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