Lymphatic Function Is Impaired Following Irradiation of a Single Lymph Node

Introduction: Lymph nodes are often the target of radiotherapy procedures. Unfortunately, the impact of nodal irradiation on lymphatic function is uncertain. In this study, our aim was to quantify the impact of lymph node irradiation on lymph flow. Methods and Results: The popliteal node or the nodal excision site of rabbits was treated with four daily 8 Gy doses of radiation. A FITC-dextran tracer was infused into a prenodal popliteal lymphatic. The area under the tracer blood recovery curve (AUC) indicated lymphatic functionality and the inflow pressure versus flow rate relationship inferred resistance through the system. Fluoroscopic and histological examination provided supporting data. Radiation of intact nodes decreased lymph transport significantly at 1 week, 1 month, and 6 months post-treatment (AUCs of 207.9±79.87, 191.6±62.95, and 250.44±46.45) in comparison to controls (667.32±104.18). Surprisingly, this functional decline was similar to that detected with a combination of node removal and irradiation of the excision site. The pressure–flow relationships in all treatment groups were significantly different from controls. This may be due in part to fibrosis and the thickening of the nodal capsules and trabeculae observed at 1 and 6 months. Fluoroscopy and Evans blue dye studies revealed vigorous new lymphatic vessel growth and occasionally, vessels anastomosed with local veins. Conclusions: Irradiation of the popliteal lymph node impaired lymph transport and increased the pressure required to maintain flow through the system. New vessel formation and the growth of lymph-venous anastomoses indicated the development of alternative drainage pathways as a compensatory response.