Facial resurfacing for nonmelanoma skin cancer prophylaxis.

OBJECTIVE: To determine the effect of facial skin resurfacing for treatment of actinic keratoses (AKs) and prophylaxis against new primary basal and squamous cell carcinomas in individuals with previous nonmelanoma skin cancer (NMSC) or severe photodamage. DESIGN: Randomized, prospective 5-year trial. SETTING: Dermatology and otolaryngology clinics of a Veterans Affairs hospital. PATIENTS: Thirty-four patients with a history of facial or scalp AKs or basal or squamous cell carcinoma were enrolled. Five of 7 eligible patients who declined study-related treatment were used as controls. Twenty-seven patients were randomized to 3 treatment arms; 3 patients were discontinued from the study. INTERVENTIONS: Carbon dioxide laser resurfacing, 30% trichloroacetic acid peel, or 5% fluorouracil cream applied twice daily for 3 weeks. MAIN OUTCOME MEASURES: Reduction in the number of AKs was measured 3 months after treatment. The incidence of new NMSC in treated areas was assessed between January 1, 2001, and June 30, 2005. Times from baseline to diagnosis of first skin cancer were compared between the treatment and control groups. RESULTS: Treatment with fluorouracil, trichloroacetic acid, or carbon dioxide laser resulted in an 83% to 92% reduction in AKs (P< or =.03), a lower incidence of NMSC compared with the control group (P<.001), and a trend toward longer time to development of new skin cancer compared with the control group (P=.07). However, no significant differences were noted among the treatment groups. CONCLUSION: All 3 modalities demonstrated benefit for AK reduction and skin cancer prophylaxis compared with controls and warrant further study in a larger trial.

Combined effect of hyberbaric oxygen and N-acetylcysteine on fibroblast proliferation.

OBJECTIVE: To examine the combined effect of hyperbaric oxygen and N-acetylcysteine, a well-studied antioxidant, on fibroblast proliferation and production of 3 specific growth factors: basic fibroblast growth factor, vascular endothelial growth factor, and transforming growth factor beta1. DESIGN: In vitro study. SUBJECTS: None. INTERVENTIONS: Human dermal fibroblasts were propagated in serum-free medium and subjected to daily 90-minute 2-atm hyperbaric oxygen treatments with varying concentrations of N-acetylcysteine for 7 consecutive days. Cell proliferation and growth factor assays were performed on days 0, 1, 3, 5, and 7. RESULTS: Population doubling time decreased significantly with 40 micromol/L of N-acetylcysteine supplementation of 2-atm hyperbaric oxygen treatment. Higher levels of N-acetylcysteine increased population doubling time. CONCLUSIONS: Supplementation of hyperbaric oxygen therapy with 40 mumol/L of N-acetylcysteine appears to increase fibroblast proliferation without producing an unfavorable growth factor profile for normal healing. This suggests that this level of N-acetylcysteine may foster an ideal redox environment for fibroblast proliferation in a hyperbaric oxygen environment.

Effect of hyperbaric oxygen on the growth factor profile of fibroblasts.

OBJECTIVES: Hyperbaric oxygen (HBO) has been used in the clinical setting to heal problem wounds, yet its direct effects on fibroblasts are not clear. The present study evaluates the effects of HBO on the growth and autocrine production of growth factors by fibroblasts grown in an in vitro, serum-free environment. METHODS: Human dermal fibroblasts were propagated in serum-free media and subjected to daily 90-minute HBO treatments at 1.0, 1.5, 2.0, 2.5, and 3.0 atm of pressure for 7 consecutive days. Cell proliferation and growth-factor assays for basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and transforming growth factor beta1 (TGF-beta1) were performed on days 1, 3, 5, and 7. RESULTS: On day 1, HBO inhibited growth of fibroblasts at all atmospheric pressures compared with control. By day 7, cell proliferation was significantly enhanced only in cells treated with 2.0-atm HBO compared with controls. Secretion of bFGF was significantly increased by HBO-treated fibroblasts on day 1; VEGF levels slightly increased with HBO treatment on day 1, but this effect was not statistically significant; TGF-beta1 levels were detectable on day 1 only for control and HBO-treated cells at 1.0 atm, and not detectable for any cell groups after day 1. CONCLUSIONS: These results suggest that daily HBO treatment enhances the growth of fibroblasts when administered to a critical degree. Also, HBO appears to directly effect fibroblast production of autocrine growth factors on initial exposure. We postulate that fibroblasts possess the ability to respond to hyperoxia directly, which causes changes in cell signaling pathways involved in cellular proliferation and growth factor production.