Gestational trophoblastic disease
General ConsiderationDefinition 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 placentaComplete mole 46 xx ( problem at time of conception)Partial mole triploidy 69xxy (70%)or 69xyy(30%)Morphology of complete mole
Numerous odematous vesicle appear as bunch of small clear grape no fetal tissueRisk 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 manPrevious 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 HCGPre-eclampsia : before 24 weeksThyroid dysfunction:2% ,molar preg. Associated with high thyroxineEmbolism: 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 tissueProper preparation of patient prior evacuation by full investigation & chest x- rayEvacuation:Suction curettage ( vacuum -60 mm) & send mat. For histopathology uterine stimulate ( pGE2, oxytocin) 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: monthlyTo rule out any vaginal or vulval metastasisSize 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: indicationRaised HCG level 6 months after evacuationHCG plateau in 3 consecutive serum sample
HCG more than 20.000 IU after 4 weeks after evacuationRising HCG in 2 consecutive serum sampleHeavy vaginal bleeding or GI, intraperitonal bleedingPulmonary, vulval or vaginal metastasis unless HCG level is falling
Brain, liver, GI metastasis or lung metastasis more than 2 cm on cxRHistological evidence of choriocarcinoma
Complication of molar pregnancyImmediateMassive bleedingSepsisSevere PERemote ( 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:asiaAge : in old is moreParity: in high paritySocioeconomic : in lowAntecedent preg,: molar 50%, abortion 25%,normal term preg 25%.Maternal blood gr: gr.A high
Clinical features: Vaginal bleedingAmenorrhea: producing HCG from distant tumour metastasisVaginal nodule or abdominal swellingPulmonary metastasis;( dyspnea, hemoptysis)
Staging: no. of factors influence prognosis of persistant GTT
Level of HCG: if it is high 100.000IU before Rx means worse prognosisMetastasis: site (brain, liver) , number, size of largest massAntecedent preg: term preg is worsePreg/ Rx interval : prolong interval (4 months) bad prognosisPrevious unsuccessful chemo therapy : bad ( drug resistant , accumlating drug toxicityAge : more than 40 yr ( bad)Parity : high parity ( bad) Each of the following prognostic factor is given score ranging from ( 0-4 )
4 2 1 0 score - - more than 40 Less than40 age - Term abortion mole Antecedent preg Brainliver GIT Spleenkidney lung Site of metastasis More than 8 5-8 1-4 number
According to this score we divide patients to Low risk patient :score less than or equal 6High risk patient : score more than or equal 7Treatment:ChemotherapySurgicalFollow 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/ IVExcreted in urine , contraindication renal failure
methotrexate Methotrexate is given in alternative day with folinic acidDuring period of therapy ,we should montering HCG ( 2t/wk) ,WBC/ daily, ( less than 1000 stop it), PLT/ daily ( less than 50.000 stop it)
Toxicity of methotrexate Mylo suppression( thrombo- cytopnea, granulocytopnea)Mucus membrane inflammation( stomatitis, conjuctivitis, vaginitis)Skin rashNephrotoxicityheptotoxicity
methotrexate After 8 days coarse of chemtherapy , 1 week rest & then 2nd coarse of RxWe need 2-4 courses to reach undetected level of HCG 2-3 extra courses of treatment is needed ( bec. Approx. 100.000 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)2nd wk ( D8) vincristine / cyclophosphamide
Surgical treatment Uterine perforation by invasive moleUncontrol uterine bleedingDrug 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 relapseMonthly HCG in first year. Then yearly in the next 5 years.