NGF and HB-EGF: potential biomarkers that reflect the effects of fesoterodine in patients with overactive bladder syndrome

PURPOSE: To determine whether levels of nerve growth factor (NGF) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) can be used to objectively assess overactive bladder syndrome (OAB) treatment outcome and to evaluate the effects of fixed-dose fesoterodine on OAB symptoms. MATERIALS AND METHODS: This study included 124 participants (62 patients with OAB and 62 controls) in Severance Hospital between 2010 and 2012. In patients with OAB, 4 mg fesoterodine was administered once daily. Repeated evaluations of putative biomarker levels, urine creatinine (Cr) levels, and questionnaire responses, including the Overactive Bladder Symptom Score (OABSS) and the Overactive Bladder Questionnaire (OAB q), were performed from baseline to 16 weeks. RESULTS: Urinary levels of NGF/Cr (OAB: 1.13±0.9 pg/mg; control: 0.5±0.29 pg/mg) and HB-EGF/Cr (OAB: 8.73±6.55 pg/mg; control: 4.45±2.93 pg/mg) were significantly higher in subjects with OAB than in controls (p<0.001). After 16 weeks of fixed-dose fesoterodine treatment, urinary NGF/Cr levels (baseline: 1.13±0.08 pg/mg; 16 weeks: 0.60±0.4 pg/mg; p=0.02) and HB-EGF/Cr levels significantly decreased (baseline: 8.73±6.55 pg/mg; 16 weeks: 4.72±2.69 pg/mg; p=0.03, respectively). Both the OABSS and OAB q scores improved (p<0.001). However, there were no a statistically significant correlations between these urinary markers and symptomatic scores. CONCLUSION: Urinary levels of NGF and HB-EGF may be potential biomarkers for evaluating outcome of OAB treatment. Fixed-dose fesoterodine improved OAB symptoms. Future studies are needed to further examine the significance of urinary NGF and HB-EGF levels as therapeutic markers for OAB.ope

Postpartum urinary retention after vaginal delivery:

Objective: To evaluate the incidence of postpartum urinary retention (PUR) after vaginal delivery and to determine the risk factors for PUR. Methods: A retrospective case-control study of parturients with PUR after vaginal delivery between June 2007 and July 2008. Four controls, matched for date of delivery, were selected for each case in univariate and multivariate conditional logistic regression analyses. Results: There were 860 deliveries and 52 cases of PUR (incidence, 6%). All cases of PUR were managed with insertion of a Foley catheter with resolution before hospital discharge. Univariate analysis showed birth weight, increasing duration of the first and second stages of labor, biparietal diameter, perineal trauma, and epidural anesthesia to be significantly associated with PUR. Only perineal trauma remained statistically significant based on multivariate analysis. Conclusion: Perineal trauma was identified as the single most important associated risk factor for PUR after vaginal delivery. The findings of this study provide information for further exploration on how to reduce perineal trauma during vaginal deliveryope

Changes in sexual function and comparison of questionnaires following surgery for pelvic oran prolapse

PURPOSE: The aim of this study was to evaluate the effect of surgical repair of pelvic organ prolapse on female sexual function and to assess correlations between the two using two current standardized questionnaires. MATERIALS AND METHODS: From October 2009 to September 2010, 143 patients with posterior compartment or combined vaginal prolapse were included. We assessed surgical outcomes according to anatomical change in the vagina and results of the Female Sexual Function Index (FSFI) and Pelvic Organ Prolapse/Urinary Incontinence Sexual Function questionnaire (PISQ-12) both pre- and postoperatively. RESULTS: Among the 143 preoperative patients, 99 and 84 patients responded to the PISQ-12 and FSFI, respectively. The mean PISQ-12 score increased after surgery (p<0.001). Specifically, postoperative scores for questions 8 and 12 were higher than their respective preoperative scores (p<0.001). Postoperatively, mean FSFI score changed only slightly (p=0.76), and only the score for the satisfaction domain was improved (p=0.023). In regards to vaginal anatomy, vaginal length was significantly greater postoperatively (6.99±0.18 vs. 7.56±1.08, p<0.001), and postoperative vaginal caliber was narrowed to a two-finger width. CONCLUSION: In this study, surgery for pelvic organ prolapse was shown to affect female sexual function. Moreover, menopause was associated with a change in postoperative sexual function.ope

Comparison of perioperative, long-term complications and recurrence rates after vaginal prolapse surgery by considering ICS POP-Q stage.

OBJECTIVE: The aim of this study was to report subjective and objective outcomes and to compare complication and recurrence rate in patients undergoing surgery for International Continence Society (ICS) stage 4 prolapse compared to ICS stage 2 or 3 prolapse. METHODS: We retrospectively reviewed the records of all patients having had surgical treatment for ICS Pelvic Organ Prolapse Quantification (POP-Q) stage 2-4 prolapse between January 2007 and December 2010 at the Yonsei University Severance Hospital. Only patients with ICS POP-Q stage 2-4 prolpase undergoing obliterative procedures or anti-incontinence surgery only were excluded. RESULTS: Three hundred ninety nine patients met inclusion criteria, including 23 with stage 2, 239 with stage 3 and 137 with stage 4 prolapse. The postoperative recurrence rate of preoperative stage IV was 2.4 times higher than that of stage III. There was a significantly higher incidence rates of perioperative and long-term complications, compared to women with other stage prolapse. The mean operative time was significantly greater in the stage 4 group compared to the stage 2, 3 group. CONCLUSION: The overall perioperative complication and recurrence rates in women undergoing surgery for pelvic organ prolapse are low. Women undergoing surgery for ICS POP-Q stage 4 prolapse were found to have a significantly greater blood loss and higher incidence rates of perioperative complications and recurrence, compared with women of other stage.ope

Outcome of mid urethral sling procedures according to age

Objective: To compare the morbidity and treatment outcomes of mid urethral sling procedures for older women and younger women, and to evaluate whether mid urethral sling procedures can be effectively used in older women. Methods: This retrospective study included 381 patients who underwent mid urethral sling procedures, tension free vaginal tape (TVT) or transobturator tape (TOT) for urodynamic stress urinary incontinence from March 2000 to June 2006. The patients were divided into two age groups: younger women (30~69 years old) and older women (70~90 years old). Patients were followed up with clinic visits at 1, 3, 6, 12 months, and every year thereafter. Results: 341 (89.7%) were in younger women, 40 (10.5%) in older women. The rates of intra and perioperative complications including hemoglobin difference, urinary retention, UTI, mesh erosion, wound infection were no significant differences between the groups. De novo urgency was more common in older women than younger women (15.9% vs. 30.0%: P0.05) showed no significant differences. Conclusion: Our data showed subjective cure rates without any significant increase in intraoperative complications in older women. Postoperative complications of de novo urgency were more common in the older women. Hospital stay and recovery period were short, making TVT and TOT a suitable procedure for all agesope

MicroRNA-30d and microRNA-181a regulate HOXA11 expression in the uterosacral ligaments and are overexpressed in pelvic organ prolapse

The balanced turnover of collagen is necessary to maintain the mechanical strength of pelvic supportive connective tissues. Homeobox (HOX) A11 is a key transcriptional factor that controls collagen metabolism and homoeostasis in the uterosacral ligaments (USLs), and the deficient HOXA11 signalling may contribute to alterations in the biochemical strength of the USLs, leading to pelvic organ prolapse (POP). However, it is unknown how HOXA11 transcripts are regulated in the USLs. In this study, we found that microRNA (miRNA)-30d and 181a were overexpressed in women with POP, and their expression was inversely correlated with HOXA11 mRNA levels. The overexpression of miR-30d or 181a suppressed HOXA11 mRNA and protein levels in 293T cells, whereas the knockdown of these miRNAs enhanced HOXA11 levels and collagen production. Cotransfection of a luciferase reporter plasmid containing the 3'-untranslated region of HOXA11 with miR-30d or 181a mimic resulted in decreased relative luciferase activity. Conversely, cotransfection with anti-miR-30d or 181a increased luciferase activity. Taken together, these results indicate that both miR-30d and 181a are important posttranscriptional regulators of HOXA11 in the USLs and could be a potential therapeutic target for POP.ope

골반장기탈출증에서 탄력섬유 대사의 변화

Dept. of Medicine/석사[한글] [영문]Objective: To compare elastin metabolism in the uterosacral ligament of women with and without pelvic organ prolapse (POP), and to define the menopausal regulation of this process.Methods: The study group consisted of 35 women who underwent hysterectomy for advanced (stage III-IV) POP. The control group consisted of 39 women without POP. A questionnaire was administered to assess age, parity, body mass index, and menopausal status. Expression levels of the mRNA and protein for elastolytic proteases, including neutrophil elastase (NE), matrix metalloproteinase (MMP)-2, and MMP-9, were determined by real-timequantitative polymerase chain reaction and enzyme-linked immunosorbentassay, respectively, using uterosacral ligament samples from each patient. Expression of alpha-1-antitrypsin (AAT), an inhibitor of NE, was also determined. ANOVA, Kruskal-Wallis test, and multivariate linear regression were utilized for statistical analysis.Results: Expression of NE and MMP-2 mRNA was higher in women with POP than without POP. Compared to premenopause, NE and MMP-2 showed a significant decrease in postmenopausal women without POP, although these remained elevated in postmenopausal women with POP. AAT was significantly less in postmenopausal women with POP than postmenopausal women without POP. The activities of NE, MMP-2, and MMP-9 were increased in women withPOP, and these trends were similar to NE and MMP-2 expression, even after adjustment for age, parity, and menopausal status.Conclusion: After menopause, elevated elastolytic protease activity could play a significant role in the development of POP.ope

Two-year urinary outcomes of sacrocolpopexy with or without transobturator tape: results of a prolapse-reduction stress test-based approach

INTRODUCTION AND HYPOTHESIS: Women undergoing sacrocolpopexy (SCP) are at risk for postoperative stress urinary incontinence (SUI). However, the optimal management for this condition remains debatable. The aim of this study was to evaluate urinary outcomes 2 years after SCP with or without transobturator tape (TOT) based on the results of a prolapse-reduction stress test. METHODS: A prospective, observational study was conducted assessing a cohort of women undergoing SCP. Patients were assigned to the TOT or non-TOT group based on results of a prolapse-reduction stress test. The primary outcome was SUI (defined as a positive cough stress test or bothersome symptoms) or additional surgery for this condition. RESULTS: Among the 247 women enrolled, 223 (90 %) received surgery per assignment and completed the follow-up. Two years after surgery, 5.4 % of women in the TOT group and 28.6 % in the non-TOT group had SUI or received additional anti-incontinence surgery (p < 0.01). In the non-TOT group, more women with symptoms of SUI prior to surgery had postoperative SUI or received additional anti-incontinence surgery than those without symptoms (42.9 % vs. 20.0 %, p = 0.01). CONCLUSIONS: A preoperative prolapse-reduction stress test alone is not sufficient to determine the need for anti-incontinence surgery at the time of SCP. In particular, women with symptoms of SUI despite a negative prolapse-reduction stress test are more likely to experience postoperative SUI or additional anti-incontinence surgery.ope

과민성 방광 치료의 최신 요법 : 약물적 치료

ope

Estrogen-related genome-based expression profiling study of uterosacral ligaments in women with pelvic organ prolapse

INTRODUCTION AND HYPOTHESIS: The aim of the study was to identify the differential expression of estrogen-related genes that may be involved in the menopause and pelvic organ prolapse (POP) using microarray analysis. METHODS: An age, parity, and menopausal status-matched case-control study with 12 POP patients and 5 non-POP patients was carried out. The study was conducted from January to December 2010 at Yonsei University, Severance Hospital. We examined microarray gene expression profiles in uterosacral ligaments (USLs) from POP and non-POP patients. Total RNA was extracted from USL samples to generate labeled cDNA, which was hybridized to microarrays and analyzed for the expression of 44,049 genes. We identified differentially expressed genes and performed functional clustering. After clustering, we focused on transcriptional response and signal transduction gene clusters, which are associated with estrogen, and then validated the changes of gene expression levels observed with the microarray analysis using quantitative polymerase chain reaction (qPCR). RESULTS: The data from the microarray analysis using more than a 1.5-fold change with p value <0.05 resulted in 143 upregulated genes and 87 downregulated genes. Of 59 genes identified to be associated with signal transduction and transcription, 4 genes were chosen for qPCR that have been classified to be associated with estrogen. We found that estrogen receptor-related receptor-α (ERRα) was downregulated and that the expression of death-associated protein kinase 2 (DAPK 2), signal-transducing adaptor protein-2 (STAP-2), and interleukin (IL)-15 were upregulated. CONCLUSIONS: We found four differentially expressed genes by microarray analysis that may account for the way in which changes in estrogen level affect POP pathophysiology.ope