Role of Fibroblasts and Myofibroblasts on the Pathogenesis and Treatment of Pelvic Organ Prolapse

Pelvic organ prolapse (POP) is a multifactorial connective tissue disorder caused by damage to the supportive structures of the pelvic floor, leading to the descent of pelvic organs in the vagina. In women with POP, fibroblast function is disturbed or altered, which causes impaired collagen metabolism that affects the mechanical properties of the tissue. Ideal surgical repair, either native tissue repair or POP surgery using an implant, aims to create a functional pelvic floor that is load-bearing, activating fibroblasts to regulate collagen metabolism without creating fibrotic tissue. Fibroblast function plays a crucial role in the pathophysiology of POP by directly affecting the connective tissue quality. On the other hand, fibroblasts determine the success of the POP treatment, as the fibroblast-to-(myo)fibroblast transition is the key event during wound healing and tissue repair. In this review, we aim to resolve the question of “cause and result” for the fibroblasts in the development and treatment of POP. This review may contribute to preventing the development and progress of anatomical abnormalities involved in POP and to optimizing surgical outcomes.

Cost-Effectiveness of perioperative Vaginally Administered estrogen in postmenopausal women undergoing prolapse surgery (EVA trial): study protocol for a multicenter double-blind randomized placebo-controlled trial

Background Surgery for pelvic organ prolapse (POP) is associated with high recurrence rates. The costs associated with the treatment of recurrent POP are huge, and the burden from women who encounter recurrent POP, negatively impacts their quality of life. Estrogen therapy might improve surgical outcome for POP due to its potential beneficial effects. It is thought that vaginal estrogen therapy improves healing and long-term maintenance of connective tissue integrity. Hence, this study aims to evaluate the cost-effectiveness of perioperative vaginal estrogen therapy in postmenopausal women undergoing POP surgery. Methods The EVA trial is a multi-center double-blind randomized placebo-controlled trial conducted in the Netherlands comparing the effectiveness and costs-effectiveness of vaginal estrogen therapy. This will be studied in 300 postmenopausal women undergoing primary POP surgery, with a POP-Q stage of ≥ 2. After randomization, participants administer vaginal estrogen cream or placebo cream from 4 to 6 weeks preoperative until 12 months postoperative. The primary outcome is subjective improvement of POP symptoms at 1 year follow-up, measured with the Patient Global Impression of Improvement (PGI-I) scale. Secondary outcomes are POP-Q anatomy in all compartments, re-interventions, surgery related complications, general and disease specific quality of life, sexual function, signs and complaints of vaginal atrophy, vaginal pH, adverse events, costs, and adherence to treatment. Follow up is scheduled at 6 weeks, 6 months and 12 months postoperative. Data will be collected using validated questionnaires and out-patient visits including gynecological examination performed by an independent gynecologist. Discussion This study investigates whether perioperative vaginal estrogen will be cost-effective in the surgical treatment of POP in postmenopausal women. It is hypothesized that estrogen therapy will show a reduction in recurrent POP symptoms and a reduction in reoperations for POP, with subsequent improved quality of life among women and cost savings. Trial registrationNetherlands Trial Registry: NL6853; registered 19-02-2018, https://www.trialregister.nl/trial/6853. EudraCT: 2017-003144-21; registered: 24-07-2017.

Laparoscopic sacral hysteropexy for pelvic organ prolapse in a patient affected by marfan syndrome: a case report

Background: Marfan Syndrome (MS) is a dominantly inherited connective tissue disorder with consequences on the strength and resilience of connective tissues that may predispose to Pelvic Organ Prolapse (POP). Literature lacks studies investigating POP surgery in patients affected by MS that might help surgical management decisions. Objective: The objective of this paper is to describe the surgical procedure of laparoscopic sacral hysteropexy (LSHP) in a 37 years old woman affected by MS with symptomatic POP. Materials and Methods and main outcome measures: We performed a nerve-sparing laparoscopic sacral hysteropexy without complications and looked for anatomical and subjective outcomes. The patient completed The Female Sexual Distress Scale (FSDS), Pelvic Floor Disability Index (PFDI-20), and Wexner questionnaires preoperatively and postoperatively. Results: The patient stated a complete resolution of all POP related symptoms and there was a total correction of the descensus. Furthermore, no perioperative and postoperative complications were noted. Conclusions: LSHP could be an effective and safe procedure for the treatment of POP in women affected by MS and this case report is the first to describe a reconstructive procedure in this category of patients. What is new? The literature lacks studies investigating POP surgery in women with MS, that might help surgeons, thus we present this case to describe surgical and functional outcomes in this patient category, underlying the higher risk of complications and relapses related to the weakness of connective tissue. This case report may represent the basis of future studies to confirm the safety, efficacy and feasibility of LSHP and sacral colpopexy in patients with MS.

Női kismedencei funkciózavarok keresztmetszeti vizsgálata magyarországi populáción

Összefoglaló. Bevezetés és célkitűzés: A női kismedencei funkciózavarok változatos tünetekkel jelentkezhetnek, és jelentősen befolyásolják az érintettek életminőségét. Vizsgálatunk célja volt felmérni a medencefenék-diszfunkciós tüneteket és azok hatását az egyén életminőségére. Módszer: Vizsgálatunkba 203 nőt vontunk be. Az adatgyűjtést két kérdőív, egy általunk összeállított és az Australian Pelvic Floor Questionnaire segítségével végeztük. Az adatok statisztikai elemzéséhez SPSS 20.0 rendszert használtunk. Spearman-korrelációt, khi-négyzet-próbát, Mann–Whitney-féle U-tesztet, Kruskal–Wallis-próbát és többváltozós lineáris regressziót alkalmaztunk. A szignifikanciaszintet p≤0,05 határnál állapítottuk meg. Eredmények: A hólyagdiszfunkciók gyakorisága (56,2%) szignifikáns kapcsolatot mutatott az életkor növekedésével (p<0,001), az obesitassal (p<0,001), a szülésszámmal és -móddal (p<0,001; p<0,001), az episiotomiával (p<0,001) és a prolapsusműtétekkel (p = 0,010). A süllyedéses kismedencei kórképek gyakorisága (27,1%) szignifikáns kapcsolatot mutatott az életkor növekedésével (p = 0,002), a szülésszámmal és -móddal (p<0,001; p<0,001) és a korábbi episiotomiával (p<0,001). Az analis incontinentia gyakorisága (58,9%) a magasabb testtömegindexszel (p = 0,029) volt szignifikáns kapcsolatban. Szexuális diszfunkciót (53,2%) allergia és tüdőbetegségek (p = 0,048) jelenlétével kapcsolatban találtunk. A többes diszfunkció előfordulási gyakorisága az életkor növekedésével (p<0,001), az obesitassal (p = 0,043), a korábbi hysterectomiával (p = 0,046) és prolapsusműtétekkel (p<0,001) mutatott szignifikáns kapcsolatot. Minden diszfunkció esetén kimutatható volt az életminőség-romlás (hólyagfunkciók: p<0,001; bél- és székletürítési funkciók: p<0,001, hüvelyfali süllyedés: p<0,001, szexuális funkciók: p<0,001). Következtetés: Az általunk vizsgált női populációban nagy arányban találtunk kismedencei funkciózavarokat, melyek kedvezőtlen hatással voltak az érintettek életminőségére. Orv Hetil. 2021; 162(43): 1724–1731. Summary. Introduction and objective: Pelvic floor dysfunction (PFD) can cause several complaints in women and has an adverse effect on the quality of life (Qol). The aim of our study was to evaluate the prevalence of pelvic floor dysfunction and its effect on Qol. Method: 203 women were included. We used two questionnaires, a self-constructed and the Australian Pelvic Floor Questionnaire. Statistical analysis was performed by SPSS 20.0. Spearman’s correlation, chi-square, Mann–Whitney U, Kruskal–Wallis tests and multivariate linear regression were used. Statistical significance was set at p≤0.05. Results: There was a significant association between the prevalence of urinary incontinence (56.2%) and age (p<0.001), obesity (p<0.001), number and mode of deliveries (p<0.001; p<0.001), episiotomy (p<0.001) and pelvic organ prolapse (POP) surgery (p = 0.010); between the occurrence of POP (27.1%) and age (p = 0.002), the number and mode of deliveries (p<0.001; p<0.001) and episiotomy (p<0.001); between the prevalence of anal incontinence (58.9%) and obesity (p = 0.029); between sexual dysfunction (SD) (53.2%) and respiratory disease and allergy (p = 0.048). Multiple PFD was significantly associated with age (p<0.001), obesity (p = 0.043), hysterectomy (p = 0.046) and POP surgery (p = 0.010). There was a significant difference between women having more severe PFD than milder complaints regarding Qol (bladder p<0.001; bowel p<0.001; SD p<0.001 and POP p<0.001). Conclusion: Pelvic floor dysfunction was common in our study population and had a great adverse effect on Qol. Orv Hetil. 2021; 162(43): 1724–1731.

Protocol for a prospective multisite cohort study investigating hysterectomy versus uterine preservation for pelvic organ prolapse surgery: the HUPPS study

IntroductionPelvic organ prolapse (POP) is the descent of pelvic organs into the vagina resulting in bulge symptoms and occurs in approximately 50% of women. Almost 20% of women will elect surgical correction of this condition by age 85. Removal of the uterus (hysterectomy) with concomitant vaginal vault suspension is a long-standing practice in POP surgery to address apical (uterine) prolapse. Yet, contemporary evidence on the merits of this approach relative to preservation of the uterus through suspension is needed to better inform surgical decision making by patients and their healthcare providers. The objective of this study is to evaluate POP-specific health outcomes and service utilisation of women electing uterine suspension compared with those electing hysterectomy and vaginal vault suspension for POP surgery up to 1-year postsurgery.Methods and analysisThis is a prospective cohort study planning to enrol 321 adult women with stage ≥2 POP from multiple sites in Alberta, Canada. Following standardised counselling from study surgeons, participants self-select either a hysterectomy based or uterine preservation surgical group. Data are being collected through participant questionnaires, medical records and administrative data linkage at four time points spanning from the presurgical consultation to 1-year postsurgery. The primary outcome is anatomic failure to correct POP, and secondary outcomes include changes in positioning of pelvic structures, retreatment, subjective report of bulge symptoms, pelvic floor distress and impact, sexual function and health service use. Data will be analysed using inverse probability weighting of propensity scores and generalised linear models.Ethics and disseminationThis study is approved by the Conjoint Health Research Ethics Board at the University of Calgary (REB19-2134). Results will be disseminated via peer-reviewed publications, presentations at national and international conferences, and educational handouts for patients.Trial registration numberNCT04890951.

Practice pattern variation: treatment of pelvic organ prolapse in The Netherlands

Introduction and hypothesis Great variety in clinical management of pelvic organ prolapse (POP) has been described over the last years. Practice pattern variation (PPV) reflects differences in care that cannot be explained by the underlying condition. We aim to explore whether PPV in management of POP in The Netherlands has changed between 2011 and 2017. Methods We conducted a multicenter cohort study, using prospective routinely collected benchmark data from LOGEX, a healthcare analytics company (Amsterdam, The Netherlands). Data of patients with a diagnosis POP from 50 hospitals (16 teaching and 34 non-teaching hospitals) were collected for the years 2011 and 2017. All treatments were categorized into three groups: conservative treatment, uterus-preserving or uterus-removing surgery. Using meta-analysis, we evaluated whether the proportions of conducted treatments changed over time and estimated the between-center variation (Cochran’s Q), reflecting the PPV in 2011 and 2017. This variation was analyzed using F-tests. Results Compared to 2011, referral for POP in 2017 decreased by 16.2% (−4505 patients), and the percentage of hysterectomies decreased by 33.6% (p < 0.0001). The PPV of POP surgery decreased significantly by 47.2% (p = 0.0137) and of hysterectomies by 41.5% (p = 0.0316). Conclusions We found a decline in PPV for POP surgery between 2011 and 2017. Furthermore, the number of surgical interventions decreased, which was mostly due to a decline of hysterectomies. This indicates a shift toward more conservative therapy and uterus preservation. A further reduction of PPV would be beneficial for the quality of health care.

EVALUATION OF THE SHORT TERM HOST RESPONSE AND BIOMECHANICS OF AN ABSORBABLE POLY-4-HYDROXYBUTYRATE SCAFFOLD IN A SHEEP MODEL FOLLOWING VAGINAL IMPLANTATION

Objective: To compare the host and biomechanical response to a fully absorbable poly-4-hydroxybutyrate (P4HB) scaffold to the response to PP mesh in an animal model of vaginal POP surgery. Design: A study employing a sheep model Setting: KU Leuven Center for Surgical Technologies Population: 14 parous female Mule sheep Methods: P4HB scaffolds were surgically implanted in the posterior vaginal wall of sheep. The comparative PP mesh data were obtained from an identical protocol. Main outcome measures: Gross necropsy, histological and biomechanical evaluation of explants, and the in vivo P4HB scaffold degradation were evaluated at 60- and 180-days post-implantation. Results: Gross necropsy revealed no implant related adverse events using P4HB scaffolds. The tensile stiffness of the P4HB explants increased at 180-days (12.498 ± 2.66 N/mm (P=0.019)) as compared to 60-days (4.585 ± 1.57 N/mm) post-implantation, while P4HB degraded gradually. P4HB scaffolds exhibited excellent tissue integration with dense connective tissue and a moderate initial host response. P4HB scaffolds induced a significantly higher M2/M1 ratio (1.70 ± 0.67 SD, score 0-4), as compared to PP mesh (0.99 ± 0.78 SEM, score 0-4) at 180-days. Conclusions: P4HB scaffold facilitated a gradual load transfer to vaginal tissue over time. The fully absorbable P4HB scaffold, in comparison to PP mesh, has a favorable host response with comparable load bearing capacity. If these results are also observed at longer follow-up, a clinical study for vaginal POP surgery may be warranted to demonstrate efficacy. Key words: Pelvic organ prolapse, vaginal surgery, Poly-4-hydroxybutyrate, degradable scaffold, host response, biomechanics.

Postoperative urinary retention after pelvic organ prolapse surgery: influence of peri-operative factors and trial of void protocol

Purpose Transient postoperative urinary retention (POUR) is common after pelvic floor surgery. We aimed to determine the association between peri-operative variables and POUR and to determine the number of voids required for post-void residuals (PVRs) to normalize postoperatively. Methods We conducted a retrospective cohort study of 992 patients undergoing pelvic floor surgery at a tertiary referral centre from January 2015 to October 2017. Variables assessed included: age, BMI, ASA score, anaesthesia type, type of surgery, length of postoperative stay, surgeon, bladder protocol used, and number of PVRs required to “pass” the protocol. Results Significant risk factors for POUR included: placement of MUS during POP surgery, anterior repair and hysterectomy with concomitant sacrospinous vault suspension. A total of 25.1% were discharged requiring catheterization. Patients receiving a concomitant mid-urethral sling (MUS) were 2.2 (95% CI1.6–2.9) and 2.3 (95% CI 1.8–3.1) times more likely to have elevated PVR after their second TOV and third TOV (p < 0.0001), respectively, compared with those without concomitant MUS. Permitting a third TOV allowed an additional 10% of women to pass the voiding protocol before discharge. The median number of voids to pass protocol was 2. An ASA > 2 and placement of MUS were associated with increasing number of voids needed to pass protocol. Conclusions While many women passed protocol by the second void, using the 3rd void as a cut point to determine success would result in fewer women requiring catheterization after discharge. Prior to pelvic floor surgery, women should be counselled regarding POUR probability to allow for management of postoperative expectations.

181 Comparison of Synthetic Mesh Erosion and Chronic Pain Rates After Surgery for Pelvic Organ Prolapse and Stress Urinary Incontinence: A Systematic Review

Background The aim of this study is to systematically compare rates of erosion and chronic pain after mesh insertion for pelvic organ prolapse (POP) and stress urinary incontinence (SUI) surgery. Method A systematic electronic search was performed on studies that evaluated the incidence of erosion and chronic pain after mesh insertion for POP or SUI. The primary outcome measurement was to compare mesh erosion and chronic pain rates for POP and SUI surgery. Results Twenty-six studies on 292,606 patients (n = 9077 for POP surgery and n = 283529 for SUI surgery) met inclusion criteria. The POP group were older (p &lt; 0.0001) and had a lower BMI (p &lt; 0.0001). Mesh erosion rates were significantly greater in the POP group compared to the SUI group (4% versus 1.9%) [OR 2.13; 95% CI 1.91-2.37; p &lt; 0.0001]. The incidence of chronic pain was significantly greater in the POP group compared to the SUI group (6.7% versus 0.6%) [OR 11.02; 95% CI 8.15-14.9; p &lt; 0.0001]. Conclusions The risk of mesh erosion and chronic pain is significantly higher after surgery for POP compared to SUI. Since a higher volume of mesh is typically used for POP surgery this supports evidence for a dose-response relationship between the volume of mesh used and the erosion risk.