participant cu lucrare prezentat\ oral BMMC, Congres XIV, Bulgaria, 2009 Participant cu lucrare prezentat\ oral Congres X ARCE Participant autor [i coautor la peste 100 de lucr\ri prezentate oral [i postere la Congresele

[i Conferin]ele Societ\]ii Romne de Obstetric\-Ginecologie, Societ\]ii Romne de ChiurgieLaparoscopic\, Asocia]ia Romn\ de Chirurgie Endoscopic\

Contracte de cercetare1. Cu firma Akzo Nobel Organon pentru produsul Ovestin, cercetare finalizat\ prin lucrarea

Ovestin `n tratamentul chirurgical al IUE2. Cu firma Pfizer Studiu clinic deschis prospectiv de evaluare a eficien]ei [i siguran]ei pro-

filaxiei antibiotice `n Histerectomia vaginal\ 1996-20003. Cu firma Laboratoires Fournier Tratamentul cu Oxybutynyn Clorhidrat `n vezica instabil\4. Cu firma Laboratoires Fournier Lomexim 600 doz\ unic\5. Cu firma Schering Diane 35 `n sindromul de androgenizare6. Cu Firma Wyeth Reducerea inciden]ei fracturilor, TSE 424 comparativ,

Inven]ii, inova]ii Procedeu original de sling suburetral `n incontinen]a urinar\ de efort la femeie Suspensia

retropubic\ cu plas\ de Mersilene; Coautor; COGI III, Washington, 2002

Asocia]ii [i Societ\]i Medicale Membru fondator al Societ\]ii de Uroginecologie din Romnia 2000 Membru titular al Societ\]ii Romne de Chirurgie Laparoscopic\ 1999 Membru titular al Uniunii Medicale Balcanice 1997 Membru al Societ\]ii Europene de Oncologie Ginecologie (ESGO) 1997 Membru al Societ\]ii Romne de Obstetric\-Ginecologie 1994 Membru al Asocia]iei Romne de Chirurgie Endoscopic\ 2001 Membru al Societ\]ii Europene de Menopauz\ [i Andropauz\ 2003 Membru al Societ\]ii Romne de Ginecologie Oncologic\ 2001 Membru al Asocia]iei Medicilor [i Farmaci[tilor Militari Membru al Societ\]ii de Medicin\ Aeronautic\ din Romnia Membru al Comitetului de Medicin\ Militar\ Balcanic\ Membru al Societ\]ii Romno-Germane de Obstetric\-Ginecologie Membru al Societ\]ii de Endocrinologie Ginecologic\ Membru al Societ\]ii de Chirurgie Oncologic\

Interes personal Chirurgia Laparoscopic\ [i Histeroscopic\ Uroginecologia Oncologia Ginecologic\

Lista lucr\rilor publicate - se anexeaz\ separatAutor: Curs practic de Laparoscopie Ginecologic\Coautor: Anatomia chirurgical\ a pelvisului

Curs practic de urodinamic\ [i manometrie ano-rectal\Urodinamica Ginecologic\

Limbi str\ine cunoscute Engleza scris [i vorbit Certificat de Competen]\ Lingvistic\ Catedra de limbi moderne,

Universitatea Iuliu Ha]ieganu, Cluj Napoca, 2002 [i UMF Bucure[ti, 2003 Franceza scris [i vorbit Diplom\ Centrul de limbi str\ine FIDES 1998

Aprilie 2010

1University of Medicine and PharmacyIuliu Ha]ieganu

Cluj-Napoca

MINIMAL INVASIVE SURGICAL TREATMENT IN FEMALE URINARY STRESS

INCONTINENCE

Doctoral thesis abstract

Scientific coordinator: Doctorand:Prof. Dr. Nicolae Costin Dr. Nicolae Niculescu

CONTENTS

General topicsI. Introduction ................................................................................................ 1

II. General Data ............................................................................................ 2III. Anatomo-topographical Data ................................................................... 6

A. Urinary bladder and urethra ............................................................ 6B. Anatomical support elements ......................................................... 9

IV. Physiopathology ..................................................................................... 18A. Urinary continence mechanism .................................................... 18B. Urinary stress incontinence physiopathology ............................... 19

V. Urinary stress incontinence etiology ...................................................... 25VI. Diagnosis in urinary stress incontinence ............................................... 27

Special topicsI. Purpose of the work ............................................................................... 35

II. Objectives .............................................................................................. 36III. Material and method .............................................................................. 37

A. Characteristics in the comparative study ...................................... 37B. Characteristics in the cases treated

by laparoscopical colposuspension .............................................. 40C. Characteristics in the case treated by personal procedure .......... 44

2IV. Diagnosis steps and selection of cases ................................................. 48A. Selection based on medical history .............................................. 48B. Clinical selection ........................................................................... 54C. Paraclinical selection .................................................................... 60

V. Principles of minimal invasive surgery in urinary stress incontinence (personal considerations) ....................................................................... 64

A. Laparoscopic urogynaecological anatomy .................................... 64B. Access techniques in laparoscopic urogynaecology .................... 74C. Extraperitoneal techniques ........................................................... 77

VI. Laparoscopic technology in urogynaecology ......................................... 79A. Standard laparoscopic devices ..................................................... 79B. Standard tools and implements in laparoscopy ............................ 81C. Electrosurgery in urogynaecological laparoscopy ........................ 83D. Ultrasound in urogynaecological laparoscopy .............................. 92

VII. Laparoscopic suturing in urinary stress incontinence ............................ 96A. Tools and prosthetic and suturing materials ................................. 96B. Suturing techniques .................................................................... 107

VIII. Description of Burch laparoscopic colposuspension ............................ 114IX. Description of personal preperitoneal procedure ................................. 129X. Results in the comparative study ......................................................... 133XI. Debate on laparoscopical procedures ................................................. 137

A. Analysis of laparoscopical colposuspension .............................. 137B. Analysis of personal procedure .................................................. 146

XII. Technical difficulties of laparoscopic treatment in urinary stress incontinence .............................................................. 148

XIII. Complications ....................................................................................... 150XIV. Discussions .......................................................................................... 152XV. Conclusions ......................................................................................... 168

Bibliography

Appendix

Key-words: urinary stress incontinence, minimal invasive surgery, laparoscopic colposuspension, prosthetic mesh materials,urodynamic investigation, intrinsic urethral sphincter deficiency

3IntroductionUrinary stress incontinence has been defined as an involuntary loss of urine through the urethra,

aside normal voiding, due to a intrinsic deficiency of the urethral closure system or bladder disfunction.This is a condition considered an important handicap, having serious consequences over the patientsquality of life.

The surgical treatment of urinary incontinence in women is only a sequence in the managementof a far more vast pathology known as defects in pelvic support.

In the present, more than 200 operations have been suggested as surgical cures for urinary incontinence, the reason being that the ideal operation has yet to be devised.

Today, the pelviperineal surgery is dominated by the newer laparoscopic techniques and/or theprocedures using prosthetic and synthetic materials to correct urinary stress incontinence and, recently,genital prolapsed.

The principles for operative management emerge from the integrative theory and from the tension-free surgery, described by Petros and Ulmsten.

We do not intend to discuss all the aspects of the laparoscopic colposuspension but to accumulateexperience regarding this procedure, underlining the right conditions that contribute to the success ofthe operative approach, solutions suggested in difficult situations and ways of preventing complications.

Anatomic and functional considerationsThe genital and the urinary tract have strong anatomic and embryological connections from the

very beginning of ontogenesis. The urinary bladder and the urethra are located right above the anteriorvaginal wall, being correlated anatomically, functionally (hormonal interrelation) and sometimes, sharingthe same pathogenesis. The term urogynaecology represents a subspeciality that manages the gynaecological aspects interfering with the anatomical and functional disruptions of the inferior urinarytract, two anatomical segments interconnected by common elements like the pelvic floor.

Each pelvic organ (urinary, genital or intestinal) goes through this fibromuscular floor and opens to the exterior at a specific orifice. The striated pelvic floor muscles together with the fascial interconnections act as a whole to prevent the displacement of these organs, both resting and duringeffort in order to maintain their continence (urinary and fecal) and to control the voiding efforts.

Purpose of the workIn 1997, given the interest for the urinary stress incontinence at the Central Military Hospital

Gynaecological Clinic, the Romanian Urogynaecology Society was founded. In 1998, the urodynamicstudy device was brought here, for the first time. We then started a prospective study on surgical procedures managing urinary stress incontinence; our goal was to prove and confirm the advantages of Burch colposuspension over the two other operations used in the clinic: anterior colporrhaphy withKelly bladder neck placation, and needle retropubic bladder neck suspension. After the introduction ofthe laparoscopic unit in 2002, we elaborated and adapted Burch technique for urinary incontinence usingthe minimal invasive procedure, in order to demonstrate its success in the objective cure of genuinestress incontinence, combined with the advantages of the minimal invasive surgery. Also, starting with2004, after accumulating experience in laparoscopic procedures and given the benefit of a solid experience in vaginal surgery, a personal procedure was developed aiming the treatment of urinaryincontinence due to intrinsic urethral sphincter deficiency (IUSD). This technique is still developing.

Objective Material and methodThe first objective was to demonstrate that the retropubic procedures are superior, on medium

and long term, to the suburethral placation and needle suspension (286 followed cases).We initiated in january 2002 the Burch laparoscopic colposuspension in treating female urinary

stress incontinence. From 1998 a prospective study was started regarding the efficiency on medium andlong term of different surgical procedures. This study tries to confirm the outcome of a metaanalysisbegun one year previousely. At that time we applied three types of surgical procedures: the Kelly bladder neck suspension, transvaginal needle suspension (or variants of this technique) and Burch colposuspension. At the beginning, the choice of operations depended on personal preferance of thesurgeon, the Kelly procedure predominating due to its technical simplicity and postoperative evolutionwithout complications in the majority of cases. Before the urodynamic study technique was at our disposal(1998) the selection between the other two techniques was exclusively clinical, that is the relapse afterKelly procedure or some more severe given situations revealed by the history of the patient and clinical

4studies. The urodynamic data gave a preoperative evaluation of incontinence type in the selected casesand used objective criteria to define outcomes. Many of the patients had not been included in a follow-upanalysis, not even clinical, to establish the efficacy of the antiincontinence procedure applied. More over,a great number of the relapses was not included in the computerized urodynamical statistics.

The second objective was to demonstrate that laparoscopic retropubic technique added the advantages of minimal invasive surgery (23 cases). Based on the partial resultsof this study and differentmetaanalysis published regarding this subject, we have started the adaptation for the laparoscopic routeof this technique considered a gold standard for the last three decades. The fundamental view was that laparoscopy is not considered an operative cure by itself but only an access route that brings its wellknown benefits combined with the classical procedure with an efficacy proven in time.

The third objective is to analyse a personal procedure developed as a variant of minimal invasivetreatment used inhypermobility and/or intrinsic sphincterian deficiency (8 cases), procedure named vaginal assisted laparoscopic sling (VALS). Using laparoscopy and given the information furnished bythe urodynamic investigation we have initiated an original procedure for the laparoscopic cureof urinaryincontinence. This procedure combines Burch colposuspension with a prosthetic technique currentlyused and with a proven efficacy (TVT, TOT).

The majority of the 286 operations were performed by the same operative team. Starting with January 2002 we have initiated a parallel prospective study, still in progress, regarding

the efficacy of Burch transperitoneal laparoscopic colposuspension in treating primary urinary incontinence and recurrent cases. Between January 2002 march 2007 we have performed Burchtransperitoneal laparoscopic colposuspension on 23 patients diagnosed with urinary stress incontinence.The selection criterium was bladder neck hypermobility.

Vaginal assisted laparoscopic sling (VALS) was imagined considering that this procedure combinesa technique that addresses both to the hypermobility incontinence and the intrinsic urethral sphincteriandeficiency with solid fixation (Cooper ligament) of the prosthetic material. The selection criteria were similar to the ones applied in laparoscopic colposuspension combined with the urodynamic investigationthat allowed us to uncover the intrinsic urethral sphincter deficiency.

We have selected patients having pelvic pathology that could beneficiate of an easy laparoscopiccure: we aimed that the laparoscopic antiincontinence procedure would not be impared by the severityof pelvic pathology (considering the necessary time sequence, possible complications and physical andmoral erosion). The reason for selecting incontinent patients that had associated pelvic pathology wasthat we desired to justify the choice of transperitoneal laparoscopic technique, especially during the developmental phase of the colposuspension technique.

The associated pathology was diagnosed clinically and by using US imagery.

Minimal invasive surgery in urogynaecology technical principles and technology

Laparoscopy is not a surgical method, it is a mean of approaching.We consider knowledge of laparoscopical access anatomy and urogynaecology anatomy the

foundation in laparoscopic surgery and laparoscopic urogynaecological surgery, along with a solidtheoretical and practical understanding of devices and implements, very complex even in the most simpleform.

Otherwise the problems that may appear could compromise or impede this method, may determinesevere accidents and deteriorate very expensive devices.

Once mastering this first condition, laparoscopic procedures in urogynaecological surgery may besolved using the key of the following three fundamental elements:

A. Techniques of creating the work chamber: pneumoperitoneum or preperitoneal (extraperitoneal)B. Techniques of hemostasis and dissectionC. Techniques of laparoscopic suture indispensable in colposuspension procedures

Laparoscopic urogynaecology has particular physics principles: sophisticated light transmissionsystems, television, instillation of fluids under pressure or gas isuflation into cavities, electric power andultrasounds.

There isnt any other alternative to approximate tissues in order to perform direct colposuspensionbut intra- or extracorporeal laparoscopical suture, thus mastering this techniques is essential.

The transperitoneal laparoscopic technique is presented as we perfomed it in Burch colposuspen-sion. The transperitoneal route was familiar to us from other types of operations, this being the reasonfor wich all the selected cases had associated pelvic pathology, requiring this method.

5We thought using a retropubic prosthetic mesh introduced transvaginally and fastened to theCooper ligament (iliopectineal) when we failed identifying the pubocervical fascia in the case of a womanscheduled for colposuspension. Thus, dissection was abandoned and we introduced transvaginally amesh by using a long clamp (like in TVT technique) on each side of the vesical neck, fixed to the Cooperligament.

ResultsIn the comparative study, the continence success rate after suburethral plication was of 82%

(43/52) of the patients diagnosed with mild urinary stress incontinence, and 49% (37/76) of the patientswith moderate urinary incontinence (P

63. Our default percentage was low and statistically correlated to the intra-/postoperative compli-cation rate. This means that avoiding complications may lead to a reduced risk of postoperativerelapse.

4. The efficacy recorded in our study is similar to the one registered in many studies published onthis matter, using classical Burch operation or other sling operations for urethral suspension.

5. In cases of recurrent urinary incontinence our success rate was of 85%, almost equal to therate obtained in primary urinary incontinence and similar to the results published by other authors.

6. This method was performed also in patients with a small degree of genital prolapsed (I or II),in these cases associating a minimal restoration surgical procedure, anterior or posterior. Thecases in which we had to perform vaginal total hysterectomy were not included in the study.The global success rate was also greater than 89%, very similar (even better) to the successrate registered in cases that did not comprised surgical repair of genital prolapsed. The percentages obtained are comparable and quasi-identical to the ones found in the literatureregarding this subject.

7. The procedure is not applicable to obese patients; in their case laparoscopic techniques comprise additional operative risks and raise more frequent postoperative severe complications.

8. The necessary operating time has an average value in our study similar to the speciality literature. There was a 3 years period during which we had to gain experience on more than1000 cases of laparoscopic pelvic operations. Also, there was an interval of two years of acquiring knowledge in extraperitoneal laparoscopic urological surgery and continuous trainingin intra- and extracorporeal suture techniques.

9. The global complications rate in our study is very low, also comparable to the results publishedby other authors, regarding all the observed complications that were thoroughly presented inour report.

10. We recorded: 1 bladder perforation, 1 space of Retzius seroma. For each of these com pli -cations the occurrence rate is lower or equal to the literature. We emphasize the absence inour cases of bleeding complications, major vessels lesions, nerve damages or accidentalbowel perforation.

11. Considering the accidental bladder perforation, this occurred in a previous failed incontinencesurgery case. Regarding this matter we consider that prior attemps at surgical cure lead to agreater risk to perforate the urinary bladder; yet, this shouldnt contraindicate the procedure.

12. Our work describes in detail the way we have solved and treated every complication, and also presents different therapeutical options found in speciality literature, examining their efficacy. One therapeutical attitude cannot fit the needs of every complication, because everycase must be regarded in a distinctive manner; the best solution has always to be thought individually.

13. We have emphasized repeatedly the need in developing a surgical experience with this procedure. This is a factor that affects complication rate and, of course, the global successrates of this method.

Both procedures that were studied imply using proper devices: laparoscopical tools and devices,presented at large in the chapter about operative technology. The devices and implements are expensive,but using them with responsibility (from the poit of view of manipulation, sterilization, maintenance) andperforming mainly the basical techniques (suturing, monopolar electrosurgery) the cost can be tempered.

Our laparoscopic devices and most of the laparoscopic implements that served us during thisstudy were in use for more than ten years, more than 3000 laparoscopic operations being performedover this period of time. Modern technology (ultrasound systems, bipolar electrosurgery, stitching devicesfor prosthetic mesh) is expensive but reduces operating time, produce a lower complication rate and offerphysical and mental comfort to the operating team.

The two minimal invasive techniques, debated in the present work were possible after many years of experience in vaginal and laparoscopical surgery and also with the aid ofprosthetic materials.We had the chance to make contact and gain knowledge about modern technology (electrosurgery, ultrasound-based surgery) on account of the excellent devices available in the clinic.

The procedures presented, both colposuspension and prosthetic mesh sling personal procedure,have a degree of difficulty because:

Mastering the basic pelvic laparoscopy surgery techniques is needed They require knowledge in laparoscopical suture

7 They imply dissection in an anatomical region having no clear limits, with the presence of afragile venous plexus surrounding urethrovesical junction

The operator has a difficult position during the pubocervical fascia dissection and while suturingit to Cooper ligament

Experience is required in tensioning the sutures and prosthetic mesh, given the fact they haveto stabilize the junction and urethra and not hang it.

Permanent cooperation with the anesthesiologist is required because of the particular gaseousand positioning conditions

Solid knowledge in laparoscopical hemostasis Experience in identifying and solving complications using the same route is needed Diagnostic cystoscopy is a mustRetrobubic suspension has better results on medium (2 ys.) and long term (5 ys.) comparative to

vaginal procedures. Laparoscopy has the advantage of the route of access and magnified view of theanatomical structures.

In cases of relapsed urinary incontinence, urodynamic investigation is essential.The main problem of laparoscopic suturing is the necessity of long sustained training; this skill

cannot be acquired in a one week training course. This isnt a surprise; any surgeon remembers the timeexercising daily the classical knots. The effort is rewarding because mastering laparoscopic suturing represents an important advantage in every type of laparoscopic intervention.

Today, laparoscopy is subject to an avalanche of new technologies (laser, ultrasound, robots), onlyin part justified. The final decision belongs to the surgeon who must choose the best way to treat the patient, given his/hers abilities, experience and devices.

CURRICULUM VITAE

Name: NICULESCU NICOLAEPosition title: MD, PhDOffice Address: Central Military Hospital Dr. Carol Davila Mircea Vulc\nescu Street nr. 88,

BucharestTelephone: 0722 232 602E-mail: nicniculescu@yahoo.comEucation/TrainingInstitution and location degree years field of study

Military College Dimitrie Cantemir Breaza Prahova 1982 Military Medicine Institute UMF Bucharest 1989 (maxim qualification) MD PhD Obstetrics and Gynecology 1999

Positions and employment MD, PhD, Department of Obstetrics and Gynecology Central Military Hospital Dr. Carol

Davila BucharestExperience in clinical research

1. Ovestin in surgical treatment of stress urinary incontinence Akzo Nobel Organon (II)2. Antibiotic prophylaxy in Vaginal Histerectomy 1996-2000 Pfizer (III)3. Dipherelline and surgical treatment of uterin leiomioma and endometriozis Beaufor Ipsen.

(II), Ovarian temporary protection of Dipherelline for reproductive women in treatment withCT for Breast Cancer Beaufor Ipsen. 2002 (II)

4. Treatment with oxybutynyn clorhidrat (Driptane) in OAB Laboratories Fournier 2002 (II)5. The efficiency of single doze of Lomexin 600 Laboratories Fournier (II)6. The effect of Diane 35 in Androgenic Sindrom Schering (II) 7. Decrease in frequency of bone fractures at pacients with osteoporosis in postmenopausal

with treatment TSE 424 in comparation with placebo and Raloxifen Wyeth (III)8. A 12 week Phase II International multicenter blind randomized placebo and

active controlled studz with PSK 3471 in health post menopausal women Praga 2003Training in good clinical practice

Clinical course of Laparoscopic Surgery (CISH, TUMA, IVH) Prof Kurt Semm 1993 Laparoscopy in Obstetrics and Gynecology 1998 Cluj Napoca Romania Surgical treatment of genital prolapse 1998 Bucharest Advanced tehnics in Gynecology Endoscopy International Centre of Gynecology

Endoscopy Clermont Ferrand France Course of Histeroscopy (Diagnostic and operatory tehnique) Clinical University of

Obstetrics and Gynecology Panait Srbu Bucharest 1998 Course of Laparoscopic Surgery UMF Cluj Napoca 1999 Course of Celioscopic and Vaginal-Laparoscopic Surgery Prof. Dargent, Hospital Eduard

Herriot, Lyon France 2001 Course of Laparoscopic and Histeroscopic Surgery IOMC Polizu and SCUMC Bucharest

2001 Clinical stage of Colposcopy SUU Obstetrics and Gynecology Bucharest 2002 Course of Colposcopy UMF Caroll Davila Bucharest 2003 Subspeciality in Laparoscopy 2002 Subspeciality in Histeroscopy 2002 Subspeciality in Colposcopy 2003 Subspeciality in Gynecology-Oncology 2004 Subspeciality in Echography 2006

April 2010