Impact of intrinsic sphincter deficiency on mid-urethral sling outcomes.

INTRODUCTION AND HYPOTHESIS: Our primary objective was to study outcomes of patients with intrinsic sphincter deficiency (ISD) following mid-urethral slings (MUS) at 1-year. Our secondary objective was to delineate factors affecting success in these patients. METHODS: Six hundred eighty-eight patients who had MUS between January 2004 and April 2017 were reviewed retrospectively; 48 women were preoperatively diagnosed with ISD. All completed urodynamic studies and validated quality-of-life (QOL) questionnaires at baseline and 1 year. Primary outcomes were objective and subjective cure of stress incontinence, defined as no involuntary urine leakage during filling cystometry and 1-h pad test < 2 g and negative response to Urogenital Distress Inventory-6 Question 3. Ultrasound was performed to determine tape position, urethral mobility and kinking at 1 year. RESULTS: Women with ISD had significantly lower objective and subjective cure rates of 52.1% and 47.9%, respectively, compared to an overall of 88.2% and 85.9%. QOL scores significantly improved in those with successful surgeries. The sling type did not make a difference. Multivariate logistic regression identified reduced urethral mobility [OR 2.11 (1.24-3.75)], lower maximum urethral closure pressure (MUCP) [OR 1.61 (1.05-3.41)] and tape position [OR 3.12 (1.41-8.71)] to be associated with higher odds of failed slings for women with ISD. CONCLUSIONS: Although there are good overall success in women undergoing MUS, those with ISD have significantly lower cure rates at 1 year. Factors related to failure include reduced urethral mobility, low MUCP and relative tape position further away from the bladder neck. Optimal management of patients with ISD and reduced urethral mobility remains challenging.

Urodynamics mixed type urinary incontinence with advanced pelvic organ prolapse, management and outcomes.

Patients with pelvic organ prolapse (POP) often have accompanying lower urinary tract symptoms. Symptoms such as stress urinary incontinence(SUI-UD) and detrusor overactivty(DO) would co-exist in a number of patients. Management entails relieving the obstructive element. To determine the clinical outcome of patients with urodynamics mixed type urinary incontinence(MUI-U) after vaginal pelvic reconstructive surgery(PRS), a retrospective study was conducted. MUI-U was defined as having urodynamic findings of both of DO/DOI (derusor overactivity incontinence) and SUI-UD. Main outcome measures: Objective cure- absence of involuntary detrusor contraction on filling cystometry and no demonstrable leakage of urine during increased abdominal pressure; Subjective cure- assessment index score of <1 on UDI-6 question #2 and #3. Of the 82 patients evaluated, 14 underwent vaginal PRS with concomitant mid-urethral sling(MUS) insertion while 68 had vaginal PRS alone. Pre-operatively, 49(60%) patients had stage III and 33(40%) had stage IV prolapse. Post-operatively, 1-year data shows an objective cure of 56% (46/82) and subjective cure of 54% (44/82). MUI-U was significantly improved. Improvement of SUIUD and results of the 1-hour pad test were more pronounced in patients with concomitant MUS insertion. Ergo, vaginal PRS cures symptoms of MUI-U in >50% of patients and concomitant MUS can be offered to SUI predominant MUI.

Increased Soluble Epoxide Hydrolase in Human Gestational Tissues from Pregnancies Complicated by Acute Chorioamnionitis.

Chorioamnionitis (CAM) is primarily a polymicrobial bacterial infection involving chorionic and amniotic membranes that is associated with increased risk of preterm delivery. Epoxyeicosatrienoic acids (EETs) are eicosanoids generated from arachidonic acid by cytochrome P450 enzymes and further metabolized mainly by soluble epoxide hydrolase (sEH) to produce dihydroxyeicosatrienoic acids (DHETs). As a consequence of this metabolism of EETs, sEH reportedly exacerbates several disease states; however, its role in CAM remains unclear. The objectives of this study were to (1) determine the localization of sEH and compare the changes it undergoes in the gestational tissues (placentas and fetal membranes) of women with normal-term pregnancies and those with pregnancies complicated by acute CAM; (2) study the effects of lipopolysaccharide (LPS) on the expression of sEH in the human gestational tissues; and (3) investigate the effect of 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a specific sEH inhibitor, on LPS-induced changes in 14,15-DHET and cytokines such as interleukin- (IL-) 1ß and IL-6 in human gestational tissues in vitro and in pregnant mice. We found that women with pregnancies complicated by acute CAM had higher levels of sEH mRNA and protein in fetal membranes and villous tissues compared to those in women with normal-term pregnancies without CAM. Furthermore, fetal membrane and villous explants treated with LPS had higher tissue levels of sEH mRNA and protein and 14,15-DHET than those present in the vehicle controls, while the administration of AUDA in the media attenuated the LPS-induced production of 14,15-DHET in tissue homogenates and IL-1ß and IL-6 in the media of explant cultures. Administration of AUDA also reduced the LPS-induced changes of 14,15-DHET, IL-1ß, and IL-6 in the placentas of pregnant mice. Together, these results suggest that sEH participates in the inflammatory changes in human gestational tissues in pregnancies complicated by acute CAM.

Clinical relevance and treatment outcomes of vesicovaginal fistula (VVF) after obstetric and gynecologic surgery.

OBJECTIVE: Vesicovaginal fistulas (VVF) are consequences from obstetric and gynecologic surgery. Treatment approach from either abdominal or vaginal route have its own pros and cons. The study aims to present the anatomical, clinical and lower urinary tract symptom outcomes of women with VVF. MATERIALS AND METHODS: A retrospective case series conducted patients with VVF. Data regarding pre-operative evaluation, surgical treatment, and post-operative follow-ups were collected. Surgical approach depended on the cause, type, number, size, location, and time of onset of the fistula. Post-operatively, foley catheter was maintained for at least 1 week with cystoscopy performed prior to removal. Follow-up evaluation included cystoscopy, bladder diary, UDI-6 and IIQ-7 questionnaires and multi-channel urodynamic study. RESULTS: Of the 15 patients that were evaluated, 1 had spontaneous closure, 8 were repaired vaginally and 6 abdominally. Patients repaired vaginally were significantly noted to have a mean age of 50.3 ± 7.1 years with VVFs located adjacent the supra-trigone area having a mean distance of 1.7 ± 0.5 cm from the ureteric orifice. Its operative time and hospital stay were significantly shorter. In contrast, abdominally repaired patients had mean age of 38.0 ± 8.2 years and VVFs with mean distance of 0.4 ± 0.4 cm from the ureteric orifice. Post-operatively, 2 cases (14.2%, 2/14) of VVF recurrence and de novo urodynamic stress incontinence (USI) (25%, 2/8) were noted after vaginal repair and 3 cases (50%, 3/6) of concurrent ureteric injury and overactive bladder after abdominal repair. CONCLUSION: Treatment outcomes for vaginal and abdominal repair yielded good results. Though the vaginal route had higher incidence of recurrence and de novo USI, its less invasiveness, faster recovery period, and no association with post-op overactive bladder made it more preferable than the abdominal approach.

Anterior-apical single-incision mesh surgery (uphold): 1-year outcomes on lower urinary tract symptoms, anatomy and ultrasonography.

INTRODUCTION AND HYPOTHESIS: Our primary objective is to determine the presence of SUI at 6-12 months after surgery. The secondary objective is to determine the objective and subjective outcomes of POP. METHODS: A retrospective study conducted between February 2015 and July 2016 at Chang Gung Memorial Hospital. The subjects had had symptomatic anterior or apical prolapse with stage III or IV and undergone pelvic reconstructive surgery using Uphold™ LITE. Patients completed a 3-day voiding diary, urodynamic study, real-time ultrasonography and validated quality-of-life questionnaires at baseline and 12-month follow-up. Primary outcome was the absence of USI. Secondary outcomes included the objective cure rate of POP, ≤ stage 1 at the anterior/apical vaginal wall, and the subjective cure rate, negative feedback to POPDI-6. RESULTS: Ninety-five women were eligible. Six were excluded because of incomplete data. The postoperative de novo USI and SUI were 22.7 and 19.7%, respectively. There was significant improvement of USI in patients who had MUS insertion (93.8%) and bladder outlet obstruction (96.7%). The objective and subjective cure rate for prolapse was 95.5 and 94.3%, respectively. POP-Q measurements pre- and postoperatively were significantly improved at all points except for Gh and Pb. There was a significant difference in the distance between the bladder neck to the distal end of the mesh during straining both at both the postoperative 3rd month and 1 year. CONCLUSIONS: Uphold™ mesh has a 20% incidence of de novo USI with acceptable objective and subjective cure rates at 1 year postoperatively. The de novo USI rate was high but not bothersome enough to require surgery.

Prophylactic midurethral sling insertion during transvaginal pelvic reconstructive surgery for advanced prolapse patients with high-risk predictors of postoperative de novo stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Our aim was to evaluate the clinical outcome of continent women with high-risk predictors for de novo stress urinary incontinence (SUI) offered prophylactic midurethral sling (MUS) insertion during vaginal pelvic reconstructive surgery (PRS) for advanced pelvic organ prolapse (POP). MATERIALS AND METHODS: This was a prospective cohort study in patients with POP stage ≥ 3 and maximum urethral closure pressure (MUCP) <60 cmH2O and functional urethral length (FUL) <2 cm. Patients were divided into PRS and PRS + MUS groups. Surgery commenced with vaginal hysterectomy, application of Uphold® and insertion of MUS to the PRS + MUS group. Main outcome measures were incidence of de novo urodynamic stress incontinence (USI), lower urinary tract symptoms (LUTS), quality of life (QoL), and topographic and anatomical relationship of implanted mesh. RESULTS: Based on sample size calculation, 40 patients were recruited-20 in each group. Rate of de novo USI in PRS + MUS was 5% objectively and 10% subjectively, while in the PRS it was 50% objectively and 60% subjectively. No significant difference was noted in patient demographics. Intraoperative blood loss was greater for PRS + MUS but was not statistically significant. No organ injuries, mesh exposure, or infections occurred. Postoperatively, MUCP significantly increased from 43.3 ± 8.9 to 58.5 ± 19.2 cmH2O and FUL from 17.2 ± 1.9 to 20.3 ± 3.1 mm in the PRS + MUS group. Residual urine significantly decreased. No patient had bladder outlet obstruction (BOO). Sonographic assessment showed no difference in mesh mobility with urethral kinking observed in 11 (55%) patients with MUS. CONCLUSION: Based on a validated small sample, prophylactic MUS for continent women at high risk for postoperative USI with advanced POP lowers its incidence to 5%. Continence is achieved in 95%. Concern for complications, LUTS, and QoL did not significantly differ.

Evaluation of Clinical Outcome and Risk Factors for Failure of Single-incision Midurethral Short Tape Procedure (Solyx Tape) for Stress Urinary Incontinence.

STUDY OBJECTIVE: To evaluate the clinical outcome and identify risk factors for failure of the Solyx (Boston Scientific Corporation, Marlborough, MA) single-incision sling (SIS) in the treatment of urodynamic stress incontinence (USI). DESIGN: A retrospective observational study (Canadian Task Force classification II-2). SETTING: A tertiary referral center. PATIENTS: Patients diagnosed with USI without needing concurrent procedures that underwent continence surgery using the Solyx SIS from February 2015 to May 2017. INTERVENTIONS: Anti-incontinence surgery. MEASUREMENTS AND MAIN RESULTS: The primary outcome of this study was the rate of objective cure defined as the absence of demonstrable leakage of urine on the cough stress test and a 1-hour pad test weight of less than 2g. The secondary outcome was the rate of subjective cure defined as a negative response to Urinary Distress Inventory question 3 (no leakage on coughing, sneezing, or laughing) and the identification of the different risk factors of cure failure. A total of 113 patients were evaluated in the study. Postoperative USI and the 1-hour pad test significantly improved from 24.2 ± 26.9 gm (range, 19.1-29.3) to 2.5 ± 8.7 gm (range, 0.9-4.2); p <0.001 through 1 year. Data analysis showed an objective cure rate of 90% (102/113) and a subjective cure rate of 86% (97/113). USI recurred in 11 patients with no repeat surgery done becausesymptoms were tolerable to the patients. No patient had bladder outlet obstruction. Peak flow rates 23.7 ± 9.1 ml/s (20.0-27.4) and residual urine volume 38.5 ± 25.8 ml (29.8-47.2) were within normal limits with no significant changes. Previous anti-incontinent surgery, previous prolapsed surgery, intrinsic sphincter deficiency, maximum urethral closure pressure <40cm H2O, and neurogenic disease were significant risk factors for sling failure. Subjective assessment on the quality of life significantly improved (p <0.001). CONCLUSION: The Solyx SIS is an effective and safe treatment option for women with USI, showing high objective and subjective cure rates with a low incidence of complications 1 year after treatment. The identified independent risk factors forfailure are related to poor urethral function and previous pelvic reconstructive surgery.

Clinical outcomes on tension-releasing suture appendage on single-incision sling devices for postoperative voiding dysfunction involving undue tape tension.

INTRODUCTION AND HYPOTHESIS: To determine the clinical outcomes of adding a tension-releasing suture (TRS) appendage for manipulation of over-tensioned single-incision slings (SIS) as a means to relieve postoperative voiding dysfunction. METHODS: A retrospective observational study conducted from January 2010 to July 2017. The records of patients with urodynamic stress incontinence (USI) without needing concurrent procedures who underwent anti-incontinence surgery using MiniArc, Solyx, and Ajust with voiding dysfunction were collated and analyzed. The primary outcome measure was the recovery of normal post-void residual urine (PVR) after TRS manipulation. The secondary outcome measures were the pain intensity noted during manipulation (quantified by visual analog scale) and the continence rate [assessed by (1) objective cure: 1-h pad test weight < 2 g and absence of USI; (2) subjective cure index score ≤ 1 on question 3 of the UDI-6: "Urine leakage related to physical activity, coughing, or sneezing?"]. RESULTS: There were 73 patients with high post-void residual (PVR) urine. The 42 (9.5%) patients with over-tensioned slings were managed with TRS manipulation while the 31 patients (7%) with high PVR and no sling over-tension were managed with intermittent catheterization. All patients in both groups regained normal PVR. The TRS-manipulated group demonstrated an objective cure rate of 92.9% (39/42) and subjective cure rate of 91% (38/42). Pain experienced during TRS manipulation was significantly higher with the Ajust system (p = 0.018). Three patients had persistence of USI, two with MiniArc and one with Solyx. CONCLUSIONS: The TRS manipulation is a well-tolerated procedure that can effectively relieve voiding dysfunction for over-tensioned SIS without affecting continence cure rates.

Five-Year Outcome of MiniArc Single-Incision Sling Used in the Treatment of Primary Urodynamic Stress Incontinence.

STUDY OBJECTIVE: To evaluate the effectiveness and safety of the MiniArc single-incision sling in the treatment of urodynamic stress incontinence (USI) through 5 years. DESIGN: Retrospective observational study (Canadian Task Force classification II-2). SETTING: Tertiary referral center. PATIENTS: Eighty-five patients with USI without needing concurrent procedures who underwent anti-incontinence surgery using the MiniArc SIMS from February 2010 to December 2011. INTERVENTIONS: Anti-incontinence surgery. MEASUREMENTS AND MAIN RESULTS: Objective cure was defined as no demonstrable leakage of urine on the cough stress test and 1-hour pad test weight <2 g. Subjective cure was based on negative response to Urinary Distress Inventory question 3, no leakage on coughing, sneezing, or laughing. Most patients were postmenopausal, overweight, and multiparous. Postoperative USI significantly improved (p < .001) through 3 years, and the 1-hour pad test showed significant improvement through 5 years (p < .001). Although 13 patients had recurrence of USI, no repeat surgery was done. The cumulative cure rates may show a declining trend of cure, yet subjective cure was 80.0% and objective cure 84.7%, with age as a significant risk factor for sling failure. CONCLUSION: MiniArc maintains its effectiveness and safety in treatment of USI through 5 years with high objective and subjective cure rates and low incidence of complications.

A 52-month follow-up on the transvaginal mesh surgery in vaginal cuff eversion.

OBJECTIVE: Transvaginal mesh anterior-posterior (TVM-AP) provides better cure rates in the surgical treatment of vaginal cuff eversion than anterior transvaginal mesh combined with sacrospinous ligament fixation (TVM-A). We determine the outcomes after TVM-A and TVM-AP surgeries in advanced vaginal cuff prolapse. MATERIALS AND METHODS: The charts of 796 women who underwent pelvic organ prolapse (POP) surgery from July 2006 to January 2012 in Chang Gung Memorial Hospitals were reviewed. We included women who presented with advanced cuff eversion and treated with TVM surgery. Data were analysed after three years post-surgery. Descriptive statistics were used for demographic and perioperative data. The paired-samples t test was used for comparison of preoperative and postoperative continuous data. The outcomes measured were objective cure (POP-Q stage ≤ 1) and subjective cure (negative response to question 2 and 3 on POPDI-6). RESULTS: A total of 97 patients was analysed. 61 patients had TVM-A and 36 patients had TVM-AP insertion. Mean follow-up was 52 months. The objective cure rate for TVM-AP was significantly higher than TVM-A, 94.4% versus 80.3%. TVM-AP also showed a higher subjective cure rate (91.7%) though there was no significant difference from TVM-A (p = 0.260). The mesh extrusion rate was low at 3.1% with no major complications seen. In TVM-A the blood loss was lesser and the operation time was shorter. CONCLUSION: TVM-AP showed better objective cure rate than TVM-A at 52 months. However, TVM-A is less invasive in comparison with an acceptably good cure rates.

Maternal Vitamin D Level Is Associated with Viral Toll-Like Receptor Triggered IL-10 Response but Not the Risk of Infectious Diseases in Infancy.

Reports on the effect of prenatal vitamin D status on fetal immune development and infectious diseases in childhood are limited. The aim of this study was to investigate the role of maternal and cord blood vitamin D level in TLR-related innate immunity and its effect on infectious outcome. Maternal and cord blood 25 (OH)D level were examined from 372 maternal-neonatal pairs and their correlation with TLR-triggered TNF-α, IL-6, and IL-10 response at birth was assessed. Clinical outcomes related to infection at 12 months of age were also evaluated. The result showed that 75% of the pregnant mothers and 75.8% of the neonates were vitamin deficient. There was a high correlation between maternal and cord 25(OH)D levels (r = 0.67, p < 0.001). Maternal vitamin D level was inversely correlated with IL-10 response to TLR3 (p = 0.004) and TLR7-8 stimulation (p = 0.006). However, none of the TLR-triggered cytokine productions were associated with cord 25(OH)D concentration. There was no relationship between maternal and cord blood vitamin D status with infectious diseases during infancy. In conclusion, our study had shown that maternal vitamin D, but not cord vitamin D level, was associated with viral TLR-triggered IL-10 response.

Clinical Relevance and Treatment Selection of Ureteral Injury After Cesarean Section.

INTRODUCTION: The aim of this case series was to report the clinical relevance and management outcomes of ureteral injuries acquired secondary to cesarean section. METHODS: This was a retrospective case series from January 2007 to September 2014. Description of the patients' characteristics, diagnostic tools for investigation, management, and postoperative follow-up was conducted on postcesarean section patients who developed symptoms of urine leakage after cesarean section and necessitated secondary surgery for ureteral injury. Descriptive statistics was used for demographics and operative data. RESULTS: A total of 5619 cases were managed by cesarean section during the study period. Six (0.107%; 95% confidence interval [CI], 0.1069%-0.1071%) patients had ureteral injury related to the cesarean section. Of 6 cases, 3 (0.053%; 95% CI, 0.0529%-0.0531%) had ureterouterine fistula. Three cases were managed by ureteroneocystostomy, 1 by ureteroneocystostomy with Boari flap, 1 by transureteroureterostomy, and the other one by ureteral stenting via ureterocystoscopy. Three patients had immediate operation because of an acute abdomen and 3 patients had delayed operation. The left ureter was the most common site of ureteral injury (5/6). The postoperative course was uneventful for all cases. CONCLUSIONS: Continuous urinary leakage and acute abdominal distention associated with fluid accumulation after emergency cesarean section should be considered as "red flag" symptoms of ureteral injury and ureterouterine fistulae complications. Delayed management for ureteral repair may not be associated with bad outcomes for management of ureterouterine fistula. Delayed management was associated with less blood loss, less operating time, and acceptable outcome among patients with ureterouterine fistulae when the renal function is not compromised.

The effects of labor on differential gene expression in parturient women, placentas, and fetuses at term pregnancy.

Labor and its associated pain are thought to have unique impacts on parturient women. The goal of this study was to investigate the effects of labor and associated pain on differential gene expression profiles in the maternal, fetal, and placental compartments. We used microarrays to analyze maternal blood (MB), fetal cord blood (CB), and placental tissue samples in pregnant women after term vaginal deliveries (laboring group) and in term pregnant women after scheduled Ceasarean sections (nonlaboring group). The upregulated genes in the MB of the laboring group are involved in cytokine and nuclear factor-kappa B signaling pathways, regulation of the networks of toll-like receptor 4, and suppressor of cytokine signaling 3. Upregulated genes in the CB of the laboring group are involved in responding to stress and stimuli by regulating the network genes of the T-cell receptor beta locus and the FK506 binding protein 8. Differentially expressed genes in the placenta of the laboring group are involved in nitric oxide transport, gas transport, response to hydrostatic pressure, oxygen transport, acute phase responses, and the tumor necrosis factor-mediated signaling pathway, which are important during the transient hypoxemia and hypoperfusion that occur in the placenta during uterine contractions. Interestingly, few of the genes exhibited simultaneous changes in all three compartments, indicating that different pathways and complex interactions may be involved in human labor. In conclusion, human labor and its associated pain elicit unique gene regulatory changes in MB, placenta, and CB.

Elevated amniotic fluid F2-isoprostane: a potential predictive marker for preeclampsia.

In the complex mechanism of preeclampsia, oxidative stress is an important pathogenic factor, and F2-isoprostane is a marker of oxidative stress and lipid peroxidation. The objective of this study was to identify if the amniotic fluid (AF) levels of F2-isoprostanes were elevated in women who later developed preeclampsia. In this study, we analyzed AF F2-isoprostane concentrations with enzyme immunoassay (EIA), and the EIA results could be validated by quantitative mass spectrometry. The mean AF concentration of F2-isoprostanes was significantly higher in pregnancies with subsequent development of preeclampsia (123.1 ± 57.6 pg/ml, n = 85) than in controls (73.8 ± 36.6 pg/ml, n = 85). The AF elevation of F2-isoprostanes was even higher in the preeclampsia with intrauterine growth restriction group (138.3 ± 65.2 pg/ml, n = 39). The area under the curve of the receiver operating characteristics analysis for AF F2-isoprostanes assay was 0.81, supporting its potential as a biomarker for preeclampsia. These results indicate that oxidative stress existed before the onset of clinical preeclampsia, further suggesting that the elevation of AF F2-isoprostanes may be used as a guide for antioxidant supplementation to reduce the risk and/or severity of preeclampsia.