Math Quiz: Basic Operations and Concepts

Gestational Trophoblastic Disease (GTD)

• GTD arises from abnormal placenta, encompassing a spectrum of pre-malignant to malignant conditions.
• Epidemiology of GTD varies geographically, potentially due to difficulties in obtaining accurate data.
• Molecular genetic studies aid in diagnosis alongside histology.
• Earlier detection of molar pregnancies through ultrasound improves clinical outcomes.
• Human chorionic gonadotropin (hCG) monitoring is crucial for early diagnosis of gestational trophoblastic neoplasia (GTN).
• The duration of hCG monitoring depends on histological type and regression rate.
• Low-risk GTN (FIGO Stages I-IIlt, score <7) is usually treated with single-agent chemotherapy but may need additional agents, achieving high survival rates.
• High-risk GTN (FIGO Stages II-III, score ≥7 and Stage IV) requires multiagent chemotherapy, potentially with surgery or radiation, to achieve around a 90% survival rate.

GTD Spectrum

• GTD includes pre-malignant (partial hydatidiform mole [PHM] and complete hydatidiform mole [CHM]) and malignant (invasive mole, choriocarcinoma, placental site trophoblastic tumor [PSTT], epithelioid trophoblastic tumor [ETT], and atypical placental site nodule [APSN]) conditions.
• The GTD spectrum has recently expanded to include APSN, with 10-15% coexisting or developing into PSTT/ETT.

Complete Mole (CHM)

• Characterized by:
  • Absence of fetal parts
  • Absence of red blood cells (RBC)
  • Absence of amniotic sac
  • Absence of placenta.
• Genetically diploid, with all chromosomes paternally derived in 90% of cases.
• Can arise from monospermic fertilization (10%)

Partial Mole (PHM)

• Characterized by:
  • Presence of fetus
  • Intrauterine growth restriction (IUGR)
  • Congenital malformations.
• Genetically triploid (69XXX or 69XXY), less commonly 69XYY).
• Arise from fertilization of an ovum with two sperm.

Risk Factors for Hydatidiform Mole

• Most important risk factor is a previous history of molar pregnancy.
• Risk of molar pregnancy increases with age (extremes of reproductive age).
• Prior molar pregnancy increases the risk tenfold.

Clinical Features of Molar Pregnancy

• Enlarged uterus with a doughy feel
• Absence of fetal parts and heart
• Human chorionic gonadotropin (hCG) hyperemesis gravidarum
• Presence of theca lutein cysts
• Severe preeclampsia or early onset preeclampsia

Cytogenetics of Gestational Trophoblastic Neoplasms (GTN)

• Complete mole (CHM), typically diploid, with 46,XX chromosomes inherited paternally.
• Partial mole (PHM), triploid, with maternal and paternal genetic input.
• Hydropic spontaneous abortion usually has 46,XX or XY chromosomes from both parents.

Choriocarcinoma

• Grossly characterized by large, hemorrhagic, and necrotic tumor masses occurring in the uterus and potentially other sites including tubes, ovaries lungs, liver, vagina, spleen, kidneys, bowel, or brain.
• Microscopically features an absence of chorionic villi with an intermediate trophoblast, and cytotrophoblast cells rimmed by syncytiotrophoblasts with areas of necrosis and hemorrhage.

Placental Site Trophoblastic Tumor (PSTT)

• Grossly appears as nodular masses (1–10 cm) in the myometrium, sometimes invading deep into the myometrium.
• Histologically characterized by mononuclear intermediate trophoblast with a moderate amount of eosinophilic/clear cytoplasm and round nuclei, often with areas of extensive necrosis.

Epithelioid Trophoblastic Tumor (ETT)

• Grossly, white-tan to brown discrete nodules/cystic hemorrhagic masses invading surrounding tissues, typically in cervix or lower segment of uterus.
• Histologically characterized by islands of relatively uniform intermediate trophoblast cells with moderate eosinophilic/clear cytoplasm and round nuclei, often with extensive necrosis.

Complications of Molar Pregnancy

• Bleeding, ranging from spotting to profuse hemorrhage.
• Embolism.
• Perforation.
• Progression to GTN.

Management of Molar Pregnancy

• Preferred treatment is suction evacuation and curettage (under ultrasound guidance) independently of uterine size, with 12-14 mm suction cannula ideally used.
• Oxytocics may be used after evacuation, usually not before.
• Second uterine evacuation may be performed in cases with residual tissue, significant bleeding or high hCG levels that are not decreasing.
• Often, hysterectomy is considered an alternative to suction curettage for childbearing-complete women with uncontrolled bleeding or other complications.
• Additional regimens are often suggested for high-risk patients, such as prophylactic methotrexate or actinomycin to reduce chances of post-molar GTN.

Postmolar Follow Up

• Continued monitoring of hCG levels for 6 months after normalization is standard, with more frequent checks for the first few weeks after evacuation until hCG is normal.
• 1 year of follow-up monitoring is common for both low or high risk patients..

Chemotherapy Response/Duration

• Chemotherapy response is monitored by measuring serum hCG levels.
• Adequate response is defined as a 50% reduction in consecutive weekly serum hCG measurements.
• Treatment is continued until hCG is within normal levels and then for a further 6 weeks.

Post-Chemotherapy Sequelae and Follow Up

• After chemotherapy completion, frequent hCG measurements are essential, usually weekly until 6 consecutive normal results, then biweekly, and after that monthly for a full year.

Pregnancy after Chemotherapy

• Patients are advised not to become pregnant for at least 12 months after chemotherapy completion.
• Follow-up blood tests (serum/urine hCG) 6 weeks and 10 weeks after delivery are recommended to monitor future pregnancies for recurrence or new GTN.

Fertility/Congenital Anomalies

• Neither low-risk nor high-risk chemotherapy affects fertility and incidence of congenital abnormalities in subsequent pregnancies significantly.

Early Onset Menopause

• Low-risk regimens, like methotrexate, are linked to earlier onset of menopause (by 1 year).
• High-risk regimens, including etoposide, may cause earlier onset of menopause (by ~3 years).

Follow Up after treatment

• After GTN treatment, continuous hCG monitoring regularly for at least 12 months is important to catch any relapses that may occur.

High Risk GTN

• Approximately ~5% of Gestational Trophoblastic Neoplasms are classified as high-risk.
• These individuals have a higher score (7 or more).

Molar Pregnancy Complications

• Most common complication of evacuation is hemorrhage.

Diagnosing Gestational Trophoblastic Disease (GTD)

• Ultrasound helps detect abnormal pregnancies.
• Histological examination of the pregnancy tissue is used to confirm.
• The karyotype of the cells can be analysed (blood tests)

Indications for Chemotherapy

• Some of the indications for chemotherapy include
• Plateauing hCG
• Rising hCG
• Elevated hCG concentrations (>20,000 IU/L)4 weeks after evacuation,
• Evidence of metastasis.

Treatment of GTN (Gestational Trophoblastic Neoplasms)

• The primary treatment approach for GTN is chemotherapy. The optimal regimen is determined by the patient's FIGO prognostic score and stage.

GTD Prognostic Scores

• WHO score or FIGO score predicts the likelihood of resistance to monotherapy (methotrexate or actinomycin D).

High Risk GTN Treatment

• For high-risk GTN, the regimen EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine) is frequently used, and survival rates are often quite high.
• In the case of resistances, alternatives like TE/TP (paclitaxel/cisplatin alternating with etoposide) and other high-dose regimens (with supportive care) may be necessary, and sometimes, surgical salvage may provide treatment success.

Test your knowledge with this math quiz covering basic operations, area calculations, equation solving, and derivatives. Each question challenges your understanding of fundamental math concepts, useful for students in middle or high school.