Lymphaticovenous bypass decreases pathologic skin changes in upper extremity breast cancer-related lymphedema Journal Article


Authors: Torrisi, J. S.; Joseph, W. J.; Ghanta, S.; Cuzzone, D. A.; Albano, N. J.; Savetsky, I. L.; Gardenier, J. C.; Skoracki, R.; Chang, D.; Mehrara, B. J.
Article Title: Lymphaticovenous bypass decreases pathologic skin changes in upper extremity breast cancer-related lymphedema
Abstract: Introduction: 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. Methods and 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. © 2015, Mary Ann Liebert, Inc.
Keywords: adult; clinical article; controlled study; human tissue; protein expression; middle aged; breast cancer; skin biopsy; cell infiltration; epidermis; interleukin 4; inflammation; microsurgery; histology; keratinocyte; hyperkeratosis; collagen type 1; lymph vessel; lymphangiogenesis; lymphedema; cd4+ t lymphocyte; transforming growth factor beta1; symptomatology; immunoglobulin e; arm edema; skinfold thickness; skin fibrosis; lymphaticovenous bypass; human; female; priority journal; article
Journal Title: Lymphatic Research and Biology
Volume: 13
Issue: 1
ISSN: 1539-6851
Publisher: Mary Ann Liebert, Inc  
Date Published: 2015-03-13
Start Page: 46
End Page: 53
Language: English
DOI: 10.1089/lrb.2014.0022
PROVIDER: scopus
PMCID: PMC4365441
PUBMED: 25521197
DOI/URL:
Notes: Export Date: 2 April 2015 -- Source: Scopus
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MSK Authors
  1. Babak Mehrara
    452 Mehrara
  2. Nicholas James Albano
    19 Albano
  3. Daniel Adam Cuzzone
    24 Cuzzone
  4. Swapna Ghanta
    19 Ghanta
  5. Walter John Joseph
    14 Joseph
  6. Jeremy   Torrisi
    27 Torrisi