RESUMO
IMPORTANCE: In the past, urethral shape, mobility, and urodynamics have been used to retrospectively demonstrate correlations with stress urinary incontinence. Our previous work has shown a relationship between urethral function and shape in symptomatic women. OBJECTIVE: This study aimed to characterize the effect of pelvic floor squeeze and strain maneuvers on urethral shapes and pressure in a cohort of patients without pelvic floor disorders. STUDY DESIGN: In this cross-sectional study, volunteers underwent dynamic pelvic floor ultrasound examination, and a modified urodynamic study. Urethral length, thickness, and proximal and distal swing angles were measured at rest, squeeze, and strain. The midsagittal urethral walls were traced so that a statistical shape model could be performed. Means and standard deviations of imaging and urodynamic measures were calculated. RESULTS: Data from 19 participants were analyzed. On average during squeeze compared with rest, urethral length increased by 6%, thickness decreased by 42% (distal, P < 0.001), 10% (middle), and urethral pressure increased by 14%. Opposite shape changes-length decreased by 10% ( P = 0.001), thickness increased by 57% (distal, P < 0.001), 20% (middle, P < 0.001)-and increased urethral mobility were observed during strain, with larger pressure increases occurring (29%, P < 0.001). Fifty-one percent of the total shape variance described the differences between maneuvers. These differences were statistically different between groups ( P < 0.001 for comparisons, all others P > 0.05). CONCLUSIONS: Dynamic ultrasound and urodynamics allow for the establishment of baseline ranges in urethral metrics (2-dimensional measures, shape, and pressure) and how they are altered during maneuvers. These data can allow for a more objective identification of incontinence via ultrasound and urodynamic testing.
Assuntos
Tosse , Incontinência Urinária por Estresse , Humanos , Feminino , Estudos Transversais , Estudos Retrospectivos , Incontinência Urinária por Estresse/diagnóstico por imagem , Uretra/diagnóstico por imagemRESUMO
ABSTRACT: We used dynamic pelvic floor ultrasound to investigate the relationship between obstructed defecation symptom (ODS) severity and the degree of rectal hypermobility/folding. In this retrospective study, women who presented with ODS from October 2017 to January 2019 and underwent an interview, pelvic examination, and pelvic floor ultrasound were recruited. Patients were diagnosed with abdominal constipation, dyssynergia, or pelvic constipation. Pelvic constipation patients were categorized based on their reported frequency of incomplete emptying of stool (<50% or ≥50% of bowel movements) representing mild and severe ODS, respectively. Using dynamic ultrasound, rectal hypermobility was quantified via rectovaginal septum length at rest and Valsalva and its compression ratio, where shorter lengths and larger compression ratios are indicative of increased rectal hypermobility. One hundred twenty-one patients (41 with abdominal constipation, 7 with dyssynergia, and 73 with pelvic constipation) were included. Compression ratios were higher in women with severe versus mild ODS (17.36 ± 16.89 vs 36.38 ± 25.82, P = 0.0039). The risk of having severe symptoms was 4 times greater (odds ratio = 4.2, 95% confidence interval = 1.4 to 12.6, P = 0.01) among those with a high compression ratio (≥20%) after controlling for age, body mass index, and levator plate descent angle. Incomplete emptying was weakly, positively, linearly correlated with rectal hypermobility/folding (r = -0.2724, -0.3767 to 0.3922, and P = 0.0197, 0.0010, 0.0006, respectively). Women with more severe ODS experienced more rectal hypermobility/folding as measured via dynamic ultrasound-a cheaper, effective alternative to magnetic resonance defecography for evaluation of obstructed defecation.
Assuntos
Constipação Intestinal , Defecação , Constipação Intestinal/diagnóstico por imagem , Feminino , Humanos , Reto/diagnóstico por imagem , Estudos Retrospectivos , UltrassonografiaRESUMO
BACKGROUND: Prolapse recurrence after transvaginal surgical repair is common; however, its mechanisms are ill-defined. A thorough understanding of how and why prolapse repairs fail is needed to address their high rate of anatomic recurrence and to develop novel therapies to overcome defined deficiencies. OBJECTIVE: This study aimed to identify mechanisms and contributors of anatomic recurrence after vaginal hysterectomy with uterosacral ligament suspension (native tissue repair) vs transvaginal mesh (VM) hysteropexy surgery for uterovaginal prolapse. STUDY DESIGN: This multicenter study was conducted in a subset of participants in a randomized clinical trial by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Overall, 94 women with uterovaginal prolapse treated via native tissue repair (n=48) or VM hysteropexy (n=46) underwent pelvic magnetic resonance imaging at rest, maximal strain, and poststrain rest (recovery) 30 to 42 months after surgery. Participants who desired reoperation before 30 to 42 months were imaged earlier to assess the impact of the index surgery. Using a novel 3-dimensional pelvic coordinate system, coregistered midsagittal images were obtained to assess study outcomes. Magnetic resonance imaging-based anatomic recurrence (failure) was defined as prolapse beyond the hymen. The primary outcome was the mechanism of failure (apical descent vs anterior vaginal wall elongation), including the frequency and site of failure. Secondary outcomes included displacement of the vaginal apex and perineal body and change in the length of the anterior wall, posterior wall, vaginal perimeter, and introitus of the vagina from rest to strain and rest to recovery. Group differences in the mechanism, frequency, and site of failure were assessed using the Fisher exact tests, and secondary outcomes were compared using Wilcoxon rank-sum tests. RESULTS: Of the 88 participants analyzed, 37 (42%) had recurrent prolapse (VM hysteropexy, 13 of 45 [29%]; native tissue repair, 24 of 43 [56%]). The most common site of failure was the anterior compartment (VM hysteropexy, 38%; native tissue repair, 92%). The primary mechanism of recurrence was apical descent (VM hysteropexy, 85%; native tissue repair, 67%). From rest to strain, failures (vs successes) had greater inferior displacement of the vaginal apex (difference, -12 mm; 95% confidence interval, -19 to -6) and perineal body (difference, -7 mm; 95% confidence interval, -11 to -4) and elongation of the anterior vaginal wall (difference, 12 mm; 95% confidence interval, 8-16) and vaginal introitus (difference, 11 mm; 95% confidence interval, 7-15). CONCLUSION: The primary mechanism of prolapse recurrence following vaginal hysterectomy with uterosacral ligament suspension or VM hysteropexy was apical descent. In addition, greater inferior descent of the vaginal apex and perineal body, lengthening of the anterior vaginal wall, and increased size of the vaginal introitus with strain were associated with anatomic failure. Further studies are needed to provide additional insight into the mechanism by which these factors contribute to anatomic failure.
Assuntos
Imageamento por Ressonância Magnética , Pelve/diagnóstico por imagem , Falha de Tratamento , Prolapso Uterino/diagnóstico por imagem , Prolapso Uterino/cirurgia , Idoso , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Humanos , Histerectomia Vaginal/efeitos adversos , Imageamento Tridimensional , Pessoa de Meia-Idade , RecidivaRESUMO
BACKGROUND: Stress urinary incontinence carries a significant healthcare burden for women worldwide. Single incision slings are minimally invasive mesh devices designed to treat stress urinary incontinence. For prolapse repair, meshes with higher porosity and lower structural stiffness have been associated with improved outcomes. OBJECTIVE: In this study, we compared the higher stiffness, lower porosity Altis sling with the lower stiffness, higher porosity Solyx sling in an ovine model. We hypothesized that SIS-B would have a negative impact on the host response. STUDY DESIGN: A total of Altis and Solyx single incision slings were implanted suburethrally into sheep according to the manufacturer's instructions on minimal tension. The mesh-urethral-vaginal complex and adjacent ungrafted vagina (no mesh control) were harvested en bloc at 3 months. Masson's trichrome and picrosirius red staining of 6 µm thin sections was performed to measure interfiber distance and tissue integration. Smooth muscle contractility to a 120 mM KCl stimulus was performed in an organ bath to measure myofiber-driven contractions. Standard biochemical assays were used to quantify glycosaminoglycan, total collagen, and elastin content, and collagen subtypes. Bending stiffness was performed in response to a uniaxial force to define susceptibility to folding/buckling. Statistical analysis was performed using Mann-Whitney, Gabriel's pairwise post hoc, Wilcoxon matched-pairs, and chi-square tests. RESULTS: The animals had similar ages (3-5 years), parity (multiparous), and weights (45-72 kg). Trichrome cross sections showed that the Altis sling buckled in a "C" or "S" shape in most samples (8 of 11), whereas buckling after Solyx sling implantation was observed in only a single sample (1 of 13; P=.004). Tissue integration, as measured by the presence of collagen or smooth muscle between the mesh fibers on trichrome 4× imaging, was increased in samples implanted with the Solyx sling compared with the Altis sling (P<.05). Total collagen content decreased significantly with both products when compared with the ungrafted vagina consistent with stress shielding. There was no difference in the 2 groups with regard to glycosaminoglycan or elastin content. The Altis sling mesh tissue complex demonstrated significantly higher amounts of both collagen types I and III than the Solyx sling-implanted tissue and the ungrafted control. Smooth muscle contractility in response to 120 mM KCl was decreased after implantation of both slings compared with the sham (P=.011 and P<.01), with no difference between mesh types (P=.099). Bending stiffness in the Altis sling was more than 4 times lower than in the Solyx, indicating an increased propensity to buckle (0.0186 vs 0.0883). CONCLUSION: The structurally stiffer Altis sling had decreased tissue integration and increased propensity to buckle after implantation. Increased collagen types I and III after the implantation of this device suggests that these changes may be associated with a fibrotic response. In contrast, the Solyx sling largely maintained a flat configuration and had improved tissue integration. The deformation of the Altis sling is not an intended effect and is likely caused by its lower bending stiffness. Both meshes induced a decrease in collagen content and smooth muscle contractility similar to previous findings for prolapse meshes and consistent with stress shielding. The long-term impact of buckling warrants further investigation.
Assuntos
Modelos Animais , Slings Suburetrais , Incontinência Urinária por Estresse/cirurgia , Vagina/cirurgia , Animais , Feminino , OvinosRESUMO
BACKGROUND: Despite good anatomic and functional outcomes, urogynecologic polypropylene meshes that are used to treat pelvic organ prolapse and stress urinary incontinence are associated with significant complications, most commonly mesh exposure and pain. Few studies have been performed that specifically focus on the host response to urogynecologic meshes. The macrophage has long been known to be the key cell type that mediates the foreign body response. Conceptually, macrophages that respond to a foreign body can be dichotomized broadly into M1 proinflammatory and M2 proremodeling subtypes. A prolonged M1 response is thought to result in chronic inflammation and the formation of foreign body giant cells with potential for ongoing tissue damage and destruction. Although a limited M2 predominant response is favorable for tissue integration and ingrowth, excessive M2 activity can lead to accelerated fibrillar matrix deposition and result in fibrosis and encapsulation of the mesh. OBJECTIVE: The purpose of this study was to define and compare the macrophage response in patients who undergo mesh excision surgery for the indication of pain vs a mesh exposure. STUDY DESIGN: Patients who were scheduled to undergo a surgical excision of mesh for pain or exposure at Magee-Womens Hospital were offered enrollment. Twenty-seven mesh-vagina complexes that were removed for the primary complaint of a mesh exposure (n = 15) vs pain in the absence of an exposure (n = 12) were compared with 30 full-thickness vaginal biopsy specimens from women who underwent benign gynecologic surgery without mesh. Macrophage M1 proinflammatory vs M2 proremodeling phenotypes were examined via immunofluorescent labeling for cell surface markers CD86 (M1) vs CD206 (M2) and M1 vs M2 cytokines via enzyme-linked immunosorbent assay. The amount of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) proteolytic enzymes were quantified by zymography and substrate degradation assays, as an indication of tissue matrix degradation. Statistics were performed with the use of 1-way analysis of variance with appropriate post hoc tests, t-tests, and Fisher's Exact test. RESULTS: Twenty-seven mesh-vaginal tissue complexes were excised from 27 different women with mesh complications: 15 incontinence mid urethral slings and 12 prolapse meshes. On histologic examination, macrophages surrounded each mesh fiber in both groups, with predominance of the M1 subtype. M1 and M2 cytokines/chemokines, MMP-9 (pro- and active), and MMP-2 (active) were increased significantly in mesh-vagina explants, as compared with vagina without mesh. Mesh explants that were removed for exposure had 88.4% higher pro-MMP-9 (P = .035) than those removed for pain. A positive correlation was observed between the profibrotic cytokine interleukin-10 and the percentage of M2 cells (r = 0.697; P = .037) in the pain group. CONCLUSION: In women with complications, mesh induces a proinflammatory response that persists years after implantation. The increase in MMP-9 in mesh explants that were removed for exposure indicates degradation; the positive association between interleukin-10 and M2 macrophages in mesh explants that are removed for pain is consistent with fibrosis.
Assuntos
Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Prolapso de Órgão Pélvico/cirurgia , Telas Cirúrgicas/efeitos adversos , Incontinência Urinária por Estresse/cirurgia , Vagina/metabolismo , Adulto , Feminino , Humanos , Macrófagos/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Prolapso de Órgão Pélvico/metabolismo , Incontinência Urinária por Estresse/metabolismo , Vagina/cirurgiaRESUMO
BACKGROUND: Although synthetic mesh is associated with superior anatomic outcomes for the repair of pelvic organ prolapse, the benefits of mesh have been questioned because of the relatively high complication rates. To date, the mechanisms that result in such complications are poorly understood, yet the textile characteristics of mesh products are believed to play an important role. Interestingly, the pore diameter of synthetic mesh has been shown to impact the host response after hernia repair greatly, and such findings have served as design criteria for prolapse meshes, with larger pores viewed as more favorable. Although pore size and porosity are well-characterized before implantation, the changes in these textile properties after implantation are unclear; the application of mechanical forces has the potential to greatly alter pore geometries in vivo. Understanding the impact of mechanical loading on the textile properties of mesh is essential for the development of more effective devices for prolapse repair. OBJECTIVE: The objective of this study was to determine the effect of tensile loading and pore orientation on mesh porosity and pore dimensions. STUDY DESIGN: In this study, the porosity and pore diameter of 4 currently available prolapse meshes were examined in response to uniaxial tensile loads of 0.1, 5, and 10 N while mimicking clinical loading conditions. The textile properties were compared with those observed for the unloaded mesh. Meshes included Gynemesh PS (Ethicon, Somerville, NJ), UltraPro (Artisyn; Ethicon), Restorelle (Coloplast, Minneapolis, MN), and Alyte Y-mesh (Bard, Covington, GA). In addition to the various pore geometries, 3 orientations of Restorelle (0-, 5-, 45-degree offset) and 2 orientations of UltraPro (0-, 90-degree offset) were examined. RESULTS: In response to uniaxial loading, both porosity and pore diameter dramatically decreased for most mesh products. The application of 5 N led to reductions in porosity for nearly all groups, with values decreasing by as much as 87% (P < .05). On loading to 10 N of force, nearly all mesh products that were tested were found to have porosities that approached 0% and 0 pores with diameters >1 mm. CONCLUSION: In this study, it was shown that the pore size of current prolapse meshes dramatically decreases in response to mechanical loading. These findings suggest that prolapse meshes, which are more likely to experience tensile forces in vivo relative to hernia repair meshes, have pores that are unfavorable for tissue integration after surgical tensioning and/or loading in urogynecologic surgeries. Such decreases in pore geometry support the hypothesis that regional increases in the concentration of mesh leads to an enhanced local foreign body response. Although pore deformation in transvaginal meshes requires further characterization, the findings presented here provide a mechanical understanding that can be used to recognize potential areas of concern for complex mesh geometries. Understanding mesh mechanics in response to surgical and in vivo loading conditions may provide improved design criteria for mesh and a refinement of surgical techniques, ultimately leading to better patient outcomes.
Assuntos
Telas Cirúrgicas , Resistência à Tração , Suporte de Carga , Fenômenos Biomecânicos , Feminino , Humanos , Teste de Materiais , Prolapso de Órgão Pélvico/cirurgia , Porosidade , TêxteisRESUMO
OBJECTIVE: We sought to determine the predominant cell type (macrophage, T lymphocyte, B lymphocyte, mast cell) within the area of implantation of the prototypical polypropylene mesh, Gynemesh PS (Ethicon, Somerville, NJ); and to determine the phenotypic profile (M1 proinflammatory, M2 antiinflammatory) of the macrophage response to 3 different polypropylene meshes: Gynemesh PS (Ethicon), and 2 lower-weight, higher-porosity meshes, UltraPro (Ethicon) and Restorelle (Coloplast, Humblebaek, Denmark). STUDY DESIGN: Sacrocolpopexy was performed following hysterectomy in rhesus macaques. Sham-operated animals served as controls. At 12 weeks postsurgery, the vagina-mesh complex was excised and the host inflammatory response was evaluated. Hematoxylin and eosin was used to perform routine histomorphologic evaluation. Identification of leukocyte (CD45(+)) subsets was performed by immunolabeling for CD68 (macrophage), CD3 (T lymphocyte), CD20 (B lymphocyte), and CD117 (mast cell). M1 and M2 macrophage subsets were identified using immunolabeling (CD86(+) and CD206(+), respectively), and further evaluation was performed using enzyme-linked immunosorbent assay for 2 M1 (tumor necrosis factor-alpha and interleukin [IL]-12) and 2 M2 (IL-4 and IL-10) cytokines. RESULTS: Histomorphologic evaluation showed a dense cellular response surrounding each mesh fiber. CD45(+) leukocytes accounted for 21.4 ± 5.4% of total cells within the perimesh area captured in a ×20 field, with macrophages as the predominant leukocyte subset (10.5 ± 3.9% of total cells) followed by T lymphocytes (7.3 ± 1.7%), B lymphocytes (3.0 ± 1.2%), and mast cells (0.2 ± 0.2%). The response was observed to be more diffuse with increasing distance from the fiber surface. Few leukocytes of any type were observed in sham-operated animals. Immunolabeling revealed polarization of the macrophage response toward the M1 phenotype in all mesh groups. However, the ratio of M2:M1 macrophages was increased in the fiber area in UltraPro (P = .033) and Restorelle (P = .016) compared to Gynemesh PS. In addition, a shift toward increased expression of the antiinflammatory cytokine IL-10 was observed in Restorelle as compared to Gynemesh PS (P = .011). CONCLUSION: The host response to mesh consists predominantly of activated, proinflammatory M1 macrophages at 12 weeks postsurgery. However, this response is attenuated with implantation of lighter-weight, higher-porosity mesh. While additional work is required to establish causal relationships, these results suggest a link among the host inflammatory response, mesh textile properties, and clinical outcomes in the repair of pelvic organ prolapse.