GTD

• Gestational Trophoblastic Diseases


  A group of tumors typified by abnormal trophoblast proliferation from the placenta
• Incidence of Gestational Trophoblastic Diseases:
• Human chorionic gonadotropin (hCG)


  Peptide hormone produced by trophoblast of placenta, essential for GTD diagnosis, management and surveillance
• Classification of Gestational Trophoblastic Diseases


  • Hydatidiform mole
  • Non-molar trophoblastic malignant disease
• Hydatidiform mole


  Non-invasive and localized tumors that result from chromosomally abnormal fertilization, which cause proliferation of trophoblastic tissues
• Types of Hydatidiform mole

  • Benign: Complete H. Mole, Partial H. Mole
  • Malignant: Invasive mole
• Complete Hydatidiform Moles


  • An empty ovum + 2 sperms = Normal 46 chromosome, Fetus absent, 6-32% chance of malignancy, Trophoblast proliferation and villi with stromal edema
• Gross findings of Complete Hydatidiform Moles:
• Microscopic findings of Complete Hydatidiform Moles:
• Partial Hydatidiform Moles


  A haploid ovum + 2 sperms (diandry) = Triploid karyotype, Fetus or fetal tissue present, Rarely malignant <5%, Focal and less advanced hydropic or hydatidiform changes
• Pathogenesis of Partial Hydatidiform Moles:
• Clinical Findings of Hydatidiform Mole

  • Amenorrhea, Vaginal bleeding, Uterine bleeding, Anemia, Acute abdomen, Passage of Vesicular tissue from vagina, Excessive Uterine enlargement, Presence of multiple theca lutein cyst, Preeclampsia, Nausea/Vomiting, Hyperemesis gravidarum, Hyperthyroidism, Pulmonary insufficiency
• Diagnosis of Hydatidiform Mole


  • Serum Beta hCG, Pelvic Sonography, Chest Radiograph, Cytogenetic and Molecular biological examinations, Laboratory Examinations
• Preoperative Management of Hydatidiform Mole


  CBC, Serum beta hCG, Creatinine, Electrolytes, Hepatic aminotransferase levels, TSH, ft4, Blood typing and Rh, Chest X-ray, Consider hygroscopic dilators, Identify possible complications

  
• Ploidy studies


  Complete moles and non-molar pregnancies with hydropic placental degeneration are both diploid
• p57KIP2 immunostaining


  • Nuclear protein p57KIP2 is only expressed in maternally donated genes
  • Complete mole - negative
  • Partial mole - positive (Mirrors presence of maternal component)
• Laboratory Examinations


  • CBC with Differential and platelet counts
  • Blood typing
  • Clotting Function studies
  • Liver Function studies (ALT, AST)
  • Renal Function studies (BUN and Crea)
  • Thyroid Function studies (FT4, TSH)
  • Urinalysis
• Preoperative


  • CBC
  • Serum beta hCG
  • Creatinine
  • Electrolytes
  • Hepatic aminotransferase levels
  • TSH, ft4
  • Blood typing and Rh
  • Chest X-ray (most recommended imaging)
  • Consider hygroscopic dilators
• Identify possible complications: preeclampsia, hyperthyroidism, anemia, electrolyte depletion (from hyperemesis), and metastatic diseases
• Intraoperative


  • Large bore IV catheters
  • Regional or general anesthesia
  • Oxytocin (20 units in 1L)
  • Other uterotonic: methylergometrine maleate, Carboprost tromethamine, Misoprostol
  • Karman cannula
  • Consider sonography machine
• Post evacuation


  • Anti-D immunoglobulin (Rhogam) if RhD negative
  • Initiate effective contraception
  • Review pathology report
  • Serum hCG levels: within 48 hours of evacuation, weekly until detectable then monthly for 6 months, Monthly for 6 months (in partial mole) or 1 year (in complete mole)
• Reliable contraceptives


  • Combination hormonal contraception or injectable medroxyprogesterone acetate
  • IUDs: not used until hCG levels are undetectable to avoid risk of uterine perforation if there is an invasive mole
  • Barrier methods: not recommended due to high failure rates
• Evaluation of Metastases


  • CBC, coagulation profiles, renal and liver function, blood type and antibody screen and pre-therapy beta-HCG levels
  • Chest X-ray, CT of the head, chest, abdomen, pelvis and ultrasound of the pelvis
• No metastatic disease found (only focal malignancy)

  • Chemotherapy - IM methothrexate
  • Surgical - Hysterectomy
• Median time to resolution


  • Complete mole = 9 weeks
  • Partial mole = 7 weeks
• Maternal deaths from molar pregnancies are rare
• Recognition and Treatment of Medical Complications

  • Anemia
  • Preeclampsia
  • Hyperthyroidism
  • Electrolyte Imbalance
  • Hyperemesis Gravidarum
  • Pulmonary Insufficiency
  • DIC
• Molar Evacuation

  • Suction Curettage
  • Hysterectomy with mole-in-situ
• Theca lutein cysts are best left alone; regresses spontaneously (8-12weeks post evacuation)
• Identification of Patients at risk for Malignant Degeneration


  • Advanced Maternal Age >35yo
  • Gravidity >4
  • Uterine size >6weeks
  • Serum b-hCG >100,000mIU/mL
  • Theca Lutein Cysts >6cm
  • Any Medical Complication: Pre-eclampsia, thyrotoxicosis, Pulmonary Insufficiency, DIC
  • Poor compliance to follow-up

  
• Chemoprophylaxis


  Methotrexate (IV not orally given) and Actinomycin D
• Contraindications for Chemoprophylaxis


  • Hgb <100g/L, Hct <0.3, WBC <3x109L, Platelet count <109L
  • Any active infection
  • Presence of liver or renal dysfunction
  • Known allergy to drug
• Post-evacuation Follow up

  • B hCG follow up: one week after molar evacuation then every 2 weeks until normal (5mIU/mL), after 3 consecutive normal levels, once a month x 6months
  • Contraception: Low dose combined oral contraceptive pill is preferred
• Molar Pregnancy Termination


  • Suction curettage: Preferred treatment regardless of uterine size, Appropriately typed and cross matched blood should be available prior, Oxytocin should be started to limit bleeding, Patient is in semifowlers dorsolithotomy position, Cervix is mechanically dilated, Intraoperative sonography is recommended, Uterotonic agents given if bleeding continues
  • Hysterectomy in situ: for women who finished child bearing, Theca lutein cysts seen during this procedure do not require removal since they spontaneously regress
• Hysterotomy and use of oxytocin or prostaglandin (Misoprostol) are not recommended due to risk of significant hemorrhage, higher incidence of post molar GTD, incomplete evacuation, and need for blood
• Indications for Immediate Referral to a Trophoblastic Disease Specialist


  • High BhCG beyond 4 weeks post evacuation (serum; 20,000mIU/mL; urine: 30,000mIU/mL)
  • Persistently elevated BhCG at 14weeks post evacuation
  • A rise in BhCGof 10% or greater (two consecutive determinations)
  • Plateauing of BhCG (<10% fall or rise) at any time after evacuation (minimum of 3 consecutive determinations)
  • Clinical or histological evidence of metastasis at any site
  • Elevation of a previously normal BhCG after evacuation, provided not pregnant
• Gestational Trophoblastic Neoplasia


  • Malignant form of gestational trophoblastic disease (GTD)
  • Aggressive invasion into myometrium and propensity to metastasize
  • Irregular bleeding with uterine sub-involution = most common finding

  
• Incidence


  • Europe and South America: 1/40,000 pregnancies
  • Southeast Asian: 3.3-9.2/40,000 pregnancies
  • Philippine National Prevalence Rate: 22.4/40,000 pregnancies
• Causative Pregnancy


  • H mole - 65%
  • Abortion - 20%
  • Term Pregnancy - 15%
• Classification


  • Invasive mole
  • Choriocarcinoma
  • Placental site trophoblastic tumor
  • Epithelioid trophoblastic tumor