EpiDex® Swiss field trial 2004-2008.

BACKGROUND: Approximately 20% of leg ulcers remain unresponsive to the best conservative standard of care. So far, these patients could either receive conventional skin grafts or had to accept their intractable wound. Skin substitutes from cell culture may represent a promising alternative to heal a major part of these patients on a non-surgical, potentially more cost-effective basis. OBJECTIVE: To systematically evaluate the first 68 patients treated in Switzerland (Swiss EpiDex® field trial 2004-2008). METHODS: Retrospective study on EpiDex treatment of a complete consecutive series of 68 patients with chronic wounds (66 chronic leg ulcers, 2 sores) unresponsive to best conservative standard of care. The primary end point was complete wound closure within 9 months after transplantation, the secondary end points change of wound surface area, pain reduction and overall judgement by the patient. Adverse effects were infection, dermatitis and others. Calculation of treatment costs was made. RESULTS: By the end of the study, 50/68 (74%) of patients had their wound completely healed [venous 29/37 (78%); mixed 7/9 (78%); others 14/22 (64%)]; 10/68 (15%) had the wound surface area reduced by >50%, and 8/68 (12%) did not respond to the EpiDex treatment. Wound pain disappeared completely in 78% and partially in 13%. Fifteen patients (22%) received antibiotics for wound infection, and 2 (3%) developed dermatitis (not related to the local therapy). Average treatment costs for venous ulcers amounted to EUR 5,357, compared to EUR 5,722-8,622 reimbursed according to the German DRG system (2010) for an in-patient skin graft. CONCLUSION: EpiDex may effectively heal up to three quarters of recalcitrant chronic leg ulcers. Thus, it represents an intermediate step to avoid costly in-patient split-skin mesh graft treatments. Patients remain mobilized, and a donor site is avoided. Large wound size or a necrotic wound bed limit the use of EpiDex. Otherwise, it offers the opportunity to avoid conventional skin grafts in a significant number of chronic leg ulcer patients.

Evaluation of apoptotic cells and immunohistochemical detection of FAS, FAS-L, Bcl-2, Bax, p53 and c-Myc in the skin of patients with chronic venous leg ulcers.

In the present study we were interested, if apoptosis plays a role in the surrounding skin of venous ulcers, where microcirculatory disorders were already observed. For this purpose laser Doppler flow and partial oxygen pressure were measured in 17 patients at the ulcer edge, the transitional area of the lower leg and the thigh. Subsequently biopsies were taken from the respective sites and subjected to terminal deoxynucleotidyl transferase labelling (TUNEL) and immunohistochemistry using antibodies to determine the protein expression of Fas, Fas-L, Bax, Bcl-2, p53 and c-Myc. Laser Doppler flow was increased and transcutaneous oxygen partial pressure was decreased, with significant differences at the ulcer edge and the lower leg compared to the thigh. The skin biopsies did not show any differences when labelling for apoptotic cells. Keratinocytes of basal and spinous layer stained with antibodies against Fas, Fas-L and Bax in all probes of the three sites. c-Myc and p53 were negative in all keratinocytes of the skin probes. However, staining with Bcl-2 was significantly decreased at the ulcer edge in comparison to the lower leg and the thigh (p=0.017). Our study revealed that a disturbed microcirculation does not increase the number of apoptotic cells at the ulcer edge in patients with venous disease. The reduced staining pattern with Bcl-2 at the ulcer edge seems not to result in higher susceptibility to apoptosis, but it remains to be proven whether it is involved in epidermal acanthosis.