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Precancer, benign and malignant tumors of the
uterus and ovaryEduard Kučera
UTERINE FIBROIDS
RISK FACTORS
● They are many risk factors1 associated with the development of uterine fibroids
1.Flake GP et al, Environmental Health Perspectives 2003; 111(8):1037-54
Mass effectsrelated to the size
and locationof fibroids
Pregnancycomplications
Bleedingcomplaints
These symptoms and consequenceshave been shown to diminish quality of life3
When symptomatic, fibroids can be linkedto at least three major problems3
WHAT ARE THE SYMPTOMS?
● Not all fibroids are symptomatic
● However, for the 50% of women with symptomatic fibroids, the condition is debilitating.1
● Symptoms can include:● Abnormal or heavy
menstrual bleeding1, 2
● Pain,1,2 pressure symptoms1,2 and urinary symptoms2
● Impairment of Quality of Life 2
1. Tropeano G, Amoroso S, Scambia G. Hum. Reprod. Update (2008) 14 (3): 259-274. 2. Downes E, Sikirica V, Gilabert-Estelles J. et al. Eur J Obstet Gynecol Reprod Biol. 2010; 152(1): 96-102.3. Viswanathan M, Hartmann K, McKoy N. et al. Evid Rep Technol Assess (Full Rep). 2007 Jul;(154):1-122. Review.
MECHANISMS FOR FERTILITY IMPACT
• Mechanistic: space; abnormal contractions
• Local inflammation for sperm and embryo
• Inadequate blood supply
DIAGNOSIS - WHEN AND HOW?
● Physical examination may be the first signal that a woman might have uterine fibroids.1
● Imaging methods to evaluatethese benign tumours:1
● Ultrasonography
● Hysteroscopy
● Magnetic resonance imaging(MRI)
1. Evans P, Brunsell S. Am Fam Physician. 2007 May 15;75(10):1503-1508.ian
TREATMENTUterine Fibroids
THERAPEUTIC APPROACH
Currently, therapies are intended to reduce or eliminate uterine fibroid symptoms through one of the following options1
● Reduction of the size of tumours
● Reduction of the amount of bleeding
● Removal of the uterine fibroids or uterus
1. Miller CE, Journal of Minimally Invasive Gynecology 2009; 16:11–21
THERAPEUTIC APPROACH
The choice of therapy is influenced by the patient’s● Symptom severity
● Tumour characteristics (e.g. volume, localisation)
● Age
● Uterine preservation wishes
● Fertility preservation wishes
Endometrial cancer
Endometrial cancer – most common gynecological malignancy
4th most frequent malignancy in women
In Czech Rep. incidence 32/100 000 year
1500 new cases diagnosed per year (e.g. in UK 6,430)
Maximum around 60 - 70 years
Obesity of women – typical phenotype
Etiology
so called „endometrial carcinoma syndrome“: obesity, (DM, hypertension) - peripheral transformation of androgens - insufficiency of ShBG
recently often used so celled.: postmenopausal syndrome age: 6. - 7. decade nulliparity (RR=2,8) Infertility (RR=8) late menopause (RR= 2,4) estrogen producing ovarian cancers high intake of animal proteins and fats exogenous estrogens - unopposed gestagens (RR=2,3) tamoxifen (RR=2,4)
Carcinogenesis in peri- and postmenopausal
women
Carcinogenesis in peri- and postmenopausal
women younger women older women
complex hyperplasia
de novo hyperplasia with atypia
endometrial carcinoma
( Type I usually well diff. ) ( Type II usually poorly diff. ) endometroid carcinoma papillary serous
clear cell carcinoma
younger women older women
complex hyperplasia de novo
hyperplasia with atypia
endometrial carcinoma
( Type I usually well diff. ) ( Type II usually poorly diff. ) endometroid carcinoma papillary serous
clear cell carcinoma
Histological types
Carcinoma (98%) endometroid adenocarcinoma adenocarcinoma with squamous cells clear cell carcinoma papillary serous spinocellular
Sarcoma (2%) leiomyosarcoma endometrial stromal sarcoma mixed mesodermal cancers
Hyperplasia of endometriumHyperplasia of endometrium
Complex atypical hyperplasia = precancerosis of endometrial carcinoma ( especially endometroid type)
- cell polymorphism, mitosis, nucleoplasmic index, hyperchromatosis
- creation is independent on estrogen stimulation in
atrophic endometrium
Motlík,K, Živný,J.:Patologie v ženském lékařství,Grada,2001.
Complex atypical hyperplasia = precancerosis of endometrial carcinoma ( especially endometroid type)
- cell polymorphism, mitosis, nucleoplasmic index, hyperchromatosis
- creation is independent on estrogen stimulation in
atrophic endometrium
Motlík,K, Živný,J.:Patologie v ženském lékařství,Grada,2001.
FIGO staging 2010The 2010 FIGO staging system is as follows: Carcinoma of the EndometriumIA Tumor confined to the uterus, no or < ½ myometrial invasionIB Tumor confined to the uterus, > ½ myometrial invasionII Cervical stromal invasion, but not beyond uterusIIIA Tumor invades serosa or adnexaIIIB Vaginal and/or parametrial involvementIIIC1 Pelvic lymph node involvementIIIC2 Para-aortic lymph node involvement, with or without pelvic node involvementIVA Tumor invasion bladder mucosa and/or bowel mucosaIVB Distant metastases including abdominal metastases and/or inguinal lymph nodes
5 – year survival year
Stage 5 year survival rate
I-A 90%
I-B 88%
I-C 75%
II 69%
III-A 58%
III-B 50%
III-C 47%
IV-A 17%
IV-B 15%
Hysteroscopy and dg. curettageHysteroscopy and dg. curettage
Curettage – frequent false negative results (10-50%) Curettage – in polyps up to 61%Hysteroscopy and targeted biopsy < 2% false negative results (Gimbelson, Loffer 1988, 1989, AJOG) Studies in 1383 histological findings obtained with D&C - 60% inadequate results (Smith, 1985)In 60% patients curetted < 1/2 cavity of the uterus (Stock, Obst.Gyn.,1975)
Curettage – frequent false negative results (10-50%) Curettage – in polyps up to 61%Hysteroscopy and targeted biopsy < 2% false negative results (Gimbelson, Loffer 1988, 1989, AJOG) Studies in 1383 histological findings obtained with D&C - 60% inadequate results (Smith, 1985)In 60% patients curetted < 1/2 cavity of the uterus (Stock, Obst.Gyn.,1975)
Diagnostic hysteroscopy - optionsDiagnostic hysteroscopy - options
Panoramatic view – magnified 1x conventional hysteroscopy allows viewing the whole uterine
cavity and locate pathologies
panoramatic macro-hysteroscopy – 20x magnification in distance < 1 cm
Micro-contact hysteroscopy – 80x magnification allows evaluation of endometrial vascularisation, gland characteristic and their openness
Panoramatic view – magnified 1x conventional hysteroscopy allows viewing the whole uterine
cavity and locate pathologies
panoramatic macro-hysteroscopy – 20x magnification in distance < 1 cm
Micro-contact hysteroscopy – 80x magnification allows evaluation of endometrial vascularisation, gland characteristic and their openness
Tamoxifen a endometriumTamoxifen a endometrium
Nonsteroidal synthetic anti-estrogen
Adjuvant therapy in breast carcinoma
Accumulation of effective substance in basal endometrium
Endometrial proliferative abnormality (up to 40% postmenopausal women) - polyps, hyperplasia as much as endometrial carcinoma (2-3/1000/year)
Higher risk of endometrial carcinoma after using more then 5 (?) years (2-7.5x)
Most safe and effective screening is hysteroscopy in yearly intervals
Nonsteroidal synthetic anti-estrogen
Adjuvant therapy in breast carcinoma
Accumulation of effective substance in basal endometrium
Endometrial proliferative abnormality (up to 40% postmenopausal women) - polyps, hyperplasia as much as endometrial carcinoma (2-3/1000/year)
Higher risk of endometrial carcinoma after using more then 5 (?) years (2-7.5x)
Most safe and effective screening is hysteroscopy in yearly intervals
Tamoxifen – endometrium pathology
Tamoxifen – endometrium pathology
Length of therapy not more then 5 yearsMetrorrhagia always indication to endometrial examinationIn asymptomatic women (cca 70%) HSK vs. UZ part of periodic yearly check upsHigh percentage of false positive results with ultrasound examination– stromal edema (vacuolar degeneration)Tamoxifen - 37 - 71% incidence of polyps – proliferative activity in epithelial and stromal partIncidence of endometrial carcinoma cca in 3%
Length of therapy not more then 5 yearsMetrorrhagia always indication to endometrial examinationIn asymptomatic women (cca 70%) HSK vs. UZ part of periodic yearly check upsHigh percentage of false positive results with ultrasound examination– stromal edema (vacuolar degeneration)Tamoxifen - 37 - 71% incidence of polyps – proliferative activity in epithelial and stromal partIncidence of endometrial carcinoma cca in 3%
Tamoxifen and endometriumTamoxifen and endometrium
International agreement – 1997
Bioptical examination of the endometrium before beginning the therapy
After 3 years of using observation in yearly intervals
Lancet,1698-1711,2000.
International agreement – 1997
Bioptical examination of the endometrium before beginning the therapy
After 3 years of using observation in yearly intervals
Lancet,1698-1711,2000.
Tamoxifen and endometriumTamoxifen and endometrium
Hysteroscopy with biopsy – first choice in patients with Tamoxifen therapy
Symptomatic patients and therapy longer then 3 years
Positive family history
Taponeco,F et al. Indication of hysteroscopy in tamoxifen treated breast cancer patients. J.Exp.Clin.Cancer,21,2002
Hysteroscopy with biopsy – first choice in patients with Tamoxifen therapy
Symptomatic patients and therapy longer then 3 years
Positive family history
Taponeco,F et al. Indication of hysteroscopy in tamoxifen treated breast cancer patients. J.Exp.Clin.Cancer,21,2002
Endometrial cancer - therapy
Surgery - radical
Radiotherapy
Hormonal therapy