Clinical significance of circulating tumor cells in predicting disease progression and chemotherapy resistance in patients with gestational choriocarcinoma.

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.

Cutaneous and systematic metastasis of testicular choriocarcinoma: Case report and literature review.

RATIONALE: Cutaneous metastasis of testicular choriocarcinoma is exceptionally uncommon. To our knowledge, only 14 cases have been reported in the past 10 years in the pubmed. We have an uncommon case of testicular choriocarcinoma who has metastasized to the adjacent skin and organ systems. PATIENT CONCERNS: An 18-year-old male was diagnosed with initial presentation of cutaneous mass at the left back. Followly,biopsy was performed under local anesthesia.Histopathological examination was consistent with the diagnosis of metastatic choriocarcinoma. DIAGNOSES: The histopathological assessment of the biopsied tissue, in combination with elevated serum ß-HCG levels and presentation of testicular mass, indicated primary testicular choriocarcinoma with cutaneous and systemic metastasis. INTERVENTIONS: Subsequently radical orchiectomy was performed. OUTCOMES: Despite the case completed one cycle of cisplatin-based regimen chemotherapy, he died of multiple organ dysfunction syndrome 2 months after surgery. LESSONS: In this report, cutaneous metastasis with testicular choriocarcinoma is extremely rare. It is important to recognize that this unusual variant of testicular choriocarcinoma has the potential to behave aggressively and to metastasize.

[Primary mediastinal choriocarcinoma: A case report and literature review].

Primary mediastinal choriocarcinoma in male is not a very common disease, with nonspecific clinical manifestations. Gynecomastia and testicular atrophy are present in some cases. The levels of serum human chorionic gonadotropin are often significantly increased. Giant lump in the mediastinum and bilateral lungs multiple metastases can be seen on the computed tomography for lung. The diagnosis for it depends on pathological biopsy. Current treatment method is a comprehensive, consisting of chemotherapy, radiotherapy and surgery. This paper reported a case of primary mediastinal choriocarcinoma in male, who were diagnosed and treated in the Second Xiangya Hospital of Central South University. He was admitted for cough and hemoptysis, and finally diagnosed by biopsy. The prognosis is very poor. Therefore, it is important to take physical examination regularly because it can be detected and diagnosed early.

Cell-free DNA in pregnancy with choriocarcinoma and coexistent live fetus: A case report.

BACKGROUND: This case report describes the use of analysis of cell-free DNA in the blood of a patient with a pregnancy with one live fetus and a choriocarcinoma diagnosed at 22 weeks of gestation. RESULTS: The result of the analysis of 16 microsatellite loci on 14 chromosomes in the cell-free DNA in plasma was consistent with the result of the analysis of a tumor biopsy indicating biparental diploid origin of the genome. The DNA markers were discordant with the markers of the placenta indicating two separate conceptions. CONCLUSION: Our results indicate that analysis of cell-free DNA in plasma allows determination of the origin of a choriocarcinoma without tissue biopsy, even in the presence of a co-existent pregnancy.

Clinical Characteristics of Gestational Trophoblastic Neoplasia: A 15-Year Hospital-Based Study.

OBJECTIVE: To analyze the clinical profile of invasive mole (IM) and choriocarcinoma (CCA) in the past 15 years in Western China. MATERIALS AND METHODS: A retrospective study was performed on 221 patients with IM and 70 patients with CCA treated in the First Affiliated Hospital of Xi'an Jiaotong University from 1994 to 2009. Patients were assigned into 3 groups by 5 years, and the clinical characteristics were compared among these groups. RESULTS: The incidence was not significantly changed in the past 15 years, whereas the mean age of gestational trophoblastic neoplasia (GTN) was increased significantly, especially for the patients 40 years or older. The symptoms of the patients with GTN did not show significant variation, but the number of patients with CCA without clinical symptoms was increased significantly. The mean values of beta human chorionic gonadotropin in the patients with IM and those with CCA were 459.43 and 661.70 mIu/L, respectively, and the size of uterine lesion was concentrated at 4 cm or less in both the patients with IM and those with CCA, without significant differences. CONCLUSIONS: In the past 15 years, the incidence of GTN was still higher than in other countries from 1994 to 2009, and the mean age of patients with GTN was increased significantly, especially for the patients older than 40 years. Furthermore, patients with no clinical manifestations increased significantly, which should be paid more attention in the future works. Serum level of beta human chorionic gonadotropin and pelvic ultrasonography are still 2 important indexes for diagnosing and monitoring condition of GTN.

Pure Choriocarcinoma of the Ovary in Silver-Russell Syndrome.

Pure ovarian choriocarcinoma is an extremely rare malignancy that can be gestational or non-gestational in origin. Silver-Russell syndrome (SRS) is a rare congenital developmental disorder characterized by pre- and postnatal growth failure, relative macrocephaly, a triangular face, hemihypotrophy, and fifth-finger clinodactyly. We report a rare case of pure ovarian choriocarcinoma occurring in a 19-year-old woman with SRS. Following surgery, multiple chemotherapy courses were effective and she was free of disease at the 10-month follow-up.

A retrospective study to evaluate single agent methotrexate treatment in low risk gestational choriocarcinoma in the United Kingdom.

OBJECTIVE: To determine whether single agent chemotherapy with intramuscular methotrexate 50mg administered on days 1, 3, 5, and 7 and oral folinic acid 15mg administered on days 2, 4, 6, and 8 in 2 weekly cycles (IM MTX/FA) is an effective treatment regimen for patients with low risk gestational choriocarcinoma. METHOD: Electronic databases were searched to identify patients with gestational choriocarcinoma at the Sheffield and Charing Cross supra-regional trophoblastic disease centres from January 2000 to December 2011. Clinical notes of low risk patients with FIGO score 0-6 were retrospectively reviewed to assess treatment outcomes and subsequent relapse. RESULTS: 65 patients were identified with low risk choriocarcinoma. Serum hCG levels normalised in 24 patients without the requirement of chemotherapy (19 with histological confirmation, 4 highly suspicious histology and 1 clinical diagnosis). Of 23 patients with histologically confirmed choriocarcinoma, 8 (35%) had a sustained complete response to IM MTX/FA and did not relapse. Both patients with FIGO score 6, and 1 patient with FIGO stage III metastatic disease developed resistance to IM MTX/FA and required further treatment. Despite the development of drug resistance or relapse all patients were successfully salvaged by subsequent treatments. CONCLUSIONS: Not all patients with low risk choriocarcinoma that have had primary intervention prior to staging, such as surgical resection or uterine evacuation will require chemotherapy, providing hCG levels continue to decline to normal. Low risk (FIGO 0-5) patients should initially receive IM MTX/FA due to its low toxicity, outpatient administration and reasonable efficacy. Patients with FIGO score 6 or FIGO stage III disease should make an informed choice between IM MTX/FA and combination chemotherapy.

[Effectiveness of plerixafor in patients undergoing mobilization autologous haematopoietic progenitor cell]. / Efectividad de plerixafor en pacientes sometidos a movilización de progenitores hematopoyéticos para autotrasplante.

OBJECTIVE: To evaluate effectiveness of treatment with plerixafor in patients undergoing posterior mobilization for hematopoietic transplant at our hospital. METHODS: Retrospective study of all patients who until September 2012, received plerixafor in their scheme of mobilization into peripheral blood hematopoietic progenitors. We reviewed the medical records and records of drug dispensing outpatient consultation. Effectiveness variables used were: CD34/kg in apheresis product obtained, and day dose received colony stimulating factor (G-CSF) and Plerixafor. Each patient was compared to the effectiveness of the drug results with those obtained earlier mobilization schemes where Plerixafor not used, if present. Data were analyzed using IBM SPSS v19. RESULTS: A total of 24 patients received plerixafor in our hospital. Diagnoses were distributed: 15 NHL, 6 patients with multiple myeloma, 2 Hodgkin's disease, and one metastatic choriocarcinoma. The effectiveness outcomes were no plerixafor mobilization (n = 18): 5 patients were mobilized with G-CSGF only, 13 with G-CSF and chemotherapy. The G-CSF dose / day was mcg 931.1 (± 179.5) for 9.5 days (± 4.7). The average product obtained CD34/kg in cells was 0.2 (± 0.5). No patient received sufficient product (≥ 2 x 106 cells/kg) for subsequent autologous transplantation. 100% of the demonstrations failed. Mobilization with plerixafor (n = 24): 13 patients were mobilized with GCSGF only, 11 with G-CSF and chemotherapy. The G-CSF dose/ day and averaged Plerixafor mcg 885.1 (± 240.1) and 19.8 (± 4.4), respectively, administered for 8.9 (± 5.1) and 1 , 5 (± 0.6) days, respectively. The average product obtained in CD34/kg was 2.3 x 106 cells (± 1.7) (p = 0.014 in relation to the demonstrations without Plerixafor). Only 12.5% (n = 3) patients were unable to undergo autologous transplant. CONCLUSIONS: In our patients, plerixafor has proven effective in mobilizing hematopoietic progenitors for autologous back.

Objetivo: Evaluar efectividad del tratamiento con plerixafor en pacientes sometidos a movilización para posterior autotrasplante de progenitores hematopoyéticos en nuestro hospital. Métodos: Estudio retrospectivo de todos los pacientes que hasta septiembre 2012, recibieron plerixafor en su esquema de movilización de progenitores hematopoyéticos a sangre periférica. Se revisaron las historias clínicas y los registros de dispensación de medicamentos de la consulta de pacientes externos. Las variables de efectividad utilizadas fueron: CD34/kg en producto de aféresis obtenidas, dosis y días recibidos de factor estimulante de colonias (G-CSF) y de plerixafor. Para cada paciente se comparó los resultados de efectividad del fármaco con los obtenidos para anteriores esquemas de movilización en los que no se utilizó plerixafor, en caso de tenerlos. Los datos se analizaron mediante IBM spss v19. Resultados: Un total de 24 pacientes recibieron plerixafor en nuestro hospital. Los diagnósticos se distribuyeron: 15 linfoma no Hodgkin , 6 pacientes con mieloma múltiple, 2 enfermedad de Hodgkin, y 1 coriocarcinoma diseminado. Los resultados de efectividad fueron: Movilización sin plerixafor (n = 18): 5 pacientes se movilizaron sólo con G-CSGF, 13 con G-CSF y quimioterapia. La dosis de G-CSF /día fue de 931,1 mcg (± 179,5), durante 9,5 días (± 4,7). El promedio de CD34/kg en producto obtenido fue de 0,2 células (± 0,5). Ningún paciente obtuvo producto suficiente (≥?2 x 106 células/kg) para el posterior autotrasplante. El 100 % de las movilizaciones fracasaron. Movilización con plerixafor (n = 24): 13 pacientes se movilizaron sólo con G-CSGF, 11 con G-CSF y quimioterapia. La dosis de G-CSF /día y de plerixafor promedio fue de 885,1 mcg (± 240,1) y 19,8 (± 4,4), respectivamente, administrados durante 8,9 (± 5,1) y 1,5 (± 0,6) días, respectivamente. El promedio de CD34/kg en producto obtenido fue de 2,3x106 células (±1,7) (p = 0,014, en relación a las movilizaciones sin plerixafor). Sólo el 12,5% (n = 3) pacientes no pudieron someterse a autotrasplante. Conclusiones: En nuestros pacientes, plerixafor ha demostrado ser efectivo en la movilización de progenitores hematopoyéticos para posterior autotrasplante.

First confirmation by genotyping of transplacental choriocarcinoma transmission.

A mother developed multimetastatic gestational choriocarcinoma 13 months after delivery, and her infant died aged 11 months from the same tumor. The transplacental choriocarcinoma transmission was confirmed by genotyping. Henceforth, we recommend a 2-year maternal human chorionic gonadotropin follow-up after neonatal choriocarcinoma and extensive imaging if the human chorionic gonadotropin rises.

Changes in clinical presentation of postterm choriocarcinoma at the New England Trophoblastic Disease Center in recent years.

OBJECTIVE: To review the last 15 year experience of choriocarcinoma following a term gestation at the New England Trophoblastic Disease Center (NETDC) and compare these results to earlier data to determine any changes in the clinical presentation and outcome of this disease. METHODS: Women with postterm choriocarcinoma from 1996 through 2011 followed by the NETDC were identified by diagnosis codes. Twenty charts were identified and reviewed. These data were then compared to published results from the NETDC of 44 women from 1964 to 1996. RESULTS: Time from antecedent pregnancy to diagnosis of choriocarcinoma was significantly longer in the current series, 46.1 vs. 19.7 weeks (p = 0.03). Despite this change, patient outcomes remained comparable, with similar overall mortality rates (13% vs. 10%, p = NS). However, patient presentation was notably different. In the early series, five (11%) infants suffered hydrops or stillbirth, while in the recent series there were no adverse infant outcomes (p = 0.08). Six women in the current series presented in the absence of symptoms suspicious for choriocarcinoma (either by an incidental positive pregnancy test without other symptoms or by placental pathology), compared to one woman in the prior series (30% vs. 2%, p = 0.001). CONCLUSIONS: In recent years postterm choriocarcinoma is being diagnosed or referred later after the antecedent pregnancy at our regional referral center. Recent patients more commonly have no other symptoms than a question of pregnancy and are less likely diagnosed due to the presence of fetal hydrops or stillbirth. Despite later diagnoses, survival with postterm choriocarcinoma continues to be high.

Spontaneous uterine perforation of choriocarcinoma with negative beta-human chorionic gonadotropin after chemotherapy.

OBJECTIVE: To report an extremely rare case of spontaneous uterine perforation of choriocarcinoma with negative beta-human chorionic gonadotropin (ß-hCG) post-chemotherapy. CLINICAL PRESENTATION AND INTERVENTION: We present a 35-year-old choriocarcinoma patient whose serial serum ß-hCG levels following a fifth course of chemotherapy had been within the normal range, but who developed spontaneous uterine perforation with intra-abdominal hemorrhage after eight courses of combined chemotherapy. The patient then underwent an emergency hysterectomy and survived. CONCLUSION: Patients with persistent focus of disease in the uterus might experience uterine perforation even after adequate chemotherapy, and therefore, the follow-up for patients after chemotherapy is very important.

Correlation levels of serum placental growth factor and human chorionic gonadotropin in gestational trophoblastic disease patients.

OBJECTIVE: To determine the correlation between serum placental growth factor (PlGF) and human chorionic gonadotropin (hCG) in patients with gestational trophoblastic disease (GTD) and to compare serum levels of PlGF in patients with gestational trophoblastic neoplasia to those of patients with hydatidiform mole. STUDY DESIGN: Blood and urine samples were collected from GTD patients. Blood and urine levels for PlGF were processed and quantitated by enzyme-linked immunosorbent assay in parallel with serum levels for hCG. Correlation levels of serum PlGF and hCG were analyzed. Serum levels of PlGF and hCG were correlated with the clinical manifestations of GTD. RESULTS: The correlation between serum levels of PlGF and hCG was not linear (r = 0.274, p = 0.229). The median PlGF levels in benign and malignant groups were 24.0 and 38.3 pg/mL, respectively (p = 0.014). The median serum hCG levels in benign and malignant groups were 7,335.0 and 9,974.5 mlU/mL, respectively (p = 0.942). The linear correlation between urine and serum levels for PlGF was not detected (r = 0.064). CONCLUSION: Levels of correlation for serum PlGF and hCG in GTD patients were not linear. Median serum levels of PlGF between benign and malignant groups were significantly different. This suggests that there is a higher production of PlGF levels in patients with choriocarcinoma or malignant GTD.

Salvage chemotherapy with methotrexate, etoposide and actinomycin D in men with metastatic nonseminomatous germ cell tumors with a choriocarcinoma component: a preliminary report.

The objective of the present study was to assess the use of salvage chemotherapy using methotrexate, etoposide and actinomycin D (MEA) in men with nonseminomatous germ cell tumor (NSGCT) with a choriocarcinoma component. Nine patients were included. They had initially received bleomycin, etoposide and cisplatin, and high-dose ifosfamide, carboplatin and etoposide as induction chemotherapies. However, they failed to achieve the normalization of ß-human chorionic gonadotropin (ß-HCG). Therefore, MEA therapy (methotrexate: 450 mg/body on day 1, actinomycin D: 0.5 mg/body on days 1­5, etoposide: 100 mg/body on days 1­5) was subsequently administered. After MEA therapy (median: 3 cycles), serum ß-HCG was normalized in five of the nine patients. Of these five, three achieved long-term disease-free survival and one died of disease unrelated to NSGCT, whereas the remaining patient developed disease recurrence and died of disease progression. All four patients who failed to achieve the normalization of ß-HCG died of disease progression. Although several severe toxicities greater than grade 3, which were mainly associated with bone marrow suppression, occurred in all patients, there was no treatment-related death. Considering the current outcomes, MEA regimen could be an attractive option as a salvage chemotherapy for metastatic NSGCT patients with a choriocarcinoma component showing resistance to intensive conventional chemotherapies.

Differences in total human chorionic gonadotropin immunoassay analytical specificity and ability to measure human chorionic gonadotropin in gestational trophoblastic disease and germ cell tumors.

OBJECTIVE: To determine the ability of several radioimmunoassays and commercial two-site immunoassays to detect the first World Health Organization International Reference Reagents (IRRs) for 6 defined human chorionic gonadotropin (hCG) variants and to compare their performance in measuring hCG in sera from patients with gestational trophoblastic disease (GTD) and germ cell tumors (GCTs) of the testis or ovary. STUDY DESIGN: The reactivity of the different assays with the 6 IRRs together with the current fourth International Standard (IS, 75/589) was tested using 5 commercial two-site assays as well as 2 competitive polyclonal radioimmunoassays (RIAs) and a competitive monoclonal immunoassay. Individual samples from 41 patients (19 GCT and 22 GTD) with high circulating levels of hCG (range, 718-6,055,000 IU/L) were diluted and measured using the various immunoassays. RESULTS: The results of 4 GCT patient samples varied markedly among the assays, including 1 sample that was grossly underestimated by 3 of the commercial assays. CONCLUSION: Comparison of each assay's reactivity to the variant isoforms revealed that recognition of the isoforms was highly variable, particularly for hCGbeta and hCGbeta core fragment (hCGbetacf).

Serum tumour markers in gynaecological cancers.

Serum tumour markers have had a role in screening, diagnosis and monitoring of some gynaecological cancers. Women with suspected ovarian malignancies have as routine a CA125 serum test, and in conjunction with scans, the risk of malignancy can be calculated. Equally, this CA125, if elevated pre-operatively can be used to predict chemotherapeutic responses, and even disease relapse prior to any symptoms or clinical findings. Other useful markers in ovarian cancer are betaHCG and AFP produced by germ cell tumours. betaHCG is also of extreme importance in both the diagnosis and management of choriocarcinomas. The level of betaHCG determines the need, and with other indicators, the type of chemotherapeutic intervention. Other serum markers are known in cervical cancer, and possibly endometrial and vulval cancer-but their clinical utility is very limited. Novel markers may help in managing patients, and in the future permit screening for certain diseases.

[A case of metastatic choriocarcinoma responding to combination chemotherapy with paclitaxel and carboplatin].

A 53-year-old woman with choriocarcinoma (high-risk gestational trophoblastic disease: FIGO score 17) was treated with paclitaxel (175 mg/m(2)) and carboplatin (AUC=5). The patient was treated with an EMA/CO regimen as initial chemotherapy, but she developed EMA/CO-induced interstitial lung disease after the 3rd course of treatment. After high-dose steroid therapy, she received combination chemotherapy with paclitaxel and carboplatin. Her hCG-/b dropped to <0.1 ng/mL after 11 courses of the chemotherapy. A paclitaxel+carboplatin regimen is potentially effective for high-risk GTD, but a more effective combination or schedule with a platinum-taxane regimen should be explored.