Gestational Trophoblastic Diseases (GTDs)

Hydatidiform mole is the most common form of gestational trophoblastic disease and is benign in nature.

2% of all miscarriages.

Its incidence varies worldwide.

• 1 in 1500 deliveries in the United States
• 1 in 400 pregnancy in Nigeria
• 1 in 200 pregnancy in Indonesia
• 1 in 125 deliveries in Mexico and Taiwan

• Race (blacks/Asians). In many Asian countries, the rates may be as high as 8–10 cases per 1,000 population.
• Age <20yrs; >40yrs. The risk of development of H. mole in women older than 40 years is about five times more than that in younger women.
• Parity- Nulliparity.
• Low SES (Socioeconomic Status).
• Deficiency of protein, folic acid and carotene.
• Blood group- O highest; A least.
• Previous history of molar pregnancy.
• Partial mole is reported to be associated with the use of oral contraceptives, history of irregular menstruation and not with dietary factors

Abnormal vaginal bleeding (75%) +/- passage of vesicles

Initially, the symptoms may be suggestive of early pregnancy; however the uterus is often larger than the period of gestation.

Absent fetal movements and heart tones

Passage of grape-like tissue is strongly suggestive of the diagnosis of H. mole.

Excessive nausea and vomiting.

Symptoms suggestive of hyperthyroidism (tachycardia, restlessness, nervousness, heat intolerance, unexplained weight loss, diarrhea, tremors in hands, etc.)

Excessive nausea and vomiting in cases of H mole may be related to high serum levels of β hCG. Hyperemesis may commonly occur.

Commonly the nausea and vomiting may be severe enough to require hospitalization.

Early-onset pre-eclampsia

Anaemia

Thrombo-embolism

Large theca lutein cysts

Metastasis to the lungs (in cases of malignant moles) may result in symptoms like dyspnea, cough, hemoptysis, chest pain, etc.

Ultrasound Scan

• USS in the first trimester may not be reliable. The typical ‘snowstorm’ appearance occurs mainly in the second trimester, showing a heterogenous mass with no fetal development.



• Large ovarian cysts, called theca-lutein cysts can also be seen. They are often bilateral

Histology

• Definitive diagnosis is made by histological examination of the product of conception.
• Different forms of GTD have distinctive morphological features, depending on which tissues they are derived from.

Serum HCG

Complete blood picture

Renal and Liver function tests

Chest X-ray

Thyroid function test

Supportive (Medical)

Stabilize patient.

• Transfuse for anemia.
• Correct any coagulopathy.
• Treat hypertention.

Watch and prepare for treatment of thyroid storm.

Definitive (Surgical)

• Suction curettage with high pressure pump is the method of choice.
• Intravenous oxytocin should be started at the commencement of Suction curettage.
• All Rh-negative patients should receive Anti-D immune globulin.
• Send Products evacuated for Histology.

1. Serial β–hCG.

• Beginning within 48 hours after evacuation and then at weekly intervals until serum -hCG declines to nondetectable levels on three successive assays.
• (In benign disease, human chorionic gonadotropin concentrations spontaneously return to normal by eight weeks following evacuation of molar pregnancy)
• Monthly for at least 1 year.

2. Gynaecologic examinations.

• Uterine size and presence of adnexal masses (theca lutein cysts) and a careful search of the vulva, vagina, urethra, and cervix should be made for evidence of genital tract metastases.
• Commence one week after evacuation.
• Repeated at 4-week intervals for one year.

3. Chest radiography.

• Pre - evacuation Chest X-ray.
• Then at 3-month intervals for one year

4. Contraception for one year

(Aim of 1, 2, 3, above is to determine if there is need for Chemotherapy)

Excellent following evacuation.

However 10–15% of patients develop malignant form of the disease.

When the plateau of HCG lasts for four measurements over a period of 3 weeks or longer (day1, 7, 14, 21)

Serum level of hCG >20,000 IU/l more than 4 weeks after evacuation

Raised hCG level six months after evacuation

When there is a rise of hCG of three weekly consecutive measurements or longer over a period of 2 weeks or more (days 1, 7, 14)

Histological evidence of Choriocarcinoma

The presence of metastases in brain, liver, gastrointestinal tract, lungs, vulvar or vaginal walls.

Invasive mole

• Villi penetrate deeply: Myometrium, blood vessels

Choriocarcinoma

• Tumor mass is dark-red, hemorrhagic, and nodular

Placenta site trophoblastic tumour

• Deep uterine penetration, myometrial mass may be well localized or ill defined. Hemorrhage is not as conspicuous as in invasive mole or as in choriocarcinoma.

Findings at post evacuation surveillance, OR

Presenting symptoms & signs of metastases -

• Sub-urethral nodule in the vagina
• Hemoptysis
• Abdominal pain/tenderness
• Hematuria
• Seizures
• Coma

Full blood count.

Renal and liver function tests.

Serum HCG.

Chest X-ray.

Ultrasound of pelvis and liver.

Brain MRI or CT Scanning

CT or MRI of other parts of body as indicated

Stage 1: Disease confined to the uterus

Stage 2: GTT extends outside the uterus but is limited to genital structures (vagina, broad ligament, adnexa)

Stage 3: GTT extends to the lungs with or without genital tract involvement.

Stage 4: All other metastatic sites

The goal of the revised FIGO staging is to improve the assessment and clinical management of patients and to unify staging to allow for international comparisons in treatment success.

• Non metastatic disease (stage I).
• Low-risk metastatic - stages II and III (score < 7).
• High-risk metastatic - stage IV (score ≥ 7)

Risk factor score based on the WHO prognostic scoring system.

Low-risk metastatic disease

• Single-agent Chemotherapy with methotrexate or Actinomycin D.

High-risk metastatic disease

Multiagent chemotherapy with or without adjuvant surgery or radiation therapy

High-risk metastatic disease multiagent Chemotherapy could be:

MAC - Methotrexate + Actinomycin D + Cyclophosphomide, OR

EMA-CO: Etoposide + Methotrexate + Actinomycin D – Cyclophosphomide + Oncovin.

Adjuvant surgical procedures that may be needed in hemorrhage or refractory nodule not responsive to Chemotherapy in High risk disease include;

• Hysterectomy
• Hepatic artery embolization
• Craniotomy
• Thoracotomy

Treatment of PSTT

• It is generally resistant to chemotherapy
• Hysterectomy is the recommended route of treatment
• Partial uterine resection involving the tumor is possible if the patient desires future fertility.
• Chemotherapy is indicated in cases of metastatic disease.

Follow-up after treatment for GTT.

• Serum quantitative hCG levels should be obtained at 1-month intervals for 12 months.
• Contraception should be maintained during treatment and for 1 year after completion of chemotherapy.
• Pelvic ultrasound is recommended in the first trimester of a subsequent pregnancy to confirm a normal gestation.
• Serum quantitative hCG level should be determined 6 weeks after any pregnancy.

Malignant non-metastatic disease.

• Quite good, as almost all patients are cured.
• 90% of patients can preserve reproductive function.

Metastatic disease

• Best results are with EMACO chemotherapy and concurrent radiation as indicated.
• About 75% - 85% of patients achieve remission with a 69% salvage rate.