Gestational trophoblastic disease includes complete and partial hydatidiform moles, invasive moles, choriocarcinoma, and placental site trophoblastic tumors, with molar pregnancies requiring surgical evacuation and strict follow up of beta HCG levels to monitor for malignant transformation into gestational trophoblastic neoplasia. Risk factors include extremes of maternal age, previous molar pregnancies, and ethnicity, while presentation is typically irregular bleeding and an enlarged uterus out of proportion to gestational age.

1. Common
Gynaecological
Carcinoma

2. Top killers of the female gender
All Females, All Ages Percent*
1) Heart disease 25.1
2) Cancer 22.1
3) Stroke 6.7
4) Chronic lower respiratory diseases 5.5
5) Alzheimer's disease 4.3
6) Unintentional injuries 3.6
7) Diabetes 2.9
8) Influenza and pneumonia 2.3
9) Kidney disease 2.0
10) Septicemia 1.6

3. : 10 Principle Cause of Deaths in
Ministry of Health, Malaysia (MOH)
Hospitals, 2006
1. Septicaemia 16.87
2. Heart Diseases & Diseases of Pulmonary Circulation 15.70
3. Malignant Neoplasms 10.59
4. Cerebrovascular Diseases 8.49
5. Pneumonia 5.81
6. Accidents 5.59
7. Diseases of the Digestive System 4.47
8. Certain Conditions Originating in The Perinatal Period 4.20
9. Nephritis, Nephrotic Syndrome & Nephrosis 3.83
10. Ill-defined conditions 3.03
All causes 100.0

4. Prevalence of various types of cancer amongst Malaysian ladies
of all ages
BREAST 3525 29.9
COLORECTAL 1247 10.6
CERVIX UTERI 1074 9.1
OVARY 685 5.8
THYROID GLAND 670 5.7
LUNG 603 5.1
CORPUS UTERI 372 3.2
STOMACH 324 2.7
BRAIN, OTHER
NS 303 2.6
LYMPHOMA 279 2.4
Taken from the Malaysian Cancer Statistics 2006

5. PATHOPHYSIOLOGY
CERVICAL ENDOMETRIAL OVARIAN
The squamo-columnar -Most commonly 80% from Ovarian
junction and the Adenocarcinoma Epithelium
Transformation zone -90%: Endometriod adenoCA 20% others: Germ cell, sex-
-10%:Serious papillary AdenoCA
cord stromal, mixed
Common site for HPV -Rarely: Clear cell mullerian,
infection
HPV infection persists in Mechanism poorly understood
certain individuals, eventually Two main theories
triggering oncogenic processes
within the TZ
Cell metaplasia occurs: 1. Incessant
Immortalization of the basal ovulationrepeated trauma
cells leading to rapid turnover to ovarian epithelium
and subsequent immature
cells
These immature cells picked 2. Excess gonadotrophin
up on PAP smear as Cervical secretionhigher level of
Intraepithelial Neoplasia CIN estrogenEpithelial
proliferation

7. AETIOLOGY & RISK FACTORS
CERVICAL ENDOMETRIAL OVARIAN
Infection by HPV Conditions that lead to Endometriosis
16,18,31,33 high levels of estrogen
-Tamoxifen
-Unopposed estrogen therapy
as HRT
Immunosupressed state Family history (debatable) Family history
leading to increased risk of -endometrial cancer -increased risk from 1.4% in
HPV infection: -colorectal/ovarian cancer general populace to 5%
-RVD -HNPCC 50% if 2 first degree relatives
-Immunosupressive drugs
Nulliparity Nulliparity
Late menopause >52 years
Obesity Obesity
Smoking Diabetes
-theory: immunosupressive
effects of nicotine within the
cx

8. Mnemonic of risk factors for
endometrial cancer
• O=Obesity
L=Late menopause
D=Diabetes mellitus
A=cAncer: ovarian, breast, colon
U=Unopposed estrogen: PCOS, anovulation,
HRT
N=Nulliparity
T=Tamoxifen, chronic use.

9. RMI score for ovarian CA
Feature RMI 1 Score RMI 2 Score
Ultrasound features: 0= none 0= none
• multilocular cyst 1= one abnormality 1= one abnormality
• solid areas 3= two or more 4= two or more
• bilateral lesions abnormalities abnormalities
• scites
• intra-abdominal
metastases
Premenopausal 1 1
Postmenopausal 3 4
CA125 U/ml U/ml
RMI score = ultrasound score x menopausal score x CA125 level in U/ml.
The RMI scoring system is the method of choice for predicting whether or not an
ovarian mass is likely to be malignant.
Women with an RMI score >200 should be referred to a centre
with experience in ovarian cancer surgery. Evidence grade 2+

10. CLINICAL FEATURES
CERVICAL ENDOMETRIAL OVARIAN
Abnormal PV bleeding Abnormal PV bleeding Persistent pelvic-
abdominal pain
1. Post-coital bleeding 1. Post-Menopausal Bleed Increased abdominal size and
*The cervical cancer is a ddx: Cervical, endometrial polyps, bloating
friable vascular mass on cervical erosion, vaginal
the cervix: Mechanical atrophy
irritation during coitus: 10% of PMB turns out to be
Endometrial CA
Post-coital bleed
2. Irregular Vaginal
bleeding
3. Advanced stage: 3. Advanced stage: 3. Advanced stage:
-constitutional sx -constitutional sx -constitutional sx
-lungs mets: Recurrent -lungs mets: Recurrent -lungs mets: Recurrent
bilateral pleural effusion bilateral pleural effusion bilateral pleural effusion
Incontinence Change in bowel habits
Anemia Sx Urinary sx
Renal failure Back ache

11. INVESTIGATIONS AND SUSPICIONS
CERVICAL ENDOMETRIAL OVARIAN
Aim of diagnostics: To provide histopathological evidence of malignant cancer tissue.
To provide sufficient information to properly stage the tumour
To confirm the malignancy To confirm the malignancy To confirm the malignancy
1. Colposcopy : outpatient 1. Sampling by Pipelle: and for staging
examination of the magnified Outapatient procedure, 1.TAHBSO
cervix using a light source results operator dependant,
Additional Lugol’s Iodine/ 5% acetic 2.CT-scan/MRI
difficult to do if nulliparous, 3.PET-scan
acid are used to highlight the
presence of abnormal cells retroverted uterus, presence
2. Cervical Biopsy: To confirm of fibroids
* In some patients (esp those
the malignancy and type 2. Hysteroscopic DD+C: done
if unable to obtain good
unfit for a major surgery such
of tumour as TAHBSO, laparascopic
sample by Pipelle /
Contraindicated for Pipelle examination and biopsy is
done instead
To assess stage To assess stage
1.CT-scan abdomen-pelvis 1.TAHBSO
2.EUA : Vaginal and rectal 2.CT-scan/MRI
3.PET-scan

12. Tumuor markers
1. Not used for diagnosis for cancer. Diagnosis of cancer is strictly based histopathological
evidence
2. Tumour markers can be useful for:
- Monitoring the response of the malignancy to anti-cancer therapies
- Monitoring patients on a regular basis to assess for reoccurance
Tumour marker Cancer
1 Ca-125 Endometrial, ovarian
2 CEA Pancreas, colon
3 a-FP Liver (HCC)
4 Ca 19-9 Pancreas

13. CERVIX ENDOMETRIAL OVARIAN
I: Cervical cancer confined to IA: Endometrium only I: Ovaries only
cervix IA: One ovary
Ia1: < 3mm IB: Two ovaries
IB: <1/2 of myometrium IC: Ruptured ovary/+ve peritoneal
Ia2: > 3mm
wash/ascites
Ib1: < 4cm IC: >1/2 of myometrium
1b2:> 4cm
II: Cervical cancer extending IIA: Endocervical glandular II: Ovaries + pelvic
beyond the cervix, but not involvement involvement
invading pelvic wall IIB: Cervical stroma invasion IIA: Uterus + Tubes
IIA: No obvious parametric invasion IIB: Pelvic/parametrial tissue
IIB: Obvious parametric invasion + IIC: Rupture/+ve peritoneal
upper 2/3 of vagina wash/ascites
III: Cervical ca extending to IIIA: Serosa/Adnexa/+ve III: Ovaries + peritoneum
pelvic wall peritoneal wash IIIA: Microscopic seedlings
IIIa: Invasion of lower 1/3 vagina IIIB: < 2cm seedling
IIIB: Invasion of vagina IIIC: > 2cm seedling
IIIb: Extention to pelvic wall with
hydronephrosis
IIIC: Invasion of pelvic/
Paraaortic LN
IVa: Growth to adjacent IVA: Invasion to IV: Distant metastasis
organs bladder/rectum Pleural effusion
IVb: Distant metastasis IVB: Distant metastasis

14. CERVICAL CANCER
FIGO
STAGING

15. ENDOMETRIAL CANCER FIGO STAGING

16. Cervical Cancer
STAGE TREATMENT PROTOCOL
Stage 1a Surgery: TAH, PLND
Modified radical trachelectomy (fertility sparing)
: remove 80% of cervix, parametrial tissues, pelvic LN ~ 40% miscarriage
Fertility sparing therapy seldom done
Radiation therapy: Brachytherapy(internal radiotherapy)
Stage 1b Wertheim’s hysterectomy
TAHBSO+Parametrial tissue excision+PLND+upper 1/3 vagina
Radiation therapy has similar success rates, and considered
who are unfit for surgery
Stage 2-4 Chemotherapy : Carboplatin + Paclitaxel
Radiotherapy: External beam: Teletherapy
Internal radiotherapy: Brachytherapy
*Surgery seldom done at this stage:
-High rates of surgical complications esp: Bleeding
-Unlikely chance of achieving complete clearance of tumour
-Requiring post op radiotherapy, and this combined treatment can lead to high
complication rates
Remember: No tumour markers for Cervical Cancer

17. Endometrial Carcinoma
Surgery
*Generally surgery indicated in all
patients diagnosed with Endometrial CA
C/I: Unfit for surgery, metastasised
cancer (Stage IV)
Stage 1A, 1B
TAHBSO (PLND also commonly done Stage 2C, 3, 4/Papillary serous/Clear
cell
as there is a high chance of spread to
LN at this stage)
TAHBSO + PLND
Adjuvant Chemotherapy
Stage 1C, 2A, 2B
TAHBSO + PLND (50% risk of LN
dissemination at these stages)
Chemotherapy
-Commence adjuvant chemotherapy
-1st Line: 6 cycles of Carboplatin + Paclitaxel
-2nd Line: 9 cycles (A+B) of Gemcitabine
Follow-up: Ca-125, CT-Scan

18. Ovarian Cancer
Surgery
*Studies show that the most important
prognostic factor is no residual disease
following laparatomy
Non fertility sparing
Fertility sparing (rarely done)
-Vertical insicion done to gain visual
-Vertical insicion done to gain visual
access to ALL areas of the abdomen
access to ALL areas of the abdomen
-Ascites and peritoneal washing samples
-Unilateral SO, Omentectomy, Peritoneal
are obtained
biopsies
-TAHBSO + Omentectomy KIV further
-PLND
debulking if required
+ Endometrial sampling to exclude
- PLND
concerrent tumour
MDT meeting between Oncogynae
with pathologist, radiologist
Chemotherapy
Stage IB, IC , II, III, IV
Stage 1A -Commence adjuvant chemotherapy
- Chemotherapy withheld in some cases -1st Line: 6 cycles of Carboplatin + Paclitaxel
-2nd Line: 9 cycles (A+B) of Gemcitabine
Follow-up: Ca-125, CT-Scan

19. Drug Mech of action AE
Cisplatin Platinum based drug Nephrotoxic (check RP before giving)
Acts by binding and cross- GIT: N+V
linking DNA leading to cell Ototoxicity
apoptosis Electrolyte imbalances
Carboplatin Neurotoxicity: peripheral neuropathy
Myelosupression  Aneamia,neutropenia,TCP
Less GIT effects compared to Cisplatin
No nephrotoxic effect
Gemcitabine Neucloside analogue. Flu-like symptoms
Kills cells in the S-phase of mitosis GIT: Mild N+V
: Cell phase specific Hair oss
Myelosupression
5-FU Pyrimidine analogue Myelosupression
Inhibits Thymidine synthase Mucositis, dermatitis
: Cell phase specific (S-phase) Diarrhoea
Paclitaxel Stabilizes the microtubules Myelosupression
preventing the Interphase thus Neurotoxicity: Peripheral neuropathy
interrupting mitosis Elevated LFT
: Cell phase specific N+V, hair loss, arthritis

20. Gestational Throphoblastic Disease
Hydatidiform Mole Invasive Mole Choriocarcinoma Placental site
throphoblastic
Complete Incomplete
tumour (PSTT)
Risk factors Extremes of age (<15, >40) – risk of complete moles
Previous molar pregnancy X 10
Ethnicity (East Asians: x 2)
Presentation Irregular first-trimester bleeding >90%
Uterus large for dates~ 25%
Abdominal pain (from hyperstimulation of theca lutien cysts)
Exxaggerated early pergnancy symptoms (hyperemesis gravidarum) ~ 10%
Diagnosis Clinical
Biochemical – excessively raised serum bHCG levels (may be normal in partial moles)
Scan findings – classic snowstorm appearance
Histological – post evacuation
Management Complete mole – surgical evacuation (higher risk of uterine perforation and significant
bleeding)
Incomplete mole – Surgical or medical evacuation

21. Follow-up Review HPE of evacauted mole – determine for sure complete or incomplete
Recommended follow-up plan
-Fortnightly bHCG until levels normal < 4
-4 weekly intervals urine bHCG levels for one year, then 3-monthly in 2nd year
-Contraception until bHCG normal for 6 months
The purpose of this follow up is to detect malignancy early
When to suspect The International Federation of Gynecology and Obstetrics considers an
malignancy? elevated serum hCG level 6 or more months after evacuation of a
hydatidiform mole to be diagnostic of malignancy (ie, GTN).
*However, serum hCG levels spontaneously return to normal without
chemotherapy in most patients with elevated but still declining serum hCG
levels 6 months after diagnosis of a hydatidiform mole.
Indication for 1. Serum bHCG levels >20000 4 weeks after uterine evacuation
chemotherapy 2. Static or rising bHCG levels post evacuation
3. Histological evidence of choriocarcinoma
4. Metastatic disease
5. Persistent symptoms

23. Choriocarcinoma
Incidence Rare : Amongst Orientals 1:11000 (1:30000 amongst Caucasians)
20% of complete hydatidiform moles become ChorioCA
Presentation Similar to hydatidiform mole
-First trimester vaginal bleeding, abdominal pain
Symptoms pointing to possibility of chorioCA
-Dyspnoea and hemoptysis (lung mets), hematuria, neurological sx
-Jaundiced, abdominal tenderness, rebound
Investigations Biochemical – Persistantly raised / pleateau or increasing trend of bHCG even after surgical
evacuation of GTD
Scan findings
CXR (lung is most frequent site of mets) CT abdomen and chest
Treatment CHEMOTHERAPY
-Regime based on prognostic scoring assestment
Low Risk : MTX + Folinic Acid / Actinomycin D
Med Risk: MTX + Etoposide
High Risk: Intensive weekly EMA (Etoposide,MTX,Dactinomycin) alternating with CE
(Cyclophosphamide and Vincristin) – the EMA-CE regiment
Prognosis Overall survival > 90% - it is one of the most curable forms of malignant cancer
Poorer prognosis if
-Age >40
-Time interval between antecedent pregnancy and start of chemotherapy > 4months
-After 12 months of normal hCG levels, less than 1% of patients with GTN have recurrences.
Next Fertility not impaired by chemo
pregnancy No increased risk of fetal anomalies