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Gynaecological tumours Prof.Dr.Póka Róbert Female genital cancer incidence (N/100.000 population/year) in 2008 Eurostat, 2010 Breast Cervix Endometrium Ovary EUR 88,4 12,8 16,7 13,7 HU 78,7 19,5 17,7 13,7 Female genital cancer mortality (N/100.000population/year) in 2008 Eurostat, 2010 Breast Cervix Endometrium Ovary EUR 24,3 5,2 3,8 7,9 HU 22,6 5,7 3,6 8,3 Cervical cancer treatment dilemmas •Early stg disease - Op, advanced - Rad •Rad limited by normal tissue tolerance •Clinically early might be biologically advanced •In early stg Op and Rad results are similar Indications and types of surgical treatment Preserve fertility Classical Wertheim-Meigs operation Neoadjuvant chemo followed by radical surgery Surgery for recurrent disease Trachelectomy’s necessity Changing morbidity Changing demography Changing technology Prerequisites of trachelectomy Ca.cx.ut. Std. Ia1,Ia2,Ib1 Parametrial spread excluded by CT, MR Fitness for surgery Fertility preservation is desired Trachelectomy cases I. ID 1. 2. 3. 4. 5. Age 31 28 25 34 36 Stg Ib1 (12*3mm) Ia1 (7*2mm) Ia2 (7*3mm) Ib1 (12*7) Ia2 (5*3) TR: trachelectomy LND: lymphadenectomy Th Follow-up grav. VTR 2x delivery (SC) VTR+LND 1x deliver (SC) VTR+LND 1x deliver (SC) VTR+LND 1x deliver (SC) VTR(R1)TAH+LND Trachelectomy cases II. ID 6. 7. 8. 9. 10. 11. Age 34 36 34 30 34 30 Stg Ia1 (3*1mm) Ib1 (12*8mm) Ib1adeno Ia1adeno Ib1 Ib1 TR: trachelectomy LND: LSC lymphadenectomy Th Follow-up VTR 61mths NED VTR+LND N1! 41mths NED ATR(R1N1)WM 23mths DOD ATR+LND 39mths NED ATR(N1)WM 25mths DOD ATR+LND 17mthsNED Aims of neoadjuvant chemoterapy Prevent spread Down-staging Tumour-demarcation Modes of administration Monotherapy or combined chemotherapy Cyclical Systemic or regional Mechanism of action Alkilating Antimitotic Antimetabolites Antibiotics Anticytosceletal Other Cytoxan,Ifosfamid Vincristin, Taxol Methotrexat, Fluorouracil Bleomycin, Mitomycin, Adriamycin, Peplomycin Taxanes Cisplatin, Carboplatin Side-effects Immediate endothel necrosis Early nausea, vomiting, emesis, myelodepression Late alopecia,myelodepression,mucositis fibrosis pulmonum, neuritis, diarrhoea,insuff.hepatorenalis, cardiomyopathy Protocol BIP Bleomycin 30mg/12hrs 1.day CDDP 50mg/m2 2.day Ifosfamid 3 g/m2 3.day Mesna 1g/m2 3* 3-weekly Neoadjuvant BIP chemoterapy at UD MHSC Ib2-IIb N=23 (out of 100 WM) Mean age 50 yrs (33-66) Adenoca = 2, Planocell = 21 pTy0N0M0=7 pTy1-3N1M0=6 Female genital cancer Incidence (n/100000/yr) in 2008 Eurostat, 2010 Breast Cervix Corpus Ovary EUR 88,4 12,8 16,7 13,7 HU 78,7 19,5 17,7 13,7 Female genital cancer Mortality (n/100000/yr) in 2008 Eurostat, 2010 Breast Cervix Corpus Ovary EUR 24,3 5,2 3,8 7,9 HU 22,6 5,7 3,6 8,3 Gynecologic tumors Staging in general I II III IV localized to organ of origin spread to adjacent tissues regional lymphatic spread distant metastasis Endometrial cancer in Hungary in 2005 1213 new cases 219 deaths Corpus cancer - Origin Endometrial Endometrial stroma sarcoma Myometrial sarcoma cancer Gynecologic tumors Staging in general I II III IV localized to organ of origin spread to adjacent tissues regional lymphatic spread distant metastasis Endometrial cancer stage-distribution (%) 80 70 60 50 40 Frequency 30 20 10 0 I II III IV Age distribution in endometrial cancer N=817 45 40 35 30 25 N 20 15 10 5 0 Frequency 30 35 40 45 50 55 60 65 Age (yr) 70 75 80 85 90 Histologic type distribution Endometrioid % Adenosquamous Mucinous Papillary serous Clear cell Squamous Other 82 6% 1% 4% 2% 0,5 % 4,5 % Pathogenesis Estrogen-dependent proliferation Lack of gestogen-suppression Insulin-resistance Tumorsuppressor-mutations (p53,p21) Extragonadal aromatase-activity Characteristic associated disorders and medical history Hypertension Diabetes mellitus Obesity PCO Anovulatory cycles Less pregnancies Shorter lactation Diagnosis Histologic verification Prognostic factors in endometrial cancer Age Histologic type Degree of differentiation Depth of myometrial invasion Cervical involvement Adnexal involvement Lymphatic spread Distant metastasis Pathologic staging (changes in 2010) Ia Localized to endometrium Ib (Ia) Superficial myometrium-invasion Ic (Ib) Deep myometrium-invasion IIa (Ib) Spread to cervix mucosa IIb (II) Cervical stromal involvement IIIa Adnex/serosa involvement IIIb Vaginal metastasis IIIc (IIIc1/IIIc2) Pelv./paraaort. nodal metastasis IVa Bladder/rectum invasion I IA (FIGO 2010) IB (FIGO 2010) IB (FIGO 2010) II (FIGO 2010) IIIc2 (FIGO 2010) IIIc1 (FIGO 2010) Treatment Surgery (TAH+BSO+lymphadenect) Radiotherapy (adjuvant or primary) Chemotherapy (adjuvant or primary) Gestogen therapy (adjuvant) Five-year survival Surgery Radiotherapy Radiosurgery Surgery+Radiotherapy Surgery+Chemotherapy Hormonal therapy 84% 45,3% 83,6% 82,4% 59,8% 42,9% Prevention Combined oral contraceptives >10yrs Bodyweight control Oncological surveillance Progestogenic opposition Cases of endometrial cancer at UD MHSC n=1368 Histogram 90 80 70 Count 60 50 40 30 20 10 0 20 30 40 50 60 AGE 70 80 90 100 Endometrial cancer young cases All cases 1368 Age <45 yrs 96 Age <45 yrs without hysterectomy 6 Endometrial cancer cases at UD MHSC without hysterectomy ID Age 1. 27 2. 43 3. 29 4. 25 5. 30 6. 23 Stg IaG1 IaG1 IIG1 IaG1 IaG1 IaG1 Th 6*Cu 2*Cu Cu+2*IC Cu+5*IC Cu+MPA Cu+MPA Grav P2 0 0 0 0 0 Follow-up 25yrs PD 8yrs NED 24yrs ov.ca.III/b 4yrs PCOD 2yrs NED 1yr NED Ovarian cancer Epidemiology Incidence, mortality Staging Diagnostic work-up Debulking surgery (pathological staging) Adjuvant chemotherapy Neoadjuvant chemotherapy Vulval carcinoma, Epidemiology Disease of the elderly 2-3% of all genital cencers In Hungary 122 new cases in 1994, 205 in 2005 90% squamous FIGO stages Ia <2cm, <1mm invasion Ib <2cm, >1mm invasion II >2cm III urethra/vagina/perineum/anus involvement, unilateral inguinal met IVa rectal/bladder involvement, bilateral inguinal met IVb distant met TNM stages FIGO Ia Ib II III IVa IVa IVb T 1a 1b 2 1-3 1-3 4 1-4 N 0 0 0 0-1 2 0-2 0-2 M 0 0 0 0 0 0 1 Macroscopic appearance Superficial Exophytic Endophytic 5-15% 40% 45% Spread 1. 2. 3. Inguinal and femoral lymph nodes Cloquet/Rosenmüller nodes Parailiac nodes Evolution of surgical treatment Parré-Jones Inguinali radiotherapy <1 mm invasion warrants no nodal disease Sentinel nodes Neville Hacker Progression free survival improved by lymphadenectomy Túlélési hányad 1 Vulvectomy+lymphadenectomy - , 8 , 6 Vulvectomy , 4 , 2 0 0 1 2 3 4 5 Műtét óta eltelt idő hónapokban kifejezve 0 0 0 0 0 6 0 Overall survival improved by lymphadenectomy 1 Vulvectomy+lymphadenectomy - Túlélési hányad , 8 Vulvectomy , 6 , 4 , 2 0 0 1 2 3 4 5 0 óta eltelt 0 idő hónapokban 0 0 kifejezve 0 Műtét 60 Summary of treatment for vulval cancer Survival of vulval cancer with no spread to urinary or GI tracts is improved by adding lymphadenectomy to wide excision of primary tumour. Advanced or regional metastatic disease treated with radiotherapy Disseminated tumours require chemotherapy