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1.
Ann Surg ; 257(5): 961-7, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23013803

RESUMO

OBJECTIVE: Our objective was to define the optimal growth factor treatment to be used in combination with lymph node transfer to normalize lymphatic vascular anatomy. BACKGROUND: In the lymph node transfer method, lymphatic anastomoses are expected to form spontaneously. However, lymphangiogenic growth factor therapies have shown promising results in preclinical models of lymphedema. METHODS: The inguinal lymphatic vasculature of pigs was surgically destroyed around the inguinal lymph node. To enhance the regrowth of the lymphatic network in the defected area, adenoviral vascular endothelial growth factor C (VEGF-C) was administered intranodally or perinodally. Control animals received injections of saline or control vector. The lymphangiogenic effect of the growth factor therapy and any potential adverse effects associated with the 2 alternative delivery routes were examined 2 months postoperatively. RESULTS: Both routes of growth factor administration induced robust growth of lymphatic vessels and helped to preserve the structure of the transferred lymph nodes in comparison with the controls. The lymph nodes of the control treated animals regressed in size and their nodal structure was partly replaced by fibro-fatty scar tissue. Intranodally injected adenoviral VEGF-C and adenoviral vector encoding control gene LacZ induced macrophage accumulation inside the node, whereas perinodal administration of VEGF-C did not have this adverse effect. CONCLUSIONS: Lymphangiogenic growth factors improve lymphatic vessel regeneration and lymph node function after lymph node transfer. The perinodal route of delivery provides a basis for future clinical trials in lymphedema patients.


Assuntos
Terapia Genética/métodos , Regeneração Tecidual Guiada/métodos , Linfonodos/transplante , Linfedema/terapia , Fator C de Crescimento do Endotélio Vascular/administração & dosagem , Adenoviridae , Animais , Terapia Combinada , Técnicas de Transferência de Genes , Terapia Genética/efeitos adversos , Vetores Genéticos , Regeneração Tecidual Guiada/efeitos adversos , Injeções Intralinfáticas , Modelos Lineares , Linfangiogênese/efeitos dos fármacos , Sus scrofa , Resultado do Tratamento , Fator C de Crescimento do Endotélio Vascular/genética , Fator C de Crescimento do Endotélio Vascular/farmacologia , Fator C de Crescimento do Endotélio Vascular/uso terapêutico
2.
Ann Surg ; 255(3): 468-73, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22233832

RESUMO

OBJECTIVE: Postoperative lymphedema after breast cancer surgery is a challenging problem. Recently, a novel microvascular lymph node transfer technique provided a fresh hope for patients with lymphedema. We aimed to combine this new method with the standard breast reconstruction. METHODS: During 2008-2010, we performed free lower abdominal flap breast reconstruction in 87 patients. For all patients with lymphedema symptoms (n = 9), we used a modified lower abdominal reconstruction flap containing lymph nodes and lymphatic vessels surrounding the superficial circumflex vessel pedicle. Operation time, donor site morbidity, and postoperative recovery between the 2 groups (lymphedema breast reconstruction and breast reconstruction) were compared. The effect on the postoperative lymphatic vessel function was examined. RESULTS: The average operation time was 426 minutes in the lymphedema breast reconstruction group and 391 minutes in the breast reconstruction group. The postoperative abdominal seroma formation was increased in patients with lymphedema. Postoperative lymphoscintigraphy demonstrated at least some improvement in lymphatic vessel function in 5 of 6 patients with lymphedema. The upper limb perimeter decreased in 7 of 9 patients. Physiotherapy and compression was no longer needed in 3 of 9 patients. Importantly, we found that human lymph nodes express high levels of endogenous lymphatic vessel growth factors. Transfer of the lymph nodes and the resulting endogenous growth factor expression may thereby induce the regrowth of lymphatic network in the axilla. No edema problems were detected in the lymph node donor area. CONCLUSION: Simultaneous breast and lymphatic reconstruction is an ideal option for patients who suffer from lymphedema after mastectomy and axillary dissection.


Assuntos
Linfonodos/transplante , Linfedema/etiologia , Linfedema/cirurgia , Mastectomia/efeitos adversos , Mastectomia/métodos , Retalhos Cirúrgicos/irrigação sanguínea , Adulto , Idoso , Feminino , Humanos , Microvasos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Vasculares/métodos
3.
Plast Reconstr Surg Glob Open ; 1(2): 1-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-25289206

RESUMO

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.

4.
Plast Reconstr Surg ; 130(6): 1246-1253, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22878480

RESUMO

BACKGROUND: Lymphedema remains a challenging clinical problem that often lacks curative treatment options. Recent reports have shown that microvascular lymph node transfer from the groin area into axillas of lymphedematous patients may improve lymphatic drainage, but the effect on donor-site lymphatic flow has not been studied. These patients may be more prone to develop lymphedema at donor sites as well; therefore, the authors' aim was to evaluate postoperative donor-site lymphatic function. METHODS: The authors performed lymphatic groin flap transfer to the axilla in 13 lymphedema patients. In 10 patients, the lymph node transfer was performed simultaneously with lower abdominal breast reconstruction. Postoperative lymphatic vessel function of the donor site was evaluated by lymphoscintigraphy and limb circumference measurements. For semiquantitative evaluation of lymphatic drainage, a numerical transport index was used. RESULTS: In six of 10 patients, postoperative lymphoscintigraphy revealed minor changes in lymphatic flow of the donor-site limbs. The transport index was considered slightly abnormal in two of 10 patients. None of the 13 patients had changes in lower limb circumferences during the 8- to 56-month follow-up. CONCLUSIONS: Lymph node transfer can be easily combined with lower abdominal breast reconstruction, and the popularity of this technique is increasing rapidly. Even though none of our patients had developed symptoms of postoperative lymphedema, the results of the first lymphoscintigrams show that it is important to reduce the surgical trauma to the lymphatic flap donor site. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Assuntos
Retalhos de Tecido Biológico , Linfonodos/transplante , Linfedema/cirurgia , Microcirurgia , Complicações Pós-Operatórias/cirurgia , Sítio Doador de Transplante/fisiopatologia , Adulto , Idoso , Axila , Neoplasias da Mama/cirurgia , Feminino , Seguimentos , Virilha , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/fisiopatologia , Vasos Linfáticos/diagnóstico por imagem , Vasos Linfáticos/fisiopatologia , Linfedema/diagnóstico por imagem , Linfedema/etiologia , Linfocintigrafia , Mamoplastia , Mastectomia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Estudos Retrospectivos , Sítio Doador de Transplante/diagnóstico por imagem , Resultado do Tratamento
5.
Trends Cardiovasc Med ; 20(8): 249-53, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22433650

RESUMO

Lymphedema after cancer treatment is a common clinical challenge, but curative treatment options are rarely available. Lymph node transfer is a novel technique in lymphedema surgery. Lymphatic tissue can be transferred as a vascularized free flap, but in this technique the lymphatic vascular network is expected to regrow spontaneously. Recently, we have learned how to regulate the growth of lymphatic vessels in experimental models. We envision that lymph node transfer should be combined with lymphatic growth factor therapy in the treatment of lymphedema patients.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Linfonodos/transplante , Linfedema/cirurgia , Animais , Terapia Combinada , Modelos Animais de Doenças , Humanos , Linfangiogênese/efeitos dos fármacos , Linfangiogênese/fisiologia , Sistema Linfático/fisiopatologia , Linfedema/tratamento farmacológico , Transplante Autólogo
7.
Microsurgery ; 27(5): 369-71, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17557288

RESUMO

Progressive hemifacial atrophy (PHA) is characterized by slow and progressive atrophy usually of one side of the face. PHA affects primarily the subcutaneous fat and muscle tissues, but may involve the bone. The cause is unknown. The treatment is symptomatic and directed at augmentation of the deficient soft-tissue volume. The reconstructive procedures may combine fat grafts, dermis fat grafts, pedicle flaps, bone grafts, microvascular free flaps, and alloplastic implants. We report a patient with of PHA whose condition was treated with a free latissimus dorsi (LD) perforator flap. The LD perforator flap was suitable for the large defect of the patient. It could easily be tailored and thinned to follow the facial contour. Minor revisions were needed for esthetic reasons. There was neither significant downward gravitation nor wasting of the flap. 23 months later, the natural appearance of the face was maintained.


Assuntos
Hemiatrofia Facial/cirurgia , Retalhos Cirúrgicos , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica
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