Marianna Alperin

Outcomes of vaginal prolapse surgery among female Medicare beneficiaries: the role of apical support.

OBJECTIVE: Recurrent pelvic organ prolapse (POP) has been attributed to many factors, one of which is lack of vaginal apical support. To assess the role of vaginal apical support and POP, we analyzed a national dataset to compare long-term reoperation rates after prolapse surgery performed with and without apical support. METHODS: Public use file data on a 5% random national sample of female Medicare beneficiaries were obtained from the Centers for Medicare and Medicaid Services. Women with POP who underwent surgery during 1999 were identified by relevant International Classification of Diseases, 9th Revision, Clinical Modification, and Current Procedural Terminology, Fourth Edition codes. Individual patients were followed-up through 2009. Prolapse repair was categorized as anterior, posterior, or anterior–posterior with or without a concomitant apical suspension procedure. The primary outcome was the rate of retreatment for POP. RESULTS: In 1999, 21,245 women had a diagnosis of POP. Of these, 3,244 (15.3%) underwent prolapse surgery that year. There were 2,756 women who underwent an anterior colporrhaphy, posterior colporrhaphy, or both with or without apical suspension. After 10 years, cumulative reoperation rates were highest among women who had an isolated anterior repair (20.2%) and significantly exceeded reoperation rates among women who had a concomitant apical support procedure (11.6%; P<.01). CONCLUSION: Ten years after surgery for POP, the reoperation rate was significantly reduced when a concomitant apical suspension procedure was performed. This analysis of a national cohort suggests that the appropriate use of a vaginal apical support procedure at the time of surgical treatment of POP might reduce the long-term risk of prolapse recurrence. LEVEL OF EVIDENCE: II

Remodeling of vaginal connective tissue in patients with prolapse

Purpose of review Pelvic organ prolapse is a common disease that negatively affects the lives of women. To date, basic science research into the pathogenesis of prolapse has been limited. The vagina and its supportive connective tissues provide one of the primary mechanisms of support to the pelvic organs. This review summarizes our current understanding of the alterations in these tissues in women with prolapse. Recent findings Current research suggests that the vagina and its supportive tissues actively remodel in response to different environmental stimuli. The literature has many shortcomings due to restricted access to tissue, absence of longitudinal data, and limited animal models. Nevertheless, recent studies indicate that within prolapsed tissue metabolism of collagen and elastin is altered. Thus, not only the synthesis of those structural proteins but also the balance between the activity of the major proteolytic enzymes that degrade them and the inhibitors of proteolysis are important components to consider in studies on the pathogenesis of pelvic organ prolapse. Summary Biochemical studies of the vagina and its supportive connective tissues have improved understanding of the contribution of altered connective tissue to the pathogenesis of prolapse. It is important to continue research in this area, as the knowledge gained from these studies will allow for the development of innovative reconstructive procedures and the establishment of preventive measures.

Impact of the 2011 FDA transvaginal mesh safety update on AUGS members' use of synthetic mesh and biologic grafts in pelvic reconstructive surgery.

Objective To describe the frequency of use and recent change in use of synthetic mesh and biologic grafts in pelvic organ prolapse (POP) and stress urinary incontinence surgery by American Urogynecology Society (AUGS) members. Methods An electronic survey of AUGS members was conducted between December 2011 and January 2012. Frequency of graft use in POP (overall and by transvaginal and transabdominal approaches) and stress urinary incontinence surgery was queried relative to the timing of the 2011 Food and Drug Administration (FDA) safety update. Rates of materials’ use before and after the statement were compared using Wilcoxon signed rank test. Results Fifty-three percent (507/962) of AUGS members responded and were included in analysis; 79% were urogynecologists. Before the FDA warning, in POP surgery, most (90%) used synthetic mesh and fewer (34%) used biologic grafts; 99% used synthetic mesh slings. After the FDA statement, respondents reported an overall decrease in the percent of POP cases in which they used synthetic mesh (P < 0.001) but no change in biologic graft use for POP (P = 0.37) or synthetic mesh sling use (P = 0.10). Specifically, transvaginal mesh use decreased: 40% reported decreased use and 12% stopped use. However, transvaginal mesh was still used by 61% of respondents in at least some cases. No change (62%) or increased use (12%) of mesh was reported for transabdominal POP procedures. Conclusions Synthetic mesh use in transvaginal POP surgery decreased after the 2011 FDA safety update, but synthetic mesh use for transabdominal POP repair and sling procedures and overall biologic graft use in POP surgery did not decrease.

Episiotomy and Increase in the Risk of Obstetric Laceration in a Subsequent Vaginal Delivery

OBJECTIVE: To examine whether episiotomy at first vaginal delivery increases the risk of spontaneous obstetric laceration in the subsequent delivery. METHODS: A review was conducted of women with consecutive vaginal deliveries at Magee-Womens Hospital between 1995 and 2005, using the Magee Obstetrical Maternal and Infant database. The primary exposure of interest was episiotomy at first vaginal delivery. Multivariable polytomous logistic regression modeling of potential risk factors was used to estimate odds ratios (ORs) for obstetric laceration in the second vaginal delivery. RESULTS: A total of 6,052 patients were included, of whom 47.8% had episiotomy at first delivery. Spontaneous second-degree lacerations at the time of second delivery occurred in 51.3% of women with history of episiotomy at first delivery compared with 26.7% without history of episiotomy (P<.001). Severe lacerations (third or fourth degree) occurred in 4.8% of women with history of episiotomy at first delivery compared with 1.7% without history of episiotomy (P<.001). Prior episiotomy remained a significant risk factor for second-degree (OR 4.47, 95% confidence interval 3.78–5.30) and severe obstetric lacerations (OR 5.25, 95% confidence interval 2.96–9.32) in the second vaginal delivery after controlling for confounders. Based on these findings, for every four episiotomies not performed one second-degree laceration would be prevented. To prevent one severe laceration, performing 32 fewer episiotomies is required. CONCLUSION: Episiotomy at first vaginal delivery increases the risk of spontaneous obstetric laceration in the subsequent delivery. This finding should encourage obstetric providers to further restrict the use of episiotomy. LEVEL OF EVIDENCE: II

LOXL1 deficiency negatively impacts the biomechanical properties of the mouse vagina and supportive tissues

Mice deficient in lysyl oxidase-like1 protein (LOXL1−/−) develop pelvic organ prolapse (POP). We sought to determine the impact of LOXL1−/− on the biomechanical properties of the vagina and its supportive tissues tested as a complex. Tissues of nulliparous LOXL1−/− and age-matched wild type (WT) mice were tested to failure to obtain load-distension curves. Data were compared utilizing one-way analysis of variance and appropriate post hoc tests. The groups demonstrated different biomechanical behavior, with LOXL1−/− animals displaying a 31% decrease in ultimate load at failure (p=0.001). Experimental disruption of specific levels of support in WT mice failed to generate load-distension curves similar to the LOXL1−/− mice indicating a global instead of a site-specific tissue defect. The decrease in the ultimate load at failure in the LOXL1−/− mice suggests mechanically weaker tissues. LOXL1 mutation results in a global defect in connective tissues and correlates with altered biomechanical behavior of the vagina and supportive tissues.

Patterns of pessary care and outcomes for medicare beneficiaries with pelvic organ prolapse.

Objectives Using a national data set, we sought to assess patterns of pessary care in older women with pelvic organ prolapse (POP) and subsequent outcomes, including rates of complications and surgical treatment of POP. Methods Public use files from the US Centers for Medicare and Medicaid Services were obtained for a 5% random national sample of beneficiaries from 1999 to 2000. Diagnostic and procedural codes (International Classification of Diseases, Ninth Revision, Clinical Modification and Current Procedural Terminology, 4th Edition) were used to identify women with POP and those treated with pessary. Individual subjects were followed longitudinally for 9 years. Across this duration, patient care and outcomes (eg, return clinic visits, repeated pessary placements, complications, and rate of surgical treatment of prolapse) were assessed. Results Of 34,782 women with a condition diagnosed as POP, 4019 women (11.6%) were treated with a pessary. In the initial 3 months after pessary placement, 40% underwent a follow-up visit with the provider who had placed the pessary, and through 9 years after the initial fitting, 69% had such a visit. During this period, 3% of the subjects developed vesicovaginal or rectovaginal fistulas, and 5% had a mechanical genitourinary device complication. Twelve percent of women underwent surgery for POP by 1 year; with 24% by 9 years. Conclusions Pessary can be effectively used for the management of POP in older women. Despite this, a low percentage of Medicare beneficiaries undergo pessary fitting. Lack of continuity of care is associated with a small but unacceptable rate of vaginal fistulas.

Salpingo-oophorectomy at the Time of Benign Hysterectomy: A Systematic Review.

OBJECTIVE: To compare the long-term risks associated with salpingo-oophorectomy with ovarian conservation at the time of benign hysterectomy. DATA SOURCES: MEDLINE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials were searched from inception to January 30, 2015. We included prospective and retrospective comparative studies of women with benign hysterectomy who had either bilateral salpingo-oophorectomy (BSO) or conservation of one or both ovaries. METHODS OF STUDY SELECTION: Reviewers double-screened 5,568 citations and extracted eligible studies into customized forms. Twenty-six comparative studies met inclusion criteria. Studies were assessed for results, quality, and strength of evidence. TABULATION, INTEGRATION, AND RESULTS: Studies were extracted for participant, intervention, comparator, and outcomes data. When compared with hysterectomy with BSO, prevalence of reoperation and ovarian cancer was higher in women with ovarian conservation (ovarian cancer risk of 0.14–0.7% compared with 0.02–0.04% among those with BSO). Hysterectomy with BSO was associated with a lower incidence of breast and total cancer, but no difference in the incidence of cancer mortality was found when compared with ovarian conservation. All-cause mortality was higher in women younger than age 45 years at the time of BSO who were not treated with estrogen replacement therapy (hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.04–1.92). Coronary heart disease (HR 1.26, 95% CI 1.04–1.54) and cardiovascular death were higher among women with BSO (HR 1.84, 95% CI 1.27–2.68), especially women younger than 45 years who were not treated with estrogen. Finally, there was an increase in the prevalence of dementia and Parkinson disease among women with BSO compared with conservation, especially in women younger than age 50 years. Clinical practice guidelines were devised based on these results. CONCLUSION: Bilateral salpingo-oophorectomy offers the advantage of effectively eliminating the risk of ovarian cancer and reoperation but can be detrimental to other aspects of health, especially among women younger than age 45 years.

Collagen scaffold: a treatment for simulated maternal birth injury in the rat model

OBJECTIVE We sought to determine the impact of a collagen scaffold on the healing response after simulated birth injury in a rodent model. STUDY DESIGN A total of 52 virgin animals were divided into the following groups: control (n = 18), injured untreated (n = 18), and injured treated with porcine small intestinal submucosa (SIS) (n = 16). Histopathology, immunofluorescence of collagens, and vaginal mechanical properties were used to assess the impact of injury and the subsequent healing response. RESULTS Collagen I/V decreased by 44% after birth injury relative to the controls (P = .001). Birth injury resulted in inferior mechanical properties of the vagina with a decrease of 38% in the tangent modulus and 44% in the tensile strength. SIS improved the collagen I/V and I/III ratios by 28% and 46%, respectively, paralleling the trend in the mechanical properties. CONCLUSION Simulated birth injury negatively affected vaginal biochemical and biomechanical properties long term. SIS treatment mitigated the impact of birth injury by enhancing tissue quality.

Conservative management of postoperatively diagnosed cystotomy.

Bladder injury is a common complication of hysterectomy that is often not recognized at the initial surgery. The conventional approach to intraperitoneal cystotomy is surgical repair. The goal of this case series was to introduce an alternative conservative treatment of posthysterectomy cystotomy. We present 3 cases of posthysterectomy cystotomy that were unrecognized at the initial surgery and were treated with assisted bladder drainage. The treatment of iatrogenic intraperitoneal cystotomy with bladder drainage facilitated complete healing and eliminated the need for surgical repair. We suggest that conservative management be considered as the first-line treatment option in appropriately selected patients.

Comparison of pelvic muscle architecture between humans and commonly used laboratory species

Introduction and hypothesisPelvic floor muscles (PFM) are deleteriously affected by vaginal birth, which contributes to the development of pelvic floor disorders. To mechanistically link these events, experiments using animal models are required, as access to human PFM tissue is challenging. In choosing an animal model, a comparative study of PFM design is necessary, since gross anatomy alone is insufficient to guide the selection.MethodsHuman PFM architecture was measured using micromechanical dissection and then compared with mouse (n = 10), rat (n = 10), and rabbit (n = 10) using the Architectural Difference Index (ADI) (parameterizing a combined measure of sarcomere length-to-optimal-sarcomere ratio, fiber-to-muscle-length ratio, and fraction of total PFM mass and physiological cross-sectional area (PCSA) contributed by each muscle). Coccygeus (C), iliocaudalis (IC), and pubocaudalis (PC) were harvested and subjected to architectural measurements. Parameters within species were compared using repeated measures analysis of variance (ANOVA) with post hoc Tukey’s tests. The scaling relationships of PFM across species were quantified using least-squares regression of log-10-transformed variables.ResultsBased on the ADI, rat was found to be the most similar to humans (ADI = 2.5), followed by mouse (ADI = 3.3). When animals’ body mass was regressed against muscle mass, muscle length, fiber length, and PCSA scaling coefficients showed a negative allometric relationship or smaller increase than predicted by geometric scaling.ConclusionIn terms of muscle design among commonly used laboratory animals, rat best approximates the human PFM, followed by mouse. Negative allometric scaling of PFM architectural parameters is likely due to the multifaceted function of these muscles.