Gestational trophoblastic disease

General Consideration Definition proliferation abnormalities originating from trophoblast tissue of the placenta Classification : benign (hydatidiform mole) Malignant ( invasive mole, choriocarcinoma)

Hydatidiform mole Abnormal proliferation of placental trophoblastic cells tends to invade myometrium( villi) more than placenta 1.Complete mole 46 xx ( problem at time of conception) 2.Partial mole triploidy 69xxy (70%)or 69xyy(30%)

Morphology of complete mole Numerous odematous vesicle appear as bunch of small clear grape no fetal tissue Risk of progress to persistant GTT 20%

Morphology of partial mole There is fetal & placental tissue ( pregnancy is complicated by hypertension & IUGR)

Epidermiology of molar preg Geographical: asian Diet ( low protein, folic acid, carotane ), low socioeconomic: Maternal age: (14-16years), ( 40years ) Blood group A married group O man Previous molar pregnancy ( 0.5-2%)

Manifestation 1. Clinical presentation Because of more proliferative activity so more exaggeration of signs &symptoms. Vaginal bleeding &anaemia : 90% Anemia is due to bleeding ( IDA), folic acid deficiency from( poor intake,increase requirement to folic acid )

Hyperemsis gravidrum :25%, related to high level of HCG Pre-eclampsia : before 24 weeks Thyroid dysfunction:2%,molar preg. Associated with high thyroxine Embolism: trophoblast tiss. Escape from uterus through venous outflow lead to emboli

DIC: emboli of troph. Tissue release thromboplastin to circulation &stimulate fibrin & PLT deposition ( coagulation failure) 2. Abdominal examination A. uterine enlargement (large for date uterus),doughy in consistancy ( no amniotic fluid), no palpable fetal part or FH.

B. Bilateral ovarian cyst( theca lutein cyst): 25-60%, prolong high level of HCG stimulate ovaries. they regress after evacuation of mole Diagnosis. U/S : echo of vesicle ( snow storm ) Quantative measurement of HCG

treatment Aim: Elimination of all trophoblastic tissue 1.Proper preparation of patient prior evacuation by full investigation & chest x- ray Evacuation: 1.Suction curettage ( vacuum -60 mm) & send mat. For histopathology 2. uterine stimulate ( pGE2, oxytocin) 3.Hysterectomy, if patient 40 years& complete her family.

Follow up: 1. serial quanatative HCG: ( 48 hr. &then every 1 wk ) complete elimination 8-10 wk, until 3 consecutive weeks are normal then do monthly for 6 month ( partial) & for 1 year to complete mole. 2. pelvic examination: monthly To rule out any vaginal or vulval metastasis Size of uterus,presence ovarian cysts &size

3. contraception: for at least 1 year,barrier method is the best, medroxy progesterone inj., low dose estrogen occp ( E = 30 micro g). 4- chemotherapy: indication Raised HCG level 6 months after evacuation HCG plateau in 3 consecutive serum sample

o HCG more than IU after 4 weeks after evacuation o Rising HCG in 2 consecutive serum sample o Heavy vaginal bleeding or GI, intraperitonal bleeding o Pulmonary, vulval or vaginal metastasis unless HCG level is falling

Brain, liver, GI metastasis or lung metastasis more than 2 cm on cxR Histological evidence of choriocarcinoma

Complication of molar pregnancy Immediate Massive bleeding Sepsis Severe PE Remote ( metastasis & malignant 20% of complete mole develop to persistant GTT &4% partial)

Persistant gestational trophoblastic disease Non metastatic (invasive mole) 15% after molar preg. Metastatic (distant) 5%

Incidence& epidemiology : geographical:asia Age : in old is more Parity: in high parity Socioeconomic : in low Antecedent preg,: molar 50%, abortion 25%,normal term preg 25%. Maternal blood gr: gr.A high

Clinical features: Vaginal bleeding Amenorrhea: producing HCG from distant tumour metastasis Vaginal nodule or abdominal swelling Pulmonary metastasis;( dyspnea, hemoptysis)

Staging: no. of factors influence prognosis of persistant GTT Level of HCG: if it is high IU before Rx means worse prognosis Metastasis: site (brain, liver), number, size of largest mass Antecedent preg: term preg is worse Preg/ Rx interval : prolong interval (4 months) bad prognosis Previous unsuccessful chemo therapy : bad ( drug resistant, accumlating drug toxicity

Age : more than 40 yr ( bad) Parity : high parity ( bad) Each of the following prognostic factor is given score ranging from ( 0-4 )

4210score --more than 40 Less than40 age -Termabortionmole Antec edent preg Brain liver GITSpleen kidney lung Site of metastasi s More than number

23 According to this score we divide patients to Low risk patient :score less than or equal 6 High risk patient : score more than or equal 7 Treatment: Chemotherapy Surgical Follow up

Low risk patients_ survival rate 100% Methotrexate( drug of choice) bec. Simplicity& low toxicity ( available antidote) Before give chemotherapy : we should send pat.to full Ix CBC ( WBC,PLT,Hb) LFT, RFT,CXR. It is given parentally IM/ IV Excreted in urine, contraindication renal failure

methotrexate Methotrexate is given in alternative day with folinic acid During period of therapy,we should montering HCG ( 2t/wk),WBC/ daily, ( less than 1000 stop it), PLT/ daily ( less than stop it)

Toxicity of methotrexate Mylo suppression( thrombo- cytopnea, granulocytopnea) Mucus membrane inflammation( stomatitis, conjuctivitis, vaginitis) Skin rash Nephrotoxicity heptotoxicity

methotrexate After 8 days coarse of chemtherapy, 1 week rest & then 2 nd coarse of Rx We need 2-4 courses to reach undetected level of HCG 2-3 extra courses of treatment is needed ( bec. Approx of trophoblastic cell may escape & undetected by HCG). Actinomycin (I.m for 5 days)

High risk patient / EMA/CO chem D1( etoposide, methotrexate, actinomycin) D2( etoposide, folinic acid, actinomycin) 2 nd wk ( D8) vincristine / cyclophosphamide

Surgical treatment Uterine perforation by invasive mole Uncontrol uterine bleeding Drug resistance focus ( HCG is high un stead of chemotherapy or focal lesion increase or plateau in size) Age is more than 40 years & complete her family

Follow up Aim: to detect remission or relapse Monthly HCG in first year. Then yearly in the next 5 years.

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