A Single Center, Prospective, Double-blinded, Randomized, Placebo-controlled Trial Evaluating the Efficacy of Fractionated Carbon Dioxide Therapy in Postoperative Lower Extremity Wound Healing

Background and Significance

With an aging population, the prevalence of cutaneous malignancies continues to pose significant burden in terms of morbidity and economic cost. It is estimated that 5.4 million new cases of non-melanoma skin cancers, i.e squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), are diagnosed each year. As the incidence of skin cancer increases, the prevalence of postoperative lower extremity wounds also increases. Epidemiologic studies consistently find up to 10% of BCC and 20% of SCC occur on the lower extremity in both men and women, and the largest portion of malignant melanoma cases occurs on the legs of women. Lower extremity ulcers are a common postoperative complication of melanoma, BCC and SCC treatment, and impose an undue health care burden by negatively impacting patient quality of life and increasing costs. Recent reports suggest that lower extremity ulcers cost $10,000 per patient per year, and patients often reported social isolation and depression, thus making an improved treatment protocol for healing lower extremity wounds essential.

After an acute injury, normal wound healing is usually complete within four weeks and can be divided into 4 phases: coagulation, inflammation, formulation of granulation tissue, and remodeling or scar formation. The initial steps of coagulation and inflammation involve the inhibition of bleeding through activation of the coagulation cascade, release of growth factors and cytokines such as platelet-derived growth factor and transforming growth factor β, and recruitment of macrophages and fibroblasts. This facilitates removal of foreign bodies and bacteria while preparing the wound site for new tissue. Around 5-7 days inflammation subsides via apoptosis of proinflammatory cells followed by formation of granulation tissue through dermal and epidermal cell migration to the wound bed. Granulation tissue has a high metabolic demand that is supplied by angiogenesis (proliferation of new blood vessels). Angiogenesis occurs due to local hypoxia during acute tissue injury which stimulates the release of several factors such as vascular endothelial growth factor and fibroblast growth factor 2. Lastly matrix remodeling and scar formation result in the restoration of primarily normal epidermis by replacing the extracellular matrix containing collagen III to primarily collagen I and myofibroblast induced tissue contraction.

Lower extremity ulcers exhibit increased infection risk compared with other body sites, and are rarely amenable to surgical closure due to a lack of suitable local skin and poor tissue vascularity. As a result, many of these defects are allowed to heal via secondary intention healing (SIH).The lower extremity suffers from poor perfusion and hypovascularity, both of which impair wound healing in this anatomic site. Therefore, post-surgical wounds on the lower extremities frequently convert into chronic wounds, defined as wounds that fail to heal within four weeks and show no sign of improvement within eight weeks. This protracted healing course drains the medical system of resources and subjects the patient to significant discomfort and distress. The major problems reported from patients include pain, immobility, sleep disturbances, lack of energy, limitations in work and leisure activities, worry, frustration, and lack of self-esteem. Given the problems associated with allowing lower extremity ulcers to heal by second intent, strategies that improve ulcer healing would be beneficial, improving patient quality of life and preventing further complications.

Ablative fractional carbon dioxide lasers, such as the CO2RE® (Syneron Candela Corp, Wayland, MA), offer a multi-depth pulse technology that delivers a precise fractionated beam pattern to treat the epidermis and dermis simultaneously. This precision technology creates areas of superficial and deep ablation and coagulation to activate remodeling at several tissue depths. The CO2RE® is FDA-approved and has demonstrated efficacy in post-surgical scar treatment, although it has not been studied in acute, lower extremity ulcers.