Dermatology Online Journal

Porcine xenograft biosynthetic wound dressings for the management of postoperative Mohs wounds
David W Raimer MD, Ashley R Group MD, Matthew S Petitt DO, Neda Nosrati MD, Mika L Yamazaki MD, Nathan A Davis MD, Brent C Kelly MD, Bernard R Gibson MD, Richard D Montilla MD, Richard F Wagner Jr MD
Dermatology Online Journal 17 (9): 1

The University of Texas Medical Branch, Galveston, Texas

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Abstract

Cadaveric allografts and a large variety of other biologic dressings have been reported as being useful for the postoperative management of Mohs micrographic surgery (MMS) wounds. Although the use of porcine xenografts for the immediate postoperative management of these wounds is known, their use has not been detailed in the dermatology literature. A case series of 15 consecutive Mohs micrographic surgery patients (mean age = 74.9 years, range = 49 to 89 years) with wounds initially managed with porcine xenografts is described. Porcine xenografts were useful in a variety of clinical settings following MMS. These included: 1. wound management when tumor margins were indeterminate pending additional dermatopathology studies and 2. wound management when there are issues such as through and through nasal defects involving the mucosa, large wound depth, exposed cartilage and or bone, or patient medical comorbidities that delay or prevent plans for immediate wound reconstruction. Future controlled studies of biologic dressings are needed to determine which options are best for micrographic surgery wounds. Comparisons should also include the traditional option of second intention healing without biologic dressings.

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Introduction

Chern et al recently reviewed biologic dressings in dermatologic surgery [1]. Human cadaveric allografts, Graftskin (Apligraf®), Integra®, AlloDerm® and FlexHD® have all been successfully used in the management of postoperative wounds. Kolenik and Leffel reported the use of cryopreserved human skin allografts on MMS wounds when immediate wound repair was relatively contraindicated [2]. None of the 16 patients reported developed wound infections and the authors concluded that human skin allografts stimulated healing, minimized wound care, and bridged later autografting when needed [2]. A later publication from this group about nasal wounds following MMS for basal cell carcinoma initially managed with human cadaveric allografts, reported that these wounds tended to heal more rapidly than standard second intention protocols and were easier to care for postoperatively [3].

Subsequent authors reported their experiences with other biologic dressings in the setting of MMS wounds [4-9]. Tarlow, Nossa, and Spencer reported their experience with Graftskin (Apligraf®, Organogenesis Inc., Canton, MA), a bilayered living skin construct comprised of neonatal foreskin keratinocytes and a matrix made from bovine collagen and fibroblasts with two patients who had MMS [4]. Each wound healed within nine weeks without complications [4]. Gohari et al compared the use of tissue-engineered skin (human skin substitute) Apligraf® to MMS and non-Mohs surgical wounds following skin cancer excisions to similar surgical wounds that were permitted to heal by second intention without biologic dressings [5]. The authors concluded that wounds treated with Apligraf® were more vascular and pliable and had better cosmetic outcomes than those wounds managed with second intention healing alone [5]. Ahmed et al reported a patient in which Integra® (Integra LifeSciences, Plainsboro, NJ), a bilaminate dermal substitute composed of an outer silicone layer and an inner layer made of cross-linked bovine collagen-glycosaminoglycan matrix, was used for the initial management of a MMS wound of the forehead that subsequently underwent successful split thickness skin grafting five weeks later [6]. Kontos et al reported on the use of AlloDerm® (LifeCell Corp., Woodlands, TX), an acellular human dermal matrix graft from human cadavers, for three MMS wounds [7]. More recently, Stebbins et al reported their experience with a human cadaveric dermal allograft (FlexHD®, Musculoskeletal Transplant Foundation, Edison, NJ), an acellular dermal allograft composed of collagen, laminin, fibronectin, and elastin for MMS wounds on the scalp in fourteen patients [8]. They concluded that FlexHD® decreased operative time, minimized wound care complexity, and produced excellent cosmetic outcomes in selected cases [8]. The use of a bovine collagen xenograft for MMS wounds (Puracol®Plus, Medline Industries Inc., Mundelein, IL) was presented as a poster at the 42nd Annual American College of Mohs Surgery in 2011 [9].

EZ-DERM™ (Brennen Medical Inc, Saint Paul, MN) is another biosynthetic dressing for wounds that, similar to Puracol®Plus, is relatively inexpensive in comparison to other biologic dressings (Table 1). It is a xenograft made from porcine collagen that has aldehyde crosslinking. EZ-DERM™ has been used in a variety of clinical settings, most frequently in the management of burns. According to Chern et al, EZ-DERM™ has not been reported in the medical literature as being used in the MMS setting [1]. This case series relates our use of EZ-DERM™ for the management of MMSwounds in fifteen consecutive patients over the last sixteen months at a tertiary care center. As with other biologic dressings, xenografts were used to facilitate wound care by patients in the postoperative setting.

Case series

Wound features of the fifteen patients reported are detailed in Table 2. All of the patients reported gave informed consent for initial porcine xenografting in their immediate wound management following MMS surgery. This modality was chosen from among the other wound management options including traditional second intention healing wound care protocols, skin grafting, flap repair, or referral to the plastic surgery service for reconstruction. Fenestrated xenografts were sutured into place with a 5-0 running polypropylene suture and the xenograft was removed two weeks postoperatively. The granulating wound was then permitted to heal by second intention, with or without additional xenografting, or underwent definitive closure with a full thickness skin graft or a flap. Our MMS treatment protocol typically includes a preoperative antibiotic, generally azithromycin (Zithromax) Z-Pak, (Pfizer, NY) 5-day dose pack (500 mg orally starting on the day before surgery followed by 250 mg po daily for four days) or doxycycline 100 mg orally twice daily for seven days, in anticipation for a potential skin graft or skin flap repair. Postoperative wound care was with white petrolatum ointment and occlusion until second intention healing was complete. However, if an autograft or skin flap was anticipated, mupirocin ointment was substituted for white petrolatum ointment.

Lentigo maligna was surgically managed with a “slow Mohs” technique using debulking of remaining visible tumor for dermatopathology staging re-evaluation followed by excision with a 5 mm margin for en face permanent tissue processing with hematoxylin and eosin and immunoperoxidase staining if needed. Residual tumor was marked on the Mohs map drawn at the time of excision and sequentially re-excised with 5 mm margins using the same tissue processing methods and mapping until a tumor free margin was achieved.

Discussion

In our hands, EZ-DERM™ has been useful in the management of occasional complex MMS wounds. EZ-DERM™ may be stored at room temperature in the clinic and has a shelf life of 18 months. It is available in fenestrated 8 x 10 cm patches, a useful and economic size for many wounds that follow MMS. There is only one published clinical study that compared EZ-DERM™ to Kaltostat® (ConvaTec, Skillman, NJ), a calcium sodium alginate dressing for the postoperative management of split-thickness skin graft donor sites [10]. Kaltostat® was found to be associated with shorter wound healing times and greater patient preference [10].

Figure 1	Figure 2
Figure 1. Preoperative neglected primary basal cell carcinoma (Patient 1). Figure 2. Stage II Mohs wound (Patient 1).

Figure 3	Figure 4
Figure 3. Fenestrated EZ-DERM™ xenograft sutured into wound (Patient 1). Figure 4. At the 10-week follow-up visit, the wound has contracted and has completely re-epithelialized, with an acceptable functional and cosmetic outcome (Patient 1).

EZ-DERM™ was found to be helpful for wounds permitted to heal by second intention (patients 1, 3, 4, 6, and 13), in the management of wounds created for tumors awaiting permanent processing and dermatopathology margin reports (patients 2, 4, 7, 10, and 11), for postoperative wound management prior to definitive full thickness skin grafting or flap repairs (patients 2, 5, 7, 8, 9, 10, 11, 12, 13, 14, and 15), and for supporting a cartilage graft while awaiting a deep alar wound to fill with granulation tissue prior to autografting (patient 14; patient 12 had delayed cartilage grafting at the time of her full thickness skin graft). It is similar in concept to the recently described technique of Campbell and Eisen, in which second intention healing without a biologic dressing supported a nasal cartilage graft [11]. Patient 2 had two xenografts sequentially placed while awaiting dermatopathology reports for his staged excision of lentigo maligna and patient 15 had two xenografts sequentially placed to support second intention healing.

Figure 5	Figure 6
Figure 5. Neglected primary basal cell carcinoma of the scalp (Patient 3). Figure 6. Stage II Mohs negative for tumor with section of periosteum removed, exposing bone (Patient 3).

Figure 7	Figure 8
Figure 7. Xenograft sutured into wound (Patient 3). Figure 8. Xenograft two weeks postoperatively (Patient 3). Note granulation tissue growing through fenestrated xenograft.

Figure 9	Figure 10
Figure 9. Postoperative wound at 6 weeks, with exposed bone surrounded by granulation tissue (Patient 3). Figure 10. Scar one year postoperatively (Patient 3).

Patient 4 developed a cosmetic ectropion of the right lower eyelid and eclabion of the right upper lip once the xenograft was removed and the wound permitted to heal by second intention. This is likely related to the large size of the MMS wound and its proximity to the free anatomic margins of the lower eyelid and the upper lip. Although wound contracture for MMS wounds permitted to heal by second intention with xenografts has not been well-studied, inhibition would not be predicted. The patient declined subsequent surgical correction because of his ability to completely close his right eyelids and lips.

In our one instance of postoperative wound infection with methicillin-resistant Staphylococcus aureus in patient 7, the isolated Staphylococcus aureus strain was also resistant to the macrolide antibiotics initially prescribed, but sensitive to tetracycline antibiotics, which quickly resolved the infection. Because of the lack of controlled clinical trials, it is currently unknown if xenografts used for the postoperative management of MMS wounds are associated with an increased risk for wound infections, but this issue deserves greater study.

Patient 13 required a local glabella-based, bilobed transposition skin flap to cover exposed bone because second intention healing was incomplete, even though nasal periosteum was intact following MMS Stage II. Additional clinical controlled studies would be useful to study EZ-DERM™ in comparison to traditional second intention wound care protocols without xenografting and with other types of biologic wound dressings.

References

1. Chern PL, Baum CL, Arpey CJ. Biologic dressings: current applications and limitations in dermatologic surgery. Dermatol Surg 2009;35:891-906. [PubMed]

2. Kolenik SA III, Leffell DJ. The use of cryopreserved human skin allografts in wound healing following Mohs surgery. Dermatol Surg 1995;21:615-620. [PubMed]

3. Carucci JA, Kolenik SA III, Lefell DJ. Human cadaveric allograft for repair of nasal defects after extirpation of basal cell carcinoma by Mohs micrographic surgery. Dermatol Surg 2002;28:340-243. [PubMed]

4. Tarlow MM, Nossa R, Spencer JM. Effective management of difficult surgical defects using tissue-engineered skin. Dermatol Surg 2001;27:71-4. [PubMed]

5. Gohari S, Sambla C, Healey M, et al. Evaluation of tissue-engineered skin (human skin substitute) and secondary intention healing in the treatment of full thickness wounds after Mohs micrographic or excisional surgery. Dermatol Surg 2002;28:1107-14. [PubMed]

6. Ahmed S, Sussein SS, Philp B, et al. Use of biologic dressing as a temporary wound dressing in reconstruction of a significant forehead Mohs defect. Dermatol Surg 2006;32:765-7. [PubMed]

7. Kontos AP, Quian Z, Urato NS, et al. AlloDerm grafting for large wounds after Mohs micrographic surgery. Dermatol Surg 2009;35:692-8. [PubMed]

8. Stebbins WG, Hanke CW, Petersen J. Human cadaveric dermal matrix for management of challenging surgical defects on the scalp. Dermatol Surg 2011;37:301-310. [PubMed]

9. Council ML, Tournas JA, Fosko SW. Use of the bovine collagen xenograft for post-Mohs surgical reconstruction. 42nd Annual Meeting of the American College of Mohs Surgery Program Book, Las Vegas, Nevada, April 27, 2011, Abstract 116, page 64.

10. Vanstraelen P. Comparison of calcium sodium alginate (KALTOSTAT) and porcine xenograft (E-Z DERM) in the healing of split thickness skin graft donor sites. Burns 1992;18:145-8. [PubMed]

11. Campbell T, Eisen DB. Free cartilage grafts for alar defects coupled with secondary-intention healing. Dermatol Surg 2011;37:510-513. [PubMed]

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