Comparison of 5-day MTX and 5-day ETP treatment results and early predictors of drug resistance to 5-day MTX in patients with post-molar low-risk gestational trophoblastic neoplasia.

OBJECTIVE: To determine the primary remission rates and predictors of drug resistance in patients with post-molar low-risk gestational trophoblastic neoplasia (GTN) who were treated with a 5-day intramuscular methotrexate (5-day IM MTX) or a 5-day drip infusion etoposide (5-day DIV ETP) regimen. METHODS: Between 1980 and 2014, 166 consecutive patients with low-risk post-molar GTN were initially treated with a 5-day IM MTX or a 5-day DIV ETP regimen. The primary remission rates, changes in chemotherapy due to drug resistance or toxicity, and relapse rates were compared. Furthermore, we analyzed the factors that influenced the development of resistance to MTX. RESULTS: Primary remission rates were significantly higher among the ETP-treated patients than among the MTX-treated patients. Among the 42 patients who required a change in chemotherapy, 23 patients (22.6%) and 4 patients (6.3%) were diagnosed as being resistant to MTX and EPT, respectively. Maternal age and the presence of metastasis did not significantly influence the development of MTX resistance, although higher FIGO scores and pre-treatment human chorionic gonadotropin (hCG) levels of >5×10(4)mIU/mL were significantly more common among patients who developed MTX resistance. Moreover, a <30% decrease in hCG after the first cycles of MTX chemotherapy was significantly associated with the development of MTX resistance. CONCLUSIONS: All patients with low-risk GTN eventually achieved complete remission, although several patients developed drug resistance to the first-line chemotherapy. A <30% decrease in hCG during the first chemotherapy cycle may be an early indicator of drug resistance after commencing a 5-day MTX regimen.

Gestational trophoblastic disease in the western region of Saudi Arabia (single-institute experience).

OBJECTIVE: To estimate the prevalence of gestational trophoblastic disease (GTD) in the western region of Saudi Arabia, and to evaluate the success of treatment and the effect of age and risk group on survival. METHODS: Between January 2001 and December 2010, all patients treated for GTD were identified from the King Abdulaziz University Hospital database. Patients with persistent disease were evaluated according to their clinical treatment outcomes. RESULTS: In total, 122 cases of GTD were identified in the database. Of these, 77 (63%) cases were diagnosed and received initial treatment at the study centre, resulting in an incidence of 1.26 cases per 1000 deliveries. The mean (±standard deviation) age of the study participants was 31.52 ± 10.8 years, mean gestational age at diagnosis was 12.42 ± 3.2 weeks, and mean follow-up for each patient was 24 months. There were 20 cases (26%) of persistent GTD after treatment. The majority of patients with low-risk disease were treated with single-agent methotrexate, with an overall success rate of 83%. The overall 5-year survival rate for all patients was 98%. Using the Wilcoxon (Gehan) test, risk group and age (cut-off 40 years) were not found to be significantly associated with survival (p=0.69). CONCLUSIONS: This single-institute study reports the first survival data for GTD for Saudi Arabia. However, the overall incidence of GTD in Saudi Arabia will be defined by establishment of a GTD registry.

Haemoptysis from a pulmonary arteriovenous malformation in a post molar pregnancy gestational trophoblast tumour patient managed by radiological embolisation: a case report.

INTRODUCTION: Gestational trophoblastic tumours are a rare form of malignancy, which in the majority of cases arise from abnormal trophoblast cells formed in a complete molar pregnancy. These tumours are extremely sensitive to chemotherapy and high cure rates approaching 100% can be expected. The disease is usually limited to the uterus where the abnormal trophoblast proliferation and human chorionic production can lead to vascular changes including the formation of arteriovenous malformations. CASE PRESENTATION: We describe the case of a 28-year-old Caucasian woman who presented to the United Kingdom's Gestational Trophoblast Tumour Service with rising human chorionic gonadotropin levels following a uterine evacuation for a complete molar pregnancy. She was commenced on chemotherapy but subsequently reported two episodes of haemoptysis. Computed tomography imaging demonstrated findings consistent with a pulmonary arteriovenous malformation, probably due to a small pulmonary metastasis, complicated by recent haemorrhage. These findings were confirmed on emergency pulmonary arteriography, and the pulmonary arteriovenous malformation was successfully embolised. CONCLUSIONS: Arteriovenous malformations secondary to gestational trophoblastic tumours at metastatic sites have only been reported in a very limited number of cases. When significant bleeding occurs, as in this case of a pulmonary lesion, urgent referral for embolisation is indicated.

Complete hydatidiform mole coexisting with a normal fetus delivered at 33 weeks of gestation and involving maternal lung metastasis: a case report.

BACKGROUND: Complete mole and coexisting fetus is rare. The incidence is 1 in 22,000-100,000 pregnancies. The optimal management of complete mole and coexisting fetus is uncertain because of severe maternal complications. The decision to continue or discontinue a current pregnancy is difficult. We report a case of complete mole and coexisting fetus delivered at 33 weeks of gestation with maternal lung metastases development. CASE: A 36-year-old female, G2 P1 A1, was sent to us for further evaluation at 15 weeks of gestation with a placental abnormality. Ultrasonography revealed that the fetal growth was normal, however, the placenta consisted of two parts. One part indicated a normal placenta and the other showed a typical classic molar pattern. Urine hCG was 440,000 mIU/mL and chest X-ray showed no metastatic finding. Genetic amniocentesis showed that the fetal karyotype was normal 46,XY. Diagnosis was determined to be a complete mole and coexisting fetus. Extensive informed consent was obtained from the parents, and they decided to continue the current pregnancy. We carefully monitored the patient, and periodic hCG measurement and chest X-ray were done at every prenatal check. At 32 weeks chest X-ray showed suddenly multiple lung metastases confirmed by CT scan. At 33 weeks and 4 days labor occurred spontaneously, and a newborn, 1,830-g male infant was delivered without any difficulty. Two days after delivery we started single-agent chemotherapy with dactinomycin. Lung metastases disappeared and the patient achieved remission. CONCLUSION: It is possible to achieve a healthy newborn in cases of complete mole and coexisting fetus in spite of subsequent gestational trophoblastic neoplasia. Patients should be carefully monitored and receive thorough informed consent.

Androgenetic complete mole with trisomy 13: report of a case with microsatellite genotyping and review of the literature.

Hydatidiform moles are gestational diseases with abnormal development of the villous trophoblast and characterized by an excess of paternal to maternal genetic material. Complete moles are usually diploid and androgenetic, and are thought to develop after the fertilization of an "empty ovum" by either a haploid spermatozoon or two spermatozoa. We report a case of a complete mole in which fluorescence in situ hybridization (FISH) incidentally disclosed trisomy 13. Microsatellite genotyping showed a single allele at each of the markers tested on the chorionic villi, and comparison with parental peripheral blood specimens revealed that the markers were all of paternal origin. These results confirmed the paternal origin of all three copies of chromosome 13, and the isodisomy for each chromosome was consistent with duplication of a monospermic fertilization event and subsequent non-disjunction. To the best of our knowledge, this is the only case of an androgenetic complete mole with trisomy 13 described in the scientific literature. We present a review of the literature and hypothesize that the trisomy 13 in our case likely resulted from non-disjunction of chromosome 13.

Gastrointestinal bleeding caused by ileal metastasis of a tubal complete mole: a case report.

BACKGROUND: Tubal hydatidiform mole is known to be an extremely rare disease, moreover, gastrointestinal metastasis from an ectopic complete mole has never been reported. MATERIALS AND METHODS: A 33-year-old woman presented with gastrointestinal bleeding. She had undergone laparoscopic left salpingectomy for a tubal complete mole a month earlier. An ileal invasion of mole was identified. The patient received nine cycles of adjuvant methotrexate chemotherapy after small bowel resection and anastomosis. She was been without recurrence 20 months after therapy. DISCUSSION: Gestational trophoblastic diseases in ectopic pregnancy are rare and gastrointestinal tract metastasis is very infrequent. There have been a few case reports of choriocarcinoma presenting gastrointestinal tract metastasis. To our knowledge, this is the first report of molar pregnancy in a Fallopian tube with ileal metastasis. CONCLUSION: Ectopic molar pregnancy with gastrointestinal metastasis carries a high risk of intestinal perforation and uncontrollable gastrointestinal bleeding. Despite its rarity, gastrointestinal metastasis should nevertheless be considered a possible cause for gastrointestinal bleeding in ectopic molar pregnancy patients after elimination of the more common etiologies.

Chest computed tomography before evacuation of hydatidiform mole.

PURPOSE OF INVESTIGATION: To evaluate the usefulness of chest CT for assessing pulmonary micrometastasis in hydatidiform moles. METHOD: We retrospectively evaluated 48 cases diagnosed with hydatidiform moles. We collected and compared data between the pulmonary micrometastatic and non-metastatic groups based on several factors. The non-parametric, Mann-Whitney, Kaplan-Meier and log-rank tests were used. RESULTS: Of 14 patients who underwent chest CT at their initial evaluation, 57% had pulmonary micrometastasis. The time to remission of serum beta-hCG after evacuation, serum beta-hCG before evacuation and the largest diameter of the uterus were statistically significant. Persistent GTD developed in 38% of the metastatic group, but in only 25% of the nonmetastatic group. Micrometastasis was missed by chest X-ray in 64% of 11 patients suspected of having micrometastasis. CONCLUSION: The chest X-ray was suspected of being ineffective in the diagnosis of pulmonary micrometastasis, but the use of chest CT should be considered during the initial evaluation of hydatidiform moles.

Ovulation stimulation after treatment for a molar pregnancy for or against?

The case of a 29-year-old patient who underwent invitro fertilization due to secondary sterility, after a spontaneous but molar pregnancy, is described. Afterwards there was no spontaneous conception for five years. With the couple's consent, we decided to perform in vitro fertilization, i.e., ovulation induction and the ICSI (intracytoplasmic sperm injection) method.

Spontaneous acute subdural haemorrhage, cerebral and pulmonary metastases in a complete mole.

Complete and partial moles remit spontaneously in most cases, following evacuation of the uterine cavity. However, either persistent trophoblastic disease or a frank trophoblastic tumour can follow a complete hydatidiform mole. To our knowledge, acute subdural haematoma, as a complication of cerebral metastases, following treatment for hydatidiform mole has not been reported. We describe a 29-year-old woman who presented with spontaneous acute subdural haemorrhage and pulmonary metastases, eight months after evacuation of a complete hydatidiform mole, with a fatal outcome.

Sex chromosome composition of complete hydatidiform moles: relationship to metastasis.

OBJECTIVE: Complete hydatidiform moles have a substantial risk for subsequent development of persistent or metastatic gestational trophoblastic tumor. We evaluated the hypothesis that presence of a Y chromosome in a complete hydatidiform mole confers an increased risk for developing metastatic gestational trophoblastic tumor. STUDY DESIGN: The polymerase chain reaction was applied to archival paraffin-embedded molar-tissue to identify Y chromosome-positive dispermic moles in patients who did or did not develop metastatic disease. To reduce the chances of analytic error, consensus polymerase chain reaction primers directed at homologous but different genes present on both X and Y chromosomes were used. RESULTS: Y-chromosome sequences were identified in 7.7% (1/13) of the metastatic group and 9.1% (2/22) of the nonmetastatic group, a statistically insignificant difference. CONCLUSION: We are unable to confirm any increased risk for metastasis in Y chromosome-positive compared with Y chromosome-negative complete hydatidiform mole.

Development of postmolar trophoblastic disease after partial molar pregnancy.

We investigated the clinical characteristics of patients with partial molar pregnancy and patients who developed invasive partial mole. Between 1981 and 1990, 349 patients were followed up by the Aichi prefecture trophoblastic disease registration center after partial molar pregnancy. Ten of the 349 patients with partial molar pregnancy developed invasive partial mole, an incidence (2.87%) significantly lower (P < 0.01) than that for the development of invasive complete mole (174/1410, 12.34%) following complete molar pregnancy during the same period. None of the patients had any histologic evidence of choriocarcinoma after partial molar pregnancy. The medical records of these 10 patients were compared with those of 85 of 174 registered patients with invasive complete mole, whose clinical information could be used. The interval from molar delivery to the diagnosis of invasive mole was under 9 weeks (mean, 4.90 weeks) for the patients with invasive partial mole and was significantly shorter than that for the patients with invasive complete mole, from 2 to 18 weeks (mean, 8.12 weeks) (P < 0.01). All 10 patients with invasive partial mole achieved a negative hCG level (< 0.5 mIU/ml) with eight courses or less of chemotherapy (mean, 5.50 courses). The number of courses was the same as that in the invasive complete mole group (mean, 5.70 courses). None of the patients with invasive partial mole developed recurrence. We conclude that all patients with partial molar pregnancy should be followed up as are those with complete molar pregnancy. Some patients with partial molar pregnancy will develop invasive partial mole with a relatively short interval, but remission can be achieved without the recurrence and choriocarcinoma seldom develops after partial molar pregnancy.

[Partial mole with lung metastases and multiple abnormalities of the fetus]. / Partielle Mole mit Lungenmetastasen und multiplen Missbildungen des Feten.

The authors report on a patient with partial mole, multiple malformations and lung metastases requiring chemotherapy. This case shows that the partial hydatidiform mole must therefore be carefully monitored by serial beta-hCG titres following evacuation to ensure the achievement of complete sustained remission.

XY and XX complete moles: clinical and morphologic correlations.

The results of clinical, morphologic, and histologic analysis of nine XY complete moles (six karyotyped, three Y-chromatin positive) were compared with the results from analysis of 16 XX moles. Five of the nine XY moles were proved to result from dispermy while all the 16 XX moles studied originated from the doubling of a haploid sperm. At follow-up delayed decrease or rebound of urinary (or serum) human chorionic gonadotropin levels was noted in three of eight women with XY moles and in five of 15 women with XX moles. One woman with an XY mole was treated for lung metastasis, but her condition remained stable over a 4-year follow-up period. No appreciable difference was noted in the gross and microscopic findings between the XY and XX moles. On the other hand, differences were noted between younger (12 weeks or less of menstrual age) and older (13 weeks or more) moles. Younger moles had smaller, elliptic or club-shaped villi with numerous secondary villous sprouts, poorly demarcated central cisternae, and frequent mesenchymal capillaries. Older moles had larger, oval or globular villi with sparse villous sprouts, well-developed central cisternae, and less frequent remnants of capillaries. Trophoblastic hyperplasia was more marked in older than in younger moles.