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Post-menopausal Bleeding and Endometrial Cancer - Coggle Diagram
Post-menopausal Bleeding and Endometrial Cancer
Overview Edometrial Cancer
Epidemiology. Pathology
Epidemiology
🥇 Most common gynaecoogical cancer in europe
4th most cancer in women
500 cases every year
Rise in obesity - rise in incidence
Highest association with obesity
Pathophysiology
Oestrogen
Oestrogen
Drives endometrial proliferation
Progesterone
inhibits growth and cell differentiation
Rises after ovulation - drops in absence of conception causing menstruation
Excess ostreogen drives endometrial hyperplasia and progression to malignany
Obesity
3 mechanisms of endometrial carcinogenesis
Excess oestrogen
Peripheral
aromatisation of androgens to oestrogen
occurs in
adipose
tissue
More adopise → more OE
Hyperinsulinaemia
Direct effect on
endometrial
proliferation
Reduces sex-hormone-binding globulin (SHBG) - increases bioavailable fraction of oestrogen
Increases
ovarian androgen production
and its peripheral aromatisation to oestroge
Inflammation
PRo-inflammatory cytokines increase with obesity
Create a tumorigenic environment through effects on cell cycle
Genetic Predispoosition: Lynch Syndrome
Inheritence
Autosomal dominant
Mutation of 1 of 4 genes of DNA mismatch repair
Epidemiology
Lifetime riskof 40% to 60% for endometrial caner
Accounts for 3% of endometrial cancers
Causes of Oestrogen Excess
Endogenous
Obesity
Anovulation
PCOS
Early menarch, late menopause
Nulliparity
Oestrogen secreting tumours - Granulosa Cell Tumour of OVeary
Exgenous
HRT
Tamoxifen
Risk Factors
Age
Obesity
Unapposed oestrogen
HRT
Tamoxifen
Diabetes
Thickened endometrium
PCOS
Early menarch / late menopause
10 + Family hx
Cancer syndrome - Lynch syndrome
Protective Factors
Parity
COCP
IUS
Breasfeeding
Late menarch
Physical activity - reduce obesity
Histopathology
Hyperplasia without Atypia
5% risk in 20yr
Atypical Hyperplasia
8% risk in 4 yr
28% risk in 20yr
Risk of occult endometrial cancer - 43%
Endometrioid Adenocarcinoma endometrium - cancer
Types of Endometrial Cancer - Histopathology
Endometrioid adenocarinoma 75%
Glandular cells
Commonly detected
High cure rate
Subdivision to low-grade and high-grade
High Grade Srous adenocarinoma 10%
More aggressive
Similar to high grade serous ovarian cancer
High Grade and Rare
Clear cell carinoma
Carcinomasarcoma
Adenosquamous carcinoma
Postmenopausal Bleeding
Definition
Bleeding occuring 12 months or more after final menstraul period in women not taking HRT
Most Common Causes
Atrophic changes / hypo-oetrogenic 60%
Endometrial hyperplasia 12.5%
Endometrial cancer 10%
Endometrial cancer until proven otherwise - reassure pt that PMB is more often benign while stressing importance of investigation
Cause by Anatomy
Vulva
Benign
Atophy
Dermatoses
Infection - candida
Malignant
Vulval cancer
Vaginal
Benign
Atrophy
Polyps
Malignant
Vaginal cancer
Cervix
Benign
Cervicitis
Cevical polyp
Malignant
Cevical cancer
Uterus
Begnin
Hyperplasia
Polyps
Atrophy
Malignant
Endometrial cancer
Tube / Ovary
Oestrogen secreting tumour
Others
Anticoagulant use
Haematuria
Haematochezia
Managment in GP
Aim to differentiate gynaecological bleeding from urological / GI
Step 1
Woman recognises PMB & self refers to GP/ community practitioner
Step 2
Urgent history, abdominal, speculum, bimanual exam
Step 3
If post-menopausal vaginal bleeding suspected → Refer to PMB clinic / gynae clinic
If suspicious lesion on cervix / vagina / vulva → direct referral to gynae onc services
Step 4
Triaged and appoitment
ideally within 28 days
- GP informed
PMB Assessment
History
Meds hx
HRT
COCP
Tamoxifen
Gynae
Early menarch / late menopause
Known endometrial hyperplasia
Parity
Confirm cervical screen hx
FHx
Obesity
Breast cancer
Lynch syndorme
Endometrial caners
PMhx
Obesity
Diabetes
Treatment for breast caner
Lynch syndrome
Triage
Women with
PMB
on
HRT
with unscheduled bleedingt, persisten, prolonged or intermentrual bleeding
Abdominal exam
Speculum exam
Pelvic bimanual exam
Women with
menorrhagia
over
45y/o
or
Irregular bleeding
or
Failure of treatment
over
45
Endometrial sampling
Examination
BMI
2.Speculum exam
Bimanual exam
Investigations
Transvaginal Ultrasoun (TV-USS)
Triage
for further investigation
Assessment of double layered endometrial
thickness
≥ 4mm should be investigated
≤ 4mm holds <1% probability of endometrial cancer
Suction Sampling
Indication
Diffuse change ≥ 4mm on TV USS
No focal lesion
Office Hysteroscopy
Indication
Focal lesion on TV USS
Inadequate views on TV USS
Diffuse thickening
Suction sampling
Focal lesion
Targeted hysteroscopic biopsy
Use
High risk women
OPD endometrial biopsy not feasible
Ideally OPD
GA - Hysteroscopy Dilation and Curettage
Special Notes
Women with unexplained, Persistent, or recurrent PMB
Hysteroscopy and repeat endometrial biopsy
Women on Tamoxifen
TVUSS - ET is not sensitive or specific
Proceed to Hysteroscopy and endometrial sampling
Incidental / Asymptomatic finding of thickened endometrium in postmenopause
Further investigation when TVUS - ET ≥ 11mm
Management
Endometrial hyperplasia without atypica (EH)
Address risk factors
1️⃣Line LNG-IUS
2️⃣Line: Oral progestogen
Endometrial biopsy (EB) at
6 months
Atypical hyperplasia (AH)
TAH +/- BSO
Fertility require / Surgery contraindicated
Adress risk factors
1️⃣ line LNG-IUS
2️⃣ Line Oral progestogen
Endometrial biospy at
3 months
Endometrial Cancer
Clinical Presentation
Abnormal vaginal bleeding
Post menopausal bleeding
HMB
Intermenstrual bleeding
Vaginal discharge pink and watery to dark and foul selling
Advanced disease
Pelvic mass
Nausea
Deacreased appetite
Lethargy
Lower abdo, back, leg pain
Presents
early
- detected following symptoms of abnormal vaginal bleeding
Staging And Grading
Staging
Stage - Anatomical distribution
Staging Imaging
CT TAP
for distant mets
MRI
for myometrial , cervical stomal invasion, lymph node mets
FIGO Staging
Stage 1
Contained within the uterus
1A Less than halfway through myometrium
1B Halfway or more through myometriumA
Stage 2
In the Cervix
Stage 3
Spread outside the uterus, but contained within the pelvis
3A Outer covering of uterus (serosa) / ovaries / fallopian tubes
3B Vagina / Parametrium
3C Nearby lymph nodes
Stage 4
Distant Metastasis
4A Bowel / bladder
4B Distant lymph nodes / lungs / liver / bones / brain
Stage at Diagnosis
60% at stage 1 - early symptoms
Grading
Characteristics generally consistent with tumour
behaviour / Differentiation - histopathology
Management
Stage I / II
Radiologically confined to uterus / cervix
TLH BSO + Sentinel lymph node biopsy
+/ adjuvant radiotherapy
Lymph node positive : chemo and radiotherapy
Stage III/IV
Fully resectable
Surgical resection + adjuvant chemo-radiotherapy
Not fully resectable
Palliative systemic therapy / radiotherapy / hormonal therapy
Fertility Sparing
Use
Atypical hyperplasia
Grade 1 endometriois carinoma without myometrial invasion
Treatment
PO high dose progesterone
Mirena coil
Ovarian Sparing
Use
Pre-menopausal pt aged <45 with low grade endometrioid endometrial carinoma with myometrial invasion < 50% and no ovbious ovarian / extra-uterine disease
Follow up
Risk Stratification
Detect potentially treatable recurrences
Isolated vaginal vault tumour in women who could tolerate alvage radiotherapy or exenterative surgery
Info on red flag symptoms
Vaginal bleeding
Discharge
Continuity of Care
Address survivorship issues
Prescribe in advance the frequency and purpose of follow-up
Endometrial Cancer and Obesity
Prevention: Obesity Driven Endometrial Cancer
Dieting
Increased insulin sensitivity
Increased SHBG levels
Lower serum OE and testosterone
Physical activity
20-30% risk reduction
Greater benefits for higher intensitiy exercise of greater duration
Bariatric surgery
Indication : BMI 40+
70-80% risk reduction
Contraception
LNG-IUS: Mirena
54% reduction
75% risk reduction if treatment prolonged
Surgical Challenges Associated with Obesity
Restricted surgical access
Intolerance of trendelenberg position
↑ Risk of postop complication - particularly wound infection
Comorbidities (CVS, OSA, DM) reduce fitness for anaesthesia
↑ Risk in intubation
Need for postop care in HDU
Long term Otucomes
Weight loss could improve overall survival in women with hx endometrial cancer by reduing risk of death from other causes
CVS death most common cause of death in women with early stage endometrial cancer
Twice as many deaths from MI, stroke, HF than cancer
endometrial cancer may be the patient's first obesity ‘symptom’ and serve as an important ‘teachable moment’
