Postoperative Systemic Inflammation following Pelvic Surgery: Mesh, Menopause, and Diabetes

Objectives: Postoperative systemic inflammatory response (PSIR) is a self-limited response to surgical trauma. However, a dysregulated PSIR may trigger or increase the risk of organ dysfunction under certain circumstances. In urogynecologic surgeries, multiple factors, including mesh implantation, menopause, and comorbidities such as diabetes, may modify the PSIR. Here, we aimed to define the impact of these factors on the PSIR following urogynecologic surgeries using a rat model.

Methods: Female Wistar rats (6–9 months, 260–350 grams) were used (n=122 in total, with 5-12 in each subgroup). Diabetes (n=56) was induced using streptozotocin (45mg/kg) 2 weeks before surgery. Animals with or without (w/wo) diabetes were randomly grouped as 1) no-surgery controls, 2) surgery without mesh, and 3) surgery with mesh. Transabdominal supracervical hysterectomy with bilateral ovariectomies (OVX) were performed w/wo implanting a polypropylene mesh on the anterior and posterior vagina via sacrocolpopexy. At 3-, 7-, and 42-days post-surgery, 11 primary proinflammatory cytokines (G-CSF, IL-6, IL-12p70, IL-1β, TNFα) and chemokines (eotaxin, MCP-1, MCP-3, IP-10, MIP-1α, GROα) in peripheral blood plasma samples were quantified using multiplex Luminex assays. Surgical groups without OVX were also evaluated at 42-days. Kruskal-Wallis with post-hoc tests and linear regression models were used for statistics. Significance was set at p< .05.

Results: OVX did not have a significant impact on the plasma proinflammatory mediators in rats w/wo mesh and those w/wo diabetes (all p >.05). In nondiabetic rats undergoing surgeries w/wo mesh, circulating proinflammatory mediators were rapidly increased at 3-days post-surgery compared to no-surgery controls (p < .001, Figure), with MCP-1 levels increased by 132% (p=.001) in the group without mesh and by 35% (p=.003) in the group with mesh. The inflammatory status decreased at 7 days and returned to normal at 42 days (p >.05). When comparing groups with vs. without mesh, eotaxin levels in the former were steadily decreased by 62%, 42%, and 37% at 3-, 7-, and 42-days (p=.012, .014, .001, respectively). Under diabetic conditions, IP-10 levels were persistently increased in groups without mesh, by 172%, 92%, and 172% at 3, 7, and 42 days, respectively (p=.012, .045, .045), while eotaxin, IP-10, and MCP-3 were increased in groups with mesh at 42 days by 165%, 194%, and 103% (p=.003, < .001, .003), respectively.

Conclusions: Urogynecologic surgery evokes a rapid PSIR aligning with an increase in plasma MCP-1. Mesh implantation modifies the response by inducing a persistent decrease of plasma eotaxin under nondiabetic conditions while diabetes induces a higher systemic proinflammatory profile in the long term with a long-lasting increase in plasma IP-10. Further studies are needed to understand the mechanisms that regulate these circulating proinflammatory chemokines and to determine their potential as biomarkers.