The vaginal microcirculation after prolapse surgery

Aims: Oxygen plays a crucial role in wound healing after prolapse surgery. Trauma to the vaginal vasculature might limit the delivery of oxygen to the surgical wound, which may negatively affect wound healing and regeneration of connective tissue. This possibly increases the future risk of recurrence. We aimed to determine the effects of vaginal prolapse surger

The ewe as an animal model of vaginal atrophy and vaginal Er:YAG laser application.

peer reviewed[en] OBJECTIVE: In sheep of reproductive age, we aimed to document decrease in epithelial thickness, glycogen amount, and other vaginal changes after castration and the effect of Er:YAG laser as used clinically. METHODS: On day 0, 16 sheep underwent ovariectomy. They were randomized to sham or three vaginal Er:YAG laser applications at monthly intervals. Primary outcome was vaginal epithelial thickness (d60, d71, d73, d77, and d160). Secondary outcomes included indicators of atrophy (vaginal health index = VHI), pH, cytology, morphology at the above time points, microcirculation focal depth (FD; d70 and d160), and at sacrifice (d160) vaginal dimensions and active and passive biomechanical testing. RESULTS: Menopausal changes between 60 and 160 days after ovariectomy included a progressive decrease in epithelial thickness, in VHI, FD, glycogen, elastin content and vasculature, and an increase in pH and collagen content. In lasered animals, the first day a few white macroscopic foci were visible and an increase in pH was measured. Both disappeared within 3 days. Seven days after laser the epithelial thickness increased. At sacrifice (d160), there were no differences between sham and laser group in vaginal dimensions, morphometry, mitotic and apoptotic activity, active contractility, vaginal compliance, except for a lower blood vessel density in the lamina propria of the midvagina in the laser group. CONCLUSIONS: In reproductive sheep, ovariectomy induces vaginal atrophy evidenced in different outcome measurements. Vaginal Er:YAG laser induced visual impact, a short-term increase in epithelial thickness yet no long-term changes compared to sham therapy in menopausal controls.Video Summary:http://links.lww.com/MENO/A672

Focal depth measurements of the vaginal wall: a new method to noninvasively quantify vaginal wall thickness in the diagnosis and treatment of vaginal atrophy

The aim of the study was to evaluate if vaginal focal depth measurement could be a noninvasive method to quantify vaginal wall thickness. Postmenopausal women undergoing topical estrogen therapy because of vaginal atrophy (VA) were recruited. VA was diagnosed based on the presence of symptoms and vaginal pH at least 5.5. The control group consisted of women above 40 years without VA. Focal depth measurements were performed before and after treatment using the Cytocam-Incident Dark Field device assessing the distance between the subepithelial microcirculation and the epithelial surface. Measurements were performed before and after treatment in the intervention group and at two different time points in the control group. Vaginal pH was measured. Symptoms were evaluated using the most bothersome symptom approach. Eight women with VA and nine controls were included. Pretreatment median focal depth was not significantly different between both groups. Pretreatment focal depth more than doubled after a median of 7 weeks of topical estrogen treatment (80 μm [interquartile range 80-120 μm] vs 220 μm [148-248 μm], P = 0.02), whereas the measurements in the control group did not change. Pretreatment vaginal pH differed between both groups (5.5 vs 5.1, respectively, P  < 0.01). Vaginal pH did not change after treatment. Using in vivo microscopy we introduced a new noninvasive measure of vaginal wall thickness. A significant increase in vaginal focal depth was observed in participants with VA treated with topical estrogens. This innovative measurement of vaginal wall thickness could become the preferred objective measure to evaluate treatment effect. Moreover, it has great potential for other applications in the field of urogynecolog

Fully absorbable poly-4-hydroxybutyrate implants exhibit more favorable cell-matrix interactions than polypropylene

Pelvic organ prolapse (POP) is a multifactorial condition characterized by the descent of the pelvic organs due to the loss of supportive tissue strength. This is presumably caused by the decreased fibroblast function and the subsequent change in the quality of the extracellular matrix. The correction of POP using an implant intends to provide mechanical support to the pelvic organs and to stimulate a moderate host response. Synthetic polypropylene (PP) implants were commonly used for the correction of prolapse. Although they were successful in providing support, these implants have been associated with clinical complications in the long term due to substantial foreign body response and inappropriate tissue integration. The complications can be avoided or minimized by engineering a biocompatible and fully absorbable implant with optimized mechanical and structural characteristics that favor more appropriate cellular interactions with the implant. Therefore, in this study, we evaluated implants comprised of poly-4-hydroxybutyrate (P4HB), a fully absorbable material with high mechanical strength, as an alternative to PP. The P4HB implants were knitted in four unique designs with different pore shapes ranging from a more rectangular geometry- as it is in PP implant- to a rounded geometry, to determine the effect of the implant structure on the textural and mechanical properties and subsequent cell-matrix interaction. The cellular response was investigated by seeding primary vaginal fibroblasts isolated from patients with POP. P4HB favored cellular functions more than PP, as indicated by greater cell attachment and proliferation (P < 0.01), and significantly more collagen deposition (P4HB vs PP, 11.19 μg vs 6.67 μg) at 28 days culture (P < 0.05). All P4HB implants had higher strength and lower stiffness than the PP scaffold. The material and the design of the implant also influenced the behavior of vaginal fibroblasts. The aspect ratio of the vaginal POP fibroblasts cultured on the PP implant (1.61 ± 0.75) was significantly (P < 0.005) smaller than those cultured on P4HB implants (average 2.31 ± 0.09). The P4HB structure with rounded pores showed the lowest stiffness and highest fibroblast attachment and proliferation (P < 0.01). Overall, P4HB induces more matrix deposition compared to PP and knit design can further optimize cell behavior

Gentle cyclic straining of human fibroblasts on electrospun scaffolds enhances their regenerative potential

The extracellular matrix of fascia-like tissues is a resilient network of collagenous fibers that withstand the forces of daily life. When overstretched, the matrix may tear, with serious consequences like pelvic organ prolapse (POP). Synthetic implants can provide mechanical support and evoke a host response that induces new matrix production, thus reinforcing the fascia. However, there is considerable risk of scar formation and tissue contraction which result in severe complications. Matrix producing fibroblasts are both mechanosensitive and contractile; their behavior depends on the implant's surface texture and mechanical straining. Here we investigate the effect of both in a newly-designed experimental setting. Electrospun scaffolds of Nylon and PLGA/PCL and a non-porous PLGA/PCL film were clamped like a drumhead and seeded with fibroblasts of POP patients. Upon confluency, scaffolds were cyclically strained for 24 or 72 h at 10% and 0.2 Hz, mimicking gentle breathing. Non-loading condition was control. Strained fibroblasts loosened their actin-fibers, thereby preventing myofibroblastic differentiation. Mechanical loading upregulated genes involved in matrix synthesis (collagen I, III, V and elastin), matrix remodeling (α-SMA, TGF-β1, MMP-2) and inflammation (COX-2, TNF-α, IL8, IL1-β). Collagen genes were expressed earlier under mechanical loading and the ratio of I/III collagen increased. Matrix synthesis and remodeling were stronger on the electrospun scaffolds, while inflammation was more prominent on the non-porous film. Our findings indicate that mechanical straining enhances the regenerative potential of fibroblasts for the regeneration of fascia-type tissues and limit the risk of scar tissue formation. These effects are stronger on an electrospun texture. Statement of significance: Pelvic organ prolapsed is a dysfunctional disease in female pelvic floor that can reduce the quality of life women. Currently, trans-vaginal knitted meshes are used to anatomically correct the dysfunctional tissues. However, the meshes can create sever adverse complications in some patients (e.g. chronic pain) in longer-term. As an alternative, we developed nanofibrous matrices by electrospinning based on different materials. We designed an in-vitro culture system and subjected cell-seeded matrices to cyclic mechanical loading. Results revealed that gentle straining of POP-cells on electrospun matrices, advances their regenerative potential at morphological and gene expression levels. Our findings, provide a proof-of-concept for using electrospun matrices as an alternative implant for pelvic floor repair, given that the parameters are designed efficiently and safely

The vaginal microcirculation after prolapse surgery

Aims: Oxygen plays a crucial role in wound healing after prolapse surgery. Trauma to the vaginal vasculature might limit the delivery of oxygen to the surgical wound, which may negatively affect wound healing and regeneration of connective tissue. This possibly increases the future risk of recurrence. We aimed to determine the effects of vaginal prolapse surgery on the microcirculation of the vaginal wall. Methods: We evaluated the vaginal microcirculation in healthy participants without known vascular disease undergoing anterior and/or posterior colporrhaphy. We used incident dark-field imaging for in vivo assessment before and after (1 day, 2 weeks, and 6 weeks) surgery. We studied perfusion (microvascular flow index [MFI]), angioarchitecture (morphology/layout of microvessels) and capillary density. Results: Ten women were included. Interindividual differences were observed 1 day postoperatively with regard to perfusion and angioarchitecture. Microvascular flow at the surgical site was absent or significantly reduced in some participants, whereas normal microvascular flow was observed in others (MFI range 0–3). Perfusion and angioarchitecture had been restored in all participants after 6 weeks (MFI range 2–3), regardless of the extent of vascular trauma 1 day postoperatively. Conclusions: The difference in the extent of vascular trauma between women undergoing seemingly identical surgical procedures suggests that some individuals are more susceptible to vascular trauma than others. Delivery of oxygen to the wound and subsequent wound healing may be compromised in these cases, which could be related to the development of anatomical recurrence. Future studies should investigate whether there is a relationship between the vaginal microvasculature and the recurrence of prolapse

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 evaluate the host- and biomechanical response to a fully absorbable poly-4-hydroxybutyrate (P4HB) scaffold in comparison with the response to polypropylene (PP) mesh. Design In vivo animal experiment. Setting KU Leuven Center for Surgical Technologies. Population Fourteen 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 study protocol performed previously. Main outcome measures Gross necropsy, host response and biomechanical evaluation of explants, and the in vivo P4HB scaffold degradation were evaluated at 60- and 180-days post-implantation. Data are reported as mean +/- standard deviation (SD) or standard error of the mean (SEM). 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 SEM [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 SD, 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 in-vivo, a clinical study using P4HB for vaginal POP surgery may be warranted to demonstrate efficacy.ISSN:1470-032

An Observational Study on the Efficacy and Complications of a Transvaginal Single-Incision Mesh for Pelvic Organ Prolapse

Objective: The aim of this study was to evaluate a new-generation, single-incision transvaginal mesh (TVM) procedure on anatomical and functional outcomes and complication rates in women with symptomatic cystoceles. Materials and Methods: Sixty-five patients with symptomatic cystoceles (POP-Q stage ≥2) were included in a prospective, multicenter study in the Netherlands to evaluate the TVM procedure using the Nuvia® Anterior Device (Bard Medical, Crawley, UK). The primary endpoint was anatomical cure after 12 months (Pelvic Organ Prolapse Quantification [POP-Q] points Aa and Ba at-2 cm or higher). Secondary endpoints were subjective reduction of pelvic organ prolapse (POP) noted on 3 disease-specific quality-of-life (QoL) questionnaires (Urogenital Distress Inventory [UDI], Incontinence Impact Questionnaire [IIQ], and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire [PISQ-12]); complications; and serious adverse events during and after surgery up to 12 months later. Repeated-measurement analyses were used for POP-Q scores and QoL outcomes. Results: Anterior and apical measurements improved after surgery with anatomical success rates of 70.6% and 60.8% after 6 and 12 months, respectively. Four patients (7.7%) developed vaginal mesh exposure and 2 (3.8%) developed significant pain related to the mesh. Three (5.7%) needed reintervention due to these complications. The apical recurrence rate was 4%, and 2 patients underwent repeat POP surgery. Functional outcomes on UDI, IIQ, and PISQ-12 were satisfactory with significant improvements in QoL reported on all questionnaires. Conclusions: This study demonstrated significant improvement in anatomical and functional outcomes with low complication rates. The single-incision approach to TVM surgery can be a valid option for patients with complex recurrent prolapse