Simultaneous breast and lymphatic reconstruction is an ideal option for patients who suffer from lymphedema after mastectomy and axillary dissection.

Diabetes impairs numerous aspects of tissue repair. Failure of wound angiogenesis is known to delay diabetic wound healing, whereas the importance of lymphangiogenesis for wound healing is unclear. We have examined whether overexpression of vascular endothelial growth factor (VEGF)-C via an adenoviral vector could improve the healing of full-thickness punch biopsy wounds in genetically diabetic (db/db) mice. We found that VEGF-C enhanced angiogenesis and lymphangiogenesis in the wound and significantly accelerated wound healing in comparison to the control wounds. VEGF-C also recruited inflammatory cells, some of which expressed VEGFR-3. On the other hand, when the function of endogenous VEGF-C/VEGF-D was blocked with a specific inhibitor, wound closure was delayed even further. These results suggest a function for VEGF-C in wound healing and demonstrate the therapeutic potential of VEGF-C in the treatment of diabetic wounds.

Background— Lymphedema after surgery, infection, or radiation therapy is a common and often incurable problem. Application of lymphangiogenic growth factors has been shown to induce lymphangiogenesis and to reduce tissue edema. The therapeutic effect of autologous lymph node transfer combined with adenoviral growth factor expression was evaluated in a newly established porcine model of limb lymphedema. Methods and Results— The lymphatic vasculature was destroyed within a 3-cm radius around an inguinal lymph node. Lymph node grafts and adenovirally (Ad) delivered vascular endothelial growth factor (VEGF)-C (n=5) or VEGF-D (n=9) were used to reconstruct the lymphatic network in the inguinal area; AdLacZ (β-galactosidase; n=5) served as a control. Both growth factors induced robust growth of new lymphatic vessels in the defect area, and postoperative lymphatic drainage was significantly improved in the VEGF-C/D–treated pigs compared with controls. The structure of the transferred lymph nodes was best preserved in the VEGF-C–treated pigs. Interestingly, VEGF-D transiently increased accumulation of seroma fluid in the operated inguinal region postoperatively, whereas VEGF-C did not have this side effect. Conclusions— These results show that growth factor gene therapy coupled with lymph node transfer can be used to repair damaged lymphatic networks in a large animal model and provide a basis for future clinical trials of the treatment of lymphedema.

Therapeutic, IV.

Free flap surgery is routine today, yet little is known of its pathophysiology. In this study, the authors evaluated the hemodynamics in different types of free microvascular flaps, by measuring intraoperative transit-time flow. Eighty-six free transplants--21 free TRAM flaps for breast reconstruction, 18 radial forearm flaps for head and neck reconstructions, and 47 muscle flaps for head and neck, trunk and lower extremity reconstructions--were studied. Donor artery flow was highest in the radial artery (mean: 57.5 +/- 50 (SD) ml/min) but dropped (p < 0.001) to one tenth (6.1 +/- 2 ml/min) after anastomosis. The flow was lowest (4.9 +/- 3 ml/min) in the recipient artery of the TRAM flap but, after anastomosis, increased significantly (13.7 +/- 5 ml/min) to the level of the flow in the donor artery. The donor-artery flow in muscle flaps had a mean of 15.9 +/- 11 ml/min, and it significantly increased after anastomosing (23.9 +/- 12 ml/min). Weight-related intake of blood was highest in the radial forearm flap (18.5 +/- 6 ml/ min/100g) and lowest in the TRAM flap (2.5 +/- 1 ml/min/100g). The study showed that blood flow through a free microvascular flap does not depend on recipient artery flow. Even low-flow arteries can be used as recipients, because the flow increases according to free-flap requirements. The blood flow through a free microvascular flap depends on the specific tissue components of the flap.

Most patients desire body contouring surgery after bariatric surgery, and our multivariate analysis showed a significant positive association between female sex, younger age, amount of weight loss, and ΔBMI with desire for body contouring.

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.

Objective: To study the safety and tolerability of Lymfactin R treatment combined with microvascular lymph node transfer surgery in patients with upper limb lymphedema. Background: Upper limb lymphedema is a common clinical challenge after breast cancer surgery and/or radiotherapy. Lymfactin R is an adenovirus type 5-based gene therapy involving expression of human vascular endothelial growth factor C (VEGF-C) in the damaged tissue. It aims to correct deficient lymphatic flow by promoting the growth and repair of lymphatic vessels.