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Gestational Trophoblastic Disease (GTD) PowerPoint Presentation

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Description : Check out this medical presentation on Gestational Trophoblastic Disease, which is titled "Gestational Trophoblastic Disease (GTD)", to know about Gestational Trophoblastic Disease/ Tumors (GTD/ GTTs), a group of disease originating from trophoblastic cells, including Hydatidiform mole, Invasive mole, Choriocarcinoma and Placental site Trophoblastic Tumor.

Tags : Gestational Trophoblastic Disease, GTD, Tumors, GTT, trophoblastic cells, Hydatidiform mole, Invasive mole, Choriocarcinoma, Placental site Trophoblastic Tumor

Published on : May 18, 2021 | Views : 2190 | Downloads : 9

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Gestational Trophoblastic Disease (GTD) Amr Nadim, MD Professor of Obstetrics & Gynecology Ain Shams Faculty of Medicine [amrnadim@link.net]
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Definition: Gestational Trophoblastic Disease/ Tumors(GTD/ GTTs)is a group of disease originating from trophoblastic cells,including Hydatidiform mole, Invasive mole, Choriocarcinoma and a Less commonly encountered : Placental site Trophoblastic Tumor These are cancers and cancer like conditions of placental elements
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Hhydatidiform mole means that the placenta trophoblastic cells proliferate abnormally: There is stromal edema , With formation of vesicules looking like grape on its appearance. Two types exist: Complete Hydatiform Mole Partial Hydatiform Mole
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Complete Vs Partial Hydatiform Mole Complete hydatidiform mole A sperm has fertilized an “empty” egg (contains no nucleus or DNA). All the genetic material comes from the father’s sperm. Therefore, there is no fetal tissue. Up to 20% of patients with complete moles will need additional surgery or chemotherapy after their initial surgery. A small percentage of complete moles may develop into choriocarcinoma, a malignant form of GTD. Partial hydatidiform mole Two sperm fertilize a normal egg. These contain some fetal tissue mixed in with the trophoblastic tissue. No viable fetus is being formed. Only a small percentage of patients with partial moles need further treatment after initial surgery. ComPartial moles rarely develop into malignant GTD.
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Invasive Mole An invasive mole (formerly known as chorioadenoma destruens) is a hydatidiform mole that penetrates the muscular wall of the uterus (myometrium). These develop in about 20% of women who have had a complete mole removed by curettage. The risk of developing these in women with complete moles is increased if: There is a long time (more than 4 months) between the time periods had stopped and treatment. The uterus has become very large. The woman is older than 40 years. The woman has had GTD in the past.
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Invasive moles can be complete or partial, Complete moles invade much more often than partial nodes. These moles sometimes disappear on their own, but most require treatment with chemotherapy. In about 15% of cases, the tumor spreads through the bloodstream (metastasizes) to other sites, usually the lungs. Pathology: Grossly: different size of vesicles in myometrium,there may be or may not be primary focus in uterine cavity. Microscopically: villous structure and trophoblastic cells proliferation and differentiation Invasive Mole
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Choriocarcinoma Choriocarcinoma is a malignant form of GTD. Most often develops from a complete hydatidiform mole, But it can occur after a normal pregnancy or after an early fetal demise. Rarely, choriocarcinomas can develop in other parts of the body in both men and women. These are not related to pregnancy: ovaries, testicles, chest, or abdomen [mixed germ cell tumor] Nongestational choriocarcinoma tends to be less responsive to chemotherapy and has a less favorable prognosis than the gestational variant. Choriocarcinoma is more likely to spread to organs away from the uterus.
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Pathology Grossly most choriocarcinoma occurs in uterus, the tumor diameter 2-10cm,its color is redin cut section, cancer embolus is often found in parauterine veins,ovarian luteinizing cyst may be formed Microscopic examination:the most obvious difference between choriocarcinoma and common cancer is that the choriocarcinoma does not have tumor intrinsic connective stromal cells nor intrinsic blood vessels. Under microscope the hyperplastic cytotrophoblastic cells and syntrophoblastic cells invade the myometrium and blood vessels accompanied by the bleeding and necrosis,so the cancer cells can not be found in the center of normal tissues We should NOT rely only on histopathology for the diagnosis of Choriocarcinoma
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Placental-site Trophoblastic Tumor Placental-site trophoblastic tumor (PSTT) is a rare form of GTD that develops where the placenta attaches to the uterus. This tumor most often develops after a normal pregnancy or abortion. Most placental-site tumors do not spread to other sites in the body. Sometimes, though, these tumors penetrate the muscle layer of the uterus. Although most forms of GTD are very sensitive to chemotherapy drugs, placental-site tumors are not and, therefore, they must be completely removed by surgery.
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Why..? Complete Mole A sperm cell fertilizes an egg that contains no nucleus. After fertilization, the chromosomes from the sperm duplicate themselves, so there are 2 copies of identical chromosomes that both come from the sperm. Sometimes an abnormal egg without any chromosomes may be fertilized by 2 sperm cells. Again, there are 2 copies of the father's chromosomes and none from the mother, and a complete mole forms. This situation prevents normal development, and no fetus is formed. Instead, a complete hydatidiform mole develops. Partial moles 2 sperm cells manage to penetrate a normal egg at the same time. Now the fertilized egg contains 3 sets of chromosomes (69) instead of the usual 2 sets (46). An embryo with 3 chromosome copies cannot develop into a fully developed infant. This situation leads to an abnormal (malformed) fetus along with some normal placental tissue and a partial hydatidiform mole. Choriocarcinomas can develop when bits of tissue are left behind in the uterus after spontaneous (miscarriage) or intended abortion or after delivery of a baby following an otherwise normal pregnancy. Most develop from persistent hydatidiform moles.
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Risk Factors Age: The risk of complete molar pregnancy is highest in women over age 40 and younger than 20. Age is less a factor for partial moles. all women of childbearing age are at risk for the disease. Pregnancy number: Nulliparous women are at more risk. Having a molar pregnancy before: Once a woman has had a hydatidiform mole, there is about a 1 in 60 chance that she will have another one. It is important to remember that 98% of subsequent pregnancies will be normal. Blood type: Women with blood type A or AB are at slightly higher risk than those with type B or O.
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Risk Factors Birth control pills: Women who take birth control pills are about 50% more likely to get GTD when they do become pregnant. This risk is lower for shorter use of birth control pills and higher for longer use. But the risk is still so low that it doesn’t outweigh the benefit of using the pills. Lifestyle: smoking and drinking alcohol can increase the risk of GTD. Number of sexual partners: Having more than 10 sexual partners increases the risk of GTD. Socioeconomic status: Lower socioeconomic status has been associated with an increased risk.
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Clinical manifestation [Hydatiform Mole] Vaginal bleeding: 97% with complete hydatidiform moles less often with incomplete (partial) moles. Bleeding typically starts during the first trimester, often between the 6th and the 16th week of pregnancy. Women with GTD often pass blood clots or watery brown discharge from the vagina (Prune juice) Sometimes, pieces of the moles resembling a bunch of grapes become dislodged from the uterus and are discharged through the vagina. Women with partial moles are mostly diagnosed after a partial or missed miscarriage. The molar pregnancy is found when the D & C is done to remove the products of conception. Anemia Abdominal swelling: A uterus larger than the period of amenorrhea is seen with complete hydatiform mole. Vomiting: Tedency toward severe emesis gravidarum and sometimes Hyperemesis gravidarum Preeclampsia: Preeclampsia develop during the first or second trimester of a complete molar pregnancy. It affects about 25% of women with complete moles but only about 4% of women with partial moles. Hyperthyroidism: Hyperthyroidism (overactivity of the thyroid gland) occurs in about 7% of women with complete hydatidiform moles. Symptoms of hyperthyroidism include rapid heartbeat, warm skin, and mild tremors (shaking).
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There is a history of: A complete mole and less commonly after a partial mole. The tumors can also develop after a normal pregnancy, ectopic pregnancy or miscarriage. Bleeding: The most common symptom is vaginal bleeding. Rarely, the tumor penetrates the uterine wall with development of internal hge Infection: Infection producing a discharge from the vagina, crampy pain in the pelvic region, and fever. Abdominal swelling: Enlarged uterus Theca-lutein cysts Vaginal mass/Ulcer. Lung symptoms after metastasis. Symptoms of distant spread: Brain GIT Clinical manifestation [Invasive Mole and Choriocarcinoma]
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Bleeding: Vaginal Bleeding. If the disease penetrates the uterine wall, there will be bleeding into the abdominal cavity along with severe abdominal pain. Persistent abdominal swelling Clinical manifestation [Placental Site Tumor]
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Investigations Blood Tests Beta subunit hCG Diagnostic Prognostic HCG resolution law: Normally after emptying the mole, the β-HCG regression curve is steadly decreased,and reach normal level within 9~14 weeks Persistent mole: if the HCG is still positive 3 months after the mole is completely emptied,called persistent mole Liver and kidney function tests Blood cell counts can detect anemia and leucopenia. Imaging Studies Ultrasonography (ultrasound): Ultrasound can identify most cases of GTD.. In a normal pregnancy, ultrasound imaging would show a picture of the developing fetus In a molar pregnancy, however, the ultrasound shows that there is no fetus. (The rare exception, occurring in less than 1% of cases, would be a "twin" pregnancy in which one of the twins is a normal fetus and the other is a hydatidiform mole.) Instead, the ultrasound detects the large, grape-like swollen villi that are typical of GTD. Ultrasound is used to help diagnose a mole and find out if it is invading local tissues. More imaging tests will be done if after the mole has been removed and the blood levels of HCG haven’t disappeared
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The Snow storm appearance
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Investigations Chest x-ray Computed tomography (CT) Magnetic resonance imaging (MRI) Positron emission tomography (PET)
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Gestational Trophoblastic Disease Classification Systems AgeScore 40 or younger 0 Older than 40 1 Prior PregnancyScore Hydatidiform mole 0 Abortion 1 Birth (term) 2 Time from end of pregnancy Score Less than 4 months 0 4 - 6 months 1 7 - 12 months 2 More than 12 months 4 HCG levels (mIU/mL) in bloodScore Less than 1,000 0 1,000 - 9,999 1 10,000 - 100,000 2 More than 100,000 4 Largest tumor, including the original one in the uterusScore Less than 3 cm (1.2 inches) 0 3 - 5 cm 1 More than 5 cm (2 inches) 2 Site of metastasesScore Lung 0 Spleen, kidney 1 Gastrointestinal tract 2 Brain, liver 4 Number of metastases found Score 1 – 4 1 5 – 8 2 More than 8 4 Prior failed chemotherapyScore Single drug 2 2 or more drugs 4 Prognostic Scoring System
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Risk LevelScore Low risk 1 - 7 points High risk 8 or more points
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Anatomic Stage Of Trophoblastic Cell Tumor I : tumor is located in uterus II: tumor spread to adnexa,vagina,broad ligament III: tumor spread to lung,there is or not tumor in reproductive system IV : metastasis to other organs
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T (Tumor) Stages T0: The original tumor can no longer be found. T1: The tumor is only in the uterus. T2: The tumor has spread to local tissues around the uterus (ovary, tubes, and/or vagina). M (Distant Metastases) Stages M0: No distant spread M1a: Lung metastases M1b: Other distant metastases Stage I: T1, M0: The tumor has not spread outside the uterus. Stage IA: Low risk (If your prognostic score shows you are low risk, your stage is Stage 1A.) Stage IB: High risk (If your prognostic score shows you are high risk, your stage is Stage 1B.) Stage II: T2, M0: The cancer has spread outside the uterus but is limited to the genital structures (vagina or pelvis or both). Stage IIA: Low risk Stage IIB: High risk Stage III: Any T, M1a: The cancer has spread to the lungs; it may or may not also involve genital structures such as the vagina or vulva. Stage IIIA: Low risk Stage IIIB: High risk Stage IV: Any T, M1b: The cancer has spread distantly to other organs (such as the brain, liver, kidneys, and/or gastrointestinal tract). Stage IVA: High risk Stage IVB: Low risk
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[Prognosis]: complete mole has the latent risk of local invasion or telemetastasis, research proved that after emptying the mole , the rate of uterine invasion or telemetastasis is 15% and 4% respectively. If the patient has the following high-risk factors,the risk of local invasion or telemetastasis may increase 10 times. The high-risk factors includes: β-HCG>100000IU/L; Uterine size is obviously larger than that with the same gestational time. Theca lutein cyst is >6cm. If age >40 years old,the risk of invasion and metastasis may be 37%, If >50 years old,the risk of invasion and metastasis may be 56%. Repeated mole:the morbidity of invasion and metastasis increase 3~4 times.
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Management Emptying uterine cavity: once the diagnosis is confirmed the uterine cavity should be emptied as soon as possible uterine aspiration and curettage application of oxytocin during operation indication of the second curettage Hysterectomy over 40 years old with high-risk factors uterine size is over 14 gestational weeks
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Preventive chemotherapy: the malignant change rate is 14.5% over 40 years old the β-HCG is over 100kIU/L before emptying mole the HCG regresion curve is not progressively declined uterus is obviously larger than the size of the amenorrhea luteinizing cyst is >6cm there is still over hyperplasia of trophoblastic cells in the second curettage no follow up conditions
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follow up… Regular follow up can find persistent or metastatic trophoblastic cells tumor HCG measurement: after emptying the mole ,the HCG should be measured once a week until it is to the normal level follow up: once a week in the first 3 monthes, then once / 2 weeks in the next 3 monthes and once a month for half a year, once half a year in the second year, and totally follow up for 2 year Overall, one should look for :HCG, abnormal vaginal bleeding, cough, hemoptysis, metastatic symptoms, gynecologic exam- ination, pelvic ultrasound and chest x-ray. The hydatidiform mole patients should take contraception for 2 years after treatment,condom is the best but COCs are an equal good option
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Chemotherapy As a general rule, women who have metastatic disease and are classified as low risk are given a single chemotherapy drug. Women with one or more risk factors usually receive combinations of drugs, often at higher doses. The drugs given may include methotrexate (often combined with leucovorin), actinomycin-D, cyclophosphamide (Cytoxan), vincristine, etoposide, and cisplatin. Chemotherapy with methotrexate alone will be used in most women with good-risk disease. The methotrexate is injected into a vein or a muscle every day for 5 days. After a 9-day "rest period," the treatment is repeated. These cycles continue until remission occurs. Folinic acid or leucovorin reduces the side effects of methotrexate. In this course of treatment (regimen), methotrexate is given on days 1, 3, 5, and 7, and leucovorin is given on days 2, 4, 6, and 8. Each cycle has 8 days of drug treatment, followed by a 7-day rest period. The cycles are repeated until blood levels of HCG remain normal for a few weeks. This method may reduce the risk of side effects. However, it involves more treatment days, so it may be less convenient, and the persistence rate is higher than methotrexate given on a daily basis. The major side effects of methotrexate are diarrhea and sores in the mouth. Actinomycin-D (sometimes called dactinomycin) is the first choice of chemotherapy for GTD in patients who also have liver or kidney disease because methotrexate is toxic to the liver and kidneys and this drug is not. It is usually given in a vein (intravenously or through an IV) every day for 5 days, followed by 7 days without treatment. These cycles are repeated until HCG levels have stayed in the normal range for several weeks. Actinomycin-D can cause fairly severe nausea and vomiting.
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Chemotherapy Women with higher-risk disease will receive combinations of drugs such as methotrexate and actinomycin together, along with a third drug such a cyclophosphamide. Cyclophosphamide can cause some nausea and hair loss. It can also cause bladder irritation. Another drug, etoposide, may also be added to the regimen or used instead of cyclophosphamide. Etoposide treatment has been occasionally associated with the development of leukemia several years later. Other drugs that are used are vincristine and cisplatin. These drugs can be neurotoxic. Patients will experience tingling and numbness, particularly in the hands and feet. Cisplatin can also cause hearing loss and kidney damage. Depending on the drugs used, other possible side effects include skin changes, fever, and problems with the heart, nervous system, ears, or kidneys.
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Hysterectomy …?
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Radiation Usually radiation isn’t used for treatment of GTD unless it has spread and is not responding to chemotherapy. Then radiation may be used to treat sites where the cancer may be causing pain or other problems. It will also be used when GTD has spread to the brain. Treatment with radiation begins with the first dose of combination chemotherapy. The type of radiation therapy used in treating GTD is called external beam therapy.
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Treatment options…Stage X Stage
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Additional lines of treatment
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Could it be early diagnosed?
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Could it be prevented?
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The pregnancy should be allowed to proceed if the mother wishes, following appropriate counselling. Twins, when there is one viable fetus and the other pregnancy is molar….
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The probability of achieving a viable baby is 40% and there is a risk of complications such as pulmonary embolism and pre-eclampsia. Twins, when there is one viable fetus and the other pregnancy is molar