Metastatic choriocarcinoma during viable pregnancy is rare worldwide, and neonate survival following pregnancy termination in the second trimester is uncommon. Here, we report the successful delivery of a pregnancy by a patient with metastatic choriocarcinoma, who received three courses of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA-CO) chemotherapy in the second trimester. After multidisciplinary discussions, she was administered paclitaxel and carboplatin (TC) chemotherapy. Regular contractions occurred during her first paclitaxel infusion, and a healthy infant was delivered by cesarean section at 26+4 gestational weeks. Choriocarcinoma was not detected in the placenta. Following delivery of the pregnancy, the patient underwent total treatment comprising one cycle of TC, seven cycles of EMA-CO, and five courses of etoposide, cisplatin, methotrexate, and dactinomycin chemotherapy; her serum level of beta-human chorionic gonadotropin gradually fell after chemotherapy. Uterine and pulmonary metastases shrank, and no distant metastasis or recurrence were found until the eighth course of maintenance treatment with immunotherapy. The patient received periodic chemotherapy for recurrence at the time of publishing this case report. The child was disease-free 15+ months after delivery. Despite serious metastases and complications, metastatic choriocarcinoma diagnosed in the second trimester of pregnancy can be successfully treated with minimal delay by multidisciplinary medical and nursing management.

BACKGROUND: Gestational trophoblastic neoplasia (GTN) with intracardiac metastasis is rare, and here we reported a patient with intracardiac metastasis of high-risk and refractory gestational choriocarcinoma and reviewed relevant literatures.
METHODS: A 37-year-old woman presented with vaginal bleeding and high level of β-human chorionic gonadotropin (β-hCG) at 199,060 (mIU/mL). It was clinically diagnosed with gestational choriocarcinoma. The patient initially received eight cycles of chemotherapy but unsatisfactory response was observed, and the level of β-hCG still ranged between 5000 and 10,000. Then there was found intracardiac masses in the right atrium (2.6*1.7 cm), anterior chordae tendineae of the tricuspid valve (1.4*0.7 cm) and the right ventricle (4.1*2.9 cm) by ultrasonic cardiogram (UCG). PET/CT highly suspected the intracardiac metastasis of choriocarcinoma (SUVmax = 9.3) and no disease was found in the lung and pelvis. The patient undertook complete intracardiac masses resection. The pathology confirmed the intracardiac metastasis of disease. After a week of operation, the UCG found a 5.4*4.2 cm mass in the right atrium again. Considering the poor prognosis, the patient received palliative care and eventually died of disease progression.
CONCLUSIONS: Intracardiac metastasis of GTN is an aggressive sign of disease. Patients can benefit from chemotherapy and surgery. Future investigation of PD-1 immunotherapy combines with chemotherapy are expected to improve the prognosis in this group of patients.

Nanoparticles that contact human cells without damaging basic human tissues are becoming more widely used in medicine. Efficient delivery to the intracellular target cell or compartment through the cell membrane must be achieved with minimal cytotoxicity to healthy cells. Fe3O4 nanoparticles have been widely used in biomedical research for their magnetic, non-toxic, and biocompatible properties. However, the effects of Fe3O4 nanoparticles coated with chitosan (CS) on gynecological cells are unclear. In this study, the Fe3O4 nanoparticles were coated with CS to enhance their cytocompatibility and dispersion in water. These CS-Fe3O4 nanoparticles were taken up by gynecological cells and did not affect cell viability in vitro. They have greater cytocompatibility in acidic environments than normal Fe3O4 nanoparticles and have the potential for drug delivery into gynecological cells.

Management of metastatic choriocarcinoma coexistent with live fetus is tricky for gynecologists. There is no consensus on treatment because of its rarity. We present a unique case of gestational choriocarcinoma with multiple metastases, who received EP chemotherapy in the third trimester. At 31 + 5 weeks, a healthy male baby was delivered by cesarean section. Then, she received six cycles of EMA/CO as postpartum chemotherapy. Her beta-human chorionic gonadotropin (β-hCG) level decreased to the normal range, and the metastases vanished. The patient had no clinical symptoms 4 years after discharge, and the baby was also free from this disease. Short tandem repeat polymorphism (STR) analysis was performed to determine the genotype of the choriocarcinoma, placenta, and normal curettage tissue of the maternal uterine. Comparing the polymorphic genetic markers revealed that the tumor was gestational choriocarcinoma, but did not originate from the coexistent pregnancy. In spite of extensive metastases, antepartum chemotherapy is an effective and safe treatment for patients with gestational choriocarcinoma concurrent with pregnancy. STR analysis can be useful in distinguishing gestational choriocarcinoma from non-gestational, as well as the causative pregnancy, and serve as a helpful examination tool for guiding clinical management.

Rare adrenal choriocarcinoma should be identified as gestational or nongestational choriocarcinoma because of their different treatment and prognosis. A 29-year-old parous women underwent curettage and right-oviduct resection successively due to irregular vaginal bleeding and positive human chorionic gonadotropin (HCG). Postoperative pathological examinations revealed no intrauterine and extrauterine pregnancy. After that, HCG continued to rise. A 7.6×10.3×11.0 cm mass was present in the left adrenal gland with an uneven inner density and a complete capsule by computed tomography (CT). A biopsy was performed on the mass, which showed us choriocarcinoma. Seven cycles of chemotherapy made her complete response and under supervision. Recurrent diagnosis was done after 3 months. The tumor specimen, the patient\'s blood, and her husband\'s blood were drawn for short tandem repeat (STR) analysis using polymerase chain reaction amplification kit. The genotype of the tumor cells was both maternal and patrilineal, which led to the diagnosis of adrenal gestational choriocarcinoma. The patient was scheduled for adrenalectomy and various chemotherapeutic interventions before and after operation. She achieved complete response and was being followed up again. STR analysis first aids in precise classification of this rare adrenal choriocarcinoma. We encourage using the method to analyze choriocarcinoma outside reproductive organs.

Non-gestational choriocarcinoma (NGCO) of the ovary is rare, with a prevalence of less than 0.6% of all ovarian germ-cell tumors; and when found with other germ cell tumors, pure NGCO is exceedingly rare. We herein report the case of a 22-year-old woman who complained of menstrual disorders for over 2 months. MRI examination revealed an 11.4 cm right adnexal mass of the uterus, and the patients manifested an elevated serum level of β-hCG of 77,928 mIU/ml. Fertility-preserving surgery was performed, and the pathologic diagnosis was pure NGCO; immunohistochemical staining showed cancer cells that were positive for β-hCG, CK, hPL, SALL4, and Ki-67 (>80% of cells stained). We performed polymorphic DNA analysis and non-gestational origin was confirmed. The patient was then treated with six courses of chemotherapy with a BEP regimen, after which her serum β-hCG levels declined to normal levels, and she was free of disease at the 30-month follow-up.

Increasing evidence indicates the pivotal role of long noncoding RNAs in a variety of cancers, but there is limited focus on the link between long noncoding RNAs and gestational choriocarcinoma. This study aimed to examine the role of long noncoding RNA OGFRP1 in JEG-3 and JAR cells. Small interfering RNA was used to downregulate long noncoding RNA OGFRP1 level. Cell proliferation was measured by cell counting kit-8 and clone formation assays. Cell cycle and apoptosis were analyzed by flow cytometry. Cell invasion was examined by transwell assay. Protein expression was determined by Western blot. A double-effect inhibitor (BEZ235) that inhibits AKT and mTOR phosphorylation was used as a positive control. Knockdown of long noncoding RNA OGFRP1 significantly inhibited the proliferation of JEG-3 and JAR cells. Knockdown of long noncoding RNA OGFRP1 induced cell cycle arrest in G1 phase and apoptosis. On the other hand, knockdown of long noncoding RNA OGFRP1 inhibited the invasion of JEG-3 and JAR cells. Finally, knockdown of long noncoding RNA OGFRP1 resulted in the inactivation of AKT/mTOR signaling pathway. In addition, knockdown of long noncoding RNA OGFRP1 caused changes in the expression of intracellular cell cycle-related proteins and apoptosis-related proteins, including downregulation of CDK4, CDK6, Cyclin D1, Nusap1, and Bcl2 protein expression and upregulation of Bax protein expression. In conclusion, we found that downregulation of long noncoding RNA OGFRP1 inhibited cell proliferation, cell cycle progression, and invasion of JEG-3 and JAR cells and induced apoptosis through AKT/mTOR pathway. This study extends the understanding of the function of long noncoding RNA OGFRP1 in tumorigenesis, and these findings may be important for developing a potential therapeutic target for gestational choriocarcinoma therapy.

BACKGROUND: Choriocarcinoma is a highly aggressive, malignant trophoblastic neoplasm that can be gestational or non-gestational in origin. Accurate discrimination between these two subtypes, the causative pregnancy type, and the pregnancy-to-treatment interval for gestational choriocarcinoma are vital for clinical management.
METHODS: Fifteen choriocarcinomas were genotyped using multiplex fluorescent polymerase chain reaction amplification of 15 short tandem repeat (STR) loci and the amelogenin locus (XY determination). Genotype patterns at each locus from tumoral and maternal tissues were compared, and any prior or concurrent mole/placenta was also compared when available. According to STR results showing the presence or absence of the paternal chromosomal complement, the gestational or non-gestational origin of the tumor and the nature of the causative pregnancy was identified.
RESULTS: Fourteen tumors were gestational. Of these, seven were androgenetic/homozygous XX, and two were androgenetic/heterozygous XX, indicating that the causative pregnancies were molar pregnancies. Among the nine molar pregnancies, five were of the occult type. A menopausal patient developed a tumor from a mole that occurred seven years ago, identified by the genetically identical allele from the tumor and prior mole. One tumor originating from a previous mole was interrupted by term delivery. Two tumors found eight weeks postpartum were identified as originating from a prior occult mole. A pelvic choriocarcinoma was separated from a genetically distinct third trimester intrauterine placenta. Five gestational tumors were biparental: 2 XX, 3 XY. Of three ovarian tumors, two were confirmed gestational (1 androgenetic/homozygous XX; 1 biparental XY), and one was an ovarian tumor (XX) with a complete match of the genotype for all 15 loci, therefore ascertaining its non-gestational origin.
CONCLUSIONS: Gestational choriocarcinoma can originate in an androgenetic or biparental manner. The majority are androgenetic/homozygous XX, while a large number of them might be occult molar pregnancies. The origin of ectopic androgenetic choriocarcinoma with concurrent intrauterine placenta might be from either dispermic twin gestation (mole and coexistent nonmolar fetus) or an antecedent molar pregnancy. Choriocarcinoma shortly postpartum might not be associated with the last placenta. STR analysis can be useful in distinguishing gestational choriocarcinoma from non-gestational, as well as the causative pregnancy, and serve as a helpful examination tool for guiding clinical management.

Gestational choriocarcinoma (GC) is a highly aggressive tumor. In our study, we systematically investigated EpCAM/CD147 expression characteristics in patients with GC and assessed the role of circulating tumor cells (CTCs) in predicting chemotherapy response and disease progression. GC tissues were positive for either epithelial cellular adhesion molecule (EpCAM) or CD147, and all samples exhibited strong human chorionic gonadotropin (HCG) expression. Among all the recruited patients (n = 115), 103 had at least 1 CTC in a 7.5-mL peripheral blood sample, and the percentage of patients with ≥4 CTCs in a particular FIGO stage group increased with a higher FIGO stage (p < 0.001). Furthermore, the pretreatment CTC count was related to tumor size (r = 0.225, p = 0.015) and the number of metastases (r = 0.603, p < 0.001). A progression analysis showed that among the 115 included patients who qualified for further examination, 52 of the 64 patients defined as progressive had ≥4 pretreatment CTCs, while only 7 of the 51 non-progressive patients had ≥4 pretreatment CTCs (p < 0.001). In multivariate analysis, CTCs (≥4) remained the strongest predictor of PFS when other prognostic markers, FIGO score and FIGO stage were included. Moreover, based on the chemotherapy response, patients with ≥4 CTCs were more likely to be resistant to chemotherapy than those with <4 CTCs (P < 0.001). These findings demonstrates the feasibility of CTC detection in cases of GC by adopting EpCAM/CD147 antibodies together as capturing antibodies. The CTC count is a promising indicator in the evaluation of biological activities and the chemotherapy response in GC patients.

The clinical presentations of gestational choriocarcinoma vary markedly, and a misdiagnosis could be made in atypical patients if simply relying on clinical features. Laparoscopic resection of uterine mass lesion is rarely used in gestational choriocarcinoma diagnosis because of the fear of heavy blood loss and distant metastasis. Five patients who were preoperatively diagnosed as having cornual pregnancy underwent laparoscopic resection of mass lesion and then proved to have gestational choriocarcinoma based on pathological examinations. Chemotherapy was started within two days after surgery, and the rate of complete remission was 100%. The mean follow-up time was 29.8±19.1 months, and no patient showed signs of relapse. Laparoscopic resection of uterine mass followed by timely postoperative chemotherapy may be an effective and safe way to obtain pathologic results in patients with suspected gestational choriocarcinoma.