Melatonin-Assisted Cisplatin Suppresses Urinary Bladder Cancer Cell Proliferation and Growth through Inhibiting PrPC-Regulated Cell Stress and Cell Proliferation Signaling.

This study investigated whether melatonin (Mel) would promote cisplatin to suppress the proliferation and growth of bladder cancer (BC) cells by inhibiting cellular prion protein (PrPC)-mediated cell stress and cell proliferation signaling. An immunohistochemical staining of tissue arrays from BC patients demonstrated that the PrPC expression was significantly upregulated from stage I to III BC (p < 0.0001). The BC cellline of T24 was categorized into G1 (T24), G2 (T24 + Mel/100 µM), G3 (T24+cisplatin/6 µM), G4 (PrPC overexpression in T24 (i.e., PrPC-OE-T24)), G5 (PrPC-OE-T24+Mel), and G6 (PrPC-OE-T24+cisplatin). When compared with a human uroepithelial cell line (SV-HUC-1), the cellular viability/wound healing ability/migration rate were significantly increased in T24 cells (G1) and further significantly increased in PrPC-OE-T24 cells (G4); and they were suppressed in Mel (G2/G5) or cisplatin (G3/G6) treatment (all p < 0.0001). Additionally, the protein expressions of cell proliferation (PI3K/p-Akt/p-m-TOR/MMP-9/PrPC), cell cycle/mitochondrial functional integrity (cyclin-D1/clyclin-E1/ckd2/ckd4/mitochondrial-cytochrome-C/PINK1), and cell stress (RAS/c-RAF/p-MEK1/2, p-ERK1/2) markers showed a similar pattern of cell viability among the groups (all p < 0.001). After the BC cell line of UMUC3 was implanted into nude mouse backs, by day 28 mthe BC weight/volume and the cellular levels of PrPC/MMP-2/MMP-9 were significantly, gradually reduced from groups one to four (all p < 0.0001). The protein expressions of cell proliferation (PI3K/p-Akt/p-m-TOR/MMP-9/PrPC), cell cycle/mitophagy (cyclin-D1/clyclin-E1/ckd2/ckd4/PINK1), and cell stress (RAS/c-RAF/p-MEK1,2/p-ERK1,2) signaling were significantly, progressively reduced from groups one to four, whereas the protein expressions of apoptotic (Mit-Bax/cleaved-caspase-3/cleaved-PARP) and oxidative stress/mitochondrial damaged (NOX-1/NOX-2/cytosolic-cytochrome-C/p-DRP1) markers expressed an opposite pattern of cell proliferation signaling among the groups (all p < 0.0001). Mel-cisplatin suppressed BC cell growth/proliferation via inhibiting the PrPC in upregulating the cell proliferation/cell stress/cell cycle signaling.

Laparoscopic pectopexy: the learning curve and comparison with laparoscopic sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: In addition to laparoscopic sacrocolpopexy (LS), laparoscopic pectopexy (LP) is a novel surgical method for correcting apical prolapse. The descended cervix or vaginal vault is suspended with a synthetic mesh by fixing the bilateral mesh ends to the pectineal ligaments. This study was aimed at developing a learning curve for LP and to compare it with results with LS. METHODS: We started laparoscopic/robotic pectopexy in our department in August 2019. This retrospective study included the initial 18 consecutive women with apical prolapse receiving LP and another group undergoing LS (21 cases) performed by the same surgeon. The medical and video records were reviewed. RESULTS: The age was older in the LP group than in the LS group (65.2 vs 53.1 years). The operation time of LP group was significantly shorter than that of the LS group (182.9 ± 27.2 vs 256.2 ± 45.5 min, p < 0.001). The turning point of the LP learning curve was observed at the 12th case. No major complications such as bladder, ureteral, bowel injury or uncontrolled bleeding occurred in either group. Postoperative low back pain and defecation symptoms occurred exclusively in the LS group. During the follow-up period (mean 7.2 months in LP, 16.2 months in LS), none of the cases had recurrent apical prolapse. CONCLUSIONS: Laparoscopic pectopexy is a feasible surgical method for apical prolapse, with a shorter operation time and less postoperative discomfort than LS. LP may overcome the steep learning curve of LS because the surgical field of LP is limited to the anterior pelvis and avoids encountering the critical organs.

Evaluation of the single-incision Elevate system to treat pelvic organ prolapse: follow-up from 15 to 45 months.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to assess the 2-year clinical outcomes of pelvic reconstructive surgery with the single-incision Elevate system (American Medical Systems, Minnetonka, MN, USA). METHODS: This retrospective study was conducted from November 2010 to August 2013, and included 210 patients with pelvic organ prolapse stage 3 or 4 who underwent pelvic reconstructive surgery with an Elevate system and were followed for 1 to 3 years postoperatively. Assessments included pre- and postoperative Pelvic Organ Prolapse Quantification (POP-Q) stage, Urogenital Distress Inventory (UDI-6), Incontinence Impact Questionnaire (IIQ-7) and multi-channel urodynamic examinations. Anatomical success was defined as postoperative POP-Q stage 0 or I. RESULTS: The anatomical success rates were 95 % for the anterior vaginal wall, 99 % for the posterior vaginal wall and 94 % for the apical vaginal wall after a median 27 months of follow-up. POP-Q, UDI-6 and IIQ-7 scores, maximal flow rate and post-voiding residual urine all improved significantly after surgery. Complications included 1 case of internal bleeding, 4 cases of mesh exposure, 5 cases of recurrent prolapse that required salvage operations, and 3 cases of urine retention that required intermittent catheterization. There were no bladder or bowel injuries during surgery. CONCLUSIONS: Pelvic reconstructive surgery with the Elevate system yielded good anatomical outcomes and symptom improvement after 2 years of follow-up.

Medium-term comparison of uterus preservation versus hysterectomy in pelvic organ prolapse treatment with Prolift™ mesh.

INTRODUCTION AND HYPOTHESIS: We conducted a medium-term assessment of clinical outcomes and complications after surgical repair of pelvic organ prolapse (POP) using Prolift™ mesh, and sought to determine whether concomitant hysterectomy clinically influenced the outcome of pelvic reconstruction in patients without a prior history of urogenital surgery. METHODS: Patients diagnosed with POP-Q stage 3/4 uterine prolapse at a tertiary referral urogynecology unit in South Taiwan who had undergone POP repair with Prolift mesh from May 2007 to July 2010 were identified by chart review. Concomitant hysterectomy was performed in 24 patients (hysterectomy group), and uterus-sparing surgery in 78 (uterus-sparing group) Preoperative and postoperative subjective assessments of urinary and prolapse symptoms, objective POP-Q score, urodynamic examination, and postoperative adverse events were compared between the groups. RESULTS: The mean follow-up periods were 25.7 months (range 6.2 - 73.1 months) and 31.7 months (range 6.0 - 78.4 months) in the concomitant hysterectomy and uterus-sparing groups, respectively. There were no between-group differences in functional and anatomic outcomes after surgery. No statistically significant differences were found in postoperative adverse events between the groups. CONCLUSIONS: Pelvic reconstruction using Prolift with concomitant hysterectomy and uterus-sparing surgery have similar anatomic and functional results at 2.5 years. Therefore, we consider uterus-sparing surgery to be an alternative to hysterectomy in uterine prolapse repair.

Overactive bladder changes with time: a 5-year longitudinal followup of changes in overactive bladder symptoms, urodynamic studies and urinary nerve growth factor levels.

PURPOSE: We compared clinical symptoms, urodynamic diagnoses and urinary nerve growth factor levels at baseline and 5 years later in patients with overactive bladder. MATERIALS AND METHODS: Patients diagnosed with overactive bladder at a tertiary teaching hospital who underwent urinary nerve growth factor tests 5 years previously were identified by chart review. Patients were invited to return for symptom evaluation, urodynamic studies and a repeat urinary nerve growth factor test. Changes in overactive bladder subtype, urgency severity score and urodynamic diagnosis were classified as improved, stable or worse. Changes in urinary nerve growth factor/creatinine were compared between baseline and 5 years later according to changes in bladder conditions. RESULTS: A total of 30 women and 45 men completed the study. Mean±SD age was 73.5±10.3 years. Urinary nerve growth factor/creatinine showed no significant difference among patients with improved, stable or worse bladder conditions based on overactive bladder or urgency severity score subtypes. However, urinary nerve growth factor/creatinine was significantly decreased in patients with an improved urodynamic diagnosis (mean 0.94±1.36 vs 0.17±0.19 pg/mg, p=0.02), significantly increased in patients with a worse urodynamic diagnosis (0.55±0.85 vs 2.08±2.81 pg/mg, p=0.04) and showed no change in those with a stable urodynamic diagnosis. Multiple linear regression analysis revealed that the change in urodynamic diagnosis was still predictive of the change in urinary nerve growth factor/creatinine after adjusting for age, gender, overactive bladder and urgency severity score subtypes (p=0.001). CONCLUSIONS: Urinary nerve growth factor/creatinine did not reflect the changes in bladder conditions based on subjective symptoms. However, the levels reflected dynamic changes in bladder pathophysiology according to urodynamic findings.

Changes in sexual function of women with refractory interstitial cystitis/bladder pain syndrome after intravesical therapy with a hyaluronic acid solution.

INTRODUCTION: Intravesical instillation with a hyaluronic acid (HA) solution is an effective treatment for interstitial cystitis/bladder pain syndrome (IC/BPS), but its impact on sexual functioning of patients is not known. AIM: The aim of this study was to evaluate the changes in sexual function of women with refractory IC/BPS who underwent a second-line intravesical HA therapy. METHODS: A total of 103 women diagnosed with refractory IC/BPS were enrolled in this prospective, multicenter study. Sexual function was evaluated using the short form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-9). Bladder-related symptoms and bother were assessed by the Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI), and a pain visual analog scale (VAS), respectively. Data were analyzed with univariate methods or multivariate logistic regression analysis accordingly. MAIN OUTCOMES MEASURES: Changes in PISQ-9, ICSI, ICPI, and pain VAS scores after treatment were assessed. RESULTS: Mean age and duration of symptoms was 43.6 ± 11.8 and 5.1 ± 5.0 years, respectively. ICSI, ICPI, and pain VAS scores were significantly (P < 0.001) improved after 1 month and 6 months of treatment. Of the 87 (84.5%) sexually active women evaluated, PISQ-9 total scores improved significantly (P < 0.001) from the baseline (mean 18.9 ± 6.4), after 1 month (20.4 ± 5.8), and 6-months (21.5 ± 5.6) of treatment. Significantly improved PISQ-9 items included "dyspareunia" (P < 0.001) and "negative reactions" (P = 0.015) during sexual intercourse, and "intensity" (P < 0.001) of sexual orgasms. After a logistic regression analysis, we found that a baseline PISQ-9 score was negatively correlated with the duration of IC/BPS symptoms (P = 0.022). Meanwhile, the changes in PISQ-9 scores were positively correlated with the reduction in ICSI scores after treatment (P = 0.045). CONCLUSIONS: Intravesical HA is an effective treatment for refractory IC/BPS. A longer duration of IC/BPS symptoms may be a predictor of poor sexual function. However, intravesical HA may improve sexual function along with the reduction of IC/BPS symptoms.

Efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms associated with menopause among women in East Asia: a phase 3 randomized study (MOONLIGHT I).

OBJECTIVE: To evaluate the efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms (VMS) associated with menopause in East Asian women. METHODS: In this phase 3, randomized, double-blind study, postmenopausal women with moderate to severe VMS (minimum average frequency in the 10 days before randomization, ≥7/day or 50/week) received fezolinetant 30 mg/day or placebo (weeks 1-12), followed by an open-label extension phase with fezolinetant 30 mg/day (weeks 13-24). The co-primary endpoints were the mean changes in the daily frequency and severity of VMS at weeks 4 and 12. RESULTS: Among 301 participants, the difference in the least squares mean change (95% confidence interval) from baseline in the daily frequency of moderate to severe VMS versus placebo was -0.65 (-1.41 to 0.12) at week 4 and -0.55 (-1.35 to 0.26) at week 12. The differences in the least squares mean change from baseline in the VMS severity score versus placebo were -0.06 (-0.14 to 0.03) and -0.13 (-0.27 to 0.01) at weeks 4 and 12, respectively. Serious adverse events occurred in 0.7% of participants receiving fezolinetant in weeks 1 to 12, compared with 1.3% of those receiving placebo. CONCLUSIONS: Fezolinetant was generally safe but did not reduce the frequency or severity of VMS versus placebo in postmenopausal women in this study.ClinicalTrials.Gov Identifier: NCT04234204.

Positioning of a suburethral sling at the bladder neck is associated with a higher recurrence rate of stress urinary incontinence.

OBJECTIVES: The purpose of this study was to investigate the relationship between the suburethral sling position and the outcome of anti-incontinence surgery. METHODS: From 1998 to 2010, the medical records of 153 consecutive women with stress urinary incontinence undergoing the pubovaginal sling procedure were retrospectively reviewed. All patients received preoperative and postoperative transrectal sonography of the bladder and urethra, and the suburethral sling position was used to compare the postoperative continence status and lower urinary tract symptoms. RESULTS: The mean patient age ± SD was 60.7 ± 10.6 years (range, 34-85 years), and the mean follow-up was 66.3 ± 42.1 months (range, 6-149 months). The slings were located at the bladder neck in 18 patients (11.8%), proximal urethra in 81 (52.9%), middle urethra in 45 (29.4%), and distal urethra in 9 (5.9%). The overall rate of recurrent stress urinary incontinence was 24.2% (37 patients). Among the 153 patients, there was a significantly higher stress urinary incontinence recurrence rate in the bladder neck group (bladder neck, 50.0%; proximal urethra, 18.5%; middle urethra, 22.2%; and distal urethra, 33.3%; P = .037). De novo urge and voiding symptoms occurred in 19.0% and 20.3% of overall patients, respectively. There was no significant difference in either de novo urge or voiding symptoms among groups. CONCLUSIONS: Positioning of the suburethral sling at the bladder neck appears to be associated with a higher stress urinary incontinence recurrence rate. Patients with slings located at the proximal and middle urethra had the best postsurgical continence rates. The suburethral sling position had no direct association with de novo urge or voiding symptoms.

Laparoscopic management of second trimester ruptured cornual heterotopic pregnancy with subsequent live birth delivery: A case report and literature review.

OBJECTIVE: Heterotopic pregnancy (HP) is the coexistence of extra- and intrauterine gestation implantation sites. A rare case of a second-trimester ruptured cornual HP (CHP) treated with laparoscopic cornual resection with the primary repair is presented. Risk factors, clinical presentations, treatments, and outcomes of CHPs are also reviewed. CASE REPORT: A 35-year-old pregnant woman with CHP presented with lower abdominal pain with hemoperitoneum and her hemoglobin level dropped. Laparoscopic management of a ruptured HP was performed, leaving the surplus intrauterine fetus intact. She delivered a 2360 g male infant via cesarean section at 34 weeks' gestation due to preterm premature rupture of membranes. We found a well-healed wound over the left uterine cornua during the cesarean section. CONCLUSION: Ruptured CHP is a rare but life-threatening complication of an obstetric emergency. Although the pregnant uterus becomes congested and fragile, using reliable laparoscopic energy devices and barbed sutures, successful treatment is feasible.

Comparison of short-term outcomes following pelvic reconstruction with Perigee and Apogee systems: hysterectomy or not?

INTRODUCTION AND HYPOTHESIS: This study aims to compare the surgical outcomes between hysterectomy and uterine preservation in pelvic reconstruction with Perigee and Apogee systems for severe pelvic organ prolapse. METHODS: Ninety-one women who have undergone transvaginal pelvic reconstructive surgery with Perigee and Apogee systems for severe pelvic organ prolapse were divided into two groups: hysterectomy (n = 39) and uterine preservation (n = 52). The pre-operative and post-operative assessments include subjective urinary and prolapse symptoms, objective pelvic organ prolapse quantification (POP-Q) system, urodynamic examination, and complications. RESULTS: The mean follow-up period was 8.9 months (range, 0.9-26.5). There were no anatomical differences between the two groups other than a longer perineal body in the hysterectomy group (3.9 vs. 3.6, p < 0.05) and a longer total vaginal length in the uterine preservation group (8.2 vs. 7.8, p < 0.05). Preservation of uterus has significantly reduced operative time, blood loss, and days of urine indwelling catheter (p < 0.001). CONCLUSIONS: Hysterectomy and uterine preservation have comparable anatomical outcomes and post-operative complications in pelvic reconstruction with Perigee and Apogee systems at short-term follow-up.

Polypropylene mesh as an alternative option for uterine preservation in pelvic reconstruction in patients with uterine prolapse.

AIM: The aim of this study was to evaluate the efficacy and safety of polypropylene mesh for uterine preservation during pelvic reconstruction in patients with severe uterine prolapse. MATERIALS AND METHODS: The study included 67 women with severe uterine prolapse (pelvic organ prolapse quantification stage III/IV) who received transvaginal mesh reconstruction with uterine preservation. Surgery combined with a transobturator membrane sling procedure (tension-free vaginal tape-transobturator route) was performed in 54 patients. Among them, 18 had urodynamic stress incontinence, 30 had occult stress urinary incontinence, and six had mixed urinary incontinence. Objective assessments were carried out with the pelvic organ prolapse quantification staging system, urodynamic examination, and 1-h pad test. Evaluation of urinary and prolapse symptoms comprised the subjective assessment. RESULTS: The mean follow-up interval was 19.6 months (12-40 months). The objective cure rate for the treatment of uterine prolapse was 89.5%, and the objective cure rate for the treatment of urinary incontinence was more than 90%. CONCLUSIONS: Uterine preservation in pelvic reconstruction is technically feasible and the subjective and objective assessments imply that uterine preservation in pelvic reconstruction is an alternative option for indicated patients.

Pelvic Floor Myofascial Pain Might Influence Treatment Outcome of Interstitial Cystitis/Bladder Pain Syndrome: A Prospective Study.

BACKGROUND: In patients with interstitial cystitis or bladder pain syndrome (IC/BPS), 85% were found to have pelvic floor myofascial pain (PFMP) and hypertonicity (PFH). However, they physicians are not typically trained to consider or assess PFMP as a contributing factor to patients' IC/BPS symptoms. OBJECTIVE: This study aimed to explore the relationship between PFMP and treatment outcomes in women with IC/BPS. STUDY DESIGN: A prospective study. SETTING: Department of Urology, Medical Center, Hualien, Taiwan. METHODS: Patients with IC/BPS who received any type of treatment were prospectively enrolled. They underwent vaginal digital examination at baseline. PFMP severity was quantified on the visual analog scale (VAS). Subject assessment items included O'Leary-Sant symptom score (OSS), Global Response Assessment (GRA), and Beck's anxiety inventory. Object assessment items included bladder computed tomography (CT), urodynamic parameters, maximum bladder capacity, and grade of glomerulation. RESULTS: A total of 65 women with IC/BPS (mean age, 57.1 ± 11.3 years) were enrolled in the study. Patients with more severe PFMP had significantly higher rate of dyspareunia (P = 0.031); more comorbidities (P = 0.010); higher number of PFMP sites (P < 0.001); and higher OSS (P = 0.012). PFMP severity was not significantly correlated with bladder conditions, whether subjective or objective. Moreover, PFMP severity (VAS) was significantly negatively associated with the GRA score. LIMITATIONS: There was a small sample size and short follow-up duration, the patients in this study are all women, and the applicability to other populations is uncertain. CONCLUSION: PFMP might affect the subjective results of IC/BPS treatment but not the bladder condition. Therefore, in the future treatment of patients with IC/BPS, digital vaginal examinations of pelvic floor muscles should be performed and focused more on the PFM-related conditions, and necessary PFM treatments, such as the vaginal pelvic floor muscle message, should be scheduled.

Comparison of Prolift, Perigee-Apogee, Prosima, and Elevate transvaginal mesh systems in pelvic organ prolapse surgery: Clinical outcomes of a long-term observational study.

OBJECTIVES: To evaluate and compare the long-term clinical outcomes of four different transvaginal mesh systems. METHODS: This retrospective study included 695 patients classified into four groups (Prolift, n = 132; Perigee-Apogee, n = 186; Prosima, n = 60; Elevate; n = 317), with a median follow-up time of 5.8 years (range 0.5-12.2 years). The outcomes were objective anatomic success (Pelvic Organ Prolapse [POP] Quantification system stage ≤1), mesh exposure, and urologic functional assessments. RESULTS: For anatomic outcomes, we stepwise analyzed the short-term (within 3 years) and long-term (after 3 years) results. Prolift had the highest long-term success rate (9 years: 82.1%, P = .007). Elevate had a comparable short-term success rate (3 years: 87.5%), but its long-term success rate significantly decreased over time (5 years: 78.6%, 9 years: 66.8%, P = .007). Prosima had the lowest short-term success rate (P = .027). For the long-term mesh exposure rate (9-year cumulative), Elevate had the lowest with 11.1%; next were Perigee-Apogee (18.8%) and Prolift (24.6%); and Prosima had the highest with 39.4%, with a significant difference. In terms of urinary functional results, we observed no significant differences in voiding dysfunction, de novo stress urinary incontinence, or de novo overactive bladder symptoms among the four mesh groups, whether combined with midurethral sling surgery or not. CONCLUSION: Different vaginal mesh designs have various advantages and features. Prolift provided the best long-term anatomic success but had a high mesh exposure rate. Elevate gave comparable short-term success but had a decreased long-term success rate. However, Elevate is superior with the lowest long-term mesh exposure rate. Prosima had the worst anatomic correction and highest mesh exposure rates. This study provides a comprehensive long-term comparative result for POP patients and surgeons.

Botulinum toxin A injection in the treatment of chronic pelvic pain with hypertonic pelvic floor in women: Treatment techniques and results.

Chronic pelvic pain (CPP) is an extremely bothersome condition which leads to major effects in women's everyday life. In addition to visceral sources of pain, pelvic floor dysfunction including myofascial pain and spasm on the pelvic floor muscles causing hypertonicity are causes often overlooked. Injecting botulinum toxin type A (BoNT-A) into hypertonic pelvic floor muscles may aid the relaxation of pelvic floor musculature. The muscles that are injected in CPP treatment include the obturator internus, levator ani (pubococcygeus, iliococcygeus, and puborectalis), and coccygeus. Generally, injections can be performed tolerably with safety under conscious sedation combined with local anesthesia. Most practitioners perform BoNT-A injection of pelvic floor muscles using anatomical landmarks identified by manual palpation only. For the precise location of injection sites, some needle guidance techniques were proposed, including electromyography, electrical stimulation, ultrasound, fluoroscopy, and/or computed tomography. Side effects of BoNT-A injection in CPP are rare and self-limiting. Because of the reversible nature of BoNT-A, reinjection appears to be necessary. Increasing proof points out that BoNT-A is a promising treatment option for CPP in women. We conducted a review of published literature in Pubmed, using chronic pelvic pain in women, hypertonic pelvic floor, and botulinum toxin as the keywords. This article aims to summarize the treatment techniques and results of BoNT-A injection for hypertonic pelvic floor in women with chronic pelvic pain.

The surgical effect on overactive bladder symptoms in women with pelvic organ prolapse.

This study aimed to explore the effect of pelvic reconstruction surgery on the relation of pelvic organ prolapse (POP) and overactive bladder (OAB) and the impact of preoperative vaginal oestrogen supplement on vaginal tissue. A total of 100 postmenopausal women with symptomatic POP who underwent pelvic reconstruction surgery (laparoscopic sacrocolpopexy or transvaginal mesh) were enrolled in this study. Preoperative vaginal oestrogen was prescribed in 28 cases. The evaluation tools consisted of POP-Q, urodynamic study, Overactive Bladder Symptom Score (OABSS), and urinary NGF. Vaginal maturation index and vaginal specimens for hormone receptors study were investigated during operation to evaluate the effect of topical oestrogen. Follow-up assessments were performed at 1, 3, and 6 months after surgery. Preoperatively, 58 (58%) were POP with OAB. After reconstruction surgery, the OABSS decreased significantly (6.87 ± 0.85 vs 3.77 ± 0.61, p < 0.001) at postoperative 6 months in the group. Remarkable increasing trends of urinary NGF levels are noted till 3 months postoperatively, then decreasing to the baseline level at 6 months postoperative follow-up. Remarkable decrease of mRNA of the androgen receptor and significant higher expression of progesterone receptor (PR) were noted after use of the vaginal oestrogen cream. The severity of OAB in the POP women shows moderate degree according to OABSS. Pelvic reconstruction surgery can significantly improve the OAB symptoms. The surgery induced inflammation effect lasts for about 6 months. Short-term preoperative supplement of topical oestrogen brings alterations of the vaginal epithelium.

Short-term results of stress urinary incontinence in women undergoing laparoscopic sacrocolpopexy with and without midurethral sling.

OBJECTIVES: This study aimed to assess the short-term results of stress urinary incontinence (SUI) in women undergoing laparoscopic sacrocolpopexy (LSC) with and without midurethral sling (MUS). METHODS: This retrospective study was conducted from July 2012 to December 2017. Women with stage 3 or 4 in the Pelvic Organ Prolapse Quantification (POP-Q) who underwent LSC were recruited. Multichannel urodynamic studies were performed in all women. Assessment included pre- and postoperative POP-Q stages, urodynamic parameters, peri- and postoperative complications, and symptoms. RESULTS: One hundred and eighteen patients met the inclusion criteria in total. A total of 19.5% (23/118) of them had concomitant MUS. The mean follow-up duration was 16.9 ±  16.0 (range 3-69) months. Meanwhile, 33.9% (40/118) of the patients were diagnosed with overt SUI, and 50% (20/40) underwent MUS. In the concomitant MUS group, the rate of having postoperative SUI was only 5% (1/20). Patients diagnosed with SUI and without concomitant MUS had a 45% rate (9/20), and 25% of them (5/20) received MUS later. Preoperatively, 16.1% (19/118) of the patients were diagnosed with occult SUI. Among the patients without anti-incontinence sling during prolapse surgery, 25% (4/16) of them complained about having SUI during the follow-up. However, none of the women required subsequent anti-incontinence surgery. Postoperative de novo SUI occurred to 13.6% (16/118) of them. None of the patients received further operation. Based on the preoperative and postoperative urodynamic studies in the combination surgery group, a significant improvement was observed in the pad test. CONCLUSIONS: The combination of LSC with MUS procedure is likely to be beneficial in selected patients.

Sacrospinous ligament fixation with uterine preservation reduces the risk of anatomical recurrence in pelvic organ prolapse.

OBJECTIVES: This study investigated the effectiveness of sacrospinous ligament fixation (SSLF) and whether uterine preservation reduces the anatomical recurrence rate. METHODS: The medical records of 82 patients who received SSLF in a single medical center were reviewed retrospectively. Anatomical recurrence was defined as Pelvic Organ Prolapse-Quantification stage 2 or higher in any compartment. The primary outcome was intergroup analysis for uterine preservation and concomitant hysterectomy patients. The secondary outcomes were anatomical recurrence risk factors and the incidence of adverse events. Propensity score matching (PSM) was used to adjust for demographic differences between groups. RESULTS: The anatomical recurrence rate was 19.5%, and the retreatment rate was 11.0% (mean follow-up duration: 22.9 months). Cystocele was the most common recurrent compartment (17.1%). The uterine preservation group (n = 66) was younger, had lower parity, and had fewer stage 3 to 4 cystoceles and uterine prolapses than the concomitant hysterectomy group (n = 16). Shorter operation times (99.4 minutes vs 153.7 minutes, P = .002) and lower anatomical recurrence rates (11.5% vs 45.5%, P = .039) were found in the uterine preservation group before and after PSM. Previous pelvic organ prolapse surgery (hazard ratio 3.14) and concomitant hysterectomy (hazard ratio 4.08) were identified as risk factors for anatomical recurrence. The most common adverse event was buttock pain (14.6%), which resolved spontaneously within 4 weeks. CONCLUSIONS: SSLF is an effective surgical method using native tissue for pelvic reconstruction. Compared with concomitant hysterectomy, SSLF with uterine preservation reduces the anatomical recurrence rate.

Extracorporeal Shock Wave Therapy Protected the Functional and Architectural Integrity of Rodent Urinary Bladder against Ketamine-Induced Damage.

This study tested the hypothesis that extracorporeal-shock-wave (ECSW) protected the functional and anatomical integrity of rat urinary-bladder against ketamine-induced damage. In in vitro study, the rat bladder smooth muscle cells (RBdSMCs) were categorized into G1 (sham-control), G2 (RBdSMCs + menadione), G3 (RBdSMCs + ECSW) and G4 (RBdSMCs + menadione + ECSW). The results showed protein expressions of oxidative-stress/mitochondrial-damaged biomarkers (NOX-1/NOX-2/oxidized protein/cytosolic-cytochrome-C/cyclophilin-D), inflammatory markers (MyD88/TRAF6/p-IKB-α/NF-κB/TNF-α/IL-6/IL-1ß/MMP-9/iNOS), and cell-stress response signalings (ASK1/p-MKK4/p-MKK7/ERK1/2//p-JNK/p-p38/p-53) were significantly increased in G2 than in G1 and G3, and those were significantly reversed in G4 (all p < 0.0001). Adult-male SD rats (n = 24) were equally categorized into group 1 (sham-control), group 2 (ketamine/30 mg/kg/daily i.p. injection for four weeks), group 3 [ketamine/30 mg/kg + ECSW/optimal energy (0.12 mJ/mm2/120 impulses/at 3 h and days 3/7/14/21/28 after ketamine administration)] and group 4 [(ketamine/30 mg/kg + ECSW/higher energy (0.16 mJ/mm2/120 impulses)] and animals were euthanized by day 42. The results showed the urine levels of pro-inflammatory cytokines (TNF-α/IL-6) were lowest in group 1, highest in group 2 and significantly higher in group 3 than in group 4 at days 1/7/14/28 (all p < 0.0001). The duration of urinary bladder contraction was lowest in group 2, highest in group 1 and significantly higher in group 4 than in group 3, whereas the maximal pressure of urinary bladder exhibited an opposite pattern of bladder contraction among the groups (all p < 0.0001). The histopathological findings of fibrosis/inflammation/keratinization and protein expressions of oxidative-stress/mitochondrial-damaged biomarkers (NOX-1/NOX-2/oxidized protein/cytosolic-cytochrome-C/cyclophilin-D), and inflammatory (TLR-2/TLR-4/MyD88/TRAF6/p-IKB-α/NF-κB/TNF-α/IL-1ß/MMP-9/iNOS) and cell-stress response (ASK1/p-MKK4/p-MKK7/ERK1/2//p-JNK/p-p38) signalings and apoptotic/fibrotic biomarkers (cleaved-caspas3/cleaved-PARB/Smad3/TFG-ß) exhibited an identical pattern of urine proinflammatory cytokine among the groups (all p < 0.0001). ECSW effectively attenuated ketamine-induced bladder damage and dysfunction.

Combined melatonin-adipose derived mesenchymal stem cells therapy effectively protected the testis from testicular torsion-induced ischemia-reperfusion injury.

BACKGROUND: This study tested the hypothesis that combined melatonin (Mel) and adipose-derived mesenchymal stem cells (ADMSCs) treatment was superior to either one alone on protecting the testis against acute testicular torsion-induced ischemia-reperfusion (TTIR) injury. METHODS AND RESULTS: Male adult SD rats (n = 30) were equally categorized into group 1 (sham-operated control), group 2 [TTIR/by torsion of right/left testis (i.e., ischemia) with rotated 720° counterclockwise for 2 h, then detorsion (i.e., reperfusion) to the original position for 72 h], group 3 (TTIR + Mel/intraperitoneal administration/50 mg/kg at 30 min after ischemia, followed by 20 mg at 3 h and days 1/2/3 after TTIR), group 4 (TTIR + ADMSCs/1.2 × 106 cells/by tail-vein administration at 30 min after ischemia, followed by days 1/2 TTIR), and group 5 (TTIR + Mel + ADMSCs/tail-vein administration). The result showed that the protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized-protein), apoptotic/mitochondrial-damaged (mitochondrial-Bax/cleaved-caspase3/cleaved-PARP/cytosolic-cytochrome C), and fibrotic (TGF-ß/Smad3) biomarkers as well as testicular damage scores were lowest in group 1, highest in group 2, and significantly higher in groups 3/4 than in group 5, but they showed no difference between groups 3/4, whereas the protein expressions of androgen receptor (AR) and vimentin showed an opposite pattern of oxidative stress (all p < 0.0001). The cellular levels of inflammation (MMP-9/MPO/CD68) exhibited an identical pattern, whereas the numbers of Sertoli cells, α-tubulin, AR and vimentin as well as thickness of seminiferous tubule exhibited an opposite pattern of oxidative stress among the groups (all p < 0.0001). CONCLUSION: Mel-ADMSCs effectively protected the testis against TTIR injury.

Factors associated with treatment outcomes after intravesical hyaluronic acid therapy in women with refractory interstitial cystitis: A prospective, multicenter study.

BACKGROUND: Bladder instillation of hyaluronic acid (HA) is an acceptable treatment for bladder pain syndrome/interstitial cystitis (BPS/IC). The treatment is limited by a high proportion of non-responders (~30%-40%). Here, we aimed to evaluate predisposing factors associated with treatment outcomes. METHODS: This is a prospective multicenter study. We enrolled a total of 137 (out of 140) women with refractory IC. They all underwent a standard protocol of 6-month intravesical HA therapy (initial 4 weeks, once weekly, followed by once monthly). To assess the outcomes, we used the pain Visual Analog Scale (Pain-VAS), Interstitial Cystitis Symptom and Problem Index (ICSI & ICPI), and a scaled Global Response Assessment (GRA). RESULTS: The age of patients was 47.6 ± 27.5 (range 24-77) years. We found statistically significant improvement (p < 0.001) in the Pain-VAS and the ICSI & ICPI scores both after the initial 4-weekly instillations and at the end of 6-month treatment. Those who reported moderate/marked improvement on GRA at the 2 follow-up visits were considered responders: 39.4% (n = 54) at the first follow-up, and 59.9% (n = 82) at the second follow-up. No remarkable side effect was noted. After statistical analyses, treatment outcomes on GRA were positively associated with baseline functional bladder capacity and with Pain-VAS scores. The initial treatment responses optimally (p < 0.001) predicted final treatment outcomes (McNemar). CONCLUSION: Intravesical HA therapy is safe and effective for most (~60%) of our patients with refractory IC. Functional bladder capacity and Pain-VAS scores before treatment, and the early treatment responses are helpful predictors of treatment outcomes.