Gestational Trophoblastic Disease General Considerations The classification system of gestational trophoblastic disease is confusing, and terminology varies between countries. For simplistic purposes we classify gestational trophoblastic disease (GTD) as a spectrum of diseases from the benign hydatidiform mole through to the malignant invasive mole, choriocarcinoma and placental site trophoblastic tumour (PSTT). We do not differentiate between GTD and gestational trophoblastic neoplasia (GTN) (142). Molar Pregnancy In part due to the earlier diagnosis of aberrant pregnancies, molar pregnancy these days is diagnosed a lot earlier than a decade ago. Most patients will present with abnormal bleeding. Often an ultrasound is performed to confirm fetal viability, with the surprise finding of a molar pregnancy. Partial moles are usually not suspected preoperatively. Often curettage is performed for a missed abortion and histological review confirms the diagnosis. The uterus may be large for dates, but the majority will be normal or small for dates. Symptomatic theca luteal cysts are not commonly seen at presentation these days. Rarely are hyperemesis or hypertension seen. The majority of women with complete molar pregnancies will follow a benign course after evacuation. Ten percent will develop locally invasive disease (invasive mole) and 5% will have metastatic choriocarcinoma. Ten percent of patients with partial mole will develop persistent, recurrent and invasive disease but no cases of choriocarcinoma have been reported (142). Investigations Prior to Evacuation of Molar Pregnancy Mandatory investigations include a blood group to ascertain Rh status and CXR to exclude pulmonary metastases and a quantitative ß-hCG to document the titre prior to evacuation. Other investigations that may be necessary depending on the clinical scenario include thyroid function tests, coagulation panel, renal and liver function tests and full blood test (142). Management of Molar Pregnancy Due to the real risk of bleeding and perforation, evacuation should be performed by an experienced clinician. The cervix should be dilated to allow the passage of a large suction catheter, preferably 12mm. Suction evacuation should be performed under cover of oxytocin and ergometrine. Serious consideration should be given to undertaking such evacuation under ultrasound guidance. If the cavity has been emptied, there is no reason to perform a sharp curettage afterwards, as this will only increase the risk of perforation, and adds little to the ongoing management. Patient’s who are Rh negative should be given Anti-D globulin. Theoretically in a complete mole, the fetal erythrocytes necessary to sensitize the mother are lacking. However a patient who is Rh negative should be given anti-D immunoglobulin as Rh D antigen has been demonstrated on the trophoblast of invasive and noninvasive molar pregnancies. Hysterectomy should be considered in patients with advanced age, who have completed their family, where there is sepsis, significant bleeding or pathology confirms PSTT or choriocarcinoma. Postmole Surveillance Program After evacuation, patients should be seen weekly and have their care supervised although not necessarily managed by a Certified Gynaecological Oncologist. Quantitative ß-hCG titres should be performed weekly until 3 normal levels have been obtained. Thereafter monthly assessment for 12 months is required. The follow up duration of patients with partial moles is unclear, but we recommend at least 6 months and depending on risk factors may need 12 months of surveillance as do patients with complete moles. In selected patients who are at low risk of developing persistent disease this period of follow-up may be shortened to 6 months if the serum hCG returns to normal within 8 weeks of a curettage. This is based on recent research which noted a very low risk of recurrent disease in these patients. Abnormal regression is indicative of persistent or recurrent disease. Patients should be counseled on the need for adequate contraception during the surveillance period. We recommend where appropriate the oral contraceptive pill. Pregnancies after Hydatidiform Mole Patients with a hydatidiform mole can anticipate normal reproduction in the future without an increased risk for obstetric complications either prenatal or intrapartum. The risk of recurrence is about 1% after one molar pregnancy and 30% after two (143). Persistent GTD Patients who undergo an abnormal regression of their hCG after evacuation are deemed to have persistent GTD. This will manifest as either an increasing or plateauing hCG. Although this group may be considered to have developed “malignant sequelae”, this is based on the future risk of their developing local complications or metastases rather than an actual change in the histology of the lesion. This will occur in 15% of patients who have had molar pregnancies evacuated. Two thirds are invasive moles and one third are choriocarcinoma. Often the histological diagnosis is never confirmed. A risk assessment or prognostic assessment is then performed (Appendix A) (144). Based upon a number of prognostic factors, patients are classified into 2 risk groups. A “low risk group” requiring single agent chemotherapy for management and a “high risk group” who are treated with multiagent chemotherapy. The latter are at high risk of recurrence and chemoresistance. Chemotherapy Single agent therapy includes is predominately methotrexate.  Actinomcyin D also has activity as a single agent. Combination chemotherapy comprises EMA-CO which consists of sequential treatment with etoposide, methotrexate, actinomycin D, vincristine and cyclophosphamide. The selection of agents may be individualized, particularly if chemotherapy has been used previously and cisplatin is frequently included (145-147). Special Circumstances Brain Metastasis Whole brain irradiation in combination with systemic chemotherapy (EMA-CO) has resulted in a 50% survival in patients with brain metastasis. This is virtually identical to results of intrathecal MTX plus systemic chemotherapy reported from the United Kingdom (148). Liver Metastasis Are probably more ominous than brain metastases. About 5-20% of poor prognosis cases have liver metastases and the collected survival rate is 33%. The role of liver irradiation is controversial (149). Asymptomatic Low Levels of ß-hCG For persistently elevated low levels of ß-hCG is it important to exclude phantom hCG by checking urine and serum. With real hCG the tires are positive in both while with phantom hCG the urine is usually negative. For persistently elevated real hCG, exclude uterine disease with (i)TVS and colour flow Doppler (CFD) (ii) hysteroscopy, D+C and (iii) MRI pelvis. When these are negative and the hCG persists then is necessary to exclude mediastinal lesions using CT of chest and choroid and pituitary lesions using MRI. Surgery for High Risk GTD If metastatic disease is excluded, then hysterectomy may be indicated to remove a focus of resistant tumor. It is perform under chemotherapy "window" i.e. administer single agent chemotherapy the night before surgery. Pulmonary wedge resection is commonly utilized to remove distant drug resistant sites.    Regression Curve