oncology human populationabout 6 000 000 000 women population about 3 500 000 000 women > 50...
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OncologyOncology
Human PopulationHuman Population about 6 000 000 000about 6 000 000 000
Women Population Women Population about 3 500 000 000about 3 500 000 000
Women > 50 yearsWomen > 50 years about 1 000 000 000about 1 000 000 000
ENDOMETRIAL CARCINOMAENDOMETRIAL CARCINOMA
150 000150 000 new cases annuallynew cases annually
Uterine Corpus TumorsUterine Corpus Tumors
• ENDOMETRIUMENDOMETRIUM
• MYOMETRIUMMYOMETRIUM
Endometrial stroma
Endometrial polyps
Endometrial glands
Endometrial carcinoma
Mixed Mesodermal
Tumors
Stromal Nodule
Stromal Sarcoma
LEIOMYOMA
LEIOMYOSARCOMA
Endometrial CarcinomaEndometrial Carcinoma
Second mSecond most common genital tract ost common genital tract malignancymalignancy
(after cervical carcinoma)(after cervical carcinoma)150 000 annually all over the world150 000 annually all over the world
35 000 annually in USA35 000 annually in USANumber of cases still risingNumber of cases still rising
Endometrial CarcinomaEndometrial Carcinoma
The best example of en estrogen-depended The best example of en estrogen-depended neoplasmneoplasm
Risk factors associated with the Risk factors associated with the estrogen-rich environmentestrogen-rich environment
With early diagnosis survival rate With early diagnosis survival rate can be excellentcan be excellent
EpidemiologyEpidemiologyIncidencesIncidences
USA (white women)USA (white women)Swiss, Denmark, GermanySwiss, Denmark, Germany
France, Sweden France, Sweden NorwayNorway
POLANDPOLAND
India, Japan, Kuwait, FilipinaIndia, Japan, Kuwait, Filipina
EpidemiologyEpidemiology
POLANDPOLAND
morbiditymorbidity - V - V placeplace (11,8%) (11,8%)
mortalitymortality- XIV - XIV placeplace (2,5%) (2,5%)
EpidemiologyEpidemiology
55-90 r.ż. 55-90 r.ż. Almost all cases in postmenopausal ageAlmost all cases in postmenopausal age
(two pick(two picks s of morbidity: about 55 y. and 78 of morbidity: about 55 y. and 78 y.)y.)
5% < 40 r.ż.5% < 40 r.ż.
PathogenesisPathogenesis
• Estrogen dependent carcinomaEstrogen dependent carcinoma ((progressing of changes about 10 yearsprogressing of changes about 10 years))
endometrialendometrial typicaltypical atypicalatypical
proliferationproliferation hyperplasiahyperplasia hyperplasia hyperplasia CarcinomaCarcinoma
• Estrogen independent carcinomaEstrogen independent carcinoma
normalnormal CarcinomaCarcinoma
endometriumendometrium
Sexual Hormones Sexual Hormones ActivityActivity
ESTROGENSESTROGENSstimulating divistimulating divissiionon of cells of cells
PROGESTAGESPROGESTAGESbreaking divibreaking divisonson of cells of cells
Sexual Hormones productionSexual Hormones production Reproductive ageReproductive age
EE11, ,
EE22, E, E33
OVARIESOVARIES ProgesteroneProgesterone
TestosteroneTestosterone
AndrostendioneAndrostendione
ADRENAL GLANDS AndrostendioneADRENAL GLANDS Androstendione
Sexual Hormones productionSexual Hormones production Premenopausal periodPremenopausal period
EE11, ,
EE22, E, E33
OVARIESOVARIES ProgesteroneProgesterone
TestosteroneTestosterone
AndrostendioneAndrostendione
ADRENAL GLANDS AndrostendioneADRENAL GLANDS Androstendione
Reletive Reletive HyperestrogenismsHyperestrogenisms
Sexual Hormones productionSexual Hormones production Postmenopausal PeriodPostmenopausal Period
OVARIESOVARIES TestosteroneTestosterone
ADRENAL GLANDS ADRENAL GLANDS AndrostendioneAndrostendione
Androgens aromatization into estrogensAndrogens aromatization into estrogensAndrostendioneAndrostendione EstronEstronTestosteroneTestosterone EstradiolEstradiol
PathogenesisPathogenesishormonal factorshormonal factors
• ESTRONESTRONEE
• ESTRADIOLESTRADIOL
• ANDROGENSANDROGENS
• ESTRIOLESTRIOL
• PROGESTERONEPROGESTERONE
RISK FACTORSRISK FACTORS
ObesityObesity Late menopause > 52 years-old womenLate menopause > 52 years-old women NulliparityNulliparity Anovulatory cyclesAnovulatory cycles PCOsPCOs Ovarian tumors (hormonal active)Ovarian tumors (hormonal active) Diabetes mellitus type IIDiabetes mellitus type II Hepatic cirrhosis Hepatic cirrhosis Hypothyroidism Hypothyroidism HyperprolactinemiaHyperprolactinemia
Protective FactorsProtective Factors
Oral contraceptionOral contraception
Complex hormonal replacement therapyComplex hormonal replacement therapy
Cigarettes smoking Cigarettes smoking
EndometrialEndometrial CarcinomaCarcinoma
Symptoms Symptoms
• Postmenopausal bleedingPostmenopausal bleeding
• Acyclic bleeding in premenopausal Acyclic bleeding in premenopausal
periodperiod
• ill – smelling leucorreasill – smelling leucorreas
• pelvic painpelvic pain
• ascitesascites
Postmenopausal bleedingPostmenopausal bleedingmain reasonsmain reasonsPostmenopausal bleedingPostmenopausal bleedingmain reasonsmain reasons
Endometrial atrophyEndometrial atrophy 50 %50 %
Endometrial polypEndometrial polyp 15 %15 %
Submucosus uterine myomaSubmucosus uterine myoma 10 %10 %
Endometrial hyperplasiaEndometrial hyperplasia 10 %10 %
Endometrial carcinomaEndometrial carcinoma 5 % 5 %
Cervix disease (CA, polypsCervix disease (CA, polyps)) 10 %10 %
AAsymptomatic casessymptomatic casesUltrasonography Ultrasonography
Estimated FeaturesEstimated Features
thicknessthickness echogenicity et structure echogenicity et structure middle echo middle echo fluid in uterine cavityfluid in uterine cavity endo-myometral borderendo-myometral border
focal lesionsfocal lesions
Normal ultrasonographic image of Normal ultrasonographic image of endometrium of postmenopausal womenendometrium of postmenopausal women
Abnormal ultrasonographic image of Abnormal ultrasonographic image of endometrium of postmenopausal womenendometrium of postmenopausal women
Precancerous LesionsPrecancerous Lesions
Simple endometrial hyperplasia Simple endometrial hyperplasia without atypia without atypia Complex hyperplasia without atypia Complex hyperplasia without atypia
Endometrial polypsEndometrial polyps
Atypical endometrial hyperplasiaAtypical endometrial hyperplasia ( simple or complex)( simple or complex)
EndometrialEndometrial CarcinomaCarcinoma
DiagnosisDiagnosis
On baseOn base
morphological research morphological research
The material The material
received from uterine cavity received from uterine cavity
Methods of Receiving of Methods of Receiving of Material from Uterine CavityMaterial from Uterine Cavity
Endometrial Cytology Endometrial Cytology (Gynoscan, Endo-Pap, Jet-Wash)(Gynoscan, Endo-Pap, Jet-Wash)
Endometrial Biopsy Endometrial Biopsy
(Pipella, Vabra)(Pipella, Vabra) D & C D & C Diagnostic HysteroscopyDiagnostic Hysteroscopy
Dilatation and CurettageDilatation and Curettage
Recamier 1843Recamier 1843
Most often diagnostic interventionMost often diagnostic intervention
executed in worldexecuted in world
„„gold standard”gold standard”
Dilatation and CurettageDilatation and Curettage
blind procedureblind procedure general anaesthesiageneral anaesthesia high grade of uterine perforation 1/99 high grade of uterine perforation 1/99 risk of haemorrhagerisk of haemorrhage risk of infectionrisk of infection most often only 50 % of most often only 50 % of
endometrial surface is receivedendometrial surface is received
Diagnostic HysteroscopyDiagnostic Hysteroscopy
estimation under eye-controlestimation under eye-control all endometrial surface is accessible to all endometrial surface is accessible to
investigationinvestigation target biopsytarget biopsy local anaesthesialocal anaesthesia video documentationvideo documentation
low grade of uterine perforations low grade of uterine perforations
abnormal USG image of endometriumabnormal USG image of endometrium
at asymptomatic womanat asymptomatic woman
focal changes in USG image of focal changes in USG image of
endometrium endometrium
abnormal USG + D&C /-/abnormal USG + D&C /-/
recurrent uterine bleeding + D&C /-/recurrent uterine bleeding + D&C /-/
unsuccessful D&Cunsuccessful D&C
Diagnostic Hysteroscopy – WHEN ?Diagnostic Hysteroscopy – WHEN ?
FIGO Surgical Staging of Endometrial FIGO Surgical Staging of Endometrial CarcinomaCarcinoma
I A Tumor limited to endometriumI A Tumor limited to endometriumI B Invasion to less then one half of the I B Invasion to less then one half of the
myometrium myometriumI C Invasion to more then one half of myometriumI C Invasion to more then one half of myometriumII A Endocervical glandular involvementII A Endocervical glandular involvementII B Cervical stromal involvementII B Cervical stromal involvementIII A Tumor involving serosa and/or adnexa or III A Tumor involving serosa and/or adnexa or
positive peritoneal cytology positive peritoneal cytologyIII B Vaginal metastasesIII B Vaginal metastasesIII C Metastases to pelvic and/or periaortic lymph III C Metastases to pelvic and/or periaortic lymph
nodes nodes IV A Tumor invades bladder mucosa or bowel IV A Tumor invades bladder mucosa or bowel IV B Distant metastases IV B Distant metastases
FIGO Surgical Staging of Endometrial CarcinomaFIGO Surgical Staging of Endometrial Carcinoma
First StageFirst StageTumor Limited to Uterine CorpusTumor Limited to Uterine Corpus
I AI A Tumor limited to endometrium Tumor limited to endometriumI BI B Invasion to less then one half of Invasion to less then one half of
myometrium myometrium
I CI C Invasion to more then one half of Invasion to more then one half of myometrium myometrium
FIGO Surgical Staging of Endometrial CarcinomaFIGO Surgical Staging of Endometrial Carcinoma
Second StageSecond Stage
Tumor Invading Uterine CervixTumor Invading Uterine Cervix
II AII A Endocervical glandular involvement Endocervical glandular involvement
II BII B Cervical stromal involvementCervical stromal involvement
Histological Grading Histological Grading of Endometrial Carcinomaof Endometrial Carcinoma
• G 1G 1 Less then 5 % Less then 5 %
undifferentiated cells undifferentiated cells
• G 2G 2 5 – 50 % undifferentiated cells5 – 50 % undifferentiated cells
• G 3G 3 More then 50 % More then 50 %
undifferentiated cellsundifferentiated cells
• G XG XNumber of undifferentiated cells Number of undifferentiated cells
is unknown is unknown
FIGO Surgical Staging of Endometrial CarcinomaFIGO Surgical Staging of Endometrial Carcinoma
Third StageThird Stage
Tumor Out of UterusTumor Out of Uterus
III AIII A Tumor involving serosa and/or adnexa Tumor involving serosa and/or adnexa
or positive peritoneal cytologyor positive peritoneal cytology
III BIII B Vaginal metastasesVaginal metastases
III CIII C Metastases to pelvic and/or Metastases to pelvic and/or
periaortic lymph nodes periaortic lymph nodes
FIGO Surgical Staging of Endometrial CarcinomaFIGO Surgical Staging of Endometrial Carcinoma
Forth StageForth Stage
IV AIV A Tumor invades bladder mucosa or bowel Tumor invades bladder mucosa or bowel
IV BIV B Distant metastasesDistant metastases
Endometrial CarcinomaEndometrial Carcinoma hystological types, WHO classification hystological types, WHO classification
Adenocarcinoma - endometrioide typeAdenocarcinoma - endometrioide type
Mucinous Mucinous aadenocarcinomadenocarcinoma
Serous Serous aadenocarcinoma denocarcinoma
Clear cell Clear cell aadenocarcinomadenocarcinoma
Carcinoma planoepithelialeCarcinoma planoepitheliale
Carcinoma mixtumCarcinoma mixtum
Undifferented Undifferented ccarcinomaarcinoma
Treatment of EndometrialTreatment of Endometrial CarcinomaCarcinoma
• SurgerySurgery
• Radiotherapy Radiotherapy
• HormonotherapyHormonotherapy
• ChemotherapyChemotherapy
Treatment of EndometrialTreatment of Endometrial CarcinomaCarcinoma
SURGERYSURGERYdependent of stagedependent of stage
• TAH with bilateral oophorectomyTAH with bilateral oophorectomy
• TAH with bilateral oophorectomy TAH with bilateral oophorectomy
and 1/3 part of vaginaand 1/3 part of vagina
• Radical HysterectomyRadical Hysterectomy
• Tumorectomy (debulking operation)Tumorectomy (debulking operation)
Treatment of EndometrialTreatment of Endometrial CarcinomaCarcinoma
RadioRadiotherapytherapydependent of stagedependent of stage
• Neo-adjuvant brachytherapyNeo-adjuvant brachytherapy
• Adjuvant brachytherapy Adjuvant brachytherapy
Radium, Cobalt, Cesium, IridiumRadium, Cobalt, Cesium, Iridium
• TeletherapyTeletherapy
X-ray, gamma-ray, electron-rayX-ray, gamma-ray, electron-ray
Treatment of EndometrialTreatment of Endometrial CarcinomaCarcinoma
HormonotherapyHormonotherapydependent of receptors statusdependent of receptors status
• Gestagens – high dosesGestagens – high doses
medroxyprogesterone, megestrol etcmedroxyprogesterone, megestrol etc
• inhibitor of aromatase inhibitor of aromatase aminoglutetymidaminoglutetymid
Treatment of EndometrialTreatment of Endometrial CarcinomaCarcinoma
Chemotherapy Chemotherapy last chance therapylast chance therapy
• Mono - chemotherapyMono - chemotherapy
CCis-platinum, Carboplatinum, Taxolis-platinum, Carboplatinum, Taxol
• Poly - chemotherapy Poly - chemotherapy Cis-platinum, cyclophosphamidum, Malfelan, Cis-platinum, cyclophosphamidum, Malfelan,
5-fluorouracyl, Doxorubicin5-fluorouracyl, Doxorubicin
PAC, CAP, FAC, ACPAC, CAP, FAC, AC
Treatment of EndometrialTreatment of Endometrial CarcinomaCarcinoma
Stage I a Grade 1Stage I a Grade 1
• TAH with bilateral oophorectomyTAH with bilateral oophorectomy
• BrachytherapyBrachytherapy
(when surgery is contraindicated)(when surgery is contraindicated)
Treatment of EndometrialTreatment of Endometrial CarcinomaCarcinoma
Stage I a Grade 2, 3Stage I a Grade 2, 3
• TAH with bilateral oophorectomy TAH with bilateral oophorectomy
andand
• BrachytherapyBrachytherapy
Treatment of EndometrialTreatment of Endometrial CarcinomaCarcinoma
Stage I b, c, Stage II Stage I b, c, Stage II Stage III a Stage III a
• TAH + BO or Radical Hysterectomy TAH + BO or Radical Hysterectomy
• BrachytherapyBrachytherapy
• TeletherapyTeletherapy
• Hormonotherapy ( EHormonotherapy ( E22R +, PgR + orR +, PgR + or EE22R -, PgR + )R -, PgR + )
Treatment of EndometrialTreatment of Endometrial CarcinomaCarcinoma
Stage III b, c Stage IV Stage III b, c Stage IV
• Tumorecromy Tumorecromy
• Hormonotherapy ( EHormonotherapy ( E22R +, PgR + orR +, PgR + or
EE22R -, PgR + )R -, PgR + )
• ChemotherapyChemotherapy
EndometrialEndometrial CarcinomaCarcinoma
Prognostic Factors Prognostic Factors
• AgeAge• StageStage• GradeGrade• Presence of myometrial invasionPresence of myometrial invasion• Presence of NEO cells in peritoneal fluidPresence of NEO cells in peritoneal fluid• Lymph node metastasesLymph node metastases• Receptor statusReceptor status• DNA content in neoplastic cellsDNA content in neoplastic cells
Prognosis in Endometrial CarcinomaPrognosis in Endometrial Carcinoma
5 YEAR SURVIVAL 5 YEAR SURVIVAL
• Stage IStage I 75 – 100 %75 – 100 %
• Stage IIStage II 50 – 65 %50 – 65 %
• Stage IIIStage III 20 – 40 % 20 – 40 %
• Stage IVStage IV below 10 %below 10 %
5 YEAR SURVIVAL 5 YEAR SURVIVAL
• Endometrial CarcinomaEndometrial Carcinoma 75 %75 %
• Vulnar CarcinomaVulnar Carcinoma 42 %42 %
• Cervical CarcinomaCervical Carcinoma 38 %38 %
• Ovarian carcinomaOvarian carcinoma 35 %35 %
Diagnostic of asymptomatic womenDiagnostic of asymptomatic women
TV - USGTV - USG
No changesNo changes Indistinct Image Indistinct Image abnormal imageabnormal image
Control TV – USGControl TV – USG
After 3 monthsAfter 3 monthsSonohysterographySonohysterography HysteroscopyHysteroscopy
No changesNo changes abnormal imageabnormal image
Control TV – USGControl TV – USG
After 3 monthsAfter 3 months HysteroscopyHysteroscopy
Histological Histological
DiagnosisDiagnosis
HistologicalHistological
DiagnosisDiagnosis
INDIRECT METHODINDIRECT METHODOF ENDOMETRAL ASSESSMENTOF ENDOMETRAL ASSESSMENT
Conventional USGConventional USG Transvaginal USGTransvaginal USG Doppler MethodDoppler Method SonohysterogrphySonohysterogrphy 3D-ultrasonography3D-ultrasonography Magnetic ResonanceMagnetic Resonance Computer TomographyComputer Tomography
Conventional UltrasonographyConventional Ultrasonography(problems)(problems)
ObesityObesity
Fill up bladder problems Fill up bladder problems
(urinary incontinence)(urinary incontinence)
retroflexion of uterine corpusretroflexion of uterine corpus
low frequency 3,5-5 MHzlow frequency 3,5-5 MHz
Transvaginal UltrasonographyTransvaginal Ultrasonography
USG head near the uterus USG head near the uterus
Empty bladder Empty bladder
High frequency 6-15 MHzHigh frequency 6-15 MHz
Low rangeLow range
USGUSG Doppler MethodDoppler Method
neoangiogenesisneoangiogenesis
uterine artery flowuterine artery flow
small endometrial arteries flow small endometrial arteries flow
RIRI PIPI
HYSTEROSONOGRAPHYHYSTEROSONOGRAPHY3D - hysterography3D - hysterography
5-10 ml 0,9 NaCl, Ringer, H5-10 ml 0,9 NaCl, Ringer, H22OO
when unclear TV-USG image when unclear TV-USG image
special to detect focal lesion special to detect focal lesion
PREPOST
T. C. Dubinsky - J Ultrasound Med 1997
Computer TomofraphyComputer TomofraphyMagnetic ResonanceMagnetic Resonance
comparable with TV-USG in comparable with TV-USG in
assessment of endometrium assessment of endometrium
better in invasion assessment better in invasion assessment
of myometrium by endometrial CA of myometrium by endometrial CA
rather expensiverather expensive
PREPOST
PREPOST
• Kratochwill 1969
• Fleischer 1984
Diagnostic method which most Diagnostic method which most contributed to development of contributed to development of gynaecology in the course last gynaecology in the course last decades is certainly decades is certainly transvaginal ultrasonographytransvaginal ultrasonography
Diagnostic method which most Diagnostic method which most contributed to development of contributed to development of gynaecology in the course last gynaecology in the course last decades is certainly decades is certainly transvaginal ultrasonographytransvaginal ultrasonography
USG image of endometriumUSG image of endometriumin postmenopausal periodin postmenopausal period
„„Pencil line”Pencil line”
FLAICHERFLAICHER 6,0 mm6,0 mm
GOLDSTEINGOLDSTEIN 5,0 mm5,0 mm
GRANBERG GRANBERG 5,0 mm5,0 mm
NASSRINASSRI 5,0 mm5,0 mm
OSMERSOSMERS 4,0 mm 4,0 mm
WIKLANDWIKLAND 4,0 mm4,0 mm
Operative HysteroscopyOperative Hysteroscopy indications et postmenopausal womenindications et postmenopausal women
removing of endometrial polypsremoving of endometrial polyps
removing of submucosus myomasremoving of submucosus myomas
( type 0 and I)( type 0 and I)
electroresection of endometriumelectroresection of endometrium
Endometrial hyperplasiaEndometrial hyperplasia treatmenttreatment
• Stimulating ovulation MDsStimulating ovulation MDs • Gestagens – High doseGestagens – High dose• IUD with gestagensIUD with gestagens• hysteroscopic endometrial resectionhysteroscopic endometrial resection• brahy - therapy brahy - therapy • hysterectomyhysterectomy
Endometrial hyperplasiaEndometrial hyperplasiaimportance of using gestagensimportance of using gestagens
• blocking of E-receptors synthesisblocking of E-receptors synthesis
• blocking of gonadotropinblocking of gonadotropin
• increase activity of 5increase activity of 5αα-reductase-reductase
• increase activity Eincrease activity E22-dehydrogenase-dehydrogenase
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