Secondary lymphedema is a common complication after removal of lymph nodes in combination with radiation therapy in the treatment of breast cancer, cervical cancer, and melanomas. Only symptomatic therapies are available at the moment, and lymphedema is for most patients a lifelong condition involving psychological and physical disabilities. Animal models exist to study the pathophysiology of lymphedema but not to study surgical treatments. The aim of this study was to show that regeneration of autologous transplanted lymph node fragments is possible in rats that were irradiated previously locally in the groin and to examine the effects of vascular endothelial growth factor (VEGF)-C injections on the rate of regeneration of transplanted lymph nodes. In all of the animals, inguinal and popliteal lymph nodes and adjacent lymphatic vessels were unilaterally removed and the inguinal region irradiated by a single dose of 15 Gy. Afterward, lymph node fragments were transplanted subcutaneously in the irradiated region. Half of the animals were treated by local VEGF-C injections after transplantation. Four weeks after transplantation, drainage of the leg was tested by injection of blue dye, and the transplanted fragments were removed and examined immunohistologically. We could show that regeneration of autologous transplanted lymph node fragments is possible in areas treated with radiotherapy in the rat. We also documented that transplants can achieve a connection to the lymphatic collectors of the leg. The results suggest that the outcome of regeneration can be improved by injection of VEGF-C in the transplantation area. Thus, lymph node fragment regeneration may be relevant for lymphedema prevention and therapy. Anat Rec, 295:786-791, 2012. V C 2012 Wiley Periodicals, Inc.

Secondary lymphedema is a common complication after lymph node excision and radiotherapy in cancer therapy. Therapies are limited to symptomatic treatment. Adequate animal models to test potential surgical therapies are needed. The aim of this study was to induce a tissue environment in the hind leg of the rat similar to the one found in operated and irradiated patients. Quantification of edematous swelling was performed by an automatic 3D-contour segmentation (ITK- Snap ©) on MR- images. Swelling was induced by excision of superficial inguinal and popliteal lymph nodes and adjacent lymphatic vessels, followed by radiotherapy of the right groin with a single dose of 15 Gy. Four weeks after irradiation, the animals were examined with MRI of both hind legs. Fluid volumes around the joint line of the knee were calculated on T2-weighted images. We documented a significant higher volume of fluid in the legs following excision of lymph nodes and lymphatic vessels, combined with radiotherapy than in control legs.

No abstract