Two-Year Preclinical Evaluation of Long-Term Absorbable Poly-4-hydroxybutyrate Scaffold for Surgical Correction of Pelvic Organ Prolapse.

INTRODUCTION AND HYPOTHESIS: Fully absorbable implants may be an alternative to permanent meshes in the correction pf pelvic organ prolapse (POP) as they may reduce adverse events by promoting tissue regeneration and collagen metabolism. This study was aimed at evaluating the long-term host and biomechanical response to a fully absorbable poly-4-hydroxybutyrate (P4HB) scaffold in comparison with polypropylene (PP) mesh. METHODS: Poly-4-hydroxybutyrate scaffold (n = 16) and PP mesh (n = 16) were surgically implanted in the posterior vaginal wall of parous female Dohne Merino sheep. Vaginal explants were evaluated in terms of gross necropsy, host response (immune response, collagen deposition, tissue regeneration), biomechanics, and degradation of P4HB at 12 and 24 months post-implantation. RESULTS: Gross necropsy revealed no infection or fluid collection using P4HB or PP. At 12 months, exposures were observed with both P4HB (3 out of 8) and PP (4 out of 8), whereas at 24 months, exposures were observed only with PP (4 out of 8). The tensile stiffness of the P4HB explants was maintained over time despite complete absorption of P4HB. The collagen amount of the vaginal tissue after P4HB implantation increased over time and was significantly higher than PP at 24 months. P4HB scaffolds exhibited significantly lower myofibroblast differentiation than PP meshes at 24 months. CONCLUSIONS: The P4HB scaffold allowed for gradual load transfer to the vaginal wall and resulted in mechanically self-sufficient tissue. P4HB scaffold had a more favorable host response than PP mesh, with higher collagen content, lower myofibroblastic differentiation, and no exposures at 24 months. P4HB scaffolds have potential as an alternative to permanent implants in treating POP.

Safety and Efficacy Report for the Use of Poly-4-Hydroxybutyrate as a Retropubic Mid-Urethral Sling (MUS) for Stress Urinary Incontinence: A Prospective 24 Months Follow-Up of New Poly-4-Hydroxybutyrate TephaFlex SUI Bioresorbable MUS.

STUDY OBJECTIVE: To investigate the feasibility and safety of the retropubic mid-urethral sling (MUS) procedure with a resorbable mesh implant made of poly-4-hydroxybutyrate (P4HB). DESIGN: A prospective clinical cohort study with 24 months follow-up. SETTING: A tertiary academic hospital. PATIENTS: Seventeen women with moderate to severe stress urinary incontinence (SUI). INTERVENTIONS: A retropubic MUS procedure with P4HB sling. MEASUREMENTS AND MAIN RESULTS: Seventeen women underwent an uncomplicated MUS procedure with a new sling made of resorbable P4HB. Following safety criteria, there has been no need to stop the study before 24 months' end point. Three serious adverse events were reported during follow-up: (1) inability to void urine after 1 week postsurgery, (2) a hysterectomy and bilateral oophorectomy performed due to a precancerous endometrial lesion at 16 months after initial MUS procedure and (3) exposed mesh with a part of device sheath left behind. These participants underwent an uncomplicated reintervention with no additional and/or permanent harm. Reinterventions because of failure of cure contained 3 second MUS procedures and one admission of urethral bulking agent. Seventy-six percent and 47 percent of patients were objectively cured of SUI at 12 and 24 months, respectively. CONCLUSIONS: Preliminary evidence suggests that a sling made of P4HB can be safely used for MUS procedures and could be an alternative for permanent polypropylene slings in patients that prefer the use of nonpermanent material.

The effect of CO2 laser therapy on vaginal microcirculatory parameters in an animal model for genitourinary syndrome of menopause.

BACKGROUND: Vaginal laser therapy for the treatment of genitourinary syndrome of menopause (GSM) has been introduced to the market with limited (pre)clinical and experimental evidence supporting its efficacy. It is suggested that vaginal laser therapy increases epithelial thickness and improves vascularization, but the underlying biological working mechanism has not been substantiated yet. OBJECTIVE: To evaluate the effects of CO2 laser therapy on vaginal atrophy using noninvasive incident dark field (IDF) imaging in a large animal model for GSM. DESIGN, SETTING, AND PARTICIPANTS: An animal study was conducted between 2018 and 2019 and included 25 Dohne Merino ewes, of which 20 underwent bilateral ovariectomy (OVX) to induce iatrogenic menopause, and 5 did not. The total study duration was 10 months. INTERVENTIONS: Five months after OVX, ovariectomized ewes received monthly applications of CO2 laser (n = 7), vaginal estrogen (n = 7), or no treatment (n = 6) for 3 months. IDF imaging was performed monthly in all animals. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the proportion of image sequences containing capillary loops (angioarchitecture). Secondary outcomes included focal depth (epithelial thickness), and quantitative measures of vessel density and perfusion. Treatment effects were evaluated using ANCOVA and binary logistic regression. RESULTS AND LIMITATIONS: Compared to OVX-only, ewes treated with estrogen demonstrated a higher capillary loops proportion (4% vs. 75%, p < 0.01), and higher focal depth (60 (IQR 60-80) vs. 80 (IQR 80-80) p < 0.05). CO2 laser therapy did not change microcirculatory parameters. As the ewes' vaginal epithelium is thinner than that of humans, it may demand different laser settings. CONCLUSIONS: In a large animal model for GSM, CO2 laser therapy does not affect microcirculatory outcomes related to GSM, whereas vaginal estrogen treatment does. Until more homogeneous and objective evidence about its efficacy is available, CO2 laser therapy should not be adopted into widespread practice for treating GSM.

Vaginal changes after ovariectomy in ewes: A large animal model for genitourinary syndrome of menopause.

OBJECTIVE: To evaluate the effect of iatrogenic menopause on the physiology of the vagina of the ewe and to evaluate if vaginal changes in ewes can be translated to women with genitourinary syndrome of menopause (GSM). METHODS: Preclinical research with Dohne Merino ewes. Iatrogenic menopause was induced by bilateral ovariectomy (OVX). Animals were randomized for surgery, blinded for allocation and outcome assessment. Differences between groups were determined by linear regression analyses at 5 months after OVX. Outcome measures were vaginal epithelial thickness, pH, vaginal maturation value, vaginal maturation index, epithelial glycogen accumulation, content of elastin fibers, collagen, and vascularity. RESULTS: OVX ewes (n = 20) showed epithelial thinning of the vaginal wall from 146 µm to 47 µm (mean, P < 0.001). Furthermore, epithelial glycogen accumulation and vascularity of the vaginal wall significantly decreased (43% and 23%, respectively) as compared with the control group (no intervention; n = 5). No significant differences were found for other outcome measures. CONCLUSION: This study established the ewe as a suitable large animal model for GSM. Furthermore, the similar relevant outcomes in humans and ewes hold great value for future translational research for the evaluation and optimization of different treatment modalities for GSM.

Retrospective review of intra- and post-operative complications with minimal versus large space of Retzius infiltration at the time of retropubic TVT placement.

INTRODUCTION AND HYPOTHESIS: A concern when using the retropubic tension-free vaginal tape (TVT) for stress urinary incontinence (SUI) is bladder perforation. This article describes a technique hypothesised to reduce the risk of intra-operative bladder perforation, termed the large space of Retzius infiltration (LSORI) technique. A large volume of infiltration of 360 ml saline-vasoconstrictor solution (180 ml × 2) into the space of Retzius (LSORI) at the time of retropubic TVT insertion will reduce the incidence of intra-operative bladder perforations. METHODS: This was a retrospective study reviewing the medical records of 89 women who underwent the retropubic TVT procedure at two urogynaecology Units. The intra- and post-operative characteristics associated with minimal (MSORI) versus large retropubic space of Retzius infiltrations (LSORI) were examined. RESULTS: Eighty-nine patients undergoing SUI surgery met the inclusion criteria. Forty-one patients had MSORI (volume range 20-60 ml bilaterally) versus 48 who had the 180-ml bilateral LSORI. No bladder perforations (0%) occurred in the LSORI group versus four in the MSORI group (9.8%), found to be statistically significant (p = 0.013). All other outcomes examined had no statistical difference. The TVT-related pain incidence: 8.3% (LSORI) versus 9.8% (MSORI). Post-operative urinary retention incidence was 6.3% (LSORI) and 14.6% (MSORI). Retropubic haematoma incidence was 0% (LSORI) and 2.4% (MSORI). Post-operative UTI rate was 12.5% (LSORI) and 17.1% (MSORI). CONCLUSIONS: This retrospective review revealed the potentially beneficial effect of the large (180 ml × 2) bilateral SORI with retropubic TVT placement in terms of the reduction in risk of bladder perforation. It also showed no potential added risk of post-operative complications.

Morbidity of a Single Incision Transvaginal Mesh to Correct Apical Prolapse.

STUDY OBJECTIVE: To determine complications and related reintervention rates associated with use of the Uphold Vaginal Support System (Boston Scientific, Boston, MA) for symptomatic vaginal apical prolapse. DESIGN: A multicenter retrospective study. SETTING: Two teaching hospitals. PATIENTS: Fifty-nine women with symptomatic vaginal apical prolapse. INTERVENTION: Vaginal apical prolapse surgery using the Uphold Mesh Kit system with or without other concomitant procedures. MEASUREMENTS AND MAIN RESULTS: A chart review was performed, including the following parameters: perioperative and postoperative complications, repeat surgery, and recurrence rate. A total of 59 patients met the criteria for inclusion in the study. Bladder perforation occurred perioperatively in 1 patient. Postoperative voiding difficulties were observed in 16 patients (27.1%), including 9 women (15.2%) who left the hospital with an indwelling catheter in place. There were 5 cases (8.5%) of transient groin pain, all of which resolved spontaneously. One patient developed a vaginal hematoma. Nine women (15%) required reoperation, including 4 (6.7%) because of recurrent prolapse and 1 (2%) for pelvic pain considered related to the mesh. Three patients (5%) required release of a midurethral sling (MUS) that had been placed concomitantly with the Uphold system. Two patients (3%) required a MUS for de novo stress incontinence. CONCLUSION: Use of the Uphold Vaginal Support System for symptomatic vaginal apical prolapse was associated with a significant risk of obstructed micturition. In our study population, 15% required repeat surgery, mainly for recurrent pelvic organ prolapse and de novo stress urinary incontinence. No surgical-related complication resulted in long-term morbidity.

Laparoscopic surgical anatomy for pelvic floor surgery.

Understanding anatomy is one of the pillars for performing a safe, effective, and efficient surgery, but recently, it is reported that there has been a decline in teaching anatomy during the preclinical years of medical school. There is also evidence that by the time a medical student becomes a clinician, a considerable proportion of the basic anatomy knowledge is lost. Hence, it is crucial for surgeons performing or assisting in pelvic floor surgery to revisit this integral clinical aspect of pelvic anatomy for performing a safe surgery. Pelvic organ prolapse repair, especially abdominal laparoscopic sacrocolpopexy, which is the gold standard of pelvic organ prolapse repair, presents a significant challenge to surgeons because the technique requires thorough and meticulous negotiation through abdomino-pelvic vascular structures and nerves supplying the pelvis, rectum, and ureters. The abdominal laparoscopic sacrocolpopexy surgery requires surgeons to have a deep understanding of anatomy to prevent potential life-threatening complications, which is as critical as it is for a pilot to understand the navigation route for a safe landing. This review is an extensive look and a great reminder to laparoscopic surgeons working in the pelvic cavity, especially those performing a pelvic floor surgery, about the anatomical safe routes for performing laparoscopic pelvic floor repairs. For easy reading and clear understanding, we have described step by step the safe anatomical journey a surgeon needs to take during laparoscopic sacrocolpopexy. We divided the technique into five critical anatomic locations (landmarks), which serves as our "flight map" for performing safe and efficient laparoscopic sacrocolpopexy.