ABSTRACT
Breast cancer-related lymphedema (BCRL) is characterized by skin changes, swelling, fibrosis, and recurrent skin infections. Clinical studies have suggested that lymphedema results in skin barrier defects; however, the underlying cellular mechanisms and the effects of bacterial contamination on skin barrier function remain unknown. In matched biopsies from patients with unilateral BCRL, we observed decreased expression of FLG and the tight junction protein ZO-1 in skin affected by moderate lymphedema or by subclinical lymphedema in which dermal backflow of lymph was identified by indocyanine green lymphography, relative to those in the controls (areas without backflow and from the unaffected arm). In vitro stimulation of keratinocytes with lymph fluid obtained from patients undergoing lymphedema surgery led to the same changes as well as increased expression of keratin 14, a marker of immature keratinocytes. Finally, using mouse models of lymphedema, we showed that similar to the clinical scenario, the expression of skin barrier proteins was decreased relative to that in normal skin and that colonization with Staphylococcus epidermidis bacteria amplified this effect as well as lymphedema severity. Taken together, our findings suggest that lymphatic fluid stasis contributes to skin barrier dysfunction in lymphedema.
ABSTRACT
BACKGROUND: The orthoplastic approach to patient care has changed the way patients with a wide variety of lower extremity pathology are treated. Through a systematic review, we aim to analyze outcomes in adult patients with lower extremity soft tissue sarcomas who undergo an orthoplastic flap management approach to their care. METHODS: A systematic review of adult lower extremity soft tissue sarcoma excision with plastic surgery flap reconstruction was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines searching the Pubmed, Embase, and Web of Science databases from inception to April 2023. RESULTS: After removal of duplicates, title and abstract screening, and full-text review, 26 articles were accepted for inclusion. The total mean follow-up duration was 32.0 ± 24.3 months. Reconstruction used microvascular free flaps in 65.5% (487/743), while 34.5% (256/743) were local flaps. 85.8% (307/358) of patients ambulated postoperatively. Revision surgery was required in 21% of patients during their respective follow-up periods. The limb salvage rate was 93.4% (958/1,026). Among pooled surgical outcomes, 22.2% (225/1,012) of patients experienced a perioperative complication. DISCUSSION: Our study demonstrates that although complication rates in lower extremity soft tissue sarcoma reconstruction may be further optimized, a multidisciplinary flap reconstructive approach provides high rates of limb salvage and functional postoperative ambulation.
