Rak grli}a materice nalazi se u vrhu u~estalosti malignih. rezime ... Radikalna trahelektomija u tretmanu ranog stadijuma karcinoma cerviksa
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1 /STRU^NI RAD UDK DOI: /ACI J Radikalna trahelektomija u tretmanu ranog stadijuma karcinoma cerviksa... K. Jeremi}, S. Petkovi} A. Stefanovi}, M. Gojni}, M. Maksimovi}, J. Stojni}, I. Liki}, S. Kadija, J. Atanackovi} Institut za ginekologiju i aku{erstvo, KC Srbije, Beograd Cilj rada je bio da se kod 12 bolesnica odredi da li radikalna trahelektomija sa pelvi~nom limfonodektomijom mo e biti metod le~enja ranog stadijuma karcinoma grli}a materice kod ena koje ele da o~uvaju sposobnost radjanja. Bolesnice su operisane u periodu od do godine. Dijagnozu cervikalnog karcinoma smo postavili histolo{kim pregledom tkiva, konizacijom ili biopsijom. Histolo{ki tip tumora je planocelularni karcinom, gradus dobro diferentovan. Dve bolesnice su imale stadijum Ia1, sedam bolesnica Ia2, a tri bolesnice Ib1. Radjena je abdominalna radikalna trahelektomija sa pelvi~nom limfonodektomijom. Sprovedena je ex tempore patohistolo{ka analiza resekcionih ivica i selektivno limfnih nodusa, koja je odredila nastavak radikalne trahelektomije. Jedna bolesnica je imala pozitivne resekcione ivice, te je uradjena radikalna histerektomija. Postoperativno, kod jedne bolesnice je nadjen pozitivni limfni nodus, i le~enje je nastavljeno zra~nom terapijom. U dvogodi{njem periodu nije bilo znakova rezidualne bolesti. Zaklju~eno je da radikalna trahelektomija sa pelvi~nom limfonodektomijom mo e biti izvodljiv metod u le~enju ranog stadijuma karcinoma grli}a. Klju~ne re~i: radikalna trahelektomija, karcinom grli}a, fertilitet rezime UVOD Rak grli}a materice nalazi se u vrhu u~estalosti malignih tumora ena. U poslednje vreme uo~ava se porast incidence ovog maligniteta kod mladih ena (<35 godina), {to ukazuje na ve}u u~estalost seksualno prenosivih bolesti posebno izazvanih onkogenim humanim papiloma virusima. S obzirom na ~injenicu da se u toj populaciji nalaze ene koje jo{ nisu zavr{ile svoju reproduktivnu funkciju, name}e se pitanje le~enja uz mogu}nost o~uvanja fertilnosti. Imaju}i u vidu sve kasnije odlu~ivanje na radjanje, u ovu populaciju ena spadaju i one bolesnice koje se nalaze u srednjem ivotnom dobu 1. Hirur{ko le~enje zauzima centralno mesto u terapiji invazivnog karcinoma grli}a materice 2. U cilju o~uvanja {to boljeg kvaliteta ivota, a samim tim i fertilnosti kod ena, u odredjenim slu~ajevima se mo e primeniti i manje radikalno hirur{ko le~enje od klasi~nog onkolo{kog zahvata, koji podrazumeva klasi~nu histerektomiju ili radikalnu histerektomiju sa obostranom adneksektomijom. Ovaj pristup je strogo selektivan, podrazumeva rane stadijume bolesti i odnosi se na bolesnice koje ele da o~uvaju sposobnost radjanja. Postoji nekoliko vrsta hirur{kog le~enja sa ciljem o~uvanja fertilnosti 2. Pored konizacije i pelvi~ne limfadenektomije sprovodi se i hemioterapija. Ipak, naju~estalija operacija danas je abdominalna radikalna trahelektomija i pelvi~na limfadenektomija, pored koje se jo{ izvodi i vaginalna radikalna trahelektomija sa pelvi~nom limfadenektomijom 2. Abdominalna radikalna trahelektomija i pelvi~na limfadenektomija Abdomen se otvara medijalnim rezom ili niskim popre~nim rezom po Mayardu. Ova tehnika podrazumeva preparisanje aa. uterine i sekciju obe cervikalne grane, preparisanje uretera, uklanjanje parametrija, grli}a, gornje tre}ine vagine, uz o~uvanje utero-ovarijalnih veza, kao i preparisanje i sekciju uterosakralnih ligamenata. Nakon toga se na~ini reanastomoza tela uterusa sa vaginalnom mukozom i plasira se serkla neresorptivnim koncem u nivou istmusa materice. U toku operacije na~ini se pelvi~na limfonodektomija, a zatim ex tempore biopsija koja }e odrediti radikalnost operacije. Pelvi~na limfo-nodektomija podrazumeva disekciju limfnih nodusa aa. illiacae communis i i aa. illiacae externae. Lateralni lanac limfnih nodusa sa a. iliace externae se odvaja distalno od v. iliacae circumflexae.
2 94 K. Jeremi} i sar. ACI Vol. LV TABELA 1 PARAMETRI BOLESTI, LE^ENJE I SEKVELE BOLESNICA KOJE SU PODVRGNUTE RADIKALNOJ TRAHELEKTOMIJI I LIMFADENEKTOMIJI REGIJE PELVISA Rezidue u uzorku Bolesnica Starost FIGO stadijum Metod dijagnoze radikalne Komplikacije trahelektomije 1 28 Ia1 konizacija Ia1 konizacija Ia2 biopsija Ib1 biopsija - hematometra 5 40 Ib1 konizacija Ia2 biopsija Ia2 biopsija Ia2 biopsija Ia2 konizacija Ia2 konizacija Ia2 konizacija - - Zatim se vr{i disekcija medijalnog lanca limfatika a. iliacae externae i nakon toga disekcija limfnih ~vorova obturatorne i ishiorektalne jame. Nakon toga na~ini se i disekcija paraaortalnih limfatika 3. Vaginalna radikalna trahelektomija i pelvi~na limfonodektomija Ova operacija je modifikacija Schauta-Stoeckel operacije (vaginalna radikalna histerektomija). Razlikuje se po tome {to se kod vaginalne radikalne trahelektomje vr{i prezervacija gornjeg dela endocervixa i tela uterusa. Tehnika obuhvata laparoskopsku pelvi~nu limfadenektomiju sa laparoskopskom parametrektomijom 4. Cilj rada je bio da se odredi da li radikalna trahelektomija sa pelvi~nom limfonodektomijom mo e biti metod le~enja ranog stadijuma karcinoma grli}a materice kod ena koje ele da o~uvaju sposobnost radjanja. MATERIJAL I METODE Prospektivno klini~ko istra ivanje je uradjeno kod 12 bolesnica sa ranim stadijumom karcinoma grli}a materice, hospitalizovanih na Preoperativnom odeljenju Instituta za ginekologiju i aku{erstvo Klini~kog centra Srbije u periodu od do godine. Bolesnice su hirur{ki le~ene i postoperativno su pra}ene u periodu od dve godine. Sve bolesnice su bile u reproduktivnom periodu. Kod svih bolesnica, dijagnozu cervikalnog karcinoma postavili smo histolo{kim pregledom tkiva, konizacijom ili biopsijom, a stadijum i veli~ina lezije su bili parametri za dono{enje odluke za uklju~ivanje u istra ivanje (FIGO stadijum Ia1, Ia2 i Ib1). Histolo{ki tip karcinoma bio je dobro diferentovan planocelularni karcinom. Adenokarcinom nije uklju~ivan u studiju. Tehnika operativnog rada bila je abdominalna radikalna trahelektomija sa pelvi~nom limfadenektomijom. Sprovedena je ex tempore freeze section patohistolo{ka analiza resekcionih ivica grli}a i limfnih nodusa, koja je odredila nastavak operacije, u smislu daljeg sprovodjenja ispitivane hirur{ke tehnike, ili pristupanja radikalnoj histerektomiji. Kontrolu ovih bolesnica vr{ili smo u toku dvogodi{njeg postoperativnog perioda (klini~ki nalaz, citolo{ka analiza, ultrazvu~ni pregled abdomena i male karlice). REZULTATI U na{em istra ivanju, kod 12 bolesnica sa ranim stadijumom karcinoma grli}a materice, histopatolo{kom analizom je utvrdjeno da je kod dve bolesnice FIGO stadijum karcinoma bio Ia1, kod sedam bolesnica bio je Ia2, a kod preostale tri Ib1. Kod sedam bolesnica materijal za preoperativnu histopatolo{ku analizu dobijen je biopsijom, a kod pet bolesnica konizacijom. Sve bolesnice su bile u reproduktivnom periodu. Prose~na starost bolesnica bila je 30,55+5,52 godina. Najstarija bolesnica u seriji je imala 40 godina, a najmladja 22 godine. Nijedna od njih u anamnezi nije davala podatke o problemima vezanim za fertilitet, kao ni postojanje steriliteta. Histolo{ki gradus tumora (modifikovan Broders sistem za planocelularni karcinom) kod svih bolesnica je prikazao dobro diferentovan tip G1 G2. U toku operacije, kod jedanaest bolesnica je ex tempore analizom resekcionih ivica grli}a i selektivno limfnih nodusa utvrdjeno da su resekcione ivice bile bez tumorskih lezija, te se procedura nastavila dalje. Kod jedne bolesnice je na ivicama resekcije bio prisutan tumor, te smo uradili radikalnu histerektomiju. Postoperativno je kod jedne bolesnice utvrdjeno prisustvo metastaza u limfnim ~vorovima, te je le~enje nastavljeno zra~nom terapijom. Kod preostalih 10 bolesnica u periodu od 2 godine nije bilo znakova rezidualne bolesti.
3 Br. 4 Radikalna traheletkomija u tretmanu ranog stadijuma 95 karcinoma crviksa Navedeni rezultati istra ivanja su prikazani tabelarno (Tabela 1). DISKUSIJA Postoji nekoliko na~ina hirur{kog le~enja ranog stadijuma karcinoma grli}a sa o~uvanjem fertilnosti. Pored konizacije i pelvi~ne limfadenektomije sprovodi se hemioterapija (Taxol, Cisplatinum, Epiburicin). U studiji koju je prikazao Landoni (2000. godine) navodi se grupa od 12 bolesnica kod kojih je dijagnostikovan invazivni karcinom grli}a materice. Nakon sprovedene hemioterapije, a potom i konizacije sa pelvi~nom limfadenektomijom, 8 bolesnica nije imalo recidiv, a 2 bolesnice su rodile decu. Ipak, ovaj hirur{ki pristup treba prihvatiti sa oprezom, s obzirom na to da jo{ uvek nije pro{ao ozbiljnu probu u klini~koj praksi 5. D Argent i autori su u engleskoj medicinskoj literaturi godine prvi opisali po{tednu ginekolo{ku operaciju koju su nazvali radikalna trahelektomija. Njihovo po~etno iskustvo je pro{ireno ali i ponovljeno od strane drugih autora 5. Roy, Plante i D Argent su postavili kriterijume za izvodjenje radikalne trahelektomije : 1. elja za o~uvanjem fertilnosti 2. bez klini~kih znakova umanjene sposobnosti radjanja 3. FIGO stadijum Ia2 ili Ib1 4. lezija koja je veli~ine manje od 2 cm, 5. odsustvo adenokarcinoma 6. odusustvo zahva}enosti limfovaskularnog prostora 7. ograni~ena endocervikalna zahva}enost pri kolposkopskom pregledu 8. bez indikacija za postojanje metastaza limfnih ~vorova male karlice Sve bolesnice u na{oj seriji su bile u reproduktivnom periodu. Nijedna od njih u anamnezi nije davala podatke o problemima vezanim za fertilitet, kao ni postojanje steriliteta. Izvestan broj bolesnica je pre{ao starosnu granicu preko 35 godina, kada se smanjuje stopa fertiliteta. I sama operacija na izvestan na~in mo e ugroziti fertilnost, u smislu stvaranja priraslica (adhezija), iako se ona izvodi radi njenog o~uvanja, a zbog ranog stadijuma invazivne bolesti grli}a. Dijagnozu cervikalnog karcinoma smo postavljali histolo{kim pregledom tkiva dobijenog konizacijom ili biopsijom, kao i kireta om cervikalnog kanala. Procenjuje se dubina invazije, {irina lezije, kao i zahva}enost limfovaskularnog prostora. Ovi parametri su bili bitni za dono{enje odluke o radikalnoj trahelektomiji. U cilju eva-luacije bolesti, osim histopatolo{ke dijagnostike koristi se klini~ki pregled, eksfolijativna citodijagnostika - PAPA razmaz, ultrazvuk male karlice i abdomena, rendgenski snimak plu}a i laboratorijske analize. FIGO stadijum i veli~ina lezije su najzna~ajnije preoperativne determinante za pristupanje radikalnoj trahelektomiji 6. Hirur{ko le~enje zauzima centralnu ulogu u le~enju cevikalnog karcinoma. Za stadijum Ia1 (invazija u stromu manja od 3 mm, promer najve}eg pre~nika lezije manji od 7 mm), bez limfovaskularne invazije, terapija izbora je konizacija, imaju}i u vidu da je incidenca metastaza u limfatike manja od 1%. Pored konizacije, ovaj stadijum se mo e le~iti i radikalnom trahelektomijom, {to je bio slu~aj kod dve na{e bolesnice koje su imale pozitivnu resekcionu ivicu nakon terapijske konizacije (mikroinvazivni karcinom na resekcionim ivicama). Takodje se ovaj stadijum le~i i klasi~nom histerektomijom, kod ena koje su zavr{ile reproduktivnu funkciju 6. Kod stadijuma Ia2 (invazija u stromu od 3 do 5 mm, a lezija do 7 mm) i Ib1 (invazija u stromu ve}a od 5 mm, promer tumora manji od 4 cm) rizik od pojavljivanja metastaza u limfaticima je zna~ajniji, pa je tradicionalna terapija usmerena ne samo na otklanjanje primarnog mesta, ve} i na limfne ~vorove, nala u}i pored radikalne trahelektomije i limfonodektomiju regije pelvisa i paraaortalnih limfatika. Kod ve}ine autora postoje indicije da se lezije Ia2 stadijuma mogu tretirati jednako adekvatno konizacijom, trahelektomijom ili histerektomijom. Oni smatraju da su prate}e promene stadijuma Ia2 vi{e limfati~ke, a manje lokalne. Po njihovom mi{ljenju, za promene tipa Ia2 konalna kru na biopsija sa jasnim resekcionim ivicama mo e omogu}iti jednaku lokalnu kontrolu kao radikalna trahelektomija ili histerektomija. Ipak, limfadenektomija karli~ne regije je i dalje neophodna 6,7. U na{oj studiji su i dve bolesnice sa karcinomom grli}a, stadijum Ib1 sa promerom tumora do 2cm, koje su tretirane radikalnom trahelektomijom. Manji broj autora smatra da postoji osnova za kombinaciju radikalne ekscizije tumora grli}a i pelvi~ne limfonodektomije za lezije Ib1 stadijuma 7. Takodje, neki autori smatraju da je veli~ina tumorske lezije ispod 2 cm bitna kod ulceroznih i infiltrativnih lezija, dok je kod egzofiti~nih promena sa uskom bazom veli~ina ipak promenljiva varijabla 7. U toku operacije, uklanja se grli} sa delom vagine, kao i limfni ~vorovi, a zatim se na~ini ex tempore analiza resekcionih ivica i selektivno limfnih nodusa. Ukoliko su resekcione ivice bez tumorskih lezija, procedura se nastavlja dalje. Ako je na ivicama resekcije prisutan tumor, neophodno je nastaviti radikalnu histerektomiju, {to je bio slu~aj kod jedne bolesnice. Metastaze selektivno ispitanih limfnih ~vorova su takodje kontraindikacija za radikalnu trahelektomiju i u tom slu~aju se radi radikalna histerektomija 8,9. Limfonodektomija regije pelvisa izvedena u na{em istra ivanju podrazumevala je ciljanu disekciju parametrijalnih limfnih nodusa, koji predstavljaju prvo mesto drena e strome grli}a. Njihovo uklanjanje smatra se zna~ajnim delom operacije, s obzirom na to da prilikom trahelektomije ipak uterus i deo parametrija ostaje. Nakon toga, uklanjaju se sve pelvi~ne lezde do ra~ve a. iliacae communis: paracervikalne, hipogastri~ne (obturatorne), zajedni~ke unutra{nje i spolja{nje ilija~ne, presakralne i lateralne sakralne 9. Izvestan broj autora smatra da adenokarcinom nije kontraindikacija za radikalnu trahelektomiju. Neki autori ~ak smatraju da u slu~ajevima adenokarcinoma koji je izvadjen putem krune konalne biopsije sa jasnim resekcionim ivicama nije neophodno raditi trahelektomiju ili histerek-
4 96 K. Jeremi} i sar. ACI Vol. LV tomiju, kod bolesnica sa eljom za o~uvanjem fertilnosti. Na{a studija nije uklju~ivala bolesnice sa adenokarcinomom, kao ni ve}ina drugih studija 10. Smatra se da je abdominalna radikalna trahelektomija tehni~ki lak{a od trahelektomije sprovedene vaginalnim putem, ali se u literaturi ~e{}e navode komplikacije tipa obimnijih krvarenja i infekcije 11,12. Jedna od komplikacija je stenoza istmi~og kanala sa posledi~nom hematometrom i amenorejom. Ukoliko dode do infekcije, javlja se piometra. Zato neki autori predla u plasiranje Folijevog katetera u uterus jo{ pre amputacije grli}a i ostajanje tokom kra}eg vremenskog perioda da bi se izbegla stenoza i sledstvena hematometra. Ukoliko do toga dodje neophodna je drena a i evakuacija sadr aja 11,12. Kontrola ovih bolesnica se vr{i na svaka 3 meseca po zavr{enom tretmanu tokom prve godine, zatim svakih 6 meseci uz citolo{ku analizu do pete godine, a potom jednom godi{nje. Ultrazvuk abdomena i male karlice treba raditi jednom godi{nje, a radiografija plu}a radi se prema indikacijama 13. Na{e iskustvo sa radikalnom trahelektomijom i limfonodektomijom kod po~etnih formi karcinoma grli}a ukazuje da se radi o adekvatnoj terapiji kod ena koje ele da o~uvaju fertilnost. Visok nivo gubitka trudno}e kod ovih bolesnica je jedno od ve}ih nere{ivih pitanja vezano za trehelektomiju. Na osnovu podataka iz literature, ve}a je u~estalost poba~aja u ranim trimestrima trudno}e usled inkompetencije u{}a materice, kao i ruptura plodovih ovojaka. Evidentno je da trudno}e nakon radikalne trahelektomije spadaju u trudno}e visokog rizika 13. Dana{nji pristup po pitanju za~e}a je slede}i: tokom prve godine nakon operacije potrebno je pra}enje ovih bolesnica i odlaganje trudno}e. Kada do koncepcije dodje, neophodno je uklju~ivanje perinatologa, s obzirom na visok stepen poba~aja i prevremenih porodjaja, kao i preduzimanje profilakti~kih mera i le~enje 13. ZAKLJU^AK Na osnovu rezultata na{eg istra ivanja zaklju~eno je da radikalna trahelektomija sa pelvi~nom limfonodektomijom mo e biti izvodljiv metod u le~enju ranog stadijuma karcinoma grli}a. SUMMARY RADICAL TREACHELECTOMY IN TREATMENT OF EARLY STAGES OF CERVICAL CANCER The aim of the study was to determine if radical trachelectomy with pelvic lymphonodectomy could be a method for treatment of early cervical cancer to preserve fertility. We examined 12 patients who were operatively treated from to year. Diagnostic method for cervical cancer was histologic examination, cone or biopsy. Histologic condition was planocelular carcinoma well differented. Two of the patients had Ia1 stage, seven had Ia2, and three of them had Ib1. We performed abdominal radical trachelectomy with pelvic lymphonodectomy. Resectional edges were patohistologically analyzed ex tempore, as well as lymphonodi, selectively. According to ex tempore analysis we determined if the radical trachelectomy should be done. In one patient resectional edges were positive, so she underwent radical hysterectomy. Postoperatively we found a positive lymphonodus in one patient, so we continued radiation therapy. In twoyear follow-up period we did not find any sign of residual cancer. We concluded that radical trachelectomy with pelvic lymphonodectomy could be appropriate method for treatment of early stage cervical cancer. Key words: radical trachelectomy, cervical cancer, fertility REFERENCE 1. Koliopoulos G, Sotiriadis A, Kyrgou M, et al. All stage I cervical cancers are not created equally: the case for individualized treatment. Gynecol Oncol 2004;93: Abu-Rustum NR, Sonoda Y, Black D, Levine DA, Chi DS, Barakat RR. Fertility-sparing radical abdominal trachelectomy for cervical carcinoma: Technique and review of the literature. Gynecol Oncol 2006;103: Shepherd JH, Crawford RA, Oram DH. Radical trachelectomy: a way to preserve fertility in the treatment of early cervical cancer. Br J Obstet Gynaecol 1998; 105: Roy M, Plante M. Pregnancies after radical vaginal trachelectomy for early-stage cervical cancer. Am J Obstet Gynecol 1998; 179: D Argent D. Using radical trachelectomy to preserve fertility in early invasive cervical cancer. Conmporary Obstet Gynecol 2000: 45(5): Covens AL, Shaw P. Is radical trachelectomy a safe alternative to radical hysterectomy for patients with stage IA-B carcinoma of the cervix? Gynecol Oncol 1999; 72: Spirtos NM, Schlaerth JB, Kimball RE, Leiphart VM, Ballon SC. Laparoscopic radical hysterectomy (type III) with aortic and pelvic lymphadenectomy. Am J Obstet Gynecol 1996; 174 (6): Hricak H et al. Role of imaging in pretreatment evaluation of early invasive cervical cancer: results of the intergroup study American College of Radiology Imaging Network 6651-Gynecologic Oncology Group 183. J Clin Oncol 2005 Dec 20;23(36): Benedet JL, Bender H, Jones H 3 rd, et al. FIGO staging slassifications and clinical practice guidelines in the management of gynecologic cancer. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet 2000;70: Dargent D, Martin X, Sacchetoni A, et al. Laparoscopic vaginal radical trachelectomy. Cancer 2000; 88: Roman LD, Felix JC, Muderspatch I, et al. Influence of quantity of lymphovascular space invasion on the risk of nodal metastasis in women with early stage squamous cell carcinoma of the cervix. Gynecol Oncol 1998;
5 Br. 4 Radikalna traheletkomija u tretmanu ranog stadijuma 97 karcinoma crviksa 12. Plante M, Renaud MC, Francois H, Roy M. Vaginal radical trachelectomy: an oncologically safe fertility-preserving surgery. An updated series of 72 cases and review of the literature. Gynecol Oncol 2004;94: Koliopoulos G, Sotriadis A, Kyrgiou M et al. Conservative surgical methods for FIGO stage IA2 squamous cervical carcinoma and the role in preserving womens fertility. Gynecol Oncol 2004;93:
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