DIJAGNOSTICKI ZNACAJ SONOGRAFSKOG BODOVNOG SISTEMA U DIFERENCIJACIJI MALIGNm I BENIGNIH TUMORA JAJNlKA

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1 Med Preg200; LIV (-4): Novi Sad: mart-april. 6 Medicinski fakultet, Novi Sad Klinicki centar, Novi Sad Klinika za ginekologiju i akuserstvo Strucni clanak Professional article UDK / DIJAGNOSTICKI ZNACAJ SONOGRAFSKOG BODOVNOG SISTEMA U DIFERENCIJACIJI MALIGNm I BENIGNIH TUMORA JAJNlKA DIAGNOSTIC VALUE OF SONOGRAPHY SCORING SYSTEMIN DIFFERENTIATION OFMALIGNANT AND BENIGN OVARIAN TUMOURS Srdan DURDEVIC Sazetak - U radu je prikazan dijagnosticki znacaj originalnog sonografskog bodovnog sistema u diferencijaciji malignih i benignih tumora jajnika. Primenom endovaginalne i abdominalne ultrazvucne sonde, u periodu god., preoperativno je pregledana 77 bolesnica koje su hirurski lecene na Klinici za ginekologiju i akuserstvo u Novom Sadu. U zavisnosti od definitivnog histoloskog nalaza pacijentkinje su razvrstane u 2 grupe: sa malignim A (7) i benignim B (06) tumorima jajnika. Pojedine karakteristike tumora (velicina, morfoloske osobine, karakteristike tumorske kapsule, prisustvo septuma i ascitne tecnosti) sonografski su ocenjene poenima od 0 do 2 a zbir svih bodova predstavljao je ukupni skor (min. 0 - maks. 0). Najveci stepen pouzdanosti bio je prisutan kadaje ukupni skor iznosio 6 i vise bodova (osetljivost 87,%, specificnost 9,5%, pozitivna vrednost predvidanja 87,%, negativna vrednost predvidanja 9,5% i tacnost testa 90,9%). Prikazani sonografski bodovni sistem predstav Ijajednostavan i koristan dijagnosticki metod u neinvazivnoj diferencijaciji malignih i benignih tumorajajnika. Klucne reci: Tumori jajnika + dijagnoza + ultrasonografija + hirurgija; Diferencijalna dijagnoza Uvod Mogucnost dobre rezolucije i ehotipizacije koju pruzaju noviji tipovi ultrazvucnih aparata Cine ovu metodu podesnom u dijagnostici razlicitih tumora u maloj karliei. Veci broj podataka u kratkom vremenskom periodu i preeiznost u toku pregleda daju prednosti endovaginalnoj sonografiji prema abdominalnoj u dijagnostiei oboljenja zenskog genitalnog trakta []. Kod postojanja sumnje na prisustvo tumora u maloj karliei za klinicara su od neprocenjivog znacaja sledece informaeije koje se dobijaju primenom ultrazvuka: velicina, oblik, grada, pripadnost odredenom organu, odnos sa okolinom i prisustvo slobodne tecnosti. Najveci broj gresaka pripisuje se nepravilnoj tehniei rukovanja ultrazvucnom sondom, povrsnom pregledu, pogresnoj interpretaeiji nalaza i smetnjama koje mogu potieati od strane intestinalnog sistema [2]. Smatra se da je oko 90% svih tumora jajnika benigne prirode pri cemu se oko 80% manifestuje u vidu cisticnih formaeija sto ih cini gotovo idealnim za ultrazvucni pregled i dijagnostiku. Maligni tumori jajnika, sa ineidencom od oko 5 na , obuhvataju oko 25% svih malignih tumora zenskog genitalnog sistema i predstavljaju vodeci uzrok smrtnosti u ovoj grupi []. U ginekologiji i akuserstvu nacinjen je do sada citav niz razlicitih bodovnih sistema sa znacajnom ulogom u prakticnom svakodnevnom radu (Apgar, Bishop skor i dr.). Cilj primene bodovnih sistema je da se izvrsi diskriminacija manje pouzdanih informaeija i paznja usmeri na svrsishodne i bitne parametre [4]. Poznato je da ultrazvucno detektovana kompleksnost tumora jajnika (prisustvo solidnih elemenata, polipoidni i papilami izrastaji na unutrasnjoj strani kapsule, septiranost i neravni zidovi cisticnih tumora) povecava rizik za malignitet [5]. Do danas je nacinjeno nekoliko razlicitih sonografskih bodovnih sistema koji su oeenjivali pojedine tumorske karakteristike u nameri da sto objektivnije ukazu na malignu prirodu bolesti [6,7,8]. Cilj rada je oeena dijagnostickog znacaja vlastitog sonografskog bodovnog sistema i proeena mogucnosti njegove primene u neinvazivnoj difereneijaeiji malignih i benignih tumora jajnika. Materijal i metode Prospektivnim ispitivanjem obuhvaceno je 77 zena sa razlicitim vrstama tumora jajnika koje su u periodu godine operisane u Zavodu za ginekologiju Klinike za ginekologiju i akuserstvo u Novom Sadu. Kod svih bolesnica uraden je ginekoloski i ultrazvucni pregled vaginalnom sondom od 5 MHz, aparatima ALOKA SSD 200 i SIEMENS sonoline prima. U slucajevima kada je najveci promer tumora iznosio vise od 5 em u eilju detaljnog pregleda uraden je i dopunski ultrazvucni pregled abdominalnom sondom od,5 MHz. Osnovni kriterijum za ulazak u ispitivanje bilo je prisustvo tumora na jajniku za koji je na osnovu klinickog, ultrazvucnog iii drugih pregleda (CT, MRI), od strane ordinirajuceg ginekologa, data preporuka za operativno lecenje. Neposredno posle izvrsenog ultrazvucnog pregleda paeijentkinje su evidentirane putem anketnog lista koji je ukljucivao podatke 0 generalijama, godinama starosti, adresi stanovanja, klinickoj dijagnozi i definitivnom patohistoloskom nalazu. U tabeli Adresa autora: Doc. dr Srdan Durdevic, Klinika za ginekologiju i akuserstvo, 2000 Novi Sad, Branimira Cosica 7, Willter@PTT.YU

2 62 Duraevic S. Dijagnosticki znacaj sonografskog bodovnog sistema Skracenice MIN MAKS CT MRI St. CA -minimalno - maksimalno - kompjuterizovana tomografija - elektromagnetna rezonanca - stadijum - karcinom antigen Tabela. Sonografski bodovni sistem u diferencijaciji tumora jajnika Table. Echographic scoring system [or ovarian tumors Sonografske Broj bodova Ocena karakteristike Number ofpoints Score Sonographic 0 characteristics 2 Velicina tumora (em) Morfoloske karakteristike Septumi Karakteristike tumorske kapsule Ascites do 4 do 0 preko 0 cistiean mesovit solidne plaze i papile iii solidan bez iste bez jednake nejednake minimalan unutar ciste, multilokularnost nejednake nejednake, neravna, proliferacije masivan Ukupni skor prikazan je sonografski bodovni sistem gde su odredene karakteristike tumora jajnika ocenjene bodovima od 0 do 2, sto je konacno predstavljeno ukupnim skorom (min. 0 - maks. 0 bodova). Prema navedenim kriterijumima svaka pacijentkinja je zasebno ocenjena putem opisanog bodovnog skora i evidentirana u anketnom listu. Definitivna dijagnoza Tabela 2. Histoloska klasifikacija malignih tumora jajnika Table 2. Histologic classification qfovarian tumors n % Histoloski tip tumora Epitelijalni tumori. Serozni cistadenokarcinom 2. Mucinozni cistadenokarcinom. Endometrioidni karcinom 4. Karcinom svetlih celija (clear cell) 5. Brenerov maligni tumor 6. Adenokarcinom Tumori germinativnog epitela I. Disgerminom Tumori porekla specijalizovanih celija strome (Sex cord - stromal tumors). Granulozocelij ski tumor 2. Tumor Sertoli-Leydigovih celija. Androblastom Metastatski tumori. Adenokarcinom (Krukenbergov tumor) 2. Maligni melanom Neklasifikovani tumori. Anaplasticni karcinom Ukupno ,2 2,7 8,4 5,5 2,8 9,8 5,6 00 postavljena je posle patohistoloskog pregleda hirurski odstranjenog materijala na osnovu koga je izvrsena podela na ispitivanu grupu A (maligni tumori jajnika, n\ = 7) i kontrolnu grupu B (benigni tumori jajnika, n 2 = 06). U analizi rezultata koriscena je metodologija koja se primenjuje za ocenjivanje dijagnostickih testova u medicini [9]. Rezultati U ispitivanoj grupi A (maligni tumori jajnika) prosecna starost bolesnica iznosila je 48, godina (9-75) au grupi B (benigni tumori jajnika) 8, godine (4-76). U tabelama 2 i prikazana je distribucija ispitanica po grupama u odnosu prema histoloskoj vrsti tumora jajnika. Tabela. Histoloska klasifikacijabenignih tumora jajnika Table. Histologic classification ofbenign ovarian tumors Histoloski tip tumora n % Epitelijalni tumori Serozni cistadenom 2, Mucinozni cistadenom 2 9,8 Tumori germinativnog epitela Zreli teratom (dermoidna cista) 4,2 Stromalni tumori Fibrom 2,9 Fibrotekom 2,8 Funkcionalne ciste Folikularna cista 5 4,7 Luteinska cista 6 5,6 "Simplex" cista 8 7,6 Zapaljenjski tumori Tuboovarijalni apsces 2, Pioovarijum 2,9 Mesovita stanja Endometriom (Terr cystis) 4,2 Hemoragicna cista 2,9 Paraovarijalna cista 5 4,8 Ukupno Tabela 4 prikazuje dijagnosticku vrednost sonografskog bodovnog sistema u diferencijaciji malignih i benignih tumora jajnika za ukupni skor od 4 do 0 Tabela 4. Dijagnosticki znacaj sonografskog bodovnog sistema Table 4. Diagnostic value ofeehographic scon'ng system Statisticki testovi (%) Ukupni bodovni skor Osetljivost Specificnost Pozitivna vrednost predvidanja Negativna vrednost predvidanja Prevalenca Tacnost testa 4~ 5~ 6~ 7~ 8~ 00 95,7 87, 70,4 46,4 66 8, 9,5 97, 99 9~ 0 2, , 77,2 87, 70,4 97, ,6 9,5 8,0 7,4 65,4 60,9 40, 40, 40, 40, 40, 40, 40, 79, ,9 86,4 77,9 68, 6,5

3 Med Preg200; LIV (-4): Novi Sad: mart-april. 6 (maligni tumori jajnika) oznacena je kao "bolesni" a grupa B (benigni tumori jajnika) kao "zdravi", u smislu nepostojanja maligne bolesti. Na slikarna - 4 prikazane su ultrazvucne slike i u prilogu dat ukupni bodovni skor benignih i malignih tumora jajnika: slika - Krukenbergov tumor (metastaza adenokarcinoma na jajniku) (skor 9), slika 2 - serozni cistadenokarcinom (skor 7), slika - luteinska cista (skor 2) i slika 4 - mucinozni cistadenom (skor 7). Slika. Krukenbergov tumor (metastaza adenokarcmoma na jajniku) Fig.. Krukenberg tumor (metastatic ovarian adenocarcinoma) Slika 4. Mucinozni cistadenom Fig. 4. Mucinous cystadenoma Diskusija Slika 2. Serozni cistadenokarcinom Fig. 2. Serous cystadenocarcinoma bodova. Srednja vrednost (x) ukupnog skora u grupi A bilaje 7,25 au grupi B,6 bodova. U toku izracunavanja dijagnosticke vrednosti ispitivana grupa A Slika. Teka luteinska cista Fig.. Theca lutein cysts U grupi malignih tumora zenskog genitalnog sistema karcinom jajnika ima najlosiju prognozu, izmedu ostalog i zbog toga sto je vise od 70% bolesnica dijagnostikovano u uznapredovalom stadijumu bolesti (st. III i IV). Rana dijagnoza i pravovremena hirurska terapija namecu se kao imperativ u lecenju ovih pacijenata [9]. Primena kompjuterizovane tomografije (CT), elektromagnetne rezonace (MRI) i kolor doplera u ove svrhe nije dala zeljene rezultate [0, ]. Cinjenica da se radi 0 skupim dijagnostickim postupcima koji se mogu primeniti sarno u dobro opremljenim dijagnostickim centrima uticala je na ponovno povecanje interesa za primenu posebno vaginalne sonografije u dijagnostici karcinoma jajnika. Znacajan pomak predstavlja primena bodovnih sistema sa narnerom da se posebno ocene pojedine karakteristike tumora i ukupnim skorom okarakterise maligna iii benigna priroda tumora [4]. Jedan od najcesce primenjivanih bodovnih sistema publikovao je Sasson sa saradnicima 99. godine [7]. Prema 0 yom sistemu, bodovima od do 5 ocenjuju se 4 sonografske karakteristike tumora jajnika (unutrasnja struktura kapsule, debljina zida, septiranost i ehogenost tumora). Najveci stepen pouzdanosti bio je kada je ukupni skor iznosio 9 i vise bodova (osetljivost 00%, specificnost 8%, pozitivna vrednost predvidanja 7%). Foglia i saradnici nacinili su zapazen

4 64 Duraevic S. Dijagnosticki znacaj sonografskog bodovnog sistema pokusaj u izradi bodovnog sistema koji je pored sonografske ocene karakteristika tumora ukljucivao i koncentraciju tumorskog markera CA-25 u serumu [8]. Prema ovom sistemu, bodovirna od do, ocenjivane 4 karakteristike: velicina, spoljasnji izged tumora, prisustvo ascitne tecnosti i koncentracije CA-25. Ukupni skor od 0 i vise bodova ukazivao je na maignu prirodu boesti sa visokim stepenom pouzdanosti (osetljivost 9,%, specificnost 97,8%, pozitivna vrednost predvidanja 9,% i prevalenca 9,5%) ali reativno mali uzorak i niska prevalenca uticali su na slabiju prakticnu primenu ovog sistema. U radu je prikazan originalni bodovni skor koji je ocenjivao ukupno 5 razlicitih sonografskih karakteristika tumora jajnika. Sa najvecim brojem bodova (2 boda) pojedinacno su ocenjene karakteristicne morfoloske osobine koje najcesce stoje u vezi sa malignim tumorima jajnika. Ukupni skor od 6 i vise bodova predstavja pouzdan dijagnosticki znacaj u diferencijaciji malignih i benignih tumora jajnika. Pomakom prema visim kriterijumima (ukupni skor 7-0 bodova) znacajno raste specificnost i pozitivna vrednost predvidanja ali opada osetljivost, negativna vrednost predvidanja i tacnost testa. Nize vrednosti skora od 4 i vise i 5 i vise bodova u vezi su sa porastom osetljivosti i negativne vrednosti predvidanja ali i padom specificnosti, pozitivne prediktivne vrednosti i tacnosti testa. Prilikom sonografske potvrde ili iskjucenja karcinoma jajnika poseban problem predstavljaju maligni tumori solidne grade bez znacajne razike u ehotipizaciji pojedinih delova. Kod (%) bolesnice (anaplasticni karcinom 2, disgerminom ) ukupni skor iznosio je sarno 4 boda, sto je uticalo na pad specificnosti, pozrtrvne prediktivne vrednosti i tacnosti testa. U grupi benignih tumora jajnika kod (2,8%) boesnice sa mucinoznim cistadenomom zabelezen je ukupni skor od 7 i 8 bodova, sto je negativno uticalo na osetljivost i tacnost testa. Zakljucak Primena opisanog sonografskog bodovnog sistema predstavlja pokusaj poboljsanja neinvazivne ultrazvucne dijagnostike karcinoma jajnika. Ukupni skor od do boda iskljucuje maligni a od 9 do 0 benigni karakter tumora. Dijagnosticki problem predstavljaju maligni tumori solidne i kompaktne morfoloske grade bez prisustva papila na povrsini i slobodne tecnosti u trbuhu, sto rezultira niskim ukupnim skorom od 4 i 5 bodova, odnosno benigni tumori kompleksne grade sa visokim skorom od 7 i 8 bodova. Visok stepen osetljivosti (95,7%) u detekciji karcinoma jajnika prisutan je kod ukupnog skora od 5 i vise bodova ali nesto niza specificnost (8,%) i tacnost testa (87%) daju prednost skoru od 6 i vise bodova gde su najmanje izrazene razlike izmedu pojedinih statistickih pararnetara (osetljivost 87,%, specificnost 9,5%, pozitivna vrednost predvidanja 87,%, negativna vrednost predvidanja 9,5% i tacnost testa 90,9%). Sonografski bodovni sistem predstavlja jednostavan i lako primenljiv neinvazivni dijagnosticki metod u diferencijaciji malignih i benignih tumora jajnika. Odredeni stepen subjektivnosti u interpretaciji i bodovanju nalaza moze se kompenzovati iskustvom ispitivaca i kontrolom vlastitog rada, sto se postize uvidom u intraoperativni i definitivni histoloski nalaz. Literatura. Wikland M, Granberg S. Ultrasonographic Diagnosis of Ovarian Cystic Tumours. In: Brnhat MA, ed. The Management of Adnexal Cysts. Oxford: Blackwell Scientific Publications, 994 : Pilic Z, Stankovic A. Ultrazvuk u ginekologiji. st ed. Beograd-Zagreb: Medicinska Knjiga, 988:280.. Fox H. Pathology of Ovarian Cancer. In: Shepherd JH, Monaghan JM, eds. Clinical Gynaecological Oncology. Oxford: Blackwell Scientific Publications, 994: Philippe HI Echographic Scoring for Ovarian Diseases. In: Brnhat MA, eds. The Management of Adnexal Cysts. Oxford: Blackwell Scientific Publications, 994: Rosenblatt R, Kutcher R. Malignant Diseases of the Ovary. In: Berman MC, Cohen HL, eds. Obstetrics and Gynaecology-diagnostic medical sonography. Philadelphia-New York: Lippincott, 997: Timor-Tritsch IE, Lamer JP, Monteagudo A. Transvaginal ultrasonographic characterization of ovarian masses by means of color flow directed Doppler measurements and a morphologic scoring system. Am J Obstet Gynecol 99;68: Seassone AM, Timor-Trich IE, Artner A, Westhoff C, Warren WB. Transvaginal sonographic characterization of ovarian disease: evaluation of a new scoring system to predict ovarian malignancy. Obstet Gynecol99;78 : Foglia M, Verri PG, Calabrese A. Echography and CA 25 in ovarian pathology. Preliminary data on a new score. J Nucl Med Allied Sci 990;4: Durdevic S. Dijagnosticki i prognosticki znacaj odredivanja tumorskih markera u bolesnica sa karcinomom ovarijuma i endometrijuma. Doktorska disertacija. Novi Sad, Srbija: Univerzitet u Novom Sadu, Medicinski fakultet, Ghossain MA, Buy IN, Lingers C. Epithelial tumors of the ovary: comparison of MR and CT findings. Radiology 99;8: Dukic M, Jurisic A, Markovic S, Rakic S, Runic S, Andelic S. Dijagnosticka vrednost kolor dopler ultrasonografije u otkrivanju malignih tumora ovarijuma. Zbornik radova XL ginekol.akus.ned, Beograd: 996;409-5.

5 Med Preg200; LIV (-4): Novi Sad: mart-april. 65 Summary Introduction There have been several different sonographic scoring systems developed for evaluation ofparticular characteristics of ovarian tumors in order to classify malignant diseases in the most objective way. The aim ofthis study was to evaluate diagnostic significance ofour own scoring system and possibilities ofits application in differentiation ofmalignant and benign ovarian tumors. Material and methods A prospective study comprised 77 women with different ovarian tumors. All patients underwent ultrasound examination using a unit with a 5 MHz probe. Certain tumor characteristics (size, morphology, septa, type ofcapsule and ascites) were estimated by scores from 0 to 2 whereas the sum ofall scores presented the total score. A final diagnosis was made after histopathologic examination: group A - malignant ovarian tumors (n=7) and group B - benign ovarian tumors (n=06). Key words: Ovarian Neoplasms + diagnosis + ultrasonography + surgery; Diagnosis, Differential Radje primljen 9. vn2000. Prihvacen za stampu 5. IT 200. BIBLID :(200):LIV:-4: Results The highest value of reliability in differentiation ofmalignant and benign ovarian tumors was score 6 and more than six (sensitivity 87.%, specificity 9.5%, positive predictive value 87.%, negative predictive value 9.5% and test accuracy 90.9%). Discussion A separate diagnostic problem during application of mentioned sonographic scoring system were solid malignant tumors with a low total score (4 and 5 scores) and benign tumors of complex consistence of high total score (7 and 8 scores). The total score - eliminates malignant tumors and the score from 9-0 eliminates benign type oftumors. Conclusion High sensitivity (95.7%) is present at the total score of5 and more than five, but low specificity (8. %) and test accuracy (87%) gives advantage to the score 6 and more, where differences between separate statistical parameters are least present. International Society of Heart Failure, Inc: 8th World Congress on Heart Failure Mechanisms and Management July 8-, 200, Hong Kong, China Contact: World Congress on Heart Failure PO Box 76759, Beverly Hills, CA USA Tel: ; Fax: ; klimedco@uda.edu

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