Short Duration of Upper Extremity Lymphedema Correlates With a Favorable Cytokine Response After Lymph Node Transfer Surgery

Abstract

Vascularized lymph node transfer surgery (VLNT) can provide benefit to lymphedema patients. Cytokines may play a role in the development of lymphedema and in the regeneration of lymphatic vessels after VLNT. Our primary aim was to investigate whether the VLNT patients have a specific cytokine profile. Our secondary aim was to see whether the preoperative lymphedema or severity affects the postoperative cytokine response. Wound exudate was gathered from 18 patients undergoing VLNT on the first and sixth postoperative day (POD). The concentrations of IL-10, TNF-α, TGF-β1 and VEGF-C were analyzed using enzyme-linked immune-sorbent assays. A general score was generated to assess the benefit of the surgery. The changes in cytokine concentrations (1st POD-6th POD) were correlated with the pre- and postoperative lymphedema related factors. A shorter duration of lymphedema preoperatively correlated with an increase in the concentration of IL-10 and TNF-β during the first six PODs (IL-10: r=0.495, p=0.051; TNF-α: r=0.737, p=0.006) and a decrease in the concentration of TGF-s1 (r= -0.613, p=0.020). The increase of the concentration of TNF-α during the first six PODs also correlated with a greater total general score (r=0.775, p=0.005) and hence indicated a better response to the surgery. The patients with a shorter duration of lymphedema preoperatively had a more favorable cytokine response during the first six PODs after VLNT.

The Role of Inflammation in Lymphedema: A Narrative Review of Pathogenesis and Opportunities for Therapeutic Intervention

“…Differences in the pro-lymphangiogenic growth factor, VEGF-C were also found among the lymph node dissection group and reconstruction/combined transfer-reconstruction groups [119]. Separate studies have corroborated these findings, noting correlation between IL-10, TNF-α, and TGFβ-1 levels and lymphedema-related factors following lymph node transfer [118]. In the context of lymphaticovenous anastomosis, histological analyses of skin samples showed decreased CD4 + cell inflammation in the lymphedematous limb biopsies, whereas the control limbs showed no difference [120].…”

“…Lymph Node Transfer and Combined Techniques Increased production of IL-10 (after combined lymph node transfer and anastomosis) [118]. Modulation of VEGF-C production, correlation between IL-10, TNF-α, TGFβ-1 and lymphedema-related factors following lymph node transfer [119].…”

“…It is hypothesized that the engrafted vascularized node transplant encourages local lymphatic regeneration. An analysis of post-operative wound exudates was undertaken to compare inflammatory cytokine profiles in patients with axillary lymph node dissection, breast reconstruction, microvascular lymph node transfer and a combined reconstruction-transplant approach [118]. These studies found that patients with the combined procedure had the highest production of the anti-inflammatory and antifibrotic cytokine, IL-10.…”