•Uterine tumors fnb nove logo N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png Masaryk University School of Medicine and Brno University Hospital Department of Obstetrics and Gynecology Head: doc. MUDr. Vít Weinberger, PhD. Eliška Gazárková Gynecology and Obstetrics 2020 Uterine tumors N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo •Tumors of the uterine body •Cervical tumors • • • •Benign (leiomyoma, polyp) •Malignant (sarcoma, endometrial cancer) Uterine tumors N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Benign tumors of the uterine body •Leiomyoma •Endometrial polyp Uterine tumors N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Leiomyoma •Body (cervix, Fallopian tubes, ovary, vagina, vulva, ligament, GIT) •20-50% of women •Most common diagnosis •35-45 years; after menopause occurs involution Uterine tumors N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Leiomyoma •Classification according to localization: Subkumosal (ev. nascent) Intramurals Subserous (ev. stopwatch) Intraligamentous •Degenerative changes Hyalinization, mukoid degeneration, cystic degeneation, kacification • Uterine tumors N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Leiomyoma •Classification according to localization: • • Obsah obrázku stůl Popis se vygeneroval automaticky. Uterine tumors N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Leiomyoma Symptomatology •60-90% asymptomatic •Irregular uterine bleeding, hypermenorrhoea, anemization •Lower abdominal pain •Urinary symptoms (pressure on the bladder, urine retention) •Obstipation •Sterility / infertility • Uterine tumors N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Leiomyoma Etiology •Hormonal dysregulation (hyperestrogenismus) •Genetic causes •Antropometric influences (BMI) • Diagnosis •Palpation, gynecological examination •Ultrasound •Complementary methods – CT, MR •Invasive methods – LSK, HSK •Histology – final diagnosis Uterine tumors N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Leiomyoma Therapy – conservative approach •Elimination of the symptoms / myoma volume reduction •Non steroid anflogistics •HAK, depot gestogens – reduction of blood loss, dysmenorrhoea •GnRh analogs – arteficial menopause – reduction of blood loss + myoma volume reduction Uterine tumors N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Leiomyoma Therapy – sugical •Myoma enucleation - laparotomic, laparoskopic, hysterosocpic •younger women, intrests in fertility • •Hysterectomy - abdominal, vaginal, laparoscopic • •(preoperative preparation – 3 month aplication of GnRh analogs) Uterine tumors N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Corporal polyp •Grows out of the pars basalis •Most frequent localisation – uterine fundus •Hyperplastic, atrofic, functional •Mostly asymptomatic X irregular uterine bleeding, pain •Dignosis: ultrasound, hysteroscopy •Therapy: surgical – curretage, HSK • Ø3.-4. most common malignancy in the world (breast, colorectal, lung) Øabsence of screening (ultrasound, hysteroscopy, cytology) Ørelatively good prognosis, 75 - 88% of patients in IA a IB stages survive more than 5 years following diagnosis Øthe most common gynecological malignancy in developed coutries Øtwo times higher incidence in white race Ølow incidence in African countries Uterine tumors N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Malignant tumors of the uterine body​ – uterine cancer – endometrial carcinoma Uterine cancer N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Uterine cancer N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Uterine cancer N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Uterine cancer N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Histologic types of uterine tumors •Epithelial tumors (98%) •- endometrioid adenocarcinoma (squamous component., viloglandular comp., secreting, sertoliform, microglandular) (78-80%) •- mucinous (1-9%) •- clear cell (2%) •- uterine papillary serous (<10%) •- spinocelular (<1%) •- Neuroendocrine Carcinoma of the Endometrium (NECa): LG -carcinoid, • HG –small cell and large cell neuroendocrine carcinoma •- mixed (I.+ II. type) •- malignant mixed müllerian tumor: carcinosarcoma •Mesenchymal tumors •- leiomyosarcoma •- endometrial stromal sarcoma (low i high grade) •- undifferentiated uterine sarcoma (high grade) •- Rare types (rhabdomyosarcoma…) Uterine cancer N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Etiopathogenesis Uterine cancer ØType I Ø- 80 - 85 % off all cases Ø- based on endometrial hyperplasia Ø- the most common somatic abnormalities: microsatellite instability (asociated with ØLynch syndrome), mutation: PTEN, PIK3CA, PIK3R1, K-ras, β-catenin (squamouse differentiation of endometrial carcinoma) Ø- typical histologic types: low grade endometrial carcinoma, mucinous adenocarcinoma Ø- better prognosis ØType II Ø- 15-20 % of all cases Ø- unclear ethiopatogenesis, frequently appeared on a background of an atrophic endometrium, not connected with hyperestrinism and endometrial hyperplasia, absence of risk factors typical for I. Type, in most cases hormonaly independent (ER-, PR-) Ø- worse prognosis than I type, older patients (60 y.o. and older) Ø- the most frequent somatic abnormalitie: mutation in p53, chromosomal instability, approximately 25% HER-2 amplification Ø- ussaul histological types: serous carcinoma, high grade endometrioid carcinoma , clear cell • Ø N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Risk factors Type I: Øwomen at age 55 and above (the risk of cancer increases with age) Øobesity (BMI ˃ 30 incresing risk 3-4x) Øearly menarche, late menopause, nulliparity, anovulation, polycystic ovary syndrome, long-term tamoxifen use Øhypertension Ødiabetes mellitus ØGenetic risk factors: approx. 5 % of endometrial carcinoma cases are hereditary ØThe manifestation of cancer is 10-20 years earlier thant in non-hereditary (sporadic) forms ØIn case of Lynch syndrome II (HNPCC = Hereditary nonpolyposis colorectal cancer) – the risk of endometrial cancer is 30-60 % ØEndometrial cancer is typically manifested prior to colorectal carcinoma Ø Type II: Øuncertain ethiopatogenesis Uterine cancer N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Ø multiparity RR 0,5 (after 1st. delivery only 50% risk compared to nulliparous women) Protective factors Ø vegetarian lifestyle, sufficient intake of vitamin A and C Øsmoking RR 0,5-0,7 Ø combined oral contraceptive use more than 5 years RR 0,5 (lasting effect for 10-15 years) Ø IUS (intrauterine system) – Mirena, RR 0,6 Ø physical activity Uterine cancer N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Ø simplex endometrial hyperplasia…………………….1 % Endometrial hyperplasia – risk of carcinoma progression Ø complex endometrial hyperplasia ……………………3 % Ø simplex atypical endometrial hyperplasia ………….. 8 % Øcomplex atypical endometrial hyperplasia……...29-40 % Øserous intraepithelial carcinoma (serous and clear cell carcinoma type II) precancerous condition Uterine cancer N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo TNM FIGO stages Surgical-pathologic findings TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis* Carcinoma in situ (preinvasive carcinoma) T1 I Tumor confined to corpus uteri T1a IA Tumor limited to endometrium or invades less than one half of the myometrium T1b IB Tumor invades one half or more of the myometrium T2 II Tumor invades stromal connective tissue of the cervix but does not extend beyond uterus** T3a IIIA Tumor involves serosa and/or adnexa (direct extension or metastasis) T3b IIIB Vaginal involvement (direct extension or metastasis) or parametrial involvement IIIC Metastases to pelvic and/or para-aortic lymph nodes IV Tumor invades bladder mucosa and/or bowel mucosa, and/or distant metastases T4 IVA Tumor invades bladder mucosa and/or bowel mucosa (bullous edema is not sufficient to classify a tumor as T4) M0 No distant metastasis M1 IVB Distant metastasis (includes metastasis to inguinal lymph nodes, intraperitoneal disease, or lung, liver, or bone metastases; it excludes metastasis to para-aortic lymph nodes, vagina, pelvic serosa, or adnexa) Prognostic factors •- stage of disease (FIGO, TNM) •- quality of surgical treatement •Negative prognostic factors: •- lymph node metastatic lesion (quantity, size), extrauterine spread, the depth of myometrial invasion, cervical invasion, tumor size greater then 2cm, invasion in lymphatic vessels •- L1CAM positivity, loss of ER, PR, mutations in the p53 •- Histological type: typ II (a 5 year surveillance 58 % in comparison to 83 % in type I) •- Other negative prognostics factors: age of 60 and above, radiotherapy for the primary treatment •Positive prognostic factors: •- Progesteron receptors positivity (type I), significant lymfoplasmocellular infiltration Uterine cancer N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Prognostic factors •According to known prognostic factors, it is possible to divide stadium I to 3 categories with different therapeutic approach (ESGO, ESMO guidelines). • •Low risk: stage IA, grade 1-2, type I (endometrioid) •Intermediate risk: stage IA, grade 3, type I (endometrioid) • stage IB, grade 1-2, type I (endometrioid) •Hish risk: stage IB, grade 3, type I (endometrioid) • non-endometrioid types • • In relation to extensiveness of surgery •Low risk •High riské riziko • Uterine cancer N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Uterine cancer hyrad1 Low risk type N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo hyrad2 Uterine cancer High risk type N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Five-year disease-specific survival rates in accordance withstages Uterine cancer Stage 5 year survival rates I 78 – 90 % II 74 % III 36 – 57 % IV 20 % N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Clinical symptoms •Early stages •irregular vaginal bleeding in premenopausal women •postmenopausal vaginal bleeding •vaginal discharge • •Advanced stage of cancer •pelvic pain, sacroiliac pain •hematuria •enterorrhagia • •Asymptomatic patients (based on ultrasound examination) Uterine cancer N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Diagnosis Absence of screening method !!! •Prebioptic methods - ultrasound examination - cytodiagnostic techniques •Bioptic methods - Pipelle endometrial sampling - dilatation & curettage - hysteroscopy with endometrial biopsy Uterine cancer N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Staging Obligatory - Gynecologic examination - Expert ultrasound of abdomen and pelvis - Chest x-ray - Laboratory tests, Internist examination Facultative - MR of abdomen and pelvis (ev. PET/MR, PET/CT) - Cystoscopy - Rectoscopy (colonoscopy) - Tumor markers (CA125, HE4) Uterine cancer N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Expert ultrasound examination Tumor in endometrial polyp limited to endometrium (without myometrium invasion) Tumor invades less than one half of the myometrium Uterine cancer N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Expert ultrasound examination Tumor invades one half or more of the myometrium Deeply invasive tumor with high colour score in Doppler mode Uterine cancer N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Therapy ØSurgical treatment - method of choice ØHormonal therapy – relapsed cancer Uterine cancer N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Surgical treatment Low risk – Hysterectomy + bilateral adnexectomy High risk - Hysterectomy + bilateral adnexectomy + aortopelvic lymphadenectomy (+ infracolic omentectomy in serous histologic type) Advanced stages - Cytoreductive surgery, icluding pelvic exenteration in IVA stage Uterine cancer N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Operační léčba Léčebné polohy. - ppt stáhnout Uterine cancer Surgical treatment N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Surgical approache Laparotomy • •Patients contraindicated to miniinvasive surgery (comorbidity, advanced stage of disease) - suprapubic incision - low risk - midline laparotomy - high risk, advanced stage of disease Uterine cancer Surgical treatment N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo N:\GPK\PRM\Dokumenty\0GPK\Onkogynekologie\LM\Stížnosti\100H0024.JPG C:\Users\51443\Desktop\Foto onkogyn\v. iliaca communis sin duplex.JPG N:\GPK\PRM\Dokumenty\0GPK\Onkogynekologie\LM\Foto medik\IMG_0915.jpg Uterine cancer N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo - high risk – in more than 50% cases with negative lymph nodes - lymph nodes positivity : 50% pelvic region : 30% pelvic and paraaortic lymph nodes lesion in the same time : 20% isolated paraaortic lymph node lesion DEVELOPMENT OF NEW METHODS FOR SENTINEL LYMPH NODES DETECTION Surgical treatment Uterine cancer N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo SENTINEL NODES DETECTION METHODS - subserous myometrial application -Hysteroscopic subendometrial application near the tumor - Intracervical application (PREFERENCE !) : „double detection technique“ – radioisotope + + methylene blue dye x ICG (indocyanin green) - využití hysteroskopické aplikace radiokoloidu pravděpodobně nejlépe respektuje anatomické souvislosti a přirozenou drenáž endometria - metodika určena pro klinické studie Uterine cancer Surgical treatment N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo C:\Users\51443\Desktop\Foto onkogyn\SN ICG pánev.png Uterine cancer N:\GPK\Klinika GPK-utvary\06 LF_mu\loga_MU_2019\muni\med-lg-eng-rgb.png fnb nove logo Thank you for your attention