Effects of autotransplanted lymph node fragments on the lymphatic system in the pig model

Abstract

Secondary lymphedema often develops after removal of lymph nodes in combination with radiation therapy, in particular in patients with breast cancer, inguinal cancer, cervical cancer and melanoma. No convincing treatment for the prevention and therapy of acquired lymphedema exists so far, therefore we wanted to show the reintegration of transplanted avascular lymph node fragments in the lymphatic system and positive effects of the transplanted fragments on the restoration of the lymphatic flow in this study. A total of 26 minipigs underwent lymphadenectomy of both groins. A minimum of one lymph node was retransplanted. The lymph nodes were cut into small pieces and retransplanted in the left groin (n = 17) or in both groins (n = 9). Different retransplantation techniques were investigated, transplantation of large versus small fragments, with and without capsule. The lymph flow was evaluated 5 and 8 months after surgery, using SPECT/CT and Berlin Blue. The results were confirmed by dissection. The lymph node transplants were assessed histologically. In contrast to the lymph flow in the transplanted groin, the lymph flow in the non-transplanted groin was often malfunctioning. Large lymph node fragments were found reintegrated in the lymphatic system more often than small slices of lymph node fragments. About 5 months after surgery impairment of lymph flow was seen especially after retransplantation of small slices of lymph node fragments. In seven out of eight minipigs a dermal backflow developed in the non-transplanted groin, 8 months after surgery. Only one minipig of these groups developed dermal backflow in both groins. All lymph node fragments showed an organized structure histologically. Autologous lymph node transplantation has positive effects on the regeneration of lymph vessels and restoration of lymph flow after lymphadenectomy.

Vascularized Lymph Node Transfer Based on the Hilar Perforators Improves the Outcome in Upper Limb Lymphedema

“…If the vascular supply is not optimal, there is less opportunity for lymph absorption into the vein and the tissue itself atrophies, 2 losing the ability to spontaneously reestablish afferent and efferent continuity following division. 6,14,15 Therefore, restoration of lymphatic function following lymph node transfer requires establishment of adequate perfusion. 3,4,16 Clinical experience with transfer of vascularized lymph nodes has been mostly limited to the inguinal region because of reduced morbidity associated with the harvest of the superficial lymph nodes and inconspicuous donor scar.…”

Surgical Management of Lymphedema: Past, Present, and Future

“…17,18 Further, successful engraftment of nonvascularized lymph node grafts has not been shown definitively, and this process is probably, at best, highly variable. 19 In fact, animal studies with nonvascularized lymph node grafts have been mostly disappointing, unless the transfer is performed in the setting of augmented vascular endothelial growth factor-C (VEGF-C) expression. 20,21 The risk of lymphedema in the donor extremity is also a concern, particularly when even trivial lymphatic injury in the form of sentinel lymph node biopsy has been shown to result in lymphedema in 5%-7% of patients.…”

Vascularized Lymph Node Transfer for Treatment of Lymphedema

“…14 In addition, a more wholly preserved nodal transplant proved beneficial according to regeneration patterns. 12,14 Timing of VLNT has been shown and affect outcomes, as seen in success rates being higher in immediate versus delayed transplants. 9…”