Lymphatic Vessel Function and Lymphatic Growth Factor Secretion after Microvascular Lymph Node Transfer in Lymphedema Patients

Abstract

Background:Recent reports have shown that microvascular lymph node transfer may improve lymphatic drainage in lymphedema patients. Lymphatic anastomoses are expected to form spontaneously in response to lymphatic growth factor [vascular endothelial growth factor C (VEGF-C)] secreted by the transferred lymph nodes.Methods:We have analyzed the results of 19 lymph node transfer patients operated on 2007–2012. Postoperat ive lymphatic function of the affected arm was evaluated using semiquantitative lymphoscintigraphy (transport index) and limb circumference measurements. To investigate the postoperative VEGF-C secretion, we examined axillary seroma fluid samples after different surgical operations, including lymph node transfer.Results:The transport index was improved postoperatively in 7 of 19 patients. Ten of the 19 patients were able to reduce or even discontinue using compression garments. Arm circumferences were reduced in 12 of 19 patients. Six of the 7 patients with preoperative erysipelas infections have not had infectious episodes postoperatively during 15–67 months follow-up. Neuropathic pain was relieved in 5 of 5 patients. VEGF-C protein was detected in the axillary seroma fluid both after lymph node transfer and normal breast reconstruction.Conclusions:Reconstructing the lymphatic anatomy of the axilla with a lymph node flap may offer possibilities that other reconstructive options are lacking. However, we will need further reports and comparative studies about the clinical efficacy of this new promising technique. In addition to the transferred lymph nodes, lymphatic growth factor production may also be induced by other factors related to microvascular breast reconstruction.

Anti-inflammatory effects of flap and lymph node transfer

“…Lymphangiogenic growth factors VEGF-C and VEGF-D Similar to our previous study with a smaller number of patients [7], significant groupwise differences in the VEGF-C concentration were observed on the first POD (Fig. 6, Supplementary Table 8).…”

“…It is therefore possible that this clinical finding is partly related to the smaller production of proinflammatory cytokines after flap transfer. However, the production of lymphangiogenic growth factor (VEGF-C) after flap transfer (also without lymph nodes) [7] probably also plays a role in inducing beneficial effects in lymphedema patients (Fig. 9).…”

“…In addition, wound exudate samples were collected from flap donor sites (n ¼ 9) on the first and sixth POD. Microvascular LN was performed to lymphedema patients as previously described [6,7]. The BR group consisted of postmastectomy patients without lymphedema symptoms.…”

“…Human lymph nodes express lymphatic vascular endothelial growth factor C (VEGF-C) [6], which is secreted into axillary wound exudate after microvascular LN [7]. Results from the preclinical lymphedema models using VEGF-C or VEGF-D have demonstrated the ability of these factors to induce the growth of new lymphatic vessels [11e13], thus providing a biological basis for the microsurgical LN method.…”

Breast Cancer-Related Lymphedema (BCRL)

“…There are few studies of the long-term effectiveness of tissue transfers for LE. Published articles are either outdated, performed on animals, or are insufficient to demonstrate lymph vessel function in breast reconstruction flaps [53][54][55][56][57].…”