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Lymphaticovenous bypass improves lymphedema mediated tissue fibrosis
Swapna Ghanta, MD1, Walter J. Joseph, III, BS1, Jeremy S. Torrisi, BA1, Daniel A. Cuzzone, MD1, Nicholas J. Albano, BS1, Ira L. Savetsky, MD1, Jason C. Gardenier1, David W. Chang, MD2, Babak J. Mehrara, MD1.
1Memorial Sloan Kettering Cancer Center, New York, NY, USA, 2University of Chicago, Chicago, IL, USA.

BACKGROUND:
Lymphedema is a common and morbid condition affecting one to three patients undergoing axillary lymph node dissection for breast cancer treatment. Recent advances in microsurgery such as lymphaticovenous bypass (LVB) have been shown to decrease limb volumes and improve subjective symptoms. However, it is unclear if these procedures can reverse pathological changes such as fibrosis, hyperkeratosis, and inflammation in patients with lymphedema. The purpose of this study was therefore to analyze tissues changes in patients after bypass to determine if LVB can ameliorate pathologic tissue changes of lymphedema.
METHODS:
LVB was performed in 6 patients with unilateral upper extremity breast cancer lymphedema (stage 1-3) as previously described by Chang, et al. To analyze tissue changes, we collected matched skin biopsy samples from the normal and lymphedematous limbs preoperatively and then 6 months after LVB. Tissues were paraffin embedded, sectioned, and analyzed for fibrosis, inflammation, and hyperkeratosis using computer assisted image analysis.
RESULTS:
At the 6 month time point 5/6 (83%) patients had symptomatic improvement in their lymphedema. Histologic analysis demonstrated significant decreases in hyperkeratosis and proliferation of keratinocytes in the lymphedematous limb (p<0.01). These changes were associated with markedly decreased tissue fibrosis as analyzed by collagen type I immunohistochemistry and TGF-B1 expression (all p<0.01). In addition, we found a significant decrease in the number of CD4+ cells. This is important because we have previously shown that the severity of lymphedema correlates with CD4+ cell inflammation. Importantly, there were no changes in these findings in the normal limb suggesting that the findings we observed were secondary to LVB rather than global systemic changes that may have occurred during the postoperative period.
CONCLUSIONS:
We have shown, for the first time, that microsurgical LVB not only improves symptomatology of lymphedema but also helps improve pathologic changes in the skin. These findings suggest that the early pathologic changes of lymphedema are reversible and are, at least in part, related to lymphatic fluid stasis.


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