Ruijin Wu

Methotrexate therapy for cesarean section scar pregnancy with and without suction curettage

OBJECTIVE To compare the clinical effects in women with cesarean scar pregnancy (CSP) who were treated with either methotrexate (MTX) regimen only or MTX regimen followed by dilation and curettage (D&C). DESIGN Prospective consecutive clinical cohort study. SETTING University hospital for obstetrics, gynecology, and reproductive medicine. SUBJECT(S) Seventy-one cases of CSP. INTERVENTION(S) The subjects were treated with either MTX only (MTX group, 21 cases) or MTX followed by D&C (combined therapy group, 50 cases). MAIN OUTCOME MEASURE(S) Success rates, hysterectomy rates, and time to resolution of serum beta-hCG and the CSP mass were compared between the two groups. RESULT(S) Compared with the MTX group, the combined therapy group had a shorter time to resolution of the CSP mass and serum beta-hCG. There was no significant difference between the MTX and combined therapy groups regarding success rates (76.2% vs. 90.0%, respectively) and hysterectomy rates (19.0% vs. 8.0%, respectively). CONCLUSION(S) Both therapies could treat the majority of CSP patients successfully, but the combined therapy resulted in a shorter time of therapy and indicated a more favorable effect.

Elevated phosphatase of regenerating liver 3 (PRL-3) promotes cytoskeleton reorganization, cell migration and invasion in endometrial stromal cells from endometrioma

STUDY QUESTION Is phosphatase of regenerating liver-3 (PRL-3) associated with increased motility of endometriotic cells from endometrioma? SUMMARY ANSWER Elevated PRL-3 promotes cytoskeleton reorganization, cell migration and invasion of endometrial stromal cells (ESCs) from endometrioma. WHAT IS KNOWN ALREADY Overexpression of PRL-3 is associated with cancer cell migration, invasion and metastatic phenotype. STUDY DESIGN, SIZE, DURATION Primary human ESCs were isolated from eutopic endometrium of women without endometriosis (EuCo, n = 10), with histologically proven endometrioma (EuEM, n = 19) and from the cyst wall of ovarian endometriosis (OvEM, n = 26). PARTICIPANTS/MATERIALS, SETTING, METHODS The expression of PRL-3 in ESCs derived from EuCo, EuEM and OvEM at different phases of menstrual cycle were compared. The protein and mRNA levels of PRL-3 were examined by western blot and RT-qPCR, respectively. ESCs from OvEM were transfected with/without short hairpin RNA (shRNA) or small interfering RNA (siRNA). Additionally, a plasmid-mediated delivery system was used to achieve PRL-3 overexpression in ESCs from EuEM. The cellular distribution of F-actin and α-tubulin were examined by immunocytochemistry. Cell motility was evaluated by a transwell migration/invasion assay. MAIN RESULTS AND THE ROLE OF CHANCE The protein and mRNA levels of PRL-3 are significantly elevated in ESCs from OvEM compared with EuCo and EuEM. The expression of PRL-3 was not altered between proliferative phase and secretory phase in ESCs from all groups. Knockdown of PRL-3 significantly modified the distribution of F-actin and α-tubulin cytoskeleton, inhibited cell migration and invasion. Endogenous inhibition of PRL-3 attenuated the expression of Ras homolog gene family members A and C (RhoA, RhoC), Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) and matrix metalloproteinase (MMP) 9, but not MMP2 in ESCs from OvEM. Additionally, overexpression of PRL-3 in ESCs from EuEM up-regulates cell migration and invasion, and increases the expression of RhoA, RhoC, ROCK1 and MMP9. LIMITATIONS, REASONS FOR CAUTION Lack of in vivo animal studies is the major limitation of our report. Our results should be further confirmed in a larger cohort of patients and extended to include eutopic and ectopic endometrium from patients with peritoneal endometriosis at different stages of the disease. WIDER IMPLICATIONS OF THE FINDINGS Our study describes that elevated expression of PRL-3 contributes to the cell motility of ESCs from endometrioma. The results emphasize the importance of metastatic-related factor PRL-3 in the pathogenesis of endometrioma. STUDY FUNDING/COMPETING INTEREST This work was supported by National Natural Science Foundation of China (No. 81170546) and Zhejiang Medicine Science and Technology Projects (No. Y13H040003). The authors declare no conflict of interest.

Increased steroid receptor RNA activator protein (SRAP) accompanied by decreased estrogen receptor-beta (ER-β) levels during the malignant transformation of endometriosis associated ovarian clear cell carcinoma.

The modulating attributes of steroid receptor RNA activator protein (SRAP) on steroid receptors have been shown in some types of tumor cells. There is compelling evidence to suggest that this molecule may play a critical role in the development of the tumor. However, little has been reported on its expression in endometriosis associated ovarian clear cell carcinoma (EAOCCC). In order to investigate the role of SRAP and estrogen receptors (ERs) in EAOCCC, we have analyzed the distribution of these proteins in the malignant transformation tissues and endometrioma tissues by immunohistochemistry. Our results revealed that the positive ratio of ER-β expression was gradually reduced during the malignant transformation from endometriosis to atypical endometriosis to clear cell carcinoma. Conversely, during the process, a gradual increase in SRAP expression was observed. Furthermore, there is a negative relationship between the expressions of these two molecules. Overall an increase in SRAP and a reduction in ER-β expression might be associated with malignant transformation of EAOCCC.

Phosphatase of regenerating liver-3: a novel and promising marker in human endometriosis

OBJECTIVE To investigate the expression of phosphatase of regenerating liver-3 (PRL-3) in ectopic, eutopic, and normal endometria and explore its relationship with endometriosis. DESIGN A clinical retrospective and molecular study. SETTING Department of obstetrics, gynecology, and reproductive medicine. PATIENT(S) One hundred and five women with histopathologically confirmed endometriosis, and 50 women with histopathologically assessed normal endometria. INTERVENTION(S) Immunohistochemical staining and Western blot analysis. MAIN OUTCOME MEASURE(S) Expression of PRL-3 protein. RESULT(S) As shown by the immunohistochemical analysis, PRL-3 was mainly located in the cytoplasm and membrane. The cells that tested positive for PRL-3 were detected in endometriotic tissues that did not occur in eutopic and normal endometria. Statistical analysis indicated that the expression of PRL-3 was closely associated with the clinical stages and recurrence of endometriosis. CONCLUSION(S) Expression of PRL-3 is related to the clinical stages and recurrence of endometriosis, which provides use with a novel marker and promising target in the treatment of human endometriosis.

A new fertility-preserving surgery for interstitial pregnancy involving hysteroscopic removal under laparoscopic guidance

Interstitial pregnancy is a rare form of tubal ectopic pregnancy, accounting for 2%–4% of all such pregnancies [1]. Although medical treatment can successfully resolve the pregnancy when detected early enough, the standard treatment is cornual resection [2]. However, surgical treatmentmay result in aweakened uterinewall, leading to reduced fertility and a risk of uterine rupture in subsequent pregnancies. Successful transcervical evacuation of interstitial pregnancy under laparoscopic guidance has been reported [2]. However, owing to the characteristics of interstitial pregnancy and potential difficulties encountered during surgery, the placenta may be left behind—necessitating further treatment [3]. Hysteroscopic removal, when possible, reduces the incidence rate of this complication. In 2013, a 26-year-old nulliparous woman presented with an interstitial pregnancy. She wanted to preserve an intact uterus, so hysteroscopic removal was carried out using a technique similar to that performed for intrauterine evacuation. Hegar dilators were used for dilation of the cervical canal and the ostium of the fallopian tube; the dilators were used to reach the uterine cornu and to carefully establish a passage to the gestational site under laparoscopic guidance. A 6-mm suction catheter was then inserted into the uterus and introduced into the gestational site. The products of conception were evacuated at a negative pressure of 180 mm Hg. The hysteroscope was then introduced into the interstitial cavity because a more dilated pathologic tubal ostium was observed. Graspers were used to remove residual tissue from the interstitial cavity, leaving it empty (Fig. 1). Had uterine perforation occurred, cornual resection and salpingectomy would have been performed via laparoscopy. Thewomanwas discharged 2 days later; her serum β-human chorionic gonadotropin levels were undetectable by the second postoperative week. Ultrasound examination 4 weeks postoperatively showed that the cornual region had a normal appearance. When there is a possibility of interstitial pregnancy that is a relatively short distance from the cornual end and is associated with an unruptured mass and hemodynamic stability, hysteroscopic removal under laparoscopic guidance—rather than cornual resection—is a feasible treatment option. Furthermore, this new treatment can prevent a large amount of blood loss; however, when there is a high risk of tubal scarring, recurrent interstitial pregnancy may occur.

Silencing of SRA1 Regulates ER Expression and Attenuates the Growth of Stromal Cells in Ovarian Endometriosis

Estradiol and its nuclear receptors, estrogen receptor (ER) α and ER-β, have important functions in endometriosis, and the transcriptional activity of these receptors is modulated by coactivators and corepressors. The steroid receptor RNA activator 1 (SRA1) produces SRA long noncoding RNA (lncRNA) and SRA protein (SRAP), which regulate ER expression at the RNA and protein levels in some hormone-dependent tumors via an alternative splicing event. However, only a few are reported on their expressions in endometriosis. Here, we observed that low expression levels of SRA lncRNA and ER-α but relatively high expression levels of SRAP and ER-β were detected in ovarian endometriotic tissues versus normal endometrial tissues. Steroid receptor RNA activator I-small interfering RNA treatment significantly increased ER-α levels but reduced ER-β levels in endometriotic stromal cells (ESCs). Furthermore, the treatment can also attenuate the proliferation and promote early apoptosis in these cells. Our results indicate that the regulation of ER via SRA in ovarian endometriosis may play a significant role in the growth of ESCs.Estradiol and its nuclear receptors, estrogen receptor (ER) α and ER-β, have important functions in endometriosis, and the transcriptional activity of these receptors is modulated by coactivators and corepressors. The steroid receptor RNA activator 1 (SRA1) produces SRA long noncoding RNA (lncRNA) and SRA protein (SRAP), which regulate ER expression at the RNA and protein levels in some hormone-dependent tumors via an alternative splicing event. However, only a few are reported on their expressions in endometriosis. Here, we observed that low expression levels of SRA lncRNA and ER-α but relatively high expression levels of SRAP and ER-β were detected in ovarian endometriotic tissues versus normal endometrial tissues. Steroid receptor RNA activator 1–small interfering RNA treatment significantly increased ER-α levels but reduced ER-β levels in endometriotic stromal cells (ESCs). Furthermore, the treatment can also attenuate the proliferation and promote early apoptosis in these cells. Our results indicate that the regulation of ER via SRA in ovarian endometriosis may play a significant role in the growth of ESCs.

Influence of ovarian endometrioma on expression of steroid receptor RNA activator, estrogen receptors, vascular endothelial growth factor, and thrombospondin 1 in the surrounding ovarian tissues.

This study investigates the influence of ovarian endometrioma on expression of steroid receptor RNA activator (SRA), estrogen receptors (ERs), vascular endothelial growth factor (VEGF), and thrombospondin 1 (TSP-1) in the surrounding ovarian tissues. Taken from the women with ovarian endometrioma and mature teratoma during laparoscopy, the biopsies were analyzed by real-time polymerase chain reaction and Western blot. Our results indicated that ovarian tissues surrounding endometrioma had lower SRA and ER-α levels but higher SRA protein (SRAP) and ER-β levels than ovarian endometrioma. With lower VEGF levels and higher TSP-1 levels, the surrounding ovarian tissues showed higher expression levels of SRA, SRAP, ER-α, and ER-β in the ovarian endometrioma group when compared to the controls. These data showed that ovarian endometrioma increases SRA, ERs, and TSP-1 but decreases VEGF levels in the surrounding ovarian tissues, suggesting that abnormal expression of these molecules may affect biological behaviors of ovarian endometrioma.

O422 Immunohistochemical detection of aquaporin expression in eutopic and ectopic endometrial from women with endometriomas

fact that the follow-up survey wanted to monitor the post training performance of newly trained doctors, trainees who intended to return to his/her site to perform uterine evacuations and agreed to take part in the follow-up survey were included in the survey. Ipas has established two training centres during 2004 at the state capital named Ranchi to improve the number of legal providers on safe abortion services. During 2006 established another four training centres in the districts named Dhanbad, Hazaribag, Palamu and Chaibasa and during 2007 another district was added named Lohardaga. To sustain the programme Ipas has built the training capacity of the senior Gyneocologist of the districts. These doctors have imparted the capacity to the doctors who are posted in the rural areas. Observations and Results: During the last five years (Feb. 2004 – Dec. 2008) a total of 449 (146 certified and 303 certification) medical doctors have been trained in CAC in Jharkhand. Comprehensive Abortion Care service is one of the basic services needs to be available at the primary health care settings. Ipas always wants to facilitate training of the doctors based in the primary level so that it becomes easily accessible for the rural women. Of the total 449 doctors trained, 229 (51%) are posted either in Primary Health Centres (PHC) or in the Addl. Primary Health Centres (APHC), i.e. in the rural areas of Jharkhand. Another 77 (17%) are posted in Referral Hospitals and Sub Dist. Hospitals which are generally based in the semi – urban locations. The rest of the 113 (29%) trained doctors are posted in Dist. Hospitals and Medical Colleges and based in urban areas. Most of the 30 (7%) private doctors who received CAC training are also based in urban areas. Trained providers who successfully completed the follow-up survey represent nine districts comprising 3 regions. While four districts Dhanbad (35), East Singbhum (14), West Singbhum (16) and Ranchi (28) accounted around 79% of these trainees, the remaining 21% included from Lohardaga (12), Bokaro (5), Ramgarh (3) and Koderma & Hazaribag (2 each). It is experienced from the intervention as the number of trained providers has increased the number of women who were seeking abortion services increased.