Prevention of postsurgical lymphedema via immediate delivery of sustained-release 9-cis retinoic acid to the lymphedenectomy site.
J Surg Oncol
; 121(1): 100-108, 2020 Jan.
Article
em En
| MEDLINE
| ID: mdl-31240729
ABSTRACT
BACKGROUND AND OBJECTIVES:
Previously, we have shown that 9-cis retinoic acid (9-cis RA) stimulates lymphangiogenesis and limits postsurgical lymphedema in animal models when administered via daily intraperitoneal injections. In this study, we investigate whether a single-use depot 9-cis RA drug delivery system (DDS) implanted at the site of lymphatic injury can mitigate the development of lymphedema in a clinically relevant mouse limb model.METHODS:
Hind limb lymphedema was induced via surgical lymphadenectomy and irradiation. Animals were divided into two treatment groups (1) 9-cis RA DDS, (2) placebo DDS. Outcomes measured included paw thickness, lymphatic clearance and density, epidermal thickness, and collagen deposition.RESULTS:
Compared with control animals, 9-cis RA-treated animals had significantly less paw swelling from postoperative week 3 (P = .04) until the final timepoint at week 6 (P = .0007). Moreover, 9-cis RA-treated animals had significantly faster lymphatic clearance (P < .05), increased lymphatic density (P = .04), reduced lymphatic vessel size (P = .02), reduced epidermal hyperplasia (P = .04), and reduced collagen staining (P = .10).CONCLUSIONS:
Animals receiving 9-cis RA sustained-release implants at the time of surgery had improved lymphatic function and structure, indicating reduced lymphedema progression. Thus, we demonstrate that 9-cis RA contained within a single-use depot DDS has favorable properties in limiting pathologic responses to lymphatic injury and may be an effective strategy against secondary lymphedema.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Alitretinoína
/
Excisão de Linfonodo
/
Linfedema
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article