[Hydatidiform mole and malignant trophoblastic tumors initiated by hydatidiform mole. Standards and innovation of diagnosis and treatment].

Malignant trophoblastic tumors are hormone and hormone-dependent allografts initiated by, in the most cases, hydatidiform mole. The absence of methodological principles for monitoring of women after evacuation of hydatidiform mole often leads to late detection of the disease, inadequate chemotherapy conducted in clinics with no experience of treatment, followed by the development of drug-resistant tumors and worse prognosis. This paper analyzes the problem at the moment.

Decidual endovascular trophoblast invasion in women with polycystic ovary syndrome: an experimental case-control study.

CONTEXT: Previous experimental and clinical data suggest impaired decidual trophoblast invasion in patients with polycystic ovarian syndrome (PCOS). OBJECTIVE: The objective of the study was to test the hypothesis that decidual endovascular trophoblast invasion in pregnant patients with PCOS is impaired and to clarify the potential mechanisms involved. DESIGN: This was an experimental case-control study. SETTING: The study was conducted at the academic Departments of Obstetrics and Gynecology and the Unit of Pathology (Italy). PATIENTS: Forty-five pregnant subjects screened from a wide population of women waiting for legal pregnancy termination were included in the final analysis. Specifically, 15 pregnant patients with PCOS were enrolled as cases and another 30 age- and body mass index (BMI)-matched healthy pregnant women without any feature of PCOS were enrolled as the controls. INTERVENTION: Interventions included the collection of trophoblastic and decidual tissue at the 12th week of gestation. MAIN OUTCOME MEASURES: Clinical, ultrasonographic, and biochemical data as well as the histological analysis of decidual endovascular trophoblast invasion. RESULTS: The rate of implantation site vessels with endovascular trophoblast invasion (ratio between total number of implantation site vessels and total number of vessels with endovascular trophoblast invasion) and the extent of endovascular trophoblast invasion (proportion between immunoreactive areas to cytokeratin 7 and to CD34) were significantly lower in patients with PCOS compared with healthy non-PCOS controls. Endovascular trophoblast invasion data were significantly and indirectly related to the markers of insulin resistance and testosterone concentrations in PCOS patients. CONCLUSIONS: Pregnant patients with PCOS patients have impaired decidual trophoblast invasion. Further studies are needed to evaluate the exact mechanisms through which insulin resistance and hyperandrogenemia exert this effect.

Increase in the incidence of gestational trophoblastic disease in The Netherlands.

OBJECTIVE: The objective of this study is to determine the incidence and time trends of gestational trophoblastic disease (GTD) in The Netherlands using population-based data. METHODS: Data on patients with a pathologically confirmed diagnosis of GTD from 1995 to 2008 were obtained from PALGA, a national archive containing all histopathology reports in The Netherlands. Data on number of deliveries were obtained from the Database of Statistics Netherlands. RESULTS: During the study period, 4249 GTD patients were registered. Overall incidence rates of hydatidiform mole (HM), choriocarcinoma and placental site trophoblastic tumor (PSTT) were 1.34 per 1000 deliveries, 3.1 per 100,000 deliveries, and 1.0 per 100,000 deliveries, respectively. Incidence rates of HM increased from 1.02 per 1000 deliveries in 1995 to 1.56 per 1000 in 2001, an increase of 0.091 per year (95% CI 0.081-0.101). After 2001 incidence rates remained constant (increase per year -0.010, 95% CI -0.045-0.024). Maternal age and ethnicity are known to influence the risk of HM. Highest incidences were observed in women under 20 and over 40years of age. The proportion of deliveries accounted for by women over 40years of age increased from 1.5% to 2.9%, whereas women under 20 accounted for 1.5% of deliveries. The proportion of live births of Asian descent increased from 2.6% to 3.7%. CONCLUSION: The incidence of GTD in The Netherlands increased significantly from 1995 to 2008. This can partially be explained by increased maternal age and increased proportion of live births of Asian descent. Part of the increase might result from improved diagnostic techniques. However, these factors do not seem to account for the total observed increase and part of the increase therefore remains unexplained.

Risk factors in early pregnancy complications.

OBJECTIVE: To determine the underlying risk factors in early pregnancy complications and outcome. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: This study was conducted at the Department of Obstetrics and Gynaecology Unit-IV, Liaquat University of Medical and Health Sciences, Jamshoro, from July 2007 to June 2008. METHODOLOGY: All the women with first trimester pregnancy with different complications were included in this study while those women with uneventful first trimester were excluded. The inducted women were registered on pre-designed proforma. Studied variables including demographic details, gestational period, type of complications, risk factors, treatment and outcome. The data was expressed in terms of mean and percentages with a confidence interval of 95%. Analysis was done on SPSS version 14. RESULTS: Out of a 204 total admissions, 115 (56.37%) patients had different early pregnancy complications. Their mean age was 29.4+6.8 years. Commonest complications found were abortion in 88 (76.52%) cases. The underlying risk factors found in abortion were antiphospholipid syndrome in 5 (5.68%) cases, Diabetes mellitus in 8 (9.09%) cases, hypertension in 16 (18.18%) cases, and polycystic ovarian syndrome and infection in 11 (12.5%) cases each. Most of the cases 69 (60%) were treated by minor surgical procedures, and 22 (19.13%) cases responded with conservative medical therapy. Outcome were anaemia in 92 (79.3%) cases, psychological upset in 72 (62.1%), infection in 55 (44%) cases and coagulopathy in 9 (7.8%) cases. CONCLUSION: Abortion was found as the most frequent early pregnancy complication and the most frequent underlying risk factor was hypertension. Outcome included anaemia, psychological upset and infection.

Recurrent gestational trophoblastic disease after hCG normalization following hydatidiform mole in The Netherlands.

OBJECTIVES: To determine the risk for recurrent trophoblastic disease after spontaneous normalization of human chorionic gonadotropin (hCG) levels in patients with hydatidiform mole and to determine the risk for tumor relapse after apparent remission following chemotherapy in patients with low- and high-risk persistent trophoblastic disease. METHODS: From 1994 until 2004, 355 patients with hydatidiform mole were registered at the Dutch Central Registry of Hydatidiform Mole and were monitored by sequential hCG assays in serum at the department of Chemical Endocrinology of the Radboud University Nijmegen Medical Centre. HCG regression curves were analyzed together with clinical information collected from the Hydatidiform Mole Database. RESULTS: Among the 355 registered hydatidiform mole patients, 265 patients attained spontaneous normalization following evacuation. Of the 265 patients, one patient (0.38%) subsequently required chemotherapeutic treatment for recurrent trophoblastic disease (95% confidence interval 0.0% to 2.1%). HCG levels did not decline to normal (<2.0 ng/ml) spontaneously in 90 patients; those patients were subsequently treated. Relapse rates were 8.1% (6/74) and 6.3% (1/16) for the low- and high-risk category respectively. CONCLUSION: Our analysis indicates that relapse risk in hydatidiform mole patients with spontaneous normalization is extremely low (one in 265 patients) after two normal hCG levels (<2.0 ng/ml) are achieved. Our results support the suggestion that two subsequent normal hCG levels may be sufficient to ensure sustained remission after hydatidiform mole evacuation. In contrary, in order to assure sustained remission, the relapse rates after chemotherapy in the current study emphasize the need for surveillance of trophoblastic tumor patients even after complete remission has apparently been achieved.

First epidemiological data from the French Trophoblastic Disease Reference Center.

OBJECTIVE: The objective of the study was to describe women registered at the new French Trophoblastic Disease Reference Center and particularly the rates of gestational trophoblastic neoplasia (GTN) after molar pregnancies. STUDY DESIGN: Epidemiological data from a prospective cohort of women registered between November 1999 and November 2004 were analyzed. RESULTS: Four hundred forty-eight women were registered. The referent pathologist reclassified 32% and 5% of assumed partial mole (PM) and complete mole (CM), respectively. GTN developed in 30 of 212 patients with singleton CM (14%) and in 5 of 108 with singleton PM (5%). Among 131 patients with GTN (35 women followed up after registration for a mole and 96 registered for a GTN), 115 (88%) were low-risk and 16 (12%) were high-risk patients according to 2000 International Federation of Gynecology and Obstetrics (FIGO) scoring system. CONCLUSION: Creation of trophoblastic disease reference centers is desirable to improve treatment of patients. Our results will have to be compared with future publications based on the new 2000 FIGO oncology committee recommendations.

Doença trofoblástica gestacional recorrente / Recurrent gestational trophoblastic disease

Objetivo: estudar a freqüência da neoplasia trofoblástica gestacional recorrente e analisar se a evoluçäo e o desfecho do episódio de repetiçäo acarretam agravado risco, assim de invasäo como de malignizaçäo, e se há necessidade de maior número de ciclos de quimioterapia e regimes mais agressivos. Métodos: vinte e nove pacientes com mola hidatiforme recorrente foram acompanhadas e eventualmente tratadas no Centro de Neoplasia Trofoblástica Gestacional da 33a Enfermaria da Santa Casa da Misericórdia do Rio de Janeiro, entre 1960 e 2001, representando incidência de 1,2 por cento (29/2262). Foram revisados os prontuários médicos para determinar a idade das pacientes, o número de gravidezes, paridade, apresentaçäo clínica e quimioterapia, caso tenha sido realizada. Um total de cinqüenta e oito episódios de neoplasia trofoblástica ocorreram nas 29 pacientes. Todos os casos tiveram comprovaçäo histopatológica. Os cálculos estatísticos foram feitos mediante o teste de X² com correçäo de Yates e analisados pelo programa Epi-Info 2000, versäo Windows, elaborado pelo Centro de Controle de Doenças de Atlanta, EUA. Resultados: ocorreu mola invasora ou coriocarcinoma, no primeiro evento molar, em apenas uma paciente (1/29 - 3,4 por cento); invasäo ou malignizaçäo, entretanto, manifestou-se no segundo evento em sete pacientes (7/29 - 24,1 por cento) [RR: 8,9; IC 95 por cento 1,5-41; p<0,05]. Conclusäo: a gravidez molar recorrente cursa com agravamento histológico e aumento na incidência de seqüela trofoblástica proliferativa, exigindo quimioterapia mais freqüente e agressiva para induzir remissäo

Gestational trophoblastic tumors in Norway, 1968-1997: patient characteristics, treatment, and prognosis.

OBJECTIVES: The aim of this study was to give an overview of the Norwegian population of gestational trophoblastic tumors (GTT), diagnosed during 1968-1997 and treated with chemotherapy at the Norwegian Radium Hospital (NRH), with regard to patient characteristics, treatment, and prognosis. METHODS: The cases were grouped according to a modified version of the WHO scoring system. Staging was performed retrospectively according to the systems adopted by FIGO. Survival estimates were calculated by the method described by Kaplan and Meier. Cox regression models were used to find the best classification system with regard to prognosis (disease-free survival). RESULTS: A total of 141 cases, 106 invasive moles (IM) and 35 choriocarcinomas (CC), were diagnosed in Norway and treated with chemotherapy at the NRH in the period 1968-1997. Altogether, 56% of the patients were assigned to the low-risk category, 20% to the medium-risk category, and 15% to the high-risk category. Most cases were classified into the clinical stages I (69%) and III (23%). The overall 5-year survival rate was 96%. A more favorable prognosis was seen in patients diagnosed in the 1980s and 1990s compared with those diagnosed in the 1970s (P = 0.04). Five patients had progressive disease and died from the disease. Nine patients relapsed. The prognosis (disease-free survival) was more favorable for IM compared with CC (P < 0.01). The FIGO classification system seemed to be a better predictor of disease-free survival than the WHO scoring system. CONCLUSIONS: This study showed that the prognosis of patients with GTT improved in the 1980s and 1990s in Norway, and that the FIGO system might be the best predictor of disease-free survival.

[The clinical analysis and results of treatment of the patients with gestational trophoblastic disease]. / Analiza kliniczna oraz wyniki leczenia chorych z ciazowa choroba trofoblastyczna.

OBJECTIVES: The aim of this work was to establish the dependence between the results of treatment and clinical stage and prognostic factors of the patients with gestational trophoblastic disease. MATERIALS AND METHODS: The retrospective analysis of 1259 patients with Gestational Trophoblastic Disease (GTD) observed in years of 1977-1995 in the Maria Sklodowska-Curie Memorial Cancer and Institute of Oncology in Warsaw, Poland was made. Out of them 281 had recommendation for treatment. The mean age of the examined women was 34.5 years and treated patient 38.0 years. The clinical structure of the treated patients according to clinical stages: I--202 (72.1%), II low risk--17(6.1%), II high risk--4 (1.4%), III low risk--22 (7.9%), III high risk--26 (9.3%), IV--9 (3.2%). The clinical structure of the treated patients by histopathological type: hydatidiform mole 148 (52.7%), invasive mole 34 (12.1%), choriocarcinoma 93 (33.1%), without histopathological diagnosis 6 (2.1%). The distribution of the treated patients by antecedent pregnancy: hydatidifrom mole 166 (59.1%), spontaneous abortion 47 (16.7%), ectopic pregnancy 9 (3.2%) term delivery 59 (21%). RESULTS: Among 281 patients who received chemotherapy 79 of them underwent surgery. In the group of 281 treated patients, 267 (95%) are alive without the signs of disease, 11 (3.9%) died, 1 (0.4%) is alive with the symptoms of disease, 2 (0.7%) were lost of observation. CONCLUSIONS: 1. Among the observed patients with GTD 23% needed treatment. 2. The most common histopathological type of observed patients was hydatidiform mole. 3. General treatment of patients with GTD consists of chemotherapy. 4. The results of treatment should be seen as successful since 96.5% of patients survived 5 years. 5. Survival of patients with GTD depends on clinical stage and risk factors.

Gestational trophoblastic disease: one more risk in adolescent pregnancy.

BACKGROUND: An evaluation of the performance of a Referral Center in the diagnosis, treatment and follow up of adolescents with gestational trophoblastic disease. METHODS: In a 13-year prospective cohort study, between March 1987 and March 2000, 124 adolescents with gestational trophoblastic disease were followed up and/or treated by a multidisciplinary team. Adolescents underwent strict clinical and laboratory control after mole evacuation to guarantee adhesion to follow up, early diagnosis, and prompt treatment of persistent disease. The Student-Fischer t-test and the chi-square test were used for the statistic analysis of the results. RESULTS: Adolescents represented 21.3% of the 583 patients with gestational trophoblastic disease: 102 (82.3%) had uncomplicated hydatidiform moles, and 22 (17.7%) underwent chemotherapy for persistent gestational trophoblastic disease or a gestational trophoblastic tumor. Complications were diagnosed earlier (p < 0.001) in patients managed and treated at the referral center. Of the adolescents with complications, 81.8% were low risk, 54.5% were at the International Federation of Gynecology and Obstetrics stage I, and 90.9% were treated with chemotherapy only. Time to remission and follow up were shorter for uncomplicated hydatidiform moles (9.8 +/- 3.4 weeks and 8.8 +/- 1.8 months, respectively) than for persistent disease (16.2 +/- 5.8 weeks and 45 +/- 24.5 months, respectively). Adhesion to follow up was similar in the two groups (84.2% and 91.8%). To this date, 50% of the adolescents have had one or more gestations, and 82% of these pregnancies were normal. CONCLUSIONS: Adolescents comprise approximately 20% of all gestational trophoblastic disease patients and have high adhesion to follow up. The disease did not affect their reproductive capacity, and chances of a normal subsequent gestation were high.

Subsequent pregnancy outcome in patients with spontaneous resolution of HCG after evacuation of hydatidiform mole: comparison between complete and partial mole.

This study compared subsequent pregnancy outcome in patients with complete and partial hydatidiform moles. Among 1052 patients with molar pregnancy (complete mole, 801; partial mole, 251) monitored at Chiba University Hospital between 1981 and 1999, 891 patients (84.7%) had spontaneous resolution of human chorionic gonadotrophin (HCG) after mole evacuation, and 161 patients (15.3%) required chemotherapy. Of the 891 patients, 438 (49.2%) had 650 subsequent pregnancies. The pregnancy outcome was not significantly different in patients with complete and partial moles, and was comparable with that in the general Japanese population. The incidence of repeat molar pregnancy in patients with complete and partial mole (1.3 and 1.5% respectively) was 5-fold higher than that of the general population, while no increased risk of persistent gestational trophoblastic tumour (GTT) associated with later molar pregnancy was observed. During HCG follow-up, 10 patients (1.1%) developed secondary high-risk GTT between 14 and 54 months after mole evacuation. The incidence of high-risk GTT in patients with and without subsequent pregnancies was 0.46% (2/438) and 1.8% (8/453) respectively (P = 0.1243). In conclusion, patients with complete and partial mole can anticipate a normal future reproductive outcome, and pregnancies after experiencing hydatidiform mole may not affect the development of high-risk GTT.

Management of gestational trophoblastic diseases: subsequent pregnancy experience.

Patients with gestational trophoblastic disease (GTD) can usually achieve complete sustained remission while retaining their fertility even in the presence of wide-spread metastasis. Following complete and partial mole, our patients had 1,239 and 205 later pregnancies, respectively, which resulted in 68.6% and 74.1% term live births, respectively. Patients with either type of hydatidiform mole have, in general, a normal later pregnancy experience. After one molar pregnancy, the risk of a molar pregnancy in a later conception was about 1%. Our patients who received chemotherapy for persistent gestational trophoblastic tumor had 522 later pregnancies, which resulted in 358 (68.6%) term live births and only 10 (2.5%) major and minor congenital anomalies. Data from other centers involving 2,598 later pregnancies also indicate that after chemotherapy patients can generally anticipate a normal future reproductive outcome.

Gestational trophoblastic diseases: new standards for therapy.

Gestational trophoblastic disease (GTD) is a spectrum of rare neoplastic conditions that are highly curable, even in the presence of widely metastatic disease. These diseases vary from partial hydatidiform mole, which rarely metastasizes and infrequently requires treatment with chemotherapy, to choriocarcinoma, for which multi-agent chemotherapy is the standard treatment. Much has been learned regarding the epidemiology of this disease, and our understanding of the genetics underlying GTD is rapidly expanding. As technology such as ultrasonography and sensitive tests for beta-human chorionic gonadotropin have evolved, the presentation of molar pregnancy has significantly changed, although the incidence of persistent GTD has not decreased. This review highlights these recent advancements in the epidemiology, genetics, diagnosis, and treatment of gestational trophoblastic disease.

Review of trophoblastic disease at Taipei Veterans General Hospital.

BACKGROUND: Trophoblastic diseases are well known and encountered frequently within most oriental populations except the Japanese. In recent decades, fewer cases have been reported in Taiwan. The purpose of this study was to review and discuss all patients diagnosed with trophoblastic disease at one particular Taiwanese medical center. METHODS: Sixty-four patients with malignant gestational trophoblastic disease (GTD) were treated at the Taipei Veterans General Hospital from 1977 to 1995. All cases, except those of placental-site trophoblastic disease, were included in this study. RESULTS: Of the 64 cases of GTD identified, 36 were nonmetastatic and 28 were metastatic. The common metastatic sites were the lungs, followed by the brain and/or liver. Six patients died of the disease. The majority of these patients (5/6) suffered from liver and/or brain metastases. CONCLUSIONS: GTD was found to be a highly chemosensitive and curable disease. However, a significant proportion of patients die of the disease. More effective therapeutic protocols may be required in such patients to improve the survival rate.

Epidemiology and time trends of gestational trophoblastic disease in Korea.

OBJECTIVES: For the purpose of determining the annual incidence and time trends of gestational trophoblastic disease (GTD), the medical records from 24 university hospitals, 13 private general hospitals and the Korean Research Institute of Gestational Trophoblastic Disease (KRI-TRD) were analyzed from 1971 to 1995. MATERIALS & RESULTS: From a total of 7198 GTD cases (H-mole=3831, Invasive mole=2163, Choriocarcinoma=1177, PSTr=27) among 838659 deliveries between 1971 and 1995, the hospital-based incidence of H-mole per 1000 deliveries declined from 40.2 during 1971-975, to 2.3 during 1991-995. The population-based incidence of H-mole, however, revealed an average of 2.05 per 1000 deliveries during 1991-995. Old age and gravidities as factors in GTD patients both decreased significantly during the study period. Time trends for the incidence of GTD in Korea revealed significant changes, not only a decrease in the incidence of GTD, but also an improvement in the annual remission rate. Korea's socio-eonomic improvement in recent decades also contributed to the decreased incidence of GTD and the increased survival rates.

The classification of gestational trophoblastic disease: a critical review.

Gestational trophoblastic disease defines a group of conditions which arises from the fetal chorion. Two of the most important advances in the management of gestational trophoblastic disease have been the standardisation of terminology, and the concept of risk assignment based on classification or staging systems which allows rationalisation of treatment. Gestational trophoblastic disease is unique as the prognosis is dependent not only on the anatomic extent but also the presence of prognostic factors. A staging system similar to that used for other cancers does not apply to this disease because in most cases diagnosis is bases not on histology but on clinical or biochemical parameters. Metastatic spread to distant organs can occur early, even in the absence of disease in the uterus or pelvis. Staging in gestational trophoblastic disease must include prognostic factors in addition to anatomic extent of disease. Broadly there are two categories of classification in current use. The first is based on the usual staging system as in other cancers, with four stages of disease, but at the same time prognostic factors are incorporated. This has the important advantages of simplicity and uniformity with other staging systems. However the main pitfall is that no recommendations are made for treatment. The other broad category consists of risk tables, based on anatomic spread as well as prognostic factors. Here patients are assigned varying risk scores, with guidelines for multiagent chemotherapy at the outset in high-risk patients to minimise drug resistant disease. The ideal system would be one which has four stages of disease, so that comparison is easier, with recommendations for combination chemotherapy beyond a certain stage of disease.