Yaxia Chen

Outcomes of conservative therapy for young women with early endometrial adenocarcinoma

Four of six patients with endometrial cancer had initial response to progesterone therapy and obtained complete response; three among them had successful pregnancies with three live births. The results suggest that progesterone therapy, combined with assisted reproductive technology, provides more chance of carrying a full-term pregnancy for patients with endometrial adenocarcinoma.

Factors associated with positive margins in patients with cervical intraepithelial neoplasia grade 3 and postconization management

To evaluate the risk factors for positive margins in cervical intraepithelial neoplasia (CIN) grade 3 and the outcomes of postconization management.

MicroRNA Detection in Cervical Exfoliated Cells as a Triage for Human Papillomavirus–Positive Women

Background Papanicolaou (Pap) triage, with high specificity, has been recommended for primary Human papillomavirus (HPV) testing but is flawed by poor sensitivity and cytologist dependence. We evaluated the potential role of microRNA (miRNA) detection in cervical exfoliated cells in HPV-positive women from a clinic-based population. Methods Primary HPV testing as well as Pap test were performed on all eligible women. Six miRNAs (miR-424/miR-375/miR-34a/miR-218/miR-92a/miR-93) were detected by RT-qPCR in cervical exfoliated cells. All HPV-positive women underwent colposcopy and further biopsy if indicated. Mann–Whitney U test, the receiver operating characteristic curve, logistic regression, and Pearson’s Chi-square were used to assess data. All tests of statistical significance were two-sided. Results A total of 1021 eligible HPV-positive women were enrolled. The expression of miR-424/miR-375/miR-34a/miR-218 in high-grade cervical intraepithelial neoplasia (CIN) and abnormal cytology was statistically significantly lower than that in low-grade CIN and normal cytology, respectively (all P < .05). Compared with the Pap test, both miR-424 and miR-375 detection achieved higher sensitivity (76.0% and 74.9% vs 63.8%, P < .05), higher negative predictive value (NPV) (85.7% and 85.4% vs 79.3%, P < .05), and comparable specificity while identifying CIN2 or worse (CIN2+). Similar results were achieved while identifying CIN3+. Multi-marker panels based on miR-424, miR-375, and miR-218 further improved the performance over any single miRNA test or Pap test. Conclusion Single miR-424 or miR-375 detection and miR-424/miR-375/miR-218–based multimarker panels in cervical exfoliated cells show superior performance over Pap triage for high-grade CIN identification in a clinic-based population. Detection of miRNA may provide a new triage option for HPV-positive women.

Evaluation of the accuracy of intra-operative gross examination for the surgical management of endometrial cancer

OBJECTIVE The aim of this study was to explore the clinical value of intra-operative gross examination for the surgical management of endometrial carcinoma. STUDY DESIGN A retrospective study was conducted in 424 women who underwent surgical treatment for endometrial carcinoma between January 2002 and December 2006. The results of myometrial invasion and cervical infiltration as assessed by intra-operative gross examination were compared with the final microscopic histopathological results in 401 patients. The accuracy, sensitivity, and specificity were calculated. Chi-squared or Fishers exact tests were used for the comparison of categorical variables. RESULTS Intra-operative gross examination correctly identified the depth of microscopic myometrial invasion in 90.3% of patients. The sensitivity in detecting myometrial invasion was 80.6% and the specificity was 92.4%. With regard to cervical involvement, gross examination had an overall accuracy of 84.3%. The sensitivity in detecting cervical involvement was 32.6% and the specificity was 99.0%. Usually, cervical involvement cannot be correctly identified by intra-operative gross examination in patients with diffuse foci. CONCLUSION The data suggest that intra-operative gross examination is a simple and good method of predicting myometrial invasion, but it may not be the ideal way to assess cervical involvement in endometrial carcinoma.

Methotrexate induces apoptosis of human choriocarcinoma cell line JAR via a mitochondrial pathway

OBJECTIVE To investigate methotrexate (MTX)-induced apoptosis and the involved pathways in human choriocarcinoma cells. STUDY DESIGN MTX-induced apoptosis of human choriocarcinoma cell line JAR was examined using a PI/Annexin V stain with flow cytometer (FCM). Mitochondrial apoptosis was detected by fluorescence microscopy, and analyzed by FCM using a MitoCapture mitochondrial apoptosis detection kit. The activities of caspase-8 and caspase-9 were quantified by microtiter plate reader at 405 nm using FLICE/Caspase-8 colorimetric assay kit and Caspase-9/Mch6 colorimetric assay kit. The changes in Bax and Bcl-2 expression were detected during apoptosis using immunocytochemistry and Western blot analysis. RESULTS JAR cells underwent apoptosis after exposure to 0.1-2.5 microg/ml MTX for 48 h. Decreased mitochondrial membrane potential was observed both by fluorescence microscopy and FCM. The activation of caspase-9 was increased 4.35+/-0.76-fold in MTX-incubated JAR, while there was no obvious change in the activation of caspase-8. When JAR cells underwent apoptosis, the expression of Bcl-2 was decreased and the expression of Bax was increased; both were detected by immunocytochemistry assay. CONCLUSION Methotrexate in lower concentrations induces apoptosis of human choriocarcinoma cells via mitochondrial-initiated pathways, including reduction of mitochondrial membrane potential, activation of caspase-9, and up-regulation of Bax/Bcl-2 expression.

Clinical features of 17 cases of placental site trophoblastic tumor.

⁎ Corresponding author at: Department of Gynecologic Oncology, Womens Hospital, School of Medicine, Zhejiang University, 2 Xueshi Road, Hangzhou 310006, China. Tel.: +86 571 87061501x2151/13575737780; fax: +86 571 87036290. E-mail address: chenyax@zju.edu.cn (Y. Chen). Placental site trophoblastic tumor (PSTT) is the least common form of gestational trophoblastic disease (GTD) and is biologically different from other forms of GTD. Information on its characteristics and clinical manifestations is limited because of its rarity. Between January 2003 and December 2010, 17 women with PSTT were identified at our institute from a total of 848 patients who were diagnosed with GTD, accounting for 2% of GTD cases. In the Sheffield Trophoblastic Disease Centre database, PSTT accounts for 0.23% of GTD cases [1]; in the Charing Cross Hospital database, PSTT accounts for 2% of GTD cases [2]. Schmid et al. [3] reported that among 35 550 women who were diagnosed with GTD in the UK between 1976 and 2006, 62were diagnosedwith PSTT, which accounted for 0.17% of GTD cases. The clinicopathological details of the 17 women with PSTT treated at our institute were reviewed. The disease was staged according to the International Federation of Gynecology and Obstetrics (FIGO) criteria for gestational trophoblastic neoplasia [4]. Treatment modality including surgery, chemotherapy with EMA-CO [4], or both, was selected. The patients’ characteristics are shown in Table 1. The mean age of the patients was 32±4 years, the mean period of amenorrhea or bleeding was 178 days, and the mean hCG level was 556.7 U/L. The mean interval from last pregnancy to diagnosis was 14 months (range, 3–36 months) compared with 18 months [1] and 3.4 years [2] in other databases. The antecedent pregnancies in 15 of the 17 (88.2%) women resulted in term deliveries, 1 was aborted, and 1 was a molar abortion. The rate of PSTT after term delivery in the present study is higher than reported previously (53%–60%) [2,3]. Serum hCG was always normal in the earlier stages of PSTT, which caused severe delays in its diagnosis. The interval between the presentation of symptoms and consideration of PSTT ranged from 2 days to 2 years, with a mean of 6 months. Two patients (11.8%) had stage III tumors, while the remaining 15 patients had stage I tumors. The interval from antecedent pregnancy to diagnosis in the 2 stage III patients was 10 and 36 months and their serum hCG was 125.8 IU/L and 6256 IU/L, respectively. Previous reports have described relative chemoresistance in patients with PSTT. In the present study, 1 stage III patient was treated initially with EMA-CO owing to a misdiagnosis of choriocacinoma. This patient showed high sensitivity to this regimen. Her serum hCG returned to normal from 6256 IU/L and the disease in her lungs disappeared after 4 courses of EMA-CO. The patient underwent hysterectomy because her uterine lesion remained unchanged. She was diagnosed with PSTT by hysterectomy specimen. Two additional cycles of EMA-COwere given after surgery. The patient was alive with no evidence of disease 9 months after the end of treatment. One patient developed recurrent PSTT 4 years after primary treatment. Serum hCG level was 186.2 IU/L. No tumors were detected by chest radiograph, CT scans of the thorax, Doppler ultrasound of the pelvis, or dual-modality positron emission tomographic (PET)computed tomographic (CT) imaging of the whole body. This case of recurrent PSTT also showed sensitivity to EMA-CO. Serum hCG was normalized from 186.2 IU/L after 2 cycles of EMA-CO and 4 additional cycles of EMA-CO were given. The patient was alive with no evidence of disease 11 months after the end of chemotherapy. The present study shows that PSTT occurred predominantly after term delivery. PSTT is difficult to diagnose by its symptoms and diagnosis is usually delayed. Hysterectomy with or without EMA-CO chemotherapy is a beneficial treatment modality.

FTY720 and cyclosporin protect ovarian tissue grafted into rabbits

OBJECTIVE To determine whether FTY720 combined with CsA has immunomodulatory effects on human ovarian tissue transplanted to the back muscle of rabbits for an 8-week period. STUDY DESIGN We selected rabbits as recipients of ovarian xenografts with and without treatment by CsA and FTY720. Ovarian fragments from twelve patients were cut into 2 mm × 2 mm, 1-2mm thick pieces and randomly distributed into four groups: Group 1 (FTY720 2 mg/kg/d+CsA 3 mg/kg/d), Group 2 (FTY720 1 mg/kg/d+CsA 3mg/kg/d), Group 3 (FTY720 0.5 mg/kg/d+CsA 3mg/kg/d) and Group 4 for control (CsA 3 mg/kg/d). FTY720 was started three days before transplantation and was given daily after transplantation. CsA was administrated post-transplantation. All the animals were killed 8 weeks post- transplantation. Levels of serum estrogen (E2), interferon-γ (IFN-γ) and interleukin-4 (IL-4) were detected by radioimmunoassay and ELISA. Anti-CD31 and anti-Ki-67 antibodies were used to evaluate neo-vascularization in xenografts and proliferation activity of ovarian follicles. Peripheral CD4+/CD8+ T cells were analyzed by flow cytometry. RESULTS Combined treatment with cyclosporin A and FTY720 improved graft survival and reduced peripheral CD4+ and CD8+ T cell counts compared to treatment with cyclosporin A alone. Neovascularization took place in the peripheral zone of the xenograft while granulosa cells, positively stained by Ki-67, were found in early-stage follicles and stromal cells in the combined treatment groups. CONCLUSION FTY720 in combination with cyclosporin A maintains human ovarian xenografts in these rabbit models.

Whole-exome sequencing reveals genetic variants in ERC1 and KCNG4 associated with complete hydatidiform mole in Chinese Han women

Complete hydatidiform mole (CHM) is a rare pregnancy-related disease with invasive potential. The genetics underlying the sporadic form of CHM have not been addressed previously, but maternal genetic variants may be involved in biparental CHM. We performed whole-exome sequencing of 51 patients with CHM and 47 healthy women to identify genetic variants associated with CHM. In addition, candidate variants were analyzed using single base extension and Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry in 199 CHM patients and 400 healthy controls. We validated candidate variants using Sanger sequencing in 250 cases and 652 controls, including 205 new controls. Two single nucleotide polymorphisms, c.G48C(p.Q16H) inERC1 and c.G1114A(p.G372S) in KCNG4, were associated with an increased risk of CHM (p<0.05). These variants may contribute to the pathogenesis of CHM and could be used to screen pregnant women for this genetic abnormality.

O173 Factors associated with cone margin involvement in CIN III and post-conization management options for these patients

Successful abortion was observed in 98.9%. For all patients, the duration of hospitalization was less than 6 hours (day patient). No serious complications such as important bleeding, perforation or endometritis occurred during or followed the MVA procedures. The procedure was easy for the operator in 82% of cases. The mean duration was 10mn (5–15mn). The MVA abortion was considered painless by 49.5% of women while 13.3% felt mild or moderate pain. Women satisfaction rate achieved 79.4%. Transvaginal ultrasound on day 15 post-abortion showed incomplete abortion in 18 patients (6.2%), only 3 of them necessitated a second suction evacuation procedure. Conclusion: These findings show that MVA is a safe and effective method for first-trimester abortions. In our practice, use of this simple technique under local anesthesia has considerably facilitated the daily management of abortions and made easier women’s access to abortion.