Objective: This study aimed to determine if the beta-human chorionic gonadotropin (hCG) levels during the first 5 weeks after a molar evacuation predict progression to gestational trophoblastic neoplasia (GTN). Materials and Methods: This was a retrospective cohort study of complete mole cases managed at a Philippine tertiary hospital from January 2009 to December 2018. Extracted data were analyzed using applicable statistical tools. The level of significance was set at a P < 0.05 using two-tailed comparisons. Results: One hundred and fifty-five complete patient records were available for review. Disease progression in 15.48% of cases while regression in 84.52% were noted. Uterine size was larger in those who eventually had postmolar GTN (t: −3.12, df: 32.64, P: 0.01). Analysis of the receiver operating characteristic curve showed that optimum cut-off levels for predicting GTN at 1, 3, and 5 weeks after evacuation were 4,152 mIU/ml (sensitivity: 50%, specificity: 94.7%, area under the curve [AUC]: 0.75), 804 mIU/ml (sensitivity: 62.5, specificity: 96.9%, AUC: 0.94), and 541 mIU/ml (70.8%, specificity: 97.7%, AUC: 0.96), respectively. Conclusion The level of hCG within the first 5 weeks after molar pregnancy evacuation is predictive of progression to GTN.
Gestational Trophoblastic Disease ; Hydatidiform Mole

Background: Gestational trophoblastic neoplasia (GTN) is considered one of the most curable malignancies, especially when diagnosis and treatment are commenced early. Identifying predictors for the development of GTN will enable prompt management equating to an excellent prognosis. Objectives: The objectives of this study were to determine the validity of uterine artery Doppler parameters (UADPs) as predictors for postmolar GTN, compare UADP values before and after evacuation, determine cutoff values and relationship with beta‑human chorionic gonadotropin (hCG) levels. Materials and methods: This was a prospective cohort study, which included histopathologically confirmed hydatidiform mole (HM) patients who underwent suction curettage. UADPs (pulsatility index (PI), resistive index, and systolic/diastolic [S/D] ratio) were measured preevacuation, 4 weeks postevacuation, and 6 weeks postevacuation. Patients were followed up to determine whether they will develop postmolar GTN or not. Results: A total of 31 HM patients were admitted during the study period, 84% (26/31) of whom underwent suction curettage. Of these, 92% (24/26) had histopathology of complete HM and were recruited. However, only 17 patients followed up and completed the study. Results showed that there was an increasing trend of the UADP from preevacuation to 6 weeks postevacuation and the trend between those with and without postmolar GTN was statistically significant. There was also an inverse relationship between the UADP and baseline β‑hCG values. UADP showed lower values among patients who developed postmolar GTN compared to those who did not. The cutoff values recommended by the area under curve (AUC) that can be a possible predictor were 4th‑week right PI of 2.14 (AUC = 0.71) and right S/D ratio of 2.60 (AUC = 0.73) and 6th‑week left PI of 2.80 (AUC = 0.70) and right PI of 2.53 (AUC = 0.74). Conclusion Neoangiogenesis, a hallmark of malignancy, is correlated with invasive disease and will show increased myometrial vascularization with lower uterine artery indices. Doppler ultrasound may be a useful tool for postmolar follow‑up and GTN diagnosis. However, the small sample size in this study is a limitation and a larger multicenter study is recommended.
Gestational Trophoblastic Disease ; Hydatidiform Mole

Background: During postmolar evacuation surveillance, beta-human chorionic gonadotropin (β-hCG) regression levels can predict invasive disease while Doppler ultrasound can assess in vivo tumor neovascularization and quantify uterine blood supply. As an ancillary tool to β-hCG monitoring, ultrasound can detect the early presence of viable trophoblastic tissues and identify patients at risk of developing postmolar gestational trophoblastic Neoplasia (PMGTN). Objective: The objective of this study was to correlate uterine artery Doppler ultrasound with β-hCG levels during pre- and postmolar evacuation surveillance among patients with complete mole. Materials and Methods: A cohort of patients with sonographic diagnosis of complete hydatidiform mole and managed with suction curettage in the same institution were prospectively followed up after evacuation. The pre- and postmolar evacuation surveillance period was at days 1, 7, 14, 21, 28, and 35. Monitoring of serum β-hCG levels was based on the standard regression curve. For Doppler ultrasound parameters, monitoring of the systolic/diastolic (S/D) ratio, pulsatility index (PI), resistance index (RI), and peak systolic velocity (PSV) was based on its relationship with its serum β-hCG levels. The ultrasound images generated were archived and reviewed by the authors. Descriptive and inferential statistics were utilized to analyze median differences. For the correlation of uterine artery Doppler flow parameters, analysis for the test of difference used Pearson correlation and multiple linear regression analysis for the odds ratio. Results: Sixteen of the 23 enrolled patients completed the protocol (16 of 23, 69.50%). A majority had spontaneous remission (13; 81%) while 3 cases (19%) presented increasing and plateauing β-hCG levels. The pre- and post evacuation median β-hCG levels showed a significant decrease (P = 0.001). As post evacuation β-hCG levels decreased, PSV also decreased (r = 0.478, P = 0.061) while Doppler parameters, RI, PI, and S/D ratio increased. However, when post evacuation β-hCG levels rose or plateaued, Doppler parameters decreased. These changes had statistical correlation (all P < 0.05). Moreover, the magnitude of the relationship for β-hCG and Doppler parameters was moderate and ranged from 0.524 to 0.581. Among the Doppler parameters, the S/D ratio and RI of the right uterine artery strongly predicted a rise in β-hCG levels. The odds ratio of predicting increased β-hCG levels and risk of gestational trophoblastic neoplasia by the right S/D ratio were − 2683.67 (confidence interval [CI] = −271.692–5095.655; P = 0.034) and by the right RI − 66,193.34 (CI = −161,818.107–29,431.433; P = 0.046). Notably, Doppler parameter changes appeared early at day 14 up to day 35 and before the appearance of abnormal β-hCG regression patterns. Conclusion There is a strong correlation between uterine artery Doppler flow changes and β-hCG levels during postmolar evacuation surveillance. The inverse relationship of the S/D ratio, PI and RI, and β-hCG regression patterns confirms spontaneous remission of the disease. For patients with abnormal β-hCG patterns, this relationship is altered. The Doppler changes become erratic, unpredictable, and significantly decreased. These changes were detected as early as 2 weeks post evacuation. Thus, the use of ultrasound as an adjunct to β-hCG post evacuation surveillance can predict abnormal β-hCG regression patterns and identify patients at risk of developing postmolar gestational trophoblastic neoplasia (PMGTN).
Hydatidiform Mole ; Gestational Trophoblastic Disease ; Hydatidiform Mole

The purpose of this study was to evaluate the significance of telomerase activity in gestational trophoblastic disease and the association of telomerase activity in complete hydatidiform mole and subsequent development of persistent gestational trophoblastic tumor. By using the standard telomerase repeat assay, we examined telomerase activity in 2 normal placentas, 31 complete hydatidiform moles, 7 invasive moles, 5 choriocarcinoma tissues and choriocarcinoma cell line (JEG-3). Telomerase activity was detected in 13 of 15 (86.7%) complete hydatidiform mole patients who eventually had chemotherapy for the treatment of persistent gestational trophoblastic tumor. All of the 9 patients with metastatic disease (FIGO Stage III) had telomerase activity in their initial molar tissue. In contrast, telomerase activity was evident in only two of 16 (12.5%) complete hydatidiform mole patients with spontaneous remission. While telomerase activity was not detected in normal placentas, high level of telomerase activity was detected in all of 7 invasive moles, 5 choriocarcinoma tissues and choriocarcinoma cell line (JEG-3). The presence of telomerase activity in a complete hydatidiform mole is associated with the development of persistent gestational trophoblastic tumor, such as invasive mole and choriocarcinoma.
Cell Line ; Choriocarcinoma ; Drug Therapy ; Female ; Gestational Trophoblastic Disease* ; Humans ; Hydatidiform Mole ; Hydatidiform Mole, Invasive ; Molar ; Placenta ; Pregnancy ; Remission, Spontaneous ; Telomerase* ; Telomere ; Trophoblastic Neoplasms

Precision medicine is a form of medicine that utilizes information about a person’s own genes to prevent, diagnose, or treat disease. In trophoblastic disease, precision medicine is important for accurate diagnosis, risk stratification, prognostication, and management. Immunohistochemistry, particularly p57kip2, has become an important ancillary procedure for the accurate identification of complete hydatidiform mole (HM). Molecular genotyping, on the other hand, is now considered the gold standard for the accurate classification of HM. Both tests are important for prognostication and the determination of the appropriate follow‑up plan. For gestational trophoblastic neoplasia, immunohistochemical markers can confirm the histologic diagnosis of its various types. Molecular genotyping differentiates gestational from nongestational tumors with overlapping histology and allows for precise identification of the index or causative pregnancy of a choriocarcinoma.
Gestational Trophoblastic Disease ; Hydatidiform Mole ; Precision Medicine

Gestational trophoblastic disease is derived from the intermediate trophoblast cells which are arisied from the fetal chorion. The incidence of invasive mole in Korea was about 1.8 per 1000 delivereies. The rate of ectopic pregnancy is about 1.9% of all pregnancies. An ectopic pregnancy located in the cornual portion of uterus occurs in only 2-4% of all ectopic pregnancies. It is rare that the invasive mole is associated with cornual pregnancy. A case of metastatic invasive mole in the lung arising from a cornual pregnancy is reported, which was cured by operation and combination chemotherapy.
Chorion ; Drug Therapy, Combination ; Female ; Gestational Trophoblastic Disease ; Hydatidiform Mole, Invasive* ; Incidence ; Korea ; Lung* ; Pregnancy ; Pregnancy* ; Pregnancy, Ectopic ; Trophoblasts ; Uterus

Gestational trophoblastic disease comprises a spectrum of interrelated conditions originating from the placenta. Malignant gestational trophoblastic disease refers to lesions that have the potential for local invasion and metastasis. This compromises many histological entities including hydatidiform moles, invasive moles, gestational choriocarcinomas, and placental site trophoblastic tumors. Before the advent of sensitive assays for human chorionic gonadotropin (hCG) and efficacious chemotherapy, the morbidity and mortality from gestational trophoblastic disease were substantial. Currently, with sensitive quantitative assays for beta-hCG and current approaches to chemotherapy, most women with malignant trophoblastic disease can be cured. We present a case of malignant gestational trophobalstic tumor with serum beta-hCG concentration over 1million IU/L that metastaze to the lungs and have a hyperthyroidism, but negative urine hCG testing. We report a case with a brief review of literatures.
Choriocarcinoma ; Chorionic Gonadotropin ; Drug Therapy ; Female ; Gestational Trophoblastic Disease ; Humans ; Hydatidiform Mole, Invasive ; Hyperthyroidism ; Lung ; Mortality ; Neoplasm Metastasis ; Placenta ; Pregnancy ; Trophoblastic Tumor, Placental Site ; Trophoblasts

For the clinical analysis and evaluation on the patients with gestational trophoblastic disease(GTD), a study was done retrospectively on 114 patients with GTD(60 in Hydatidiform mole, 10 in invasive mole, 44 in choriocarcinoma) treated from Jan. 1, 1985 to Dec. 31, 1994 at the Department of Obstetrics and Gynecology, Kosin Medical College, Pusan, Korea. We obtained the following results ; The incidence of GTD was 1 per 73 deliveries in H. mole, 1 per 437 deliveries in invasive mole, and 1 per 99 deliveries in choriocarcinoma. The most prevalent age was 21-40 groups. Abnormal vaginal bleeding was a main symptom and sign. 30.6% of H. mole was managed by dilatation and curettage. 90.0% of invasive mole and 51.4% of choriocarcinoma were managed by surgical treatment and chemotherapy. The overall remissinon rate of choriocarcinoma was 71.4%(100.0% in stage I, 66.7% in stage II, 54.5% in stage III, 50.0% in stage IV).
Busan ; Choriocarcinoma ; Dilatation and Curettage ; Drug Therapy ; Female ; Gestational Trophoblastic Disease* ; Gynecology ; Humans ; Hydatidiform Mole ; Hydatidiform Mole, Invasive ; Incidence ; Korea ; Obstetrics ; Pregnancy ; Retrospective Studies ; Trophoblasts ; Uterine Hemorrhage

Mutations in the tumor suppressor p53 gene are the most frequently observed genetic lesions in human cancers. It seems that wild type p53 does significant role on growth and differentiation of normal cells, Mutations and allelic loss of the p53 gene are thought to be a cause of tumor development and to be correlated with the prognostic factors in various human cancers such as breast, ovary and lung cancer. Mutant p53 proteins have a prolonged half-life and can be detected by immunohistochemistry. In case of GTD(gestational trophoblastic disease), although the mutation of p53 gene mutation was revealed to be very rare, the overexpression of p53 in immunohistochemical staining has been reported in wide range of discrepancy and its role or prognostic significance in GTD is uncertain. This study is performed to define the status of p53 overexpression in GTD and to evaluate the correlations between p53 overexpression and prognostic factors of GTD. THE RESULTS WERE AS FOLLOWS: 1. p53 overexpression was detected in none of normal placental tissue, in 58.3%(14/24) of hydatidiform mole, in 15%(6/8) of invasive mole, in 75%(3/4) of choriocarcinoma, and in 100%(1/1) of placental site trophoblastic tumor, and showed significant difference between normal placenta and GTD. We could not find any difference of the p53 overexpression between benign group(H-mole) of GTD and malignant one(invasive mole, choriocarcinoma, and placental site trophoblastic tumor) 2. In H-mole, low-risk group showed significantly higher prevalence of p53 overexpression than high-risk group did. In malignant group, there is no difference in the prevalence of p53 overexpression between early(FIGO stage I) and late(II- IV)stage-diseases, but the prevalence of p53 overexpression of low-risk group is slightly higher than that of high-risk group although we failed to find statistical significance. In conclusion, the high prevalence of p53 overexpression in GTD suggests that p53 may have a certain role in the pathogenesis of GTD or at least represent generalized DNA damage or genetic instability of GTD. And the higher prevalence of p53 overexpression in low-risk group suggests that accumulation of wild-type p53 may be related with favorable prognosis in GTD.
Breast ; Choriocarcinoma ; DNA Damage ; Female ; Genes, p53 ; Gestational Trophoblastic Disease* ; Half-Life ; Humans* ; Hydatidiform Mole ; Hydatidiform Mole, Invasive ; Immunohistochemistry ; Loss of Heterozygosity ; Lung Neoplasms ; Ovary ; Placenta* ; Pregnancy ; Prevalence ; Prognosis ; Trophoblastic Tumor, Placental Site ; Trophoblasts

OBJECTIVE: The study aims to correlate the histopathologic characteristics of patients diagnosed with complete hydatidiform moles with the risk of developing postmolar gestational trophoblastic neoplasia.
METHODOLOGY: A retrospective review of 71 histopathologically-confirmed cases of complete hydatidiform moles was made. Group 1 consisted of 65 patients who achieved normal titers and remained to have normal ?-hCG titers after at least 1 year of follow up. Group 2 included 6 patients who developed postmolar gestational trophoblastic neoplasia. Histopathologic slide review was done to assess the following: trophoblastic proliferation, nuclear atypia, hemorrhage, necrosis along with measurement of the shortest diameter of the largesthydropic villus. The association of the histopathologic features and the development of postmolar gestational trophoblastic neoplasia was done using chi square. Analysis of the association of histopathologic features included in the study predictive of the development of postmolar gestational trophoblastic neoplasia was done.
RESULTS: Analysis of several histopathologic parameters which may precisely identify which patients with complete hydatidiform moles were more likely to develop postmolar gestational trophoblastic neoplasia failed to produce statistically significant results. However, among all the features studied, the presence of extensive necrosis favored the occurrence of postmolar sequela.
CONCLUSION: Trophoblastic proliferation, nuclear atypia, hemorrhage and villus size of complete hydatidiform moles do not predict progression to postmolar disease. In spite of this, all patients with complete hydatidiform moles should be considered for prophylactic chemotherapy  should be monitored closely.