Pathogenesis of polypropylene mesh complications in female pelvic floor surgery.

Abstract

<h4>Background</h4>The pathogenesis of female pelvic floor polypropylene mesh complications is unclear, as trials evaluating explanted mesh have not included asymptomatic controls.<h4>Objective</h4>This study aimed to compare women undergoing ex-plantation of polypropylene mesh with and without complications to determine the pathogenesis of the complications.<h4>Study design</h4>Between August 2019 and July 2020, 66 patients who visited the Wesley and Royal Brisbane and Women's Hospital Urogynecology departments with mesh complications and 15 patients who underwent repeat prolapse and/or continence surgery after a previous polypropylene mesh implantation were included. Investigations included 14 histology and immunohistochemical biomarkers and a subgroup of 21 patients who underwent scanning electron microscopy to evaluate degradation and Fourier transform infrared spectroscopy to determine whether any degradation was secondary to oxidation from free radical oxygen species. All scoring was standardized, and reviewers were blinded to group allocation. The mean differences in biomarkers between cases and controls were estimated after accounting for intracluster correlation because of repeated measurements through generalized estimating equation using a linear model framework. The Gwet agreement coefficient was used to assess the consistency in independent reviews, and the Spearman correlation was used to explore biomarker relationships.<h4>Results</h4>Cases had significantly increased staining of smooth muscle antigen (suggesting myofibroblasts; mean difference, 0.65; P<.01) and Masson trichome (collagen; mean difference, 0.22; P=.01) and lower levels of foreign body giant cells (mean difference, -0.39; P<.01), blood vessels (mean difference, -0.34; P<.01), CD86 (M1 macrophages; P=.05), and CD4 helper cells (mean difference, -0.58; P<.01) compared with control explants. Cases and controls demonstrated moderate and equal levels of degradation on histology, scanning electron microscopy (P=.86), and oxidation on Fourier transform infrared spectroscopy (P=.01). Degradation correlated poorly with all biomarkers (r<0.04). Persistent and equal levels of CD206 (M2 macrophages), CD68 (total macrophages), CD45 (leucocytes), CD31 (endothelial cells), and CD8 (cytotoxic T Cell) were identified in cases and controls, and the ratio of type I collagen to type III collagen was similar in both groups. Univariate analysis demonstrated that the prolapse mesh was associated with increased foreign body giant cells, CD86 marker, and histologic degradation compared with the continence mesh (P≤.001). Postmenopausal status (P=.04) was independently associated with increased degradation. Smoking status was associated with increased type I collagen deposition (P=.009) and lower foreign body giant cells (P=.03) compared with nonsmoking status. The use of systemic hormone replacement therapy was associated with increased CD31 (P=.01), foreign body giant cells (P=.003), blood vessels (P=.024), and Sirius red staining for type III collagen (P=.001) and decreased CD45 (P=.009) compared with no use of systemic hormone replacement therapy. After duration and mesh type adjustment, foreign body giant cells, blood vessels, CD4, smooth muscle antigen, and Masson trichome remained significant between cases and controls. Multivariate analysis indicated that histologic degradation increased by a score of 0.1/year implantation (P<.01) and was reduced in continence tapes compared with prolapse mesh (mean difference, -0.5 [95% confidence interval, -0.8 to -0.2]). In addition, the duration of implantation was associated with an increased Masson trichome score of 0.02/year, and smooth muscle antigen was increased in cases (mean difference, 0.65 [95% confidence interval, 0.30-1.00]) and explanted prolapse meshes (mean difference, 0.40 [95% confidence interval, 0.02-0.7]) compared with continence tapes. The intraobserver scoring consistency of the Gwet coefficient ranged from fair to very high.<h4>Conclusion</h4>Oxidation degradation was demonstrated equally in all cases and controls of polypropylene mesh explants. As such we were unable to confirm this was the cause of complications that were related to increased fibrosis and myofibroblast activity possibly secondary to a prolonged inflammatory response.