Investigating Novel Genes Potentially Involved in Endometrial Adenocarcinoma using Next-Generation Sequencing and Bioinformatic Approaches.

Endometrial cancer is one of the most common cancers in women worldwide, affecting more than 300,000 women annually. Dysregulated gene expression, especially those mediated by microRNAs, play important role in the development and progression of cancer. This study aimed to investigate differentially expressed genes in endometrial adenocarcinoma using next generation sequencing (NGS) and bioinformatics. The gene expression profiles and microRNA profiles of endometrial adenocarcinoma (cancer part) and normal endometrial tissue (non-cancer part) were assessed with NGS. We identified 56 significantly dysregulated genes, including 47 upregulated and 9 downregulated genes, in endometrial adenocarcinoma. Most of these genes were associated with defense response, response to stimulus, and immune system process, and further pathway analysis showed that human papillomavirus infection was the most significant pathway in endometrial adenocarcinoma. In addition, these genes were also associated with decreased cell death and survival as well as increased cellular movement. The analyses using Human Protein Atlas, identified 6 genes (PEG10, CLDN1, ASS1, WNT7A, GLDC, and RSAD2) significantly associated with poorer prognosis and 3 genes (SFN, PIGR, and CDKN1A) significantly associated with better prognosis. Combining with the data of microRNA profiles using microRNA target predicting tools, two significantly dysregulated microRNA-mediated gene expression changes in endometrial adenocarcinoma were identified: downregulated hsa-miR-127-5p with upregulated CSTB and upregulated hsa-miR-218-5p with downregulated HPGD. These findings may contribute important new insights into possible novel diagnostic or therapeutic strategies for endometrial adenocarcinoma.

KRAS mutation coupled with p53 loss is sufficient to induce ovarian carcinosarcomas in mice.

Ovarian carcinosarcoma cancer is the most lethal form of gynecological malignancy, but the pathogenesis and biological function for this ovarian cancer remain unknown. We establishment the transgenic mouse model of K-rasG12D p53loxP/loxP and found that K-ras mutation and p53 deletion within the ovarian surface epithelium gave rise to ovarian lesions with a hyperproliferation and endometrioid glandular morphology. Furthermore, double mutant ovaries formed ovarian carcinosarcomas that were high grade and poorly differentiated. Induction was widely metastatic and spread to abdominal organs including liver, spleen, and kidney at 4 wk. We also confirmed the role of K-rasG12D in ovarian cancer cell lines MCAS and PA-1 and showed that K-rasG12D overexpression strongly induced cell proliferation, migration, and invasion. The ovarian cancer model we developed recapitulates the specific tumor histomorphology and the probable mechanism of malignant transformation in endometriosis.

Tape-Releasing Suture with "Long Loop" on Mid-Urethral Sling: A Novel Procedure for Management of Iatrogenic Urethral Obstruction.

BACKGROUND: To report our experiences of a tape-releasing suture with "long-loop" in women with iatrogenic urethral obstruction following the mid-urethral sling procedure. METHODS: A total of 149 women underwent a tape-releasing suture with "Long Loop" during the operation. Post-void residual volume was evaluated after Foley removal. Lower urinary tract symptoms and urodynamic studies were assessed before and six months postoperatively. RESULTS: Nine women out of 149 who underwent mid-urethral sling surgery were found to have iatrogenic urethral obstruction post-operatively based on their urinary symptoms and ultrasound findings. There was no apparent difference between tested groups in mid-urethral sling products and concomitant procedures. 77.8% had successful releases after the first Long-loop manipulation procedure, and 22.2% required two or more releases. However, the SUI cure rate is similar in groups receiving the Long-loop manipulation or not (88.9% and 87.1%, respectively). CONCLUSIONS: We are convinced of the practicability and efficacy of the tape-releasing suture "Long-loop." We adopted subjective and objective means to evaluate both groups before and after a six-month follow-up. The Long-loop manipulation procedure can successfully resolve the iatrogenic urethral obstruction without compromising the effectiveness of mid-urethral sling for the treatment of SUI.

Zinc Finger Protein 90 Knockdown Promotes Cisplatin Sensitivity via Nrf2/HO-1 Pathway in Ovarian Cancer Cell.

Our study discussed the role of Zfp90 in ovarian cancer (OC) cell lines' sensitivity to cisplatin. We used two OC cell lines, SK-OV-3 and ES-2, to evaluate their role in cisplatin sensitization. The protein levels of p-Akt, ERK, caspase 3, Bcl-2, Bax, E-cadherin, MMP-2, MMP-9 and other drug resistance-related molecules, including Nrf2/HO-1, were discovered in the SK-OV-3 and ES-2 cells. We also used a human ovarian surface epithelial cell to compare the effect of Zfp90. Our outcomes indicated that cisplatin treatment generates reactive oxygen species (ROS) that modulate apoptotic protein expression. The anti-oxidative signal was also stimulated, which could hinder cell migration. The intervention of Zfp90 could greatly improve the apoptosis pathway and block the migrative pathway to regulate the cisplatin sensitivity in the OC cells. This study implies that the loss of function of Zfp90 might promote cisplatin sensitization in OC cells via regulating the Nrf2/HO-1 pathway to enhance cell apoptosis and inhibit the migrative effect in both SK-OV-3 and ES-2 cells.

Effect of pelvic floor muscles exercises by extracorporeal magnetic innervations on the bladder neck and urinary symptoms.

BACKGROUND: This study aimed to investigate the changes in the bladder neck (BN) and urinary symptoms using extracorporeal magnetic innervation (ExMI) therapy before and after performing passive pelvic floor exercises. METHODS: Twenty women with stress urinary incontinence (SUI) were assessed by transperineal ultrasound and questionnaires before and after the ExMI therapy from January 2011 to February 2021. RESULTS: The incidence of urinary frequency and SUI were significantly decreased after the therapy (McNemar test, p < 0.01). The therapeutic efficacy of SUI was 75%. A significant decrease was noted in pad test results (paired t test, p < 0.05). At the same time, there was a considerable difference in Urinary Distress Inventory-6 scale measures (paired t test, p < 0.001). However, results for the Incontinence Impact Questionnaire-7 showed a marginally significant difference (paired t test, p = 0.066). Three domains of lubrication, orgasm, and satisfaction in the Female Sexual Function Index showed significant differences (paired t test, p < 0.05). Transperineal ultrasound found that BN mobility and Q-tip straining angle were not statistically significant (paired t test, p > 0.05). CONCLUSION: The ExMI is effective for SUI by strengthening the pelvic floor muscle without significantly decreasing BN mobility.

Predictors of voiding dysfunction following Uphold™ mesh repair for the treatment of pelvic organ prolapse.

OBJECTIVE: To identify factors associated with voiding dysfunction after Uphold™ transvaginal mesh (TVM) repair in women with pelvic organ prolapse (POP). STUDY DESIGN: We performed a retrospective analysis of 110 women with symptomatic pelvic organ prolapse (POP), anterior vaginal wall prolapse and/or apical prolapse (stage II to IV) who were scheduled for Uphold™ mesh surgery from September 2015 through December 2016. All subjects underwent urinalyses, UDI-6, IIQ-7, ICI-Q, POPDI-6, and pelvic examinations using the POP quantification (POP-Q) staging system before and after surgeries, with follow-up durations ranging from 24-36 months. RESULTS: A total of 12 (10.9 %) of 110 women reported voiding dysfunction after Uphold™ mesh surgery. Using univariate analysis, there were no differences in body mass index and urodynamic parameters between normal voiding group and dysfunctional voiding group (P > 0.05). However, in patients aged above 71, POPDI-6 score≧13, preoperative concomitant urinary hesitancy, and incomplete emptying were found to be significant predictors of voiding dysfunction following Uphold™ mesh surgeries (P < 0.05). CONCLUSION: In patients aged above 71, POPDI-6 score≧13, preoperative concomitant urinary hesitancy, and incomplete emptying were significant predictors of voiding dysfunction after Uphold™.

Evaluation of single-incision apical vaginal suspension for treatment of pelvic organ prolapse.

OBJECTIVE: To present a comprehensive evaluation of anterior/apical and/or posterior prolapse repair systems with a focus on safety and surgical efficacy. METHODS: Two hundred and twenty women with pelvic organ prolapse (POP) stage II-IV were referred for single-incision transvaginal mesh procedures in a single institution. Pre- and postoperative assessments included pelvic examination, urodynamic studies, and personal interviews about patients' quality of life and urinary symptoms. RESULTS: The anatomical success rate was 92.3 % (203/220), regardless of primary or de-novo POP, at 12-38 month follow-up. The POP quantification parameters, except total vaginal length, improved significantly after surgery (p < 0.05). Complications included bladder injury (one case), mesh exposure (six cases) and urinary retention that required intermittent catheterization (five cases). There were no cases of bowel injury during surgery. The results indicated that 29 % of patients had de-novo stress urinary incontinence and 7.7 % of patients had de-novo POP after surgery. CONCLUSION: The apical vaginal suspension system is a safe and effective procedure, creating good anatomical restoration and significant improvement in quality of life. However, the rate of de-novo POP in the anterior compartment of the vagina (31.8 %) seems high after treatment with apical and posterior prolapse repair systems.

Learning Curve Analysis of Different Stages of Robotic-Assisted Laparoscopic Hysterectomy.

Objective. To analyze the learning curves of the different stages of robotic-assisted laparoscopic hysterectomy. Design. Retrospective analysis. Design Classification. Canadian Task Force classification II-2. Setting. Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Patient Intervention. Women receiving robotic-assisted total and subtotal laparoscopic hysterectomies for benign conditions from May 1, 2013, to August 31, 2015. Measurements and Main Results. The mean age, body mass index (BMI), and uterine weight were 46.44 ± 5.31 years, 23.97 ± 4.75 kg/m2, and 435.48 ± 250.62 g, respectively. The most rapid learning curve was obtained for the main surgery console stage; eight experiences were required to achieve duration stability, and the time spent in this stage did not violate the control rules. The docking stage required 14 experiences to achieve duration stability, and the suture stage was the most difficult to master, requiring 26 experiences. BMI did not considerably affect the duration of the three stages. The uterine weight and the presence of adhesion did not substantially affect the main surgery console time. Conclusion. Different stages of robotic-assisted laparoscopic hysterectomy have different learning curves. The main surgery console stage has the most rapid learning curve, whereas the suture stage has the slowest learning curve.

Factors Associated with Types and Intensity of Postoperative Pain following Gynecological Laparoscopic Surgery: A Cross-Sectional Study.

OBJECTIVE: To evaluate influences of various factors on the types and intensity of postoperative pain following gynecologic laparoscopic surgery. STUDY DESIGN: Cross-sectional questionnaire and chart review. RESULTS: A total of 84 questionnaires were distributed and returned. The types of postlaparoscopic pain are different in multiparous women and nulliparous ones (71.43% surgical wound pain versus 63.64% nonsurgical wound pain, p = 0.0033) and those with striae gravidarum and without striae gravidarum (93.94% surgical wound pain versus 52.94% nonsurgical wound pain, p < 0.0001). On postoperative day 1, the average VAS score is higher in nonsurgical wound pain than in surgical wound pain (5.62 ± 1.50 versus 3.51 ± 1.68, p < 0.0001). The CO2 removal procedure has a significant negative correlation with the VAS of nonsurgical wound pain (coefficient: -0.4339, p = 0.0187). CONCLUSION: Our study suggests that women with abdominal rigidity (nulliparous, no striae gravidarum) experience mainly nonsurgical wound pain, while women with abdominal wall laxity mostly experience surgical wound pain. The VAS score of nonsurgical wound pain is greater than surgical wound pain on postoperative day 1. The CO2 removal procedure has negative correlation to the VAS score of nonsurgical wound pain on postoperative day 1.