HNRNPC mediates lymphatic metastasis of cervical cancer through m6A-dependent alternative splicing of FOXM1.

Cervical cancer (CCa) patients with lymph node (LN) metastasis face poor prognoses and have limited treatment options. Aberrant N6-methyladenosine (m6A) modification of RNAs are known to promote tumor metastasis, but their role in CCa remains unclear. Our study reveals that HNRNPC, an alternative splicing (AS) factor and m6A reader, increases tumor-related variants through m6A-dependent manner, thereby promoting lymphatic metastasis in CCa. We found that HNRNPC overexpression correlates with lymphatic metastasis and poorer prognoses in CCa patients. Functionally, knocking down HNRNPC markedly inhibited the migration and invasion of several CCa cell lines, while supplementing HNRNPC restored the malignant phenotypes of these cells. Mechanistically, HNRNPC regulates exon skipping of FOXM1 by binding to its m6A-modified motif. Mutating the m6A site on FOXM1 weakened the interaction between HNRNPC and FOXM1 pre-RNA, leading to a reduction in the metastasis-related FOXM1-S variant. In conclusion, our findings demonstrate that m6A-dependent alternative splicing mediated by HNRNPC is essential for lymphatic metastasis in CCa, potentially providing novel clinical markers and therapeutic strategies for patients with advanced CCa.

Effectiveness of Sequential Chemoradiation vs Concurrent Chemoradiation or Radiation Alone in Adjuvant Treatment After Hysterectomy for Cervical Cancer: The STARS Phase 3 Randomized Clinical Trial.

IMPORTANCE: There is no current consensus on the role of chemotherapy in addition to radiation for postoperative adjuvant treatment of patients with early-stage cervical cancer with adverse pathological factors. OBJECTIVE: To evaluate the clinical benefits of sequential chemoradiation (SCRT) and concurrent chemoradiation (CCRT) compared with radiation alone (RT) as a postoperative adjuvant treatment in early-stage cervical cancer. DESIGN, SETTING, AND PARTICIPANTS: After radical hysterectomy at 1 of 8 participating hospitals in China, patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB to IIA cervical cancer with adverse pathological factors were randomized 1:1:1 to receive adjuvant RT, CCRT, or SCRT. Data were collected from February 2008 to December 2018. INTERVENTIONS: Patients received adjuvant RT (total dose, 45-50 Gy), CCRT (weekly cisplatin, 30-40 mg/m2), or SCRT (cisplatin, 60-75 mg/m2, plus paclitaxel, 135-175 mg/m2) in a 21-day cycle, given 2 cycles before and 2 cycles after radiotherapy, respectively. MAIN OUTCOMES AND MEASURES: The primary end point was the rate of disease-free survival (DFS) at 3 years. RESULTS: A total of 1048 women (median [range] age, 48 [23-65] years) were included in the analysis (350 in the RT group, 345 in the CCRT group, and 353 in the SCRT group). Baseline demographic and disease characteristics were balanced among the treatment groups except that the rate of lymph node involvement was lowest in the RT group (18.3%). In the intention-to-treat population, SCRT was associated with a higher rate of DFS than RT (3-year rate, 90.0% vs 82.0%; hazard ratio [HR], 0.52; 95% CI, 0.35-0.76) and CCRT (90.0% vs 85.0%; HR, 0.65; 95% CI, 0.44-0.96). Treatment with SCRT also decreased cancer death risk compared with RT (5-year rate, 92.0% vs 88.0%; HR, 0.58; 95% CI, 0.35-0.95) after adjustment for lymph node involvement. However, neither DFS nor cancer death risk was different among patients treated with CCRT or RT. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, conducted in a postoperative adjuvant treatment setting, SCRT, rather than CCRT, resulted in a higher DFS and lower risk of cancer death than RT among women with early-stage cervical cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00806117.

Class I versus Class III radical hysterectomy in stage IB1 (tumor ≤ 2 cm) cervical cancer: a matched cohort study.

Background & Aims: The long-term oncological outcome of Class I hysterectomy to treat stage IB1 cervical cancer is unclear. The aim of the present study was to compare the surgical and long-term oncological outcomes of Class I hysterectomy and Class III radical hysterectomy for treatment of stage IB1 cervical cancer (tumor ≤ 2 cm). Methods: Seventy stage IB1 cervical cancer patients (tumor ≤ 2 cm) underwent Class I hysterectomy and 577 stage IB1 cervical cancer patients (tumor ≤ 2 cm) underwent Class III radical hysterectomy were matched with known risk factors for recurrence by greedy algorithm. Clinical, pathologic and follow-up data were retrospectively collected. Five-year survival outcomes were assessed using Kaplan-Meier model. Results: After matching, a total of 70 patient pairs (Class I - Class III) were included. The median follow-up times were 75 (range, 26-170) months in the Class III group and 75 (range, 27-168) months in the Class I group. The Class I and Class III group had similar 5-year recurrence-free survival rates (RFS) (98.6% vs. 97.1%, P = 0.56) and overall survival rates (OS) (100.0% vs. 98.5%, P = 0.32). Compared with the Class III group, the Class I group resulted in significantly shorter operating time, less intra-operative blood loss, less intraoperative complications, less postoperative complications, and shorter hospital stay. Conclusions: These findings suggest that Class I hysterectomy is an oncological safe alternative to Class III radical hysterectomy in treatment of stage IB1 cervical cancer (tumor ≤ 2 cm) and Class I hysterectomy is associated with fewer perioperative complication and earlier recovery.

Tripartite motif containing 62 is a novel prognostic marker and suppresses tumor metastasis via c-Jun/Slug signaling-mediated epithelial-mesenchymal transition in cervical cancer.

BACKGROUND: TRIM62 (tripartite motif containing 62) has been found to act as a tumor suppressor of several cancers. However, its precise biological role and related mechanism remain unknown in cervical cancer (CC). METHODS: Quantitative Real-time PCR and western blot were adopted to detect the mRNA and protein expression level of TRIM62 in both human CC cell lines and tissues. Immunohistochemistry was used to measure the TRIM62 expression in 30 normal cervical and 189 CC tissues. Univariate and multivariate Cox regression analyses and Kaplan-Meier survival analyses performed to investigate the association between TRIM62 expression and CC patients' prognosis. The effect of TRIM62 on CC growth and metastasis was studied in vitro and in vivo. Multi-pathway reporter array were utilized to identify the potential signaling manipulated by TRIM62. RESULTS: TRIM62 was frequently down-regulated in both human CC cells and tissues. Low expression of TRIM62 in CC tissues was associated with aggressive clinicopathological features of CC patients. In addition, TRIM62 was also an independent poor prognostic factor for overall and disease-free survival of CC patients after surgery. Moreover, enforced expression of TRIM62 in CC cells significantly inhibited their abilities of proliferation, migration and invasion in vitro. Besides, subcutaneous xenograft tumor model and xenograft mouse metastatic model respectively displayed that TRIM62 impeded the growth and metastasis of CC in vivo. Furthermore, mechanism study exhibited that TRIM62 could suppress epithelial-mesenchymal transition (EMT) by inhibiting c-Jun/Slug signaling. The inhibitory role of TRIM62 in tumor proliferation might be through regulating cell cycle related proteins CyclinD1 and P27 by targeting c-Jun. CONCLUSION: TRIM62 is a potential prognostic biomarker in CC and suppresses metastasis of CC via inhibiting c-Jun/Slug signaling-mediated EMT.

Long-Term Oncological Outcomes After Laparoscopic Versus Abdominal Radical Hysterectomy in Stage IA2 to IIA2 Cervical Cancer: A Matched Cohort Study.

OBJECTIVE: The aim of the study was to investigate the long-term oncological outcomes of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for treatment of stage IA2 to IIA2 cervical cancer. METHODS: We matched stage IA2 to IIA2 cervical cancer patients with known risk factors for recurrence who underwent ARH or LRH. RESULTS: After matching, a total of 203 patient pairs (LRH-ARH) were included. The LRH and ARH group had similar 5-year recurrence-free survival (RFS) rates (91.3% vs 90.4%, P = 0.83) and overall survival (OS) rates (93.2% vs 92.1%, P = 0.94). Patients with different tumor size (≤2, 2-4, >4 cm) had similar 5-year OS and RFS. Even in patients with pelvic lymph node metastasis, the 5-year RFS (69.20% vs 69.20%, P = 0.87) and OS (77.4% vs 76.3%, P = 0.83) did not differ statistically between the 2 groups. The LRH and ARH group had similar mean time to recurrence (16.29 vs 22.15 months, P = 0.68) and pattern of recurrence (P = 0.63). Compared with ARH, LRH resulted in significantly shorter operating time, less blood loss, and shorter hospital stay. The intraoperative complications rate was similar between the 2 groups (P = 0.72). The rate of postoperative complications was significantly lower in the LRH group than in the ARH group (P = 0.004). CONCLUSIONS: Laparoscopic radical hysterectomy was associated with fewer operating time, blood loss, postoperative complication, and earlier recovery. Laparoscopic radical hysterectomy is an oncologically safe alternative to ARH.

FABP5 correlates with poor prognosis and promotes tumor cell growth and metastasis in cervical cancer.

Fatty acid-binding protein 5 (FABP5) was found in our previous study to be a potential biomarker for lymph node metastasis of cervical cancer. However, the roles of FABP5 in cervical cancer remain unclear. In the present study, FABP5 expression was found to be significantly upregulated in cervical cancer tissues, and high FABP5 expression was significantly correlated with lymph node metastasis, lymphovascular space invasion, the International Federation of Gynecology and Obstetrics (FIGO) stage, and tumor size. Moreover, FABP5 was an independent factor for poor prognosis in cervical cancer patients. Silencing of FABP5 inhibited cell proliferation, colony formation, cell migration, and invasion in vitro. Furthermore, FABP5 silencing significantly reduced tumor growth and lung metastases in a murine allograft model in vivo. In addition, FABP5 silencing decreased the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in vitro and in vivo. Collectively, these findings indicated that FABP5 plays an important role in the carcinogenesis and metastasis of cervical cancer, and FABP5 may be a novel predictor for prognostic assessment of cervical cancer patients.

Barcoded sequencing reveals diverse intrauterine microbiomes in patients suffering with endometrial polyps.

Results of this study showed that the bacterial composition in vagina (V) greatly differed from intrauterine microbiome (I). Microbiomes were present in all intrauterine samples of healthy women (Group H (I)) and patients with endometrial polyps (EP) (including Group EP (I) and Group EP/chronic endometritis (CE) (I)). Indeed, the intrauterine bacteria population in Group EP/CE (I) were more diverse than those in Groups EP (I) and H (I). The result also confirmed the bacterial composition differences between vagina and uterus as well as the intrauterine microbiome alteration in the patients, compared to the healthy. Although bacteria of Proteobacteria, Firmicutes and Actinobacteria, dominated the intrauterine microbiome in all samples, however, proportions of Firmicutes from Group EP/CE (I) and Group EP (I) were much higher than that from Group H (I), in contrast, the proportions of Proteobacteria were far lower than the healthy. At the genus level, compared to Group H (I), it is found that proportions of Lactobacillus, Gardnerella, Bifidobacterium, Streptococcus, and Alteromonas were significantly higher, and that of Pseudomonas were significantly lower in Group EP/CE (I) or Group EP (I). In addition, lower proportions of Enterobacter and Sphingomonas and a higher proportion of Prevotella were also observed in Group EP/CE (I). In conclusion, uterine microbiomes between patients with EP and the healthy are significantly different and all the potentially important variation of uterine microbes may cause EP, but not definitively related to CE. Further experiments should be performed to test these relationships to endometritis occurrence.

Pharmacologic Interventions in Preventing Ovarian Hyperstimulation Syndrome: A Systematic Review and Network Meta-Analysis.

Ovarian hyperstimulation syndrome (OHSS) is a severe iatrogenic complication of controlled ovarian stimulation. Randomised controlled trials (RCTs) have proven several pharmacologic interventions to be effective in OHSS prevention, but these trials have seldom compared multiple drugs. We identified randomised controlled trials (RCTs) through June 2015 by searching databases and compared 11 intervention strategies in preventing OHSS (primary outcome) and their influence on pregnancy rate (secondary outcome). A network meta-analysis was used to evaluate the relative effectiveness among treatments and to create a rank probability table. Thirty-one RCTs were identified, including 7181 participants. Five pharmacologic interventions were superior to placebo in decreasing OHSS incidence: aspirin [relative risk (RR) 0.07, 95% credible interval (CrI) 0.01-0.30, p < 0.05], intravenous (IV) calcium [RR 0.11, 95% CrI 0.02-0.54, p < 0.05], cabergoline [RR 0.17, 95% CrI 0.06-0.43, p < 0.05], metformin [RR 0.20, 95% CrI 0.07-0.59, p < 0.05] and IV hydroxyethyl starch (HES) [RR 0.26, 95% CrI 0.05-0.99, p < 0.05]. The rank probability demonstrated aspirin (Rank 1: 36%) and IV calcium (Rank 1: 35%) to be the most efficacious. Additionally, albumin might decrease the pregnancy rate when compared with placebo [RR 0.85, 95% CI 0.74-0.97, p < 0.05]. This conclusion provides a relative standard and objective reference for choosing an OHSS prophylactic agent.

CPE overexpression is correlated with pelvic lymph node metastasis and poor prognosis in patients with early-stage cervical cancer.

PURPOSE: Elevated carboxypeptidase E (CPE) levels play crucial roles in tumorigenesis and metastasis. This study investigated the expression and clinicopathological significance of CPE in early-stage cervical cancer. METHODS: Elevated carboxypeptidase E expression was analyzed using quantitative polymerase chain reaction and western blotting in normal cervical tissue, cervical cancer cell lines, and in cervical cancer tissues and adjacent noncancerous tissues (ANTs) from the same patient. Immunohistochemistry (IHC) was used to examine CPE expression in tissue samples from 112 patients with early-stage cervical cancer (FIGO stages Ia2-IIa2), 60 patients with cervical intraepithelial neoplasia, and 19 patients with normal cervical tissues (NCTs). Associations between CPE expression and prognostic and diagnostic factors were evaluated statistically. RESULTS: CPE expression was significantly higher in cervical cancer cell lines and tissues than in normal tissues and ANTs. Semi-quantitative analysis of IHC indicated that CPE gradually increased from CIN I to cervical cancer, but was absent in NCTs. CPE expression was seen in 40.2 % (45/112) of the cervical cancer samples. CPE expression was significantly associated with FIGO stage (P = 0.003), tumor size (P = 0.012), stromal invasion (P < 0.001), lymphovascular space invasion (P = 0.016), parametrial infiltration (P = 0.027), vaginal involvement (P = 0.007), postoperative adjuvant therapy (P = 0.024), recurrence (P < 0.001), survival (P < 0.001), and pelvic lymph node metastasis (PLNM) (P < 0.001), and it was significantly higher in tissues from patients with PLNM than without PLNM. Logistic regression analysis identified high-level CPE expression as an independent risk factor for PLNM (P = 0.001). Patients with higher CPE expression had shorter overall survival duration than patients with lower CPE expression. Univariate and multivariate Cox-regression analyses suggested that high-level CPE expression is an independent prognostic factor for overall survival in early-stage cervical cancer. CONCLUSIONS: High-level CPE expression was associated with a poor prognosis in early-stage cervical cancer. CPE may serve as a biomarker for predicting PLNM and survival in these patients.

Early cervical cancer impact of peritoneal vaginoplasty combined with laparoscopic radical hysterectomy improved sexual function.

OBJECTIVE: We investigated the impact of laparoscopic radical hysterectomy (LRH) in combination with peritoneal vaginoplasty (PV) in improving sexual function after radical hysterectomy (RH) in patients with early cervical cancer. METHODS: A total of 79 patients with early-stage cervical cancer younger than 45 years were assigned to receive LRH in combination with PV (the LRH-PV group; n = 31) or LRH alone (the LRH group; n = 48). Other 40 healthy females were selected as controls (the control group). The sexual function was assessed with Female Sexual Functioning Index (FSFI). The FSFI scores and sexual function in the postoperative 1 year were compared between the LRH-PV and LRH groups, LRH-PV and control groups, and LRH and control groups, respectively. RESULTS: Patients with LRH-PV showed significantly higher scores in sexual satisfaction, lubrication, pain, and total score than those with LRH alone (P < 0.05) but were not statistically different in scores regarding sexual desire, arousal, and orgasm (P > 0.05). Healthy controls showed the highest in total scores and 6 domains among all subjects. In addition, the FSFI total scores in the LRH-PV group, LRH group, and LRH-PV + LRH group were significantly decreased compared with the control (P < 0.05). CONCLUSIONS: Peritoneal vaginoplasty to lengthen the vagina improves sexual function of patients with early cervical cancer receiving LRH in sexual satisfaction, lubrication, and pain.

Analyzing simultaneous positive expression of EZH2 and P53 protein to improve predictive value in cervical squamous cell carcinoma.

OBJECTIVE: The current study was undertaken to investigate the predictive value of simultaneous enhancer of zeste homolog 2 (EZH2) and P53 expression in lesions of patients with cervical squamous cell carcinoma. METHODS: Quantum dot double fluorescence staining was applied to detect EZH2 and P53 protein in biopsy tissue of 168 patients with cervical squamous cell carcinoma. The expression was classified into double positive (EZH2 and P53 were positively expressed), single positive (either EZH2 or P53 was positively expressed), and double negative (neither was positively expressed). The EZH2 and P53 expression, clinical stages of cervical cancer, lymph node metastasis, progression-free survival, and overall survival were analyzed. RESULTS: A relationship of EZH2 and P53 expression with the clinical stage of cervical cancer and lymph node metastasis was indicated. Simultaneous detection of both proteins could partly predict prognosis, consistent with previous studies' results. The current study demonstrated that the expression levels of EZH2 and P53 in tumor tissue and the proportion of cases with double-positive expression significantly increased with increasing clinical stages of cancer, also confirming up-regulated expression of EZH2 and P53 with increasing stages. These findings may suggest that the 2 proteins were involved in the development of cervical cancer, but the nature of their interaction is undefined. The increase of EZH2 and P53 expression in patients with lymph node metastasis indicated that they may be involved in metastasis of cervical cancer. CONCLUSION: Simultaneous positive EZH2 and P53 expression could improve the predictive value of a poor prognosis in cervical cancer.

Transvaginal surgical management of cesarean scar pregnancy: analysis of 49 cases from one tertiary care center.

OBJECTIVE: To investigate the safety and effectiveness of transvaginal surgical management of cesarean scar pregnancy (CSP). STUDY DESIGN: Retrospective analysis of 49 CSP patients who received transvaginal surgery in our hospital between December 2009 and April 2013. Patients were divided into two groups. Group A (30 patients) was defined as patients who had not received any treatment before transvaginal surgical management. Group B (19 patients) referred to patients who had received any previous treatment. Preoperative, intraoperative and postoperative data of both groups were collected and analyzed retrospectively. RESULTS: Preoperative serum ß-hCG level, preoperative hemoglobin level and average serum ß-hCG resolution time of group A and group B were 53,458.50 (36,382.00-94,100.50) versus 9779.00 (932.50-29623.00)U/l, 123.87±10.95 versus 109.94±16.05 g/l and 3.55±1.81 versus 1.83±1.15 weeks (P<0.05). Vaginal bleeding and gestational age in group A were significantly lower than in group B, 2.5 (0.50-11.00) versus 15.00 (3.50-31.50) days and 52.50 (46.50-56.70) versus 60.00 (48.00-90.00) days, respectively (P<0.05). The operative time, estimated blood loss, postoperative hospital stay, hospitalization expenses and menstruation recovery time of group A and group B were 56.61±24.40 versus 67.56±43.52 min, 45.65±27.83 versus 76.67±50.87 ml, 5.10±2.89 versus 5.33±3.99 days, 9001.94±1848.37 versus 11,032.33±5534.14 RMB and 1.16±0.47 versus 1.26±0.63 month respectively, which were similar between the two groups (P>0.05). The intraoperative complication rate in group A was significantly lower than group B, 0 (0/30) versus 21.05% (4/19) (P<0.05). The postoperative complication rate and total complication rate in group A and group B were 10.00% (3/30) versus 21.05% (4/19) and 10.00% (3/30) versus 31.58% (6/19) (P>0.05), respectively. CONCLUSION: Transvaginal surgery is an effective and relatively safe treatment option for CSP patients.

Successful treatment of cervical incompetence using a modified laparoscopic cervical cerclage technique: a cohort study.

OBJECTIVE: We introduce a modified surgical method for laparoscopic cervical cerclage (LCC) and compare the operative data and obstetric outcomes to those obtained by traditional vaginal cerclage (TVC). STUDY DESIGN: This is a prospective cohort study in a university-affiliated hospital from August 2008 through February 2013. Nineteen patients treated by LCC were prospectively monitored and the treatment outcomes were compared to a control group consisted of 25 patients that were retrospectively studied and treated with TVC using traditional McDonald suture. Laparoscopic cervical cerclage was performed with Mersilene tape and a modified surgical technique. Perioperative complications and obstetric outcomes were compared between LCC and TVC treatment groups. RESULTS: No perioperative complications occurred during LCC treatment. Of the 19 LCC patients, 15 (78.9%) became pregnant during the study period. The fetal salvage rate was 92.3% (12/13) and no adverse events were encountered. The mean gestational age in LCC group was 36.4 weeks, and it was 17.4 weeks longer than their previous pregnancy age, which was significantly higher than obtained by TVC. CONCLUSION: This modified technique for laparoscopic cervical cerclage demonstrates good obstetric outcomes with low risk of adverse events, which may provide a reasonable alternative to achieve pregnancy success in patients with cervical incompetence.

Marine compound catunaregin inhibits angiogenesis through the modulation of phosphorylation of akt and eNOS in vivo and in vitro.

Angiogenesis is the formation of blood vessels from pre-existing vasculature. Excessive or uncontrolled angiogenesis is a major contributor to many pathological conditions whereas inhibition of aberrant angiogenesis is beneficial to patients with pathological angiogenesis. Catunaregin is a core of novel marine compound isolated from mangrove associate. The potential anti-angiogenesis of catunaregin was investigated in human umbilical vein endothelial cells (HUVECs) and zebrafish. HUVECs were treated with different concentrations of catunaregin in the presence or absence of VEGF. The angiogenic phenotypes including cell invasion cell migration and tube formation were evaluated following catunaregin treatment in HUVECs. The possible involvement of AKT, eNOS and ERK1/2 in catunaregin-induced anti-angiogenesis was explored using Western blotting. The anti-angiogenesis of catunaregin was further tested in the zebrafish embryo neovascularization and caudal fin regeneration assays. We found that catunaregin dose-dependently inhibited angiogenesis in both HUVECs and zebrafish embryo neovascularization and zebrafish caudal fin regeneration assays. In addition, catunaregin significantly decreased the phosphorylation of Akt and eNOS, but not the phosphorylation of ERK1/2. The present work demonstrates that catunaregin exerts the anti-angiogenic activity at least in part through the regulation of the Akt and eNOS signaling pathways.

Treatment of uterine arteriovenous malformation by myometrial lesion resection combined with artery occlusion under laparoscopy: a case report and literature review.

Uterine arteriovenous malformation (AVM) is an uncommon, potentially life-threatening condition, and the primary therapeutic method is embolization. We describe a case of a 36-year-old woman with acquired uterine AVM accompanied by abnormal vaginal bleeding. The diagnosis was established by Doppler flow ultrasonography combined with magnetic resonance arteriography. Because this uterine AVM was extensive and multiple, uterine arterial embolization could not be considered. We therefore employed a combined method under laparoscopy, in which the uterine arteries were first occluded, then uterine myometrial lesions were resected and abnormal pelvic blood vessels were ablated. Finally, the uterus was reconstructed with an intact uterine cavity. Abnormal vaginal bleeding was successfully stopped after operation, but amenorrhea due to uterine adhesions occurred. This method is suitable for the treatment of uterine AVM with extensive and multiple lesions, but it should be chosen cautiously for women of reproductive age with AVM and fertility requirement.

Laparoscopic uterine anastomosis for traumatic separation of the cervix from the uterine corpus caused by closed pelvic fracture: case report and literature review.

Primary amenorrhea caused by separation of the cervix from the uterine body resulting from pelvic trauma is exceptionally rare. This case report describes the diagnosis and successful laparoscopic approximation of traumatic separation of the cervix from the uterine corpus. A 16-year-old girl who was involved in a car accident at age 2 years had primary amenorrhea and cyclic abdominal pain. A closed pelvic fracture was managed nonsurgically, with an uneventful recovery. Since age 13 years, the patient has been experiencing cyclic abdominal pain. Ultrasonography suggested a 5-cm left adnexal mass. Diagnostic laparoscopy revealed complete separation of the uterine corpus from the cervix, and an endometrioma in the left ovary. The uterine corpus was approximated to the cervix with circumferentially placed sutures under direct laparoscopic guidance. The endometrioma was resected concomitantly. Normal cyclic menstruation resumed 2 months postoperatively, without cyclic abdominal pain. This case report demonstrates successful laparoscopic approximation of traumatic separation of the uterine corpus from the cervix, manifested as primary amenorrhea.

Management and reproductive outcome of complete septate uterus with duplicated cervix and vaginal septum: review of 21 cases.

AIM: To evaluate the reproductive outcomes of complete septate uterus with duplicated cervix and vaginal septum. METHODS: Twenty-one patients who have complete septate uterus with duplicated cervix and vaginal septum were retrospectively reviewed in this study. In Group I, 11 patients with a poor reproductive outcome (spontaneous miscarriage or infertility) or dyspareunia underwent hysteroscopic metroplasty and removal of vaginal septum with the preservation of cervical septum. In Group II, 10 patients without a history of spontaneous miscarriage did not undergo hysteroscopic transection of the uterine septum. Of 10, four underwent vaginal septum incision due to dyspareunia, two underwent mere laparoscopic pelvic adhesiolysis because of infertility, and four without symptoms had no intervention. The primary endpoints included the pregnancy rate and outcomes of pregnancies. RESULTS: In Group I, the pregnancy rate after surgery is 81.8 % (9/11). Of nine women who conceived, six had term delivery, one encountered induced abortion due to the malformation of the fetal heart, and two had ongoing pregnancy. In Group II, among six patients accepting surgery, three had term delivery. The pregnancy rate after operation is 50 % (3/6). CONCLUSIONS: The uterine septum may not necessarily be transected for patients who have complete septate uterus with duplicated cervix and vaginal septum, and meanwhile have no a history of poor reproductive outcome.

Expression of human ß-defensin-2 in the eutopic and ectopic endometrial tissues in patients with endometriosis.

OBJECTIVE: To investigate the expression of human ß-defensin-2 (hBD-2) in the endometrium of patients with endometriosis (EMS) and explore the potential role of hBD-2 in the pathogenesis of EMS. DESIGN: Prospective controlled study. SAMPLE: 50 women including EMS patients undergoing laparoscopic ovarian cystectomy and non-EMS patients undergoing hysterectomy for uterine fibroids. SETTING: Large university teaching hospital. METHODS: Patients were divided into EMS and non-EMS groups. The gene expressions of hBD-2, interleukin (IL)-1ß and tumor necrosis factor (TNF)-α in the endometrial tissues of each group were detected with real-time quantitative polymerase chain reaction (PCR), and hBD-2 protein expression with immunohistochemical method. RESULTS: The gene expression levels of hBD-2, TNF-α, and IL-1ß as well as the positive expression rate of hBD-2 protein in the ectopic endometrium of EMS patients were significantly higher than those in the eutopic endometrium of EMS and non-EMS patients (all P < 0.05). Correlation analysis showed that the gene expression levels of hBD-2 in the ectopic and eutopic endometrium of EMS patients were positively correlated with the gene expression levels of IL-1ß and TNF-α (P < 0.01). CONCLUSION: High levels of hBD-2 gene and protein expressions in the ectopic endometrium of EMS patients may be an important contributor in the pathogenesis of EMS. TNF-α and IL-1ß may promote the upregulation of hBD-2 expression.

FOXM1 promotes tumor cell invasion and correlates with poor prognosis in early-stage cervical cancer.

OBJECTIVE: The forkhead box M1 (FOXM1) transcription factor plays crucial roles in regulating the proliferation, differentiation, and transformation of cells. Overexpression of FOXM1 is associated with a variety of aggressive solid carcinomas, including cervical cancer. However, the precise role and molecular mechanism responsible for the aggressive action of FOXM1 in cervical cancer remain unclear. This study investigated the cellular and molecular aggressive function of FOXM1 in cervical cancer. METHODS: The FOXM1 gene and protein expression profiles were determined by quantitative polymerase chain reaction, Western blotting and immunohistochemical staining, and other cellular and molecular approaches including gene transfection, short hairpin RNA interference (RNAi), and wound-healing, migration, and invasion assays. RESULTS: FOXM1 expression was significantly up-regulated at both mRNA and protein levels in early-stage cervical cancer, compared to cervical intraepithelial neoplasia and normal cervical tissues. High levels of FOXM1 expression were significantly associated with aggression in cervical cancer, and were an independent prognostic factor for poor survival in early-stage cervical cancer patients. Moreover, enforced expression of FOXM1 increased migration and invasion of cancer cells, whereas RNAi-mediated knockdown of FOXM1 had the opposite effect. In addition, up-regulation of FOXM1 increased the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 in vitro and in vivo, and activated the Akt/glycogen synthase kinase-3ß/Snail pathway, resulting in the promotion of migration and invasion of cervical cancer cells. CONCLUSIONS: These results suggest that FOXM1 up-regulation is associated with poor prognosis in early-stage cervical cancer, and therefore it may act as a prognostic marker and a new potential target for cervical cancer treatment.