ENDOMETRIAL CARCINOMA Oncology Human Population about 6 000 000 000 Women Population about 3 500 000 000 Women > 50 years about 1 000 000 000 ENDOMETRIAL CARCINOMA 150 000 new cases annually

Endometrial carcinoma Uterine Corpus Tumors Endometrial polyps ENDOMETRIUM MYOMETRIUM Endometrial carcinoma Endometrial glands Stromal Nodule Endometrial stroma Stromal Sarcoma Mixed Mesodermal Tumors LEIOMYOMA LEIOMYOSARCOMA

Endometrial Carcinoma Second most common genital tract malignancy (after cervical carcinoma) 150 000 annually all over the world 35 000 annually in USA Number of cases still rising

Endometrial Carcinoma The best example of en estrogen-depended neoplasm Risk factors associated with the estrogen-rich environment With early diagnosis survival rate can be excellent

Epidemiology Incidences USA (white women) Swiss, Denmark, Germany France, Sweden Norway POLAND India, Japan, Kuwait, Filipina

POLAND morbidity - V place (11,8%) mortality- XIV place (2,5%) Epidemiology POLAND morbidity - V place (11,8%) mortality- XIV place (2,5%)

Epidemiology 55-90 r.ż. 5% < 40 r.ż. Almost all cases in postmenopausal age (two picks of morbidity: about 55 y. and 78 y.) 5% < 40 r.ż.

Pathogenesis Estrogen dependent carcinoma (progressing of changes about 10 years) endometrial typical atypical proliferation hyperplasia hyperplasia Carcinoma Estrogen independent carcinoma normal Carcinoma endometrium

Sexual Hormones Activity ESTROGENS stimulating division of cells PROGESTAGES breaking divison of cells

Sexual Hormones production Reproductive age E1, E2, E3 OVARIES Progesterone Testosterone Androstendione ADRENAL GLANDS Androstendione

Sexual Hormones production Premenopausal period E1, E2, E3 OVARIES Progesterone Testosterone Androstendione ADRENAL GLANDS Androstendione Reletive Hyperestrogenisms

Sexual Hormones production Postmenopausal Period OVARIES Testosterone ADRENAL GLANDS Androstendione Androgens aromatization into estrogens Androstendione Estron Testosterone Estradiol

Pathogenesis hormonal factors ESTRONE ESTRADIOL ANDROGENS ESTRIOL PROGESTERONE

RISK FACTORS Obesity Late menopause > 52 years-old women Nulliparity Anovulatory cycles PCOs Ovarian tumors (hormonal active) Diabetes mellitus type II Hepatic cirrhosis Hypothyroidism Hyperprolactinemia

Protective Factors Oral contraception Complex hormonal replacement therapy Cigarettes smoking

Endometrial Carcinoma Symptoms Postmenopausal bleeding Acyclic bleeding in premenopausal period ill – smelling leucorreas pelvic pain ascites

Postmenopausal bleeding main reasons Endometrial atrophy 50 % Endometrial polyp 15 % Submucosus uterine myoma 10 % Endometrial hyperplasia 10 % Endometrial carcinoma 5 % Cervix disease (CA, polyps) 10 %

Asymptomatic cases Ultrasonography Estimated Features thickness echogenicity et structure middle echo fluid in uterine cavity endo-myometral border focal lesions

Normal ultrasonographic image of endometrium of postmenopausal women

Abnormal ultrasonographic image of endometrium of postmenopausal women

Precancerous Lesions Simple endometrial hyperplasia without atypia Complex hyperplasia without atypia Endometrial polyps Atypical endometrial hyperplasia ( simple or complex)

Endometrial Carcinoma Diagnosis On base morphological research The material received from uterine cavity

Methods of Receiving of Material from Uterine Cavity Endometrial Cytology (Gynoscan, Endo-Pap, Jet-Wash) Endometrial Biopsy (Pipella, Vabra) D & C Diagnostic Hysteroscopy

Dilatation and Curettage Recamier 1843 Most often diagnostic intervention executed in world „gold standard”

Dilatation and Curettage blind procedure general anaesthesia high grade of uterine perforation 1/99 risk of haemorrhage risk of infection most often only 50 % of endometrial surface is received

Diagnostic Hysteroscopy estimation under eye-control all endometrial surface is accessible to investigation target biopsy local anaesthesia video documentation low grade of uterine perforations

Diagnostic Hysteroscopy – WHEN ? abnormal USG image of endometrium at asymptomatic woman focal changes in USG image of endometrium abnormal USG + D&C /-/ recurrent uterine bleeding + D&C /-/ unsuccessful D&C

FIGO Surgical Staging of Endometrial Carcinoma I A Tumor limited to endometrium I B Invasion to less then one half of the myometrium I C Invasion to more then one half of myometrium II A Endocervical glandular involvement II B Cervical stromal involvement III A Tumor involving serosa and/or adnexa or positive peritoneal cytology III B Vaginal metastases III C Metastases to pelvic and/or periaortic lymph nodes IV A Tumor invades bladder mucosa or bowel IV B Distant metastases

FIGO Surgical Staging of Endometrial Carcinoma First Stage Tumor Limited to Uterine Corpus I A Tumor limited to endometrium I B Invasion to less then one half of myometrium I C Invasion to more then one half of myometrium

FIGO Surgical Staging of Endometrial Carcinoma Second Stage Tumor Invading Uterine Cervix II A Endocervical glandular involvement II B Cervical stromal involvement

Histological Grading of Endometrial Carcinoma G 1 Less then 5 % undifferentiated cells G 2 5 – 50 % undifferentiated cells G 3 More then 50 % G X Number of undifferentiated cells is unknown

FIGO Surgical Staging of Endometrial Carcinoma Third Stage Tumor Out of Uterus III A Tumor involving serosa and/or adnexa or positive peritoneal cytology III B Vaginal metastases III C Metastases to pelvic and/or periaortic lymph nodes

FIGO Surgical Staging of Endometrial Carcinoma Forth Stage IV A Tumor invades bladder mucosa or bowel IV B Distant metastases

Endometrial Carcinoma hystological types, WHO classification Adenocarcinoma - endometrioide type Mucinous adenocarcinoma Serous adenocarcinoma Clear cell adenocarcinoma Carcinoma planoepitheliale Carcinoma mixtum Undifferented carcinoma

Treatment of Endometrial Carcinoma Surgery Radiotherapy Hormonotherapy Chemotherapy

Treatment of Endometrial Carcinoma SURGERY dependent of stage TAH with bilateral oophorectomy and 1/3 part of vagina Radical Hysterectomy Tumorectomy (debulking operation)

Treatment of Endometrial Carcinoma Radiotherapy dependent of stage Neo-adjuvant brachytherapy Adjuvant brachytherapy Radium, Cobalt, Cesium, Iridium Teletherapy X-ray, gamma-ray, electron-ray

medroxyprogesterone, megestrol etc inhibitor of aromatase Treatment of Endometrial Carcinoma Hormonotherapy dependent of receptors status Gestagens – high doses medroxyprogesterone, megestrol etc inhibitor of aromatase aminoglutetymid

Treatment of Endometrial Carcinoma Chemotherapy last chance therapy Mono - chemotherapy Cis-platinum, Carboplatinum, Taxol Poly - chemotherapy Cis-platinum, cyclophosphamidum, Malfelan, 5-fluorouracyl, Doxorubicin PAC, CAP, FAC, AC

Treatment of Endometrial Carcinoma Stage I a Grade 1 TAH with bilateral oophorectomy Brachytherapy (when surgery is contraindicated)

Treatment of Endometrial Carcinoma Stage I a Grade 2, 3 TAH with bilateral oophorectomy and Brachytherapy

Treatment of Endometrial Carcinoma Stage I b, c, Stage II Stage III a TAH + BO or Radical Hysterectomy Brachytherapy Teletherapy Hormonotherapy ( E2R +, PgR + or E2R -, PgR + )

Treatment of Endometrial Carcinoma Stage III b, c Stage IV Tumorecromy Hormonotherapy ( E2R +, PgR + or E2R -, PgR + ) Chemotherapy

Endometrial Carcinoma Prognostic Factors Age Stage Grade Presence of myometrial invasion Presence of NEO cells in peritoneal fluid Lymph node metastases Receptor status DNA content in neoplastic cells

Prognosis in Endometrial Carcinoma 5 YEAR SURVIVAL Stage I 75 – 100 % Stage II 50 – 65 % Stage III 20 – 40 % Stage IV below 10 %

5 YEAR SURVIVAL Endometrial Carcinoma 75 % Vulnar Carcinoma 42 % Cervical Carcinoma 38 % Ovarian carcinoma 35 %

Diagnostic of asymptomatic women

INDIRECT METHOD OF ENDOMETRAL ASSESSMENT Conventional USG Transvaginal USG Doppler Method Sonohysterogrphy 3D-ultrasonography Magnetic Resonance Computer Tomography

Conventional Ultrasonography (problems) Obesity Fill up bladder problems (urinary incontinence) retroflexion of uterine corpus low frequency 3,5-5 MHz

Transvaginal Ultrasonography USG head near the uterus Empty bladder High frequency 6-15 MHz Low range

USG Doppler Method uterine artery flow small endometrial arteries flow neoangiogenesis uterine artery flow small endometrial arteries flow RI PI

HYSTEROSONOGRAPHY 3D - hysterography 5-10 ml 0,9 NaCl, Ringer, H2O when unclear TV-USG image special to detect focal lesion T. C. Dubinsky - J Ultrasound Med 1997

Computer Tomofraphy Magnetic Resonance comparable with TV-USG in assessment of endometrium better in invasion assessment of myometrium by endometrial CA rather expensive

Diagnostic method which most contributed to development of gynaecology in the course last decades is certainly transvaginal ultrasonography Kratochwill 1969 Fleischer 1984

USG image of endometrium in postmenopausal period „Pencil line” FLAICHER 6,0 mm GOLDSTEIN 5,0 mm GRANBERG 5,0 mm NASSRI 5,0 mm OSMERS 4,0 mm WIKLAND 4,0 mm

Operative Hysteroscopy indications et postmenopausal women removing of endometrial polyps removing of submucosus myomas ( type 0 and I) electroresection of endometrium

Endometrial hyperplasia treatment Stimulating ovulation MDs Gestagens – High dose IUD with gestagens hysteroscopic endometrial resection brahy - therapy hysterectomy

Endometrial hyperplasia importance of using gestagens blocking of E-receptors synthesis blocking of gonadotropin increase activity of 5α-reductase increase activity E2-dehydrogenase