Update on the diagnosis and management of gestational trophoblastic disease

Abstract

Gestational trophoblastic disease (GTD) arises from abnormal placenta and is composed of a spectrum of premalignant to malignant disorders. Changes in epidemiology of GTD have been noted in various countries. In addition to histology, molecular genetic studies can help in the diagnostic pathway. Earlier detection of molar pregnancy by ultrasound has resulted in changes in clinical presentation and decreased morbidity from uterine evacuation. Follow‐up with human chorionic gonadotropin (hCG) is essential for early diagnosis of gestational trophoblastic neoplasia (GTN). The duration of hCG monitoring varies depending on histology type and regression rate. Low‐risk GTN (FIGO Stages I–III: score <7) is treated with single‐agent chemotherapy but may require additional agents; although scores 5–6 are associated with more drug resistance, overall survival approaches 100%. High‐risk GTN (FIGO Stages II–III: score >7 and Stage IV) is treated with multiple agent chemotherapy, with or without adjuvant surgery for excision of resistant foci of disease or radiotherapy for brain metastases, achieving a survival rate of approximately 90%. Gentle induction chemotherapy helps reduce early deaths in patients with extensive tumor burden, but late mortality still occurs from recurrent resistant tumors.

Evaluation of High-Dose Vitamin A Treatment in Postmolar Patients with Low and Plateauing Serum Human Chorionic Gonadotropin Levels

“…Clinically (external validity), our treatment of women with a molar pregnancy and persistent L&P serum hCG levels using HD Vit-A resulted in a 3-fold increase in the number of cases of spontaneous remission, a finding that is in agreement with that reported by Andrijono et al 14 However, those authors used HD Vit-A for patients with complete HM since uterine evacuation to GTD outcome, which led to a measurement bias in their results, as they did not include the high percentage of expected spontaneous remission ($ 80%), as well as the possible risks of HD Vit-A supplementation for long periods. [1][2][3][4][5][6][7] For patients initially treated with HD Vit-A in our study, even in cases that later required ChT, the prognosis of treatment outcome was similar to that of patients that underwent initially expectant management after the diagnosis of persistent L&P serum hCG levels. This may be assigned to the short duration of HD Vit-A use (median of 40 days), which did not have any significantly important effects on time to ChT initiation, WHO/FIGO prognostic risk score, or even response to ChT regimens in the group of patients that progressed to GTN when compared with those patients that underwent expectant management initially.…”

“…Gestational trophoblastic diseases include six clinical and pathological entities with different rates of remission, invasion and metastatic spread, from benign forms, such as the complete and partial hydatidiform moles (HM), to malignant forms, classified as gestational trophoblastic neoplasia (GTN), which include invasive HM, choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor. [1][2][3][4] Human chorionic gonadotropin (hCG), a hormone produced by the placenta in any type of pregnancy, is the biologic tumor marker of GTD. Quantitative serum hCG testing, an aid in the diagnosis of HM and the pillar of postmolar follow-up, provides information that may be used to predict cases that will go into spontaneous remission or, on the contrary, that will develop GTN.…”

Choriocarcinoma associated with ectopic pregnancy. A case report

“…The most common site of origin of Choriocarcinoma is uterus and occurs mainly a er the malignant transforma on of molar pregnancy, but some mes it has been seen a er term pregnancy, spontaneous abor on 1,2,4 or ectopic pregnancy at various sites. Choriocarcinoma 3,6 a er an ectopic pregnancy (0.76% to 4%) is a rare en ty. The reported incidence of ectopic tubal choriocarcinoma is approximately one in 5333 tubal pregnancies and 1.5/1,000,000 1,[3][4][5]7 births.…”

“…Mul agent chemotherapy is required only in the cases where there is a significant eleva on in hCG level, development of metastasis or resistance to sequen al single agent chemotherapy. Higher risk score (5)(6) and clinicopathological diagnosis of choriocarcinoma are both associated with an increased risk of resistance to single agent chemotherapy and there should me lower threshold for mul agent chemotherapy in this subset of low risk pa ents.High risk GTN are treated with the mul agent chemotherapy (EMA-CO chemotherapy, but there are subset in the group also called as ultra-high risk GTN (risk score 13 or more, liver/brain or extensive metastasis) do poorly when treated with the first line chemotherapy. Besides chemotherapy, surgery has important role in controlling the bleeding and in resec on of the isolated drug- 4,6 resistant tumor.…”

Macrophage migration inhibitory factor is differentially expressed in normal and choriocarcinoma trophoblast cells

“…However, it has high metastatic potential and a pronounced vascular invasion, and as a result, many choriocarcinomas are hemorrhagic [2]. It often invades the uterus and surrounding organs, and usually gives distant metastasis, particularly to the lung and brain, but can also metastasize to liver, spleen, kidneys and bowels [2,3]. Molecular mechanisms and sequential events leading to the pathogenesis of the gestational diseases remain largely unknown.…”