title: Lymphaticovenous bypass decreases pathologic skin changes in upper extremity breast cancer-related lymphedema.
abstract: BACKGROUND
  Recent advances in microsurgery such as lymphaticovenous bypass (LVB) have been shown to decrease limb volumes and improve subjective symptoms in patients with lymphedema. However, to date, it remains unknown if these procedures can reverse the pathological tissue changes associated with lymphedema. Therefore, the purpose of this study was to analyze skin tissue changes in patients before and after LVB.
  
  
  RESULTS
  Matched skin biopsy samples were collected from normal and lymphedematous limbs of 6 patients with unilateral breast cancer-related upper extremity lymphedema before and 6 months after LVB. Biopsy specimens were fixed and analyzed for inflammation, fibrosis, hyperkeratosis, and lymphangiogenesis. Six months following LVB, 83% of patients had symptomatic improvement in their lymphedema. Histological analysis at this time demonstrated a significant decrease in tissue CD4(+) cell inflammation in lymphedematous limb (but not normal limb) biopsies (p<0.01). These changes were associated with significantly decreased tissue fibrosis as demonstrated by decreased collagen type I deposition and TGF-β1 expression (all p<0.01). In addition, we found a significant decrease in epidermal thickness, decreased numbers of proliferating basal keratinocytes, and decreased number of LYVE-1(+) lymphatic vessels in lymphedematous limbs after LVB.
  
  
  CONCLUSIONS
  We have shown, for the first time, that microsurgical LVB not only improves symptomatology of lymphedema but also helps to improve pathologic changes in the skin. These findings suggest that the some of the pathologic changes of lymphedema are reversible and may be related to lymphatic fluid stasis.
authors.affiliation: 1 Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan-Kettering Cancer Center , New York, New York.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Torrisi
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Joseph
authors.forename: Swapna
authors.initials: S
authors.lastname: Ghanta
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Cuzzone
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Albano
authors.forename: Ira L
authors.initials: IL
authors.lastname: Savetsky
authors.forename: Jason C
authors.initials: JC
authors.lastname: Gardenier
authors.forename: Roman
authors.initials: R
authors.lastname: Skoracki
authors.forename: David
authors.initials: D
authors.lastname: Chang
authors.forename: Babak J
authors.initials: BJ
authors.lastname: Mehrara
mesh_terms: D000328:Adult; D001706:Biopsy; D001943:Breast Neoplasms / Q000150:complications*; D005260:Female; D005355:Fibrosis; D006801:Humans; D007642:Keratosis / Q000378:metabolism / Q000473:pathology; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000378:metabolism; D008209:Lymphedema / Q000175:diagnosis / Q000209:etiology* / Q000601:surgery*; D008875:Middle Aged; D012867:Skin / Q000473:pathology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D034941:Upper Extremity / Q000473:pathology*; D058017:Vascular Grafting / Q000379:methods*
chemical_list: D053773:Transforming Growth Factor beta1