Urethral sensation following reconstructive pelvic surgery.

INTRODUCTION AND HYPOTHESIS: Most urethral neuromuscular function data focus on efferent rather than afferent innervation. We aimed to determine if changes exist in urethral afferent nerve function before and after reconstructive pelvic surgery (RPS). Secondarily, we compared afferent urethral innervation in women with and without stress urinary incontinence undergoing RPS. METHODS: Participants underwent current perception threshold (CPT) and urethral anal reflex (UAR) testing prior to surgery and again post-operatively. Wilcoxon signed ranked test and Spearman's correlations were used and all tests were two-sided. p = 0.05 was considered to indicate statistical significance. RESULTS: Urethral CPT thresholds increased significantly after RPS, consistent with decreased urethral afferent function. Pre-operative urethral CPT thresholds at 5 and 250 Hz were lower in SUI women (10 [IQR 5-29], 40 [32-750]) compared with continent women (63 [14-99], 73 [51-109]; p = 0.45, p = 0.020), signifying increased urethral sensation or easier activation of urethral afferents in SUI women. CONCLUSIONS: Reconstructive pelvic surgery is associated with a short-term deleterious impact on urethral afferent function, as demonstrated by the higher levels of stimuli required to activate urethral afferent nerves (decreased urethral sensation) immediately after RPS. Women with SUI required lower levels of stimuli to activate urethral afferent nerves prior to RPS, although UAR latencies were similar regardless of concomitant SUI.

Abdominal Colpopexy: Comparison of Endoscopic Surgical Strategies (ACCESS).

INTRODUCTION: Robotic assistance during laparoscopic surgery for pelvic organ prolapse rapidly disseminated across the United States without level I data to support its benefit over traditional open and laparoscopic approaches [1]. This manuscript describes design and methodology of the Abdominal Colpopexy: Comparison of Endoscopic Surgical Strategies (ACCESS) Trial. METHODS: ACCESS is a randomized comparative effectiveness trial enrolling patients at two academic teaching facilities, UCLA (Los Angeles, CA) and Loyola University (Chicago, IL). The primary aim is to compare costs of robotic assisted versus pure laparoscopic abdominal sacrocolpopexy (RASC vs LASC). Following a clinical decision for minimally-invasive abdominal sacrocolpopexy (ASC) and research consent, participants with symptomatic stage≥II pelvic organ prolapse are randomized to LASC or RASC on the day of surgery. Costs of care are based on each patient's billing record and equipment costs at each hospital. All costs associated with surgical procedure including costs for robot and initial hospitalization and any re-hospitalization in the first 6weeks are compared between groups. Secondary outcomes include post-operative pain, anatomic outcomes, symptom severity and quality of life, and adverse events. Power calculation determined that 32 women in each arm would provide 95% power to detect a $2500 difference in total charges, using a two-sided two sample t-test with a significance level of 0.05. RESULTS: Enrollment was completed in May 2011. The 12-month follow-up was completed in May 2012. CONCLUSIONS: This is a multi-center study to assess cost as a primary outcome in a comparative effectiveness trial of LASC versus RASC.

Evaluation of OPRM1 variants in heroin dependence by family-based association testing and meta-analysis.

OPRM1, which codes for the mu-opioid receptor, is the most frequently studied candidate gene for opioid dependence. Despite numerous allelic association studies, no definitive conclusion has been reached regarding the role of OPRM1 polymorphisms in determining risk for opioid dependence. We attempted to resolve this by conducting a family-based association study and meta-analysis which may be more robust and powerful, respectively, than traditional case-control analyses. First, we genotyped three single nucleotide polymorphisms (SNPs) of OPRM1 in 1208 individuals from 473 Han Chinese families ascertained on the basis of having two or more siblings with DSM-IV-defined opioid dependence. The Val6Ala and Arg111His SNPs were detected, but with low minor allele frequencies (0.002 and 0.001, respectively). The Asn40Asp SNP was more informative (minor allele frequency: 0.419), but no significant evidence was observed for either a dominant (p=0.810) or additive (p=0.406) effect of this polymorphism on risk for opioid dependence. In addition, a meta-analysis of case-control studies of opioid dependence was performed, and found a similar lack of evidence for an association with the Asn40Asp SNP (p=0.859). Although a role of OPRM1 polymorphisms in determining risk for opioid dependence cannot be entirely discounted, a major contribution of the Asn40Asp polymorphism seems unlikely. Further analysis is warranted in samples from specific ancestral groups. In addition, it is critical that other OPRM1 variants, including all haplotype-tagging and amino-acid-coding SNPs, be tested for an influence on risk for opioid dependence, since the Asn40Asp polymorphism is only one of several hundred known mutations in the gene.

Urodynamic prolapse reduction alters urethral pressure but not filling or pressure flow parameters.

PURPOSE: To test the hypothesis that advanced stages of pelvic organ prolapse can result in a functional obstruction of the urethra, we studied the effects of manual prolapse reduction on urodynamic and urethral electromyographic parameters in women with stage III and IV pelvic organ prolapse. MATERIALS AND METHODS: Women with advanced pelvic organ prolapse undergoing clinical multichannel urodynamics with concentric needle electromyography of the urethra were invited to participate in this institutional review board approved study. Women underwent filling cystometry and electromyography with prolapse everted and with prolapse reduced. Women were randomized to cystometry order (reduced vs everted). All subjects underwent a third study with prolapse reduction. Maximum urethral closure pressure and quantitative electromyography of the striated urethral sphincter were determined at maximum cystometric capacity. During the pressure flow study voiding parameters, including urethral electromyography quieting, were determined. The nonparametric paired sign test was used to evaluate differences in urodynamic parameters and quantitative electromyography with pelvic organ prolapse reduced and unreduced. Results were considered significant at the 5% level. RESULTS: The 31 participants had mean age of 60 years (range 36 to 78) and 83% were white. There were no clinically significant differences in maximum cystometric capacity, voided volume, maximal flow and detrusor pressure at maximal flow or time to maximal flow between the reduced and everted prolapse states. Prolapse reduction resulted in a clinically and statistically significant decrease in maximum urethral closure pressure (-31%) but it had no impact on quantitative urethral electromyography. CONCLUSIONS: These findings demonstrate that, although prolapse reduction significantly decreases maximum urethral closure pressure, it does not alter intrinsic neuromuscular activity of the striated urethral sphincter. Prolapse reduction does not alter any other filling or pressure flow parameter.

Polymorphisms and haplotypes of the regulator of G protein signaling-2 gene in normotensives and hypertensives.

Regulator of G protein signaling (RGS) proteins stimulate the GTPase activity of Galpha subunits of heterotrimeric G proteins, thereby negatively regulating G protein-coupled receptor signaling. RGS2, which preferentially alters Galphaq-mediated signaling, may be important for cardiovascular health, because knockout of RGS2 in mice is associated with altered smooth muscle relaxation and hypertension. In this study, we determined genetic variation in the human RGS2 gene by sequencing DNA in normotensive and hypertensive populations of whites (n=128) and blacks (n=122). We identified 14 single nucleotide polymorphisms and 2 two-base insertion/deletions (in/del; 1891 to 1892 TC and 2138 to 2139 AA). Although most of the genetic variants were found at low allelic frequency, in particular in coding regions, the 1891 to 1892 TC and 2138 to 2139 AA intronic in/del were in linkage disequilibrium and were associated with hypertension in blacks (P<0.05). We defined several haplotypes for the RGS2 gene, certain of which showed striking differences between whites and blacks. Additionally, 2 haplotypes had significantly different frequencies between hypertensive and normotensive black groups (P<0.05). We conclude that RGS2 is genetically conserved within coding regions but that the intronic in/del define ethnicity-specific haplotypes. Moreover, certain RGS2 variants that occur at greater frequency in hypertensive blacks may serve as ethnicity-specific genetic variants for this disease.

Assessment of multiple displacement amplification for polymorphism discovery and haplotype determination at a highly polymorphic locus, MC1R.

The identification of common genetic variants such as single nucleotide polymorphisms (SNPs) in the human genome has become central in human population genetics and evolution studies, as well as in the study of the genetic basis of complex traits and diseases. Crucial for the accurate identification of genetic variants is the availability of high quality genomic DNA (gDNA). Since popular sources of gDNA (buccal cells, lymphocytes, hair bulb) often do not yield sufficient quantities of DNA for molecular genetic applications, whole genome amplification methods have recently been introduced to generate a renewable source of double-stranded linear DNA. Here, we assess the fidelity of one method, multiple displacement amplification (MDA), which utilizes bacteriophage Phi29 DNA polymerase to generate amplified DNA from an original source of gDNA, in a representative SNP discovery and genetic association study at the melanocortin 1 receptor (MC1R) locus, a highly polymorphic gene in humans involved in skin and hair pigmentation. We observed that MDA has high fidelity for novel SNP discovery and can be a valuable tool in generating a potentially indefinite source of DNA. However, we observed an allele amplification bias that causes genotype miscalls at heterozygous sites. At loci with multiple polymorphic sites in linkage disequilibrium, such as at MC1R, this bias can create a significant number of heterozygote genotype errors that subsequently misrepresents haplotypes.

Responsiveness of quality of life measurements to change after reconstructive pelvic surgery.

OBJECTIVE: We sought to determine whether Incontinence Impact Questionnaire (IIQ-7) and Urogenital Distress Inventory (UDI-6) scores are sensitive to changes in clinical status after surgery for genuine stress incontinence (GSI) or pelvic organ prolapse (POP). STUDY DESIGN: Patients were included in this study if they had completed the IIQ-7 and UDI-6 scales and had undergone urodynamic testing before and 3 months after surgery for GSI or POP. Kruskal-Wallis tests and logistic regression were used to compare IIQ-7 and UDI-6 scores according to the outcome of surgery. RESULTS: Among 55 patients satisfying inclusion criteria for the study, 34 (62%) underwent Burch colposuspension, and 21 (38%) underwent suburethral sling procedures for GSI; 44 (80%) patients were subjectively continent after surgery. Thirty-four (62%) patients underwent surgical treatment of their POP; 31 (90%) were subjectively cured of their POP symptoms. Mean IIQ-7 and UDI-6 scores were lower in patients who were subjectively continent, and UDI-6 scores were lower in patients who were objectively cured of GSI. CONCLUSION: UDI-6 and IIQ-7 scores change after surgery for GSI and POP, with patients who are subjectively continent having lower postoperative scores on both scales.

Role of urethral electromyography in predicting outcome of Burch retropubic urethropexy.

OBJECTIVE: To establish preoperative urethral electromyographic parameters that predict which women are unlikely to be cured of genuine stress incontinence by Burch retropubic urethropexy procedures. STUDY DESIGN: Eighty-nine women who underwent preoperative urodynamic testing with urethral electromyography and retropubic urethropexy for genuine stress incontinence were prospectively studied. Raw electromyographic signals were processed by an electromyographic instrument equipped with automated motor unit analysis software programs. Quantitative electromyographic software was used to analyze the electrical activity of the urethral sphincter with use of mean rectified voltage (MRV)-mean amplitude calculated over the entire tracing after the waveform is rectified-with women at rest and during voluntary urethral squeezing, repetitive coughing, and bladder filling. Objective outcomes were determined 3 months after the operation with single-channel cystometrograms performed while subjects were standing. Nonparametric statistical analyses included the chi(2) test of association for nominal data and the Mann-Whitney test for comparison of population medians. RESULTS: All women had urethral hypermobility and met our standard clinical criteria for retropubic urethropexy. Fifteen women had incomplete follow-up data and were excluded from final analysis. Fifty-nine of 74 women (80%) were objectively cured, and 15 women had persistent genuine stress incontinence. Women who were cured did not differ from those who were not cured in age, parity, menopausal status, maximum urethral closure pressure, Valsalva leak point pressure, maximum cystometric capacity, detrusor instability, or prolapse stage. Women with persistent genuine stress incontinence were more likely to have had previous pelvic operations (P =.01). There were no differences in any electromyographic parameters at rest, with urethral squeezing, or during bladder filling between the groups. Women who were objectively cured had larger MRV values with repetitive coughing (P =.05) and larger increases from resting MRV values (DeltaMRV) with repetitive coughing (P =.04). Twenty-seven of 30 women with MRV values > or =25 microV with repetitive coughing were cured (positive predictive value [PPV] = 90%; negative predictive value [NPV] = 32%), and 22 of 24 women with more than a 10-microV increase in resting MRV values with repetitive coughing (DeltaMRV > 10 microV) were cured (PPV = 92%; NPV = 29%). If women had both an MRV value > or =25 microV and a DeltaMRV value >10 microV, the PPV was 100%; however, the NPV remained at 30%. CONCLUSION: Women who were cured of genuine stress incontinence with Burch retropubic urethropexy procedures had better motor unit action potential activation with repetitive coughing than women with persistent genuine stress incontinence. Urethral electromyography may be used to assess the neuromuscular integrity of the striated urethral sphincter and to help predict which women will have successful retropubic urethropexy procedures.

Outcome after rectovaginal fascia reattachment for rectocele repair.

OBJECTIVE: This study was undertaken to determine the effects of rectovaginal fascia reattachment on symptoms and vaginal topography. STUDY DESIGN: Standardized preoperative and postoperative assessments of vaginal topography (the Pelvic Organ Prolapse staging system of the International Continence Society, American Urogynecologic Society, and Society of Gynecologic Surgeons) and 5 symptoms commonly attributed to rectocele were used to evaluate 66 women who underwent rectovaginal fascia reattachment for rectocele repair. All patients had abnormal fluoroscopic results with objective rectocele formation. RESULTS: Seventy percent (n = 46) of the women were objectively assessed at 1 year. Preoperative symptoms included the following: protrusion, 85% (n = 39); difficult defecation, 52% (n = 24); constipation, 46% (n = 21); dyspareunia, 26% (n = 12); and manual evacuation, 24% (n = 11). Posterior vaginal topography was considered abnormal in all patients with a mean Ap point (a point located in the midline of the posterior vaginal wall 3 cm proximal to the hymen) value of -0.5 cm (range, -2 to 3 cm). Postoperative symptom resolution was as follows: protrusion, 90% (35/39; P <.0005); difficult defecation, 54% (14/24; P <.0005); constipation, 43% (9/21; P =.02); dyspareunia, 92% (11/12; P =.01); and manual evacuation, 36% (4/11; P =.125). Vaginal topography at 1 year was improved, with a mean Ap point value of -2 cm (range, -3 to 2 cm). CONCLUSION: This technique of rectocele repair improves vaginal topography and alleviates 3 symptoms commonly attributed to rectoceles. It is relatively ineffective for relief of manual evacuation, and constipation is variably decreased.

The anatomic and functional variability of rectoceles in women.

Fluoroscopic parameters of the rectum in women with pelvic organ prolapse were studied. Ninety-eight consecutive women undergoing reconstructive pelvic surgery completed a urogynecologic history with physical examination and pelvic floor fluoroscopy. The presence of rectocele and contrast trapping was determined on each fluoroscopic study. Each frame of the study was measured to determine the rectal width. Seventy-eight per cent of the women had fluoroscopically demonstrated rectoceles. Their maximum and minimum rectal widths were larger than those of women without rectoceles. Contrast-retaining rectoceles were larger than non-contrast retaining rectoceles. Fluoroscopic evidence of contrast retention did not relate to patient symptoms. There was no difference in the grade of posterior wall prolapse in women with and without rectoceles. Rectoceles have anatomic and functional variability. Fluoroscopy may be a valuable adjunct to the physical examination in assisting gynecologic surgeons to refine their surgical approach for rectocele repair.

A comparison of women with primary and recurrent pelvic prolapse.

OBJECTIVE: Our purpose was to identify clinically relevant differences in women with primary and recurrent pelvic organ prolapse. STUDY DESIGN: Consecutive women undergoing reconstructive surgery completed a urogynecologic history and physical examination and underwent either multichannel urodynamic testing or pelvic floor fluoroscopy, or both. Two groups were compared: primary (no prior surgery for pelvic organ prolapse) and recurrent. RESULTS: One hundred eighty-one consecutive women were studied-103 with primary and 78 with recurrent prolapse. The groups were similar with respect to age, race, weight, vaginal parity, prolapse stage, urodynamic diagnosis, extent of visceral malposition, and common urinary, anorectal, and sexual symptoms. Clinically relevant differences were found, with the recurrent group having shorter vaginal lengths (P =. 0005), being more likely to have had a hysterectomy for a nonprolapse indication (P =.00018) and to be receiving hormone replacement therapy (P =.00003). CONCLUSION: The women with primary and recurrent pelvic organ prolapse in this population were remarkably similar in many quantifiable parameters measured. The clinical differences may be related to previous surgery for pelvic organ prolapse.

Vaginal topography does not correlate well with visceral position in women with pelvic organ prolapse.

The objective was to determine whether vaginal topography accurately predicts the location of the pelvic viscera on fluoroscopy in women with pelvic organ prolapse. Eighty-nine women undergoing preoperative evaluation for reconstructive pelvic surgery at a tertiary care referral practice formed the study population. Each woman completed a comprehensive urogynecologic history and physical examination, which included a quantified (POP-Q) assessment of her vaginal topography, as described by Bump et al. In addition each woman underwent pelvic floor fluoroscopy (PFF). Visceral sites were selected which corresponded clinically to the vaginal sites measured by the POP-Q. The most dependent portion of the bladder, small intestine, rectum and urethrovesical junction was measured. Twenty-five (28%) women had stage II prolapse, 34 (38%) had stage III prolapse, and 28 (32%) had stage IV prolapse. The remaining 2 women were symptomatic, with stage I prolapse. For the entire study population there was no correlation between the fluoroscopic position of the small bowel and/or rectum and any apical or posterior wall POP-Q site (C, Ap or Bp). There was no correlation with the fluoroscopic position of the UVJ at rest or with straining and the corresponding POP-Q site (Aa). The fluoroscopic position of the most dependent portion of the bladder correlated only modestly with the upper (Ba, rho = 0.51) and lower Aa, rho = 0.68) anterior vaginal wall POP-Q sites. In women without prior surgery (n = 33) there was only modest correlation between the fluoroscopic position of the bladder and the corresponding POP-Q site (Aa, rho = 0.71). In this unoperated subpopulation there was no correlation with PFF and any other POP-Q site. In women who had undergone prior hysterectomy (n = 25) or hysterectomy with anterior and/or posterior colporrhaphy (n = 17), there was only a modest correlation of the most dependent portion of the bladder and the upper anterior vaginal wall site (Bb, rho = 0.67 and rho = 0.55, respectively). It was concluded that vaginal topography does not reliably predict the position of the associated viscera on PFF in women with primary or recurrent pelvic organ prolapse.