Vaginal Mesh Complications: Is There a Systemic Inflammatory Response?

Objectives: Hernia mesh implantation has been associated with increased levels of IL-6 and CRP – markers of systemic inflammation; however, limited data exists regarding systemic inflammation following vaginal mesh implantation despite patient concerns. Previous studies of mesh-tissue complexes excised from patients with mesh complications vs controls showed no differences in peripheral white blood cell counts. Here, we performed a more comprehensive assessment of systemic inflammation in women undergoing mesh removal surgery with the hypothesis that patients with mesh complications would show evidence of inflammation compared to controls.

Methods: Patients undergoing excision of vaginal mesh were offered enrollment in a Mesh Biorepository study (n=136). Patients were excluded for autoimmune disorders, chronic immunosuppression, or hematologic malignancies. Serum for systemic marker analysis was collected on a random subset of mesh biorepository patients with complications of exposure (n=13) and pain (n=12). Serum from patients enrolled in a separate study of women ≥60 years old undergoing surgery served as controls. Serum in these patients was collected either 2 weeks after mesh implantation without complication (n=7) or in women with prolapse on the day of but prior to surgery (n=8). Sample size calculation for our primary outcome, IL-6 serum levels, demonstrated a need for 7 patients per group to demonstrate a 2pg/mL difference, as seen in prior studies. Multiplex electrochemiluminescence was performed on serum to perform a comprehensive assessment of markers of inflammation including IL-6, CRP, ICAM1, VCAM1, SAA, IFN-gamma, IL-10, IL-13, IL-4, IL-8, TNFα, IL-12p70, IL-1β and IL2. ANOVA and Kruskal-Wallis tests were used to compare analyte concentrations by group. ANCOVA analysis was planned to control for age given differences in enrollment criteria for mesh complications vs controls.

Results: Demographic variables were similar between groups except for age, with women in the control groups significantly older (73.1±3.8 and 76.4±5.1 years for controls vs 57.2±9.7 and 54.1±12.1 years for complication groups; p=0.015, Table 1). Although VCAM1 showed a difference between groups on univariate analysis with exposure having a median of 994 nJg/mL (IQR 267) pain 1,086 ng/mL (460); integrated mesh 1,316 ng/mL (621); control 1,542 ng/mL (417), this was no longer significant when controlling for age, which was linearly associated with VCAM1 (p=0.16, Figure 1). Samples were also grouped by mesh complication (n=25) and no mesh/no mesh complication (n=15) as well as by presence (n=32) and absence (n=8) of mesh with no difference in systemic markers when controlling for age. Finally, given the importance of the selecting the best control group, an additional analysis was performed with a control group of women 2 weeks after native tissue repair with no change in these results.

Conclusions: There was no evidence of systemic inflammation in patients undergoing mesh excision surgery for a complication. Additional investigation in a larger cohort is warranted.