Experimental assessment of pro-lymphangiogenic growth factors in the treatment of post-surgical lymphedema following lymphadenectomy

Introduction: Lymphedema is a frequent consequence of lymph node excision during breast cancer surgery. Current treatment options are limited mainly to external compression therapies to limit edema development. We investigated previously, postsurgical lymphedema in a sheep model following the removal of a single lymph node and determined that autologous lymph node transplantation has the potential to reduce or prevent edema development. In this report, we examine the potential of lymphangiogenic therapy to restore lymphatic function and reduce postsurgical lymphedema. Methods: Lymphangiogenic growth factors (vascular endothelial growth factor C (VEGF-C)) and angiopoietin-2 (ANG-2) were loaded into a gel-based drug delivery system (HAMC; a blend of hyaluronan and methylcellulose). Drug release rates and lymphangiogenic signaling in target endothelial cells were assessed in vitro and vascular permeability biocompatibility tests were examined in vivo. Following, the removal of a single popliteal lymph node, HAMC with the growth factors was injected into the excision site. Six weeks later, lymphatic functionality was assessed by injecting 125Iodine radiolabeled bovine serum albumin (125I-BSA) into prenodal vessels and measuring its recovery in plasma. Circumferential leg measurements were plotted over time and areas under the curves used to quantify edema formation. Results: The growth factors were released over a two-week period in vitro by diffusion from HAMC, with 50% being released in the first 24 hr. The system induced lymphangiogenic signaling in target endothelial cells, while inducing only a minimal inflammatory response in sheep. Removal of the node significantly reduced lymphatic functionality (nodectomy 1.9 ± 0.9, HAMC alone 1.7 ± 0.8) compared with intact groups (3.2 ± 0.7). In contrast, there was no significant difference between the growth factor treatment group (2.3 ± 0.73) and the intact group indicating improved function with the molecular factors. An increase in the number of regenerated lymphatic vessels at treatment sites was observed with fluoroscopy. Groups receiving HAMC plus growth factors displayed significantly reduced edema (107.4 ± 51.3) compared with nontreated groups (nodectomy 219.8 ± 118.7 and HAMC alone 162.6 ± 141). Conclusions: Growth factor therapy has the potential to increase lymphatic function and reduce edema magnitude in an animal model of lymphedema. The application of this concept to lymphedema patients warrants further examination

Investigation of lymph node transplantation as therapy for breast cancer related lymphedema

THESIS 9235Humans have hundreds of lymph nodes, collections of which are found in the underarms, groin, neck, chest, and abdomen. They have long been considered \u27neutral\u27 elements in terms of lymph transport. An assumption has always been made that the impediment to lymph transport in post-surgical lymphedema is due to lymphatic vessel injury. However, these vessels are damaged routinely in surgical procedures, despite this, post- surgical edema usually resolves over time as the lymphatics regenerate and chronic edema rarely if ever occurs under these circumstances. In contrast, it is clear that the removal of a lymph node or nodes appears to be a prerequisite for lymphedema development especially if this is combined with radiotherapy. Consequently, there is reason to believe that there are other factors that require consideration. In the first instance the aim of the studies reported here was to develop an animal model of post-surgical lymphedema that would permit quantitation of lymphatic transport function after the removal of a single popliteal lymph node in sheep and correlate this with edema formation. Secondly, we used this model to test whether the transplantation of an autologous lymph node into a nodal excision site would restore lymphatic transport function and reduce the magnitude of post-surgical lymphedema

Lateral Inframammary Approach for Asian Augmentation Mammaplasty

Background:. The inframammary fold (IMF) approach for augmentation mammaplasty is less popular in Asia. The incision was modified to lateral IMF(L-IMF) for easy access and better outcome. The aim of this study was to evaluate if L-IMF approach is feasible in Asian women. Methods:. Between 2002 and 2016, 53 patients with 96 augmentation mammaplasties were performed using lateral (L-IMF, 31 cases, 56 breasts) and traditional IMF approaches (T-IMF, 22 cases, 40 breasts). Surgical outcome was compared between L-IMF and T-IMF groups. Scar was assessed using photographic images by 4 assessors with a modified Manchester Scar Score, and telephone surveys available in L-IMF group. Results:. The average age was 41 ± 10.7 years (range, 20–73 years). There were no statistical differences in demographics in both groups besides of implant type (P < 0.01). At a follow-up of 80.1 months (range, 20–173 months), the capsular contracture rate and overall complication rate were statistically lower in L-IMF group, 3.6%, and 3.6%, than in T-IMF group, 15%, and 20% (P = 0.05, and P < 0.01, respectively). The modified Manchester Scar for L-IMF scars was 8.47 ± 2.4. The average score of 24 of 31 patients with L-IMF incision was 3.8 ± 0.96/5 points with patient-reported questionnaire. Nineteen patients (79.2%) would recommend or strongly recommend the procedure to friends. Conclusions:. The scar of L-IMF group healed satisfactorily with lower capsular contracture and overall complication rates than T-IMF group. Patients were satisfied with the outcome of breast augmentation and scar appearance using L-IMF approach