Gestational Trophoblastic Disease

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Nathaniel Amo Jr. BSN 3-A Gestational trophoblastic disease (GTD) is a term used for a group of pregnancy-related tumours.These tumours are rare, and they appear when cells in the womb start to grow out of control. The cells that form gestational trophoblastic tumours are called trophoblasts and come from tissue that grows to form the placenta during pregnancy. There are several different types of GTD. Some, such as molar pregnancy (or hydatidiform mole) are nearly always curable. Others, such a
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   Nathaniel Amo Jr. BSN 3-A Gestational trophoblastic disease (GTD) is a term used for a group of pregnancy-relatedtumours.These tumours are rare, and they appear when cells in the womb start to grow out of control. The cells that form gestational trophoblastic tumours are called trophoblasts and comefrom tissue that grows to form the placenta during pregnancy. There are several different types of GTD. Some, such as molar pregnancy (or hydatidiform mole   )are nearly always curable. Others, such aschoriocarcinoma, are more likely to spread and can bedifficult to treat. Gestational trophoblasts are of particular interest to cell biologists because, likecancer, these cells invade tissue (the uterus), but unlike cancer, sometimes know when to stop.GTD can simulate pregnancy, because the uterus may contain fetal tissue, albeit abnormal. Thistissue may grow at the same rate as a normal pregnancy, and produces chorionic gonadotropin, ahormone which is measured to monitor fetal well-being.While GTD overwhelmingly affects women of child-bearing age, it may rarely occur in postmenopausal women. Types GTD is the common name for five closely related tumours (one benign tumour , and four malignant tumours   ): ã The benign tumour  o Hydatidiform moleHere, first a fertilised egg implants into the uterus, but some cells around the fetus (the chorionicvilli) do not develop properly. The pregnancy is not viable, and the normal pregnancy processturns into a benign tumour. There are two subtypes of hydatidiform mole: complete hydatidiformmole, and partial hydatidiform mole. ã The four malignant tumours o Invasive mole o Choriocarcinoma o Placental site trophoblastic tumour  o Epithelioid trophoblastic tumour All five closely related tumours develop in the placenta. All five tumours arise fromtrophoblastic cells. Thetrophoblast is the membrane that forms the wall of the  blastocystin the early development of the fetus. In a normal pregnancy, trophoblastic cells aid the implantation of the fertilised egg into the uterine wall. But in GTD, they develop into tumour cells.  Incidence Overall, GTD is a rare disease. Nevertheless, the incidence of GTD varies greatly betweendifferent parts of the world. The reported incidence of hydatidiform mole ranges from 23 to 1299cases per 100,000 pregnancies. The incidence of the malignant forms of GTD is much lower,only about 10% of the incidence of hydatidiform mole. The reported incidence of GTD fromEurope and North America is significantly lower than the reported incidence of GTD from Asiaand South America. One proposed reason for this great geographical variation is differences inhealthy diet in the different parts of the world (e.g., carotene deficiency).However, the incidence of rare diseases (such as GTD) is difficult to measure, becauseepidemiologic data on rare diseases is limited. Not all cases will be reported, and some cases willnot be recognised. In addition, in GTD, this is especially difficult, because one would need toknow all gestational events in the total population. Yet, it seems very likely that the estimatednumber of births that occur at home or outside of a hospital has been inflated in some reports. Risk Factors Two main risk factors increase the likelihood for the development of GTD: 1) The woman beingunder 20 years of age, or over 35 years of age, and 2) previous GTD.Approximate numbers of risk: Women under 16 years of age have a six times higher risk of developing a molar pregnancy than those aged 16–40 years, and women 50 years of age or older have a one in three chance of having a molar pregnancy.The ABO blood groups of the parents appear to be a factor in choriocarcinoma development, i.e.women with blood group A have been shown to have a greater risk than blood group O women. Diagnosis Cases of GTD can be diagnosed through routine tests given during pregnancy, such as bloodtests and ultrasound, or through tests done after miscarriage or abortion. Vaginal bleeding,enlarged uterus, pelvic pain or discomfort, and vomiting too much (hyperemesis   ) are thecommonest symptoms of GTD. But GTD also always leads to elevated serum hCG (humanchorionic gonadotropin hormone). Since pregnancy is by far the commonest cause of elevatedserum hCG, clinicians generally first suspect a pregnancy with a complication. However, inGTD, the beta subunit of hCG (beta hCG) is also always elevated. Therefore, if GTD is clinicallysuspected, serum beta hCG is also measured.The initial clinical diagnosis of GTD should be confirmed histologically, which can be done after the evacuation of pregnancy (see «Treatment» below) in women with hydatidiform mole.However, malignant GTD is highly vascular. If malignant GTD is suspected clinically, biopsy iscontraindicated, because biopsy may cause life threatening haemorrhage.  Treatment Treatment is always necessary.The treatment for hydatidiform mole consists of the evacuation of pregnancy. Evacuation willlead to the relief of symptoms, and also prevent later complications.Suction curettageis the preferred method of evacuation.Hysterectomy is an alternative if no further pregnancies are wished for by the female patient. Hydatidiform mole also has successfully been treated withsystemic (intravenous) methotrexate.The treatment for invasive mole or choriocarcinoma generally is the same. Both are usuallytreated with chemotherapy.Methotrexateanddactinomycinare among the chemotherapydrugs used in GTD. Only a few women with GTD suffer from poor prognosis metastatic gestationaltrophoblastic disease. Their treatment usually includes chemotherapy.Radiotherapycan also begiven to places where the cancer has spread, e.g. the brain.Women who undergo chemotherapy are advised not to conceive for one year after completion of treatment. These women also are likely to have an earlier menopause. It has been estimated bythe Royal College of Obstetricians and Gynaecologists that the age at menopause for womenwho receive single agent chemotherapy is advanced by 1 year, and by 3 years for women whoreceive multi agent chemotherapy. Follow up Follow up is necessary in all women with gestational trophoblastic disease, because of the possibility of persistent disease, or because of the risk of developing malignant uterine invasionor malignant metastatic disease even after treatment in some women with certain risk factors.The use of a reliable contraception method is very important during the entire follow up period, because the follow-up depends on measuring hCG. If a reliable contraception method is not usedduring the follow-up, there can be great confusion if hCG rises: Why did it rise? Because the patient became pregnant again? Or because the gestational trophoblastic disease is still present?Therefore, during the prescribed follow up period, the patients must not become pregnant.In women who have a malignant form of GTD, hCG concentrations stay the same (plateau) or they rise. Persistent elevation of serum hCG levels after a non molar pregnancy (i.e., normal pregnancy [term pregnancy], or preterm pregnancy, or ectopic pregnancy[pregnancy taking place in the wrong place, usually in the fallopian tube], or abortion) always indicate persistentGTD (very frequently due to choriocarcinoma or placental site trophoblastic tumour), but this isnot common, because treatment mostly is successful.In rare cases, a previous GTD may be reactivated after a subsequent pregnancy, even after several years. Therefore, the hCG tests should be performed also after any subsequent pregnancy  in all women who had had a previous GTD (6 and 10 weeks after the end of any subsequent pregnancy). Which other women should also undergo hCG testing Women with persistent abnormal vaginal bleeding after any pregnancy, and women developingacute respiratory or neurological symptoms after any pregnancy, should also undergo hCGtesting, because these may be signs of a hitherto undiagnosed GTD. Prognosis and staging Women with a hydatidiform mole have an excellent prognosis.Also women with a malignant form of GTD usually have a very good prognosis.Choriocarcinoma, for example, is an uncommon, yet almost always curable cancer. Althoughchoriocarcinoma is a highly malignant tumour and a life threatening disease, theoverall survivalrateof women who receive early appropriate chemotherapy is almost 90%. There are efforts indeveloping countries to detect choriocarcinoma as early as possible, thereby significantlyreducing the mortality rate also in developing countries.Only a few women with GTD have a poor prognosis, e.g. some forms of stage IV GTN. TheFIGO staging system is used. Becoming pregnant again Most women with GTD can become pregnant again and can have children again. The risk of afurther molar pregnancy is low. More than 98% of women who become pregnant following amolar pregnancy will not have a further hydatidiform mole or be at increased risk of complications.In the past, it was seen as important not to get pregnant straight away after a GTD. Specialistsrecommended a waiting period of 6 months after the hCG levels become normal. Recently, thisstandpoint has been questioned. New medical data suggest that a significantly shorter waiting period after the hCG levels become normal is reasonable for approximately 97% of the patientswith hydatidiform mole. Risk of a repeat GTD The risk of a repeat GTD is approximately 1 in 100, compared with approximately 1 in 1000 risk in the general population. Especially women whose hCG levels remain significantly elevated areat risk of developing a repeat GTD.
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