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Endometriumkarzinom - Diagnose und Therapie C Tempfer.

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Präsentation zum Thema: "Endometriumkarzinom - Diagnose und Therapie C Tempfer."—  Präsentation transkript:

1 Endometriumkarzinom - Diagnose und Therapie C Tempfer

2 Allgemeines n Häufigstes Malignom - Genitaltrakt n neue Fälle/5400 Todesfälle pro Jahr n hohe Prävalenz – westl. Industriestaaten n geringe Prävalenz - Entwicklungsländer, Südasien, Indien n Östrogen-abhängig –ERT, BMI, Ernährung, anovulatorische Zyklen –Alter/Postmenopause, ger. Parität, hoher Sozialstatus

3 PAP Test PAP Test n Kein Screening-Test für Endometriumkarzinom n Sensitivität 50% (rp/k) –50% aller Frauen mit EK zeigen abnormale Endometriumzellen im Abstrich n Spezifität 25% (rp/pt) –75% falsch positiv

4 TVS – N. endometrii  n=5013; TVS-Doppler  N. endometrii stage I: 6 (Kurjak 1994) n=1000; TVS n=1000; TVS 4mm cut-off; N. endometrii stage I: 1 (Karlsson 1996)4mm cut-off; N. endometrii stage I: 1 (Karlsson 1996) n=1074; TVS+Doppler n=1074; TVS+Doppler  4mm cut-off/PI; N. endometrii stage I: 3 (Vuento 1999)  n=2025; TVS  N. endometrii: 3 (Ciatto 1995) Summe: 9112/13; NNS 701

5 Screening Screening n Kein etabliertes Massenscreening –Kein adäquater Bluttest, kein Tumormarker –Keine ideale sampling-Methode n Hochrisikopopulationen –Tamoxifen –Lynch II/HNPCC

6 TVS und TAM  Gerber 2000; n=247; 10mm cut-off; 5a; 1 asymptomatic cancer; 52 D&Cs; 4 perfor.  Love 1999; n=487; 5mm cut-off; 0 cancers; 134 D&Cs  Fung 2003; 9mm cut-off; 304 D&Cs - 6 cancers-all with bleeding 1/525 D&C

7 n TVS – 2 Studien (Rijcken 2003; Dove 2002) n n=41; 5 yrs; 17/179 TVS positive: 3 atyp. Hyperpl.; 1 Ca nicht entdeckt n n=269; 3 yrs; 2 Endometrium-Ca; 0/2 durch TVS n TVS + CA keine Daten n TVS + endometrial sampling –1 Studie (Renkonen 2006) n n=175; 5 yrs; 11/14 entdeckt (8 durch Biopsie) + 14 atypische Hyperplasien; 0/4 N. ovarii entdeckt HNPCC

8 Empfehlung n Empfehlung American Cancer Society, US Preventive Task Force –‚…annual screening with endometrial biopsy beginning at age 35‘ Smith et al. ACS guidelines for the early detection of cancer, CA Cancer J Clin. 2006;56:11-25

9 Klinik n Persist. perimenopausale Blutung n Hämatometra/Pyometra in Postm. n PMB –endometrial cancer: 15% of PMB - specificity 15% –90% of women with endometrial cancer - sensitivity 90% (Hacker et al. 1986)

10 Diagnose n Histologie 1) Endometrium-Biopsie (Pipelle®, Kevorkian-Curette) 2) D&C 3) advanced stage disease – LAP/LSK

11 –65 Studien, n= (Clark et al. 2002) –Sensitivität 86.4% Spezifität 99.2% –13.7% of cancers will be missed –post-test LR 0.15 not low enough to negate need for further testing –ERSETZT NICHT ABRASIO –zusätzlich zu Abrasio? - keine Daten Hysteroskopie

12 Hysteroskopie n Upstaging? Prognose? n 10/113 (9%) pos. periton. Zytologie (Obermair et al. 2000) – FIGO IIIa n n=262, Ia, Ib +/- HSK –assoziiert mit HSK (p=0.04), nicht Stadium, Grading, Histologie n n=123; CO2 1.4% vs. saline 14%; p= (Lo et al. 2002) n 5-yr DFS, n=135+HSK; 127-HSK: 92.4% vs. 84.7% (p=0.5) (Obermair et al. 2000)

13 Endometriumhyperplasie Endometriumhyperplasie n 2 unterschiedliche Entitäten –+/- Atypien (Kurman 1985) n Risiko Progression 1.6% vs. 23% (Kurman 1985; n=170) n Ansprechen auf MPA 94% vs. 50% (Ferenczy 1989; n=85) 1) Die meisten Frauen mit EMH ohne Atypien sprechen auf MPA an 2) Hysterektomie: Atypien, non-Responder MPA

14 Endometriumhyperplasie Endometriumhyperplasie n Konkomitantes Karzinom –n=54; EMH+Atypien, HE (Hunter 1994) n Karzinom 19/54 (35%) –n=46; EMH+Atypien, HE (Bilgin 2004) n Karzinom 11/46 (24%) –n=289; EMH+Atypien, HE (Trimble 2006) n Karzinom 123/289 (43%)

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17 Biologie n Ausbreitungsrouten –Direkte Extension - häufigste –lymphatisch - pelvin/paraaortal –hämatogen - Lunge –Tube - Hysteroskopie

18 Staging þ Surgically staged disease (FIGO 1988) þreplaced clinical staging system (1971) þ Unterschied? þsignificant understaging (Tiitinen 1986)

19 Staging (FIGO 1988) I - corpus Ia - endometrium; Ib/Ic - 50% myometrium II - cervix III -extrauterine spread IIIa - serosa/adnexae/pos. washing, IIIb - vagina, IIIc -nodes IV - bladder or distant

20 Verteilung nach Stadium Tumor StageNumber (n)Percent (%) I II III IV No Stage Total

21 Pelvine Lymphknotenmetastasen Depth of Inv.G1 (n=180)G2 (n=288) G3 (n=153) Endometrium 0 (0%) 1 (3%) 0 (0%) Inner Third 3 (3%) 7 (5%) 5 (9%) Middle Third 0 (0%) 6 (9%) 1 (4%) Outer Third 2 (11%) 11 (19%) 22 (34%) Creasman et al. 1987

22 Lnn-Metastasen - Tumorgrösse Depth of Inv. 2cm (%) Surf. (%) None 0/17 (0) 0/8 (0) 0/0 (0) <50% 0/27 (0) 5/41 (12) 2/9 (22) >50% 2/9 (22) 6/23 (26) 4/8 (50) Schink et al. 1987

23 Paraaortale Lnn-Metastasen Depth of Inv.G1 (n=180)G2 (n=288) G3 (n=153) Endometrium 0 (0%) 1 (3%) 0 (0%) Inner Third 1 (1%) 5 (4%) 2 (4%) Middle Third 1 (5%) 0 (0%) 0 (0%) Outer Third 1 (6%) 8 (14%) 15 (23%) Creasman et al. 1987

24 Prognosefaktoren n Alter –young women better prognosis (stage, grading) n Histo 52/388 (13%) (Wilson 1990) n adenosquamous, clear cell, USPC, undifferentiated n 33% vs. 92% 5-yr OS n Stadium, Grading, LVSI n Spülzytologie+: 10.8%-22% (7 studies, n=1541) n ER+, PR+ better prognosis (Palmer et al. 1988) n DNA-Ploidie aneuploid worse prognosis

25 Treatment Stage I þ Abdominal washing þ Total abdominal hysterectomy and bilateral oophorectomy (TAH-BSO) þ full pelvic lymphadenectomy þ >50% (Ic), poor histology, G3, G2>2cm, stage II þ paraaortic lymphadenectomy? þG2/3 outer third invasion, grossly positive pelvic nodes or adnexae, palp. paraaortic nodes (GOG-study, Morrow 1991)

26 Therapie I þ Adjuvant irradiation does not improve OS þ Adjuvant irradiation improves local control þvault irrad. recurrences: 14%-1.7% (Lotocki 1983) þpelvic irrad. G3, Ic, II, pN+ þextended field irrad. G2/3+outer third, aN+, multiple pN+ þwhole adominal irrad. perit., oment. metast., +cytology?

27 PORTEC þ n=715; Stadium I (G1 Ic, G2, G3 Ib) þ adjuvant pelvic irradiation vs. no therapy þ no lymphadenectomy; 46 Gray þ Lokalrezidive 4 vs. 14% (p<0.001) þ 5-YOS: 81 vs. 85% (p=n.s.) þ complications: 25 vs. 6% þ keine adjuvante Bestrahlung þ Prädiktiver Faktor: Alter >60yrs

28 PORTEC þ G1 Ia,b keine Irrad þ G1 Ic, G2 Ib Irrad >60 yrs þ G2 Ic, G3………….………..Irrad þ pelvic irradiation þ G1 Ia, Ib, G1 Ic <60 yrs, G2 Ib <60 yrs þ vaginal vault irradiation

29 þ Stage II: surgery, combined radiation/surgery, Wertheim-procedure þ Stage III: surgical removal of all macroscopic tumor þ Stage IV: combination þsurgery: local control - palliation, bowel; exenteration (sole bladder or rectum involvement) þirradiation, progestins: 10% CR, 28% PR (Thigpen 1986; n=331) þchemotherapy: Carbo/Taxol Therapie II

30 Prognose 5-Jahres Überleben GradeStage (%) Ia Ib Ic IIaIIb Stage III-IV: 5-Year OS rates 0%-16% (Aalders 1984) Stage III ovary/tube only: 80% 5-Year OS (Bruckman 1980)

31 UPSC/CCC/recurrent

32 UPSC/CCC/recurrent

33 Serös-papillär n Prognosis, treatment n 50% of all relapses caused by UPSC & CC n subsequent breast cancer: 3.2% vs. 25% (Geisler et al. 2001) n paclitaxel - III, IV, recurrent; n=20 (Ramondetta et al. 2001) –OR rate 77%; med. time to progess. 7.3 mos n treat equivalent to ovarian cancer (Carbo/Taxol)


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