Lymphaticovenous Anastomosis Supermicrosurgery Decreases Oxidative Stress and Increases Antioxidant Capacity in the Serum of Lymphedema Patients

Abstract

Background: Excess lymphedematous tissue causes excessive oxidative stress in lymphedema. Lymphaticovenous anastomosis (LVA) supermicrosurgery is currently emerging as the first-line surgical intervention for lymphedema. No data are available regarding the changes in serum proteins correlating to oxidative stress and antioxidant capacity before and after LVA.

Methods: A total of 26 patients with unilateral lower limb lymphedema confirmed by lymphoscintigraphy were recruited, and venous serum samples were collected before (pre-LVA) and after LVA (post-LVA). In 16 patients, the serum proteins were identified by isobaric tags for relative and absolute quantitation-based quantitative proteomic analysis with subsequent validation of protein expression by enzyme-linked immunosorbent assay. An Oxidative Stress Panel Kit was used on an additional 10 patients. Magnetic resonance (MR) volumetry was used to measure t limb volume six months after LVA.

Results: This study identified that catalase (CAT) was significantly downregulated after LVA (pre-LVA vs. post-LVA, 2651 ± 2101 vs. 1448 ± 593 ng/mL, respectively, p = 0.033). There were significantly higher levels of post-LVA serum total antioxidant capacity (pre-LVA vs. post-LVA, 441 ± 81 vs. 488 ± 59 µmole/L, respectively, p = 0.031) and glutathione peroxidase (pre-LVA vs. post-LVA, 73 ± 20 vs. 92 ± 29 U/g, respectively, p = 0.018) than pre-LVA serum. In addition, after LVA, there were significantly more differences between post-LVA and pre-LVA serum levels of CAT (good outcome vs. fair outcome, -2593 ± 2363 vs. 178 ± 603 ng/mL, respectively, p = 0.021) and peroxiredoxin-2 (PRDX2) (good outcome vs. fair outcome, -7782 ± 7347 vs. -397 ± 1235 pg/mL, respectively, p = 0.037) in those patients with good outcomes (≥40% volume reduction in MR volumetry) than those with fair outcomes (<40% volume reduction in MR volumetry).

Conclusions: The study revealed that following LVA, differences in some specific oxidative stress markers and antioxidant capacity can be found in the serum of patients with lymphedema.

Keywords: Enzyme-linked immunosorbent assay (ELISA); LVA; antioxidant; iTRAQ; lymphaticovenous anastomosis; lymphedema; lymphovenous bypass (LVB); oxidative stress; reactive oxygen species (ROS).

Figure 1

Lymphaticovenous anastomosis (LVA). (A) Two lymphatic vessels with diameter 0.7 mm and 0.5 mm were anastomosed to a recipient vein in an end-to-side orientation with 11-0 nylon suture. (B) The lumen of the recipient vein became enhanced under near-infrared lymphography. The indocyanine green (ICG)-containing lymph has flowed from the lymphatic vessel into the recipient vein, indicating good antegrade lymphatic flow. Note: the background grid is 1 * 1 mm².

Figure 2

A 55-year-old woman with a BMI of 22.1 kg/m² post-cervical cancer ablation and lymph node dissection (23 years prior). She has suffered from stage III lymphedema on her left lower limb for the past seven years with frequent cellulitis. A total of nine lymphaticovenous anastomoses (LVAs) were performed. (Upper left) Pre-LVA. (Upper right) Six months post-LVA follow-up. (Lower left) Preoperative MR volumetry showing a left lower limb volume of 8785.0 mL; right lower limb volume of 5843.0 mL. The volume gained in the left lower limb due to lymphedema was 2942.0 mL (8785.0 mL minus 5843.0 mL). (Lower right) Six months post-LVA MR volumetry showing left limb volume of 6976.6 mL. Post-LVA volume reduction was −1808.4 mL (a −61.5% lymphedema volume reduction).