ABSTRACT
Background: Chronic lymphedema is a common complication of lymphatic obstruction, particularly after cancer treatment, characterized by an increased volume of the affected extremity, partly caused by the accumulation of excessive adipose tissue. The relationship between lymph vessels' obstruction and fat deposit is, however, poorly understood. Objective: Our central hypothesis was that the inflammatory process caused by lymph stasis precedes the adipocyte differentiation and fat deposition. Methods and Results: We used a modified mouse tail model to produce secondary lymphedema. Animals were treated with dexamethasone, or the procedure was performed in nitric oxide synthase 2 (NOS2)-deficient mice to evaluate the role of inflammation in lymphedema formation. Adipose tissue (Lipin) and inflammatory markers (IL-6, MCP-1, and F4-80) were analyzed in histological samples and by quantitative polymerase chain reaction. We observed an increased deposition of fat into the affected area that starts 3 weeks after lymph vessel ligation; it further increased after 6 weeks. Genes involved in the inflammatory process were upregulated before adipocyte maturation. Treatment with dexamethasone or the use of inducible nitric oxide synthase knockout mice blocked the inflammatory reaction and inhibited the accumulation of fat distal to the lymphatic obstruction. Conclusion: In the modified mouse tail lymphedema, inflammation precedes adipogenesis. Our data suggest that MCP-1 and nitric oxide may be potential targets for lymphedema management.
Subject(s)
Lymphatic Vessels , Lymphedema , Animals , Disease Models, Animal , Inflammation , Mice , Mice, Inbred C57BLABSTRACT
OBJECTIVE: The aim of this study is to assess the incidence and risk factors for lymphedema in women submitted to mastectomy, with or without breast reconstruction. METHODS: A cohort study was performed on women submitted to mastectomy with axillary lymphadenectomy in a single center. The follow-up included clinical evaluation and arm column measurements before surgery, at 30 days, 6 months, 5 years, and 10 years after surgery. For women subjected to late reconstruction, the time of occurrence of lymphedema (before or after reconstruction) was observed. RESULTS: We followed up on 622 patients submitted to mastectomy and axillary lymphadenectomy for an average period of 57 months after surgery. In total, 94 women were submitted to breast reconstruction, 47 (8%) of them immediate and 47 (8%) late reconstructions. Incidence of lymphedema in the whole group was 33% (n = 204). Among the patients submitted to reconstruction, 28% of them developed lymphedema, on average, 93 months (CI 95%, 88-98) after surgical treatment. In women not subjected to reconstruction, 179 (34%) developed lymphedema, on average, after 106 months (CI 95%, 96-116) (p = 0.03). Breast reconstruction reduced lymphedema risk in 36% (HR = 0.64, CI 96%, 0.42-0.98, p = 0.04). After adjustment for pathological staging and radiotherapy, this was not statistically significant (HR = 0.79, CI 95%, 0.52-1.21, p = 0.28). CONCLUSION: Breast reconstruction does not increase the risk of lymphedema in long-term follow-up.
Subject(s)
Breast Neoplasms/surgery , Forecasting , Lymphedema/surgery , Mammaplasty/methods , Mastectomy/adverse effects , Breast Neoplasms/diagnosis , Female , Follow-Up Studies , Humans , Lymphedema/etiology , Middle Aged , Neoplasm Staging , Prospective Studies , Risk FactorsABSTRACT
Este documento tenta resumir o largo espectro de diferentes protocolos utilizados pra o diagnóstico e tratamento do linfedema em uma declaraçäo que represente um consenso da comunidade internacional. O documento näo pretende prevalecer sobre consideraçöes clínicas individuais para pacientes específicos nem, tampouco, objetiva ser uma fórmul a legal sobre a qual variaçöes possam ser consideradas erros médicos. Antes de tudo, representa o melhor julgamento dos membros do Comitê Executivo da Sociedade Internacioanl de Linfologia de como abordar pacientes com linfedema em 1995. Antecipamos que o documento será questionado, debatido nas páginas do Lymphology (por exemplo, nas Cartas ao Editor)e, idealmente, tornar-se um ponto de grande discussäo em conferências linfológicas locais, nacionais e internacionais. Prevemos de antemäo que, com o desenvolvimento da experiência e aparecimento de novas idéias, este documento "atual" sofreráa ajustes e revisöes periódicas.
