title: Spatio-temporal changes of lymphatic contractility and drainage patterns following lymphadenectomy in mice.
abstract: OBJECTIVE
  To investigate the redirection of lymphatic drainage post-lymphadenectomy using non-invasive near-infrared fluorescence (NIRF) imaging, and to subsequently assess impact on metastasis.
  
  
  BACKGROUND
  Cancer-acquired lymphedema arises from dysfunctional fluid transport after lymphadenectomy performed for staging and to disrupt drainage pathways for regional control of disease. However, little is known about the normal regenerative processes of the lymphatics in response to lymphadenectomy and how these responses can be accelerated, delayed, or can impact metastasis.
  
  
  METHODS
  Changes in lymphatic "pumping" function and drainage patterns were non-invasively and longitudinally imaged using NIRF lymphatic imaging after popliteal lymphadenectomy in mice. In a cohort of mice, B16F10 melanoma was inoculated on the dorsal aspect of the paw 27 days after lymphadenectomy to assess how drainage patterns affect metastasis.
  
  
  RESULTS
  NIRF imaging demonstrates that, although lymphatic function and drainage patterns change significantly in early response to popliteal lymph node (PLN) removal in mice, these changes are transient and regress dramatically due to a high regenerative capacity of the lymphatics and co-opting of collateral lymphatic pathways around the site of obstruction. Metastases followed the pattern of collateral pathways and could be detected proximal to the site of lymphadenectomy.
  
  
  CONCLUSIONS
  Both lymphatic vessel regeneration and co-opting of contralateral vessels occur following lymphadenectomy, with contractile function restored within 13 days, providing a basis for preclinical and clinical investigations to hasten lymphatic repair and restore contractile lymphatic function after surgery to prevent cancer-acquired lymphedema. Patterns of cancer metastasis after lymphadenectomy were altered, consistent with patterns of re-directed lymphatic drainage.
authors.affiliation: Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center, Houston, Texas, United States of America.
authors.forename: Sunkuk
authors.initials: S
authors.lastname: Kwon
authors.affiliation: Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center, Houston, Texas, United States of America; The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Germaine D
authors.initials: GD
authors.lastname: Agollah
authors.affiliation: Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center, Houston, Texas, United States of America.
authors.forename: Grace
authors.initials: G
authors.lastname: Wu
authors.affiliation: Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center, Houston, Texas, United States of America.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Sevick-Muraca
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D008197:Lymph Node Excision / Q000379:methods*; D008198:Lymph Nodes / Q000473:pathology / Q000503:physiopathology; D008207:Lymphatic Metastasis; D008208:Lymphatic System / Q000473:pathology / Q000503:physiopathology*; D042601:Lymphatic Vessels / Q000473:pathology / Q000503:physiopathology; D008209:Lymphedema / Q000473:pathology / Q000503:physiopathology; D008546:Melanoma, Experimental / Q000473:pathology / Q000503:physiopathology*; D008810:Mice, Inbred C57BL; D012038:Regeneration; D012878:Skin Neoplasms / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D005456:Fluorescent Dyes