Innovative Use of dHACM in Conjunction With Hyperbaric Oxygen Therapy to Treat a Nonhealing Nasal Wound Subsequent to Squamous Cell Carcinoma Resection and Radiation: A Case Study

More than 2.2 million people worldwide have a diagnosis of cutaneous squamous cell skin cancer, making it the second most common skin cancer, closely following basal cell carcinoma.¹ The incidence of squamous cell carcinoma (SCC) is increasing both in the developed world and globally.¹ Treatment for SCC is most often exclusively surgical, particularly when diagnosed in stage 1 or 2²; however, some cases are more advanced at presentation or recur, thus requiring a multimodality approach. The addition of adjuvant radiation therapy for advanced (stage 3 or 4) SCC is intended to prevent local recurrence by causing tumor cell death²; unfortunately, it also can damage the surrounding tissue. 

Acute and chronic radiation changes may occur, which can result in impaired wound healing, particularly of large incisions of high tension or thin-skinned areas following tumor resection.³ Radiation can result in edema of the walls of the local vasculature, potentially initiating a cascade of vessel stasis and occlusion.³ Such an obstructive process directly prevents platelet activity. As a result of the vessel stasis and occlusion, angiogenesis is disrupted, and there is increased local expression of matrix metalloproteinases. Reduced influx of cytokines inhibits recruitment of fibroblasts in the wound bed. Radiation also causes direct damage to the fibroblasts, and this in turn causes loss of tensile strength of the wound due to the reduced production of collagen and altered function of the collagen matrix. Recent findings³ attribute the pathophysiology of the radiation-induced fibrosis to the presence of reactive oxygen species, which leads to the dysregulated production of abnormal myofibroblasts. These tissues have an abnormal production of collagen and are paucicellular. There is a loss of normal tissue architecture with diminished healing capacity.³ Trauma to this compromised tissue results in poor healing due to the absence of blood vessels and inflammatory cells.⁴ As a result, patients undergoing resection of cutaneous SCC and adjuvant radiation therapy are at an increased risk for developing nonhealing wounds, particularly if they also have other known risk factors for poor wound healing (ie, diabetes, wound infection, advanced age, and poor nutrition).⁵

Little has been published to date regarding the use of dehydrated human amnion/chorion membrane (dHACM) in wounds associated with irradiated skin.⁶ Based on the proven success of this material in other wound care settings,⁶ the authors had a unique opportunity to evaluate whether the addition of dHACM, in conjunction with hyperbaric oxygen therapy (HBOT), would result in improved wound healing in a patient with a nonhealing nasal wound who had failed standard of care therapy, HBOT, and previous allogenic tissue grafting. Based on previous successes in other settings, particularly refractory venous stasis ulcers, the authors proposed that the use of dHACM would result in improved healing in conjunction with HBOT. 

A 75-year-old man with a history of SCC of the nose who was suffering from a nonhealing nasal wound following initial resection, radiation therapy, and failure of both full-thickness skin and auricular cartilage grafting presented to the McLaren Greater Lansing Wound Care and Hyperbaric Center (Lansing, MI). On evaluation, he was found to have a nasal cutaneous fistula of the right nare (measuring 1.1 cm x 0.6 cm x 0.3 cm) with associated rhinorrhea, adjacent skin irritation, and discomfort related to the passage of air through the fistulous tract (Figure 1). 

Prior to referral to the authors’ wound clinic, the patient had undergone several months of routine wound care with his otolaryngologist. Following 30 days of wound care, consisting of weekly sharp debridement as needed with application of silver-containing collagen and/or absorbent foam dressings, the patient continued to have an open, nonhealing wound. As he had already undergone full-thickness skin and cartilage grafting with poor outcomes, the next surgical option likely would have been a more complex flap reconstruction.⁷ Due to the high risk of failure and the extent of this surgery, the patient chose not to proceed with another surgical procedure. 

Upon evaluation and prior to initiation of a treatment regimen, the patient underwent culture and punch biopsy of the wound edge to rule out the presence of recurrent SCC and/or infection as causes for delayed healing. The wound cultured positive for Klebsiella species, and the patient received antibiotic therapy based on final culture and sensitivity data consisting of a 7-day course of daily 750 mg oral levofloxacin. Following the return of negative repeat cultures and negative biopsy results, the patient was started on a regimen of weekly selective debridement and application of silver-embedded collagen dressing (Puracol Plus Ag+; Medline, Mundelein, IL) and/or protective foam dressing (Mepilex Lite; Mölnlycke Health Care, Gothenburg, Sweden) in an effort to reinitiate healing in this stalled chronic wound. 

After 30 days of the aforementioned protocol with limited forward progress, HBOT was initiated in addition to the existing wound care regimen in an attempt to further facilitate healing. A routine chronic wound HBOT protocol, consisting of 90-minute dives to 2.4 absolute atmospheres with 2 five-minute breaks, was started.⁸ An initial response was noted with reduction in wound size and improved appearance of granulation tissue. After 30 dives, however, the progression of wound healing had stalled, with the wound measuring 0.7 cm x 0.4 cm x 0.1 cm and persistence of symptoms of discomfort and drainage.

At that time (16 weeks from initial presentation), the decision was made to add dHACM (EpiFix; MiMedx, Marietta, GA) to the wound care regimen. The patient received a total of 4 applications of 14-mm dHACM sheet graft once weekly for 3 weeks and then the fourth application 3 weeks later. The graft was secured in place with a silicone contact layer (Versatel Contact Layer Silicone Wound Dressing; Medline, Mundelein, IL) and 3M Steri-Strip (3M, St Paul, MN) adhesive bandages. The patient continued to undergo selective debridement and extended HBOT therapy concurrently while the dHACM grafts were being applied, with temporary cessation of previously described silver and foam dressings to allow for integration of the dHACM material. A total of 15 additional HBOT dives were added following the initial 30, given the noted improvement in the patient’s wound. A total of 45 dives were completed over the course of 20 weeks. Figure 2 shows the wound after the second application of dHACM.

Ultimately, this treatment approach resulted in complete reepithelization of the wound and a 45% decrease in defect area, from 0.7 cm² on treatment day 1 to 0.25 cm² after 24 weeks. The patient’s symptoms of nasal drainage and physical discomfort due to air passage through the fistula also had resolved completely. Although the fistula was still present at the conclusion of treatment, the tract was well-epithelialized and overall size of the defect diminished greatly. The patient reported satisfaction with his improved quality of life as a result of the resolution of his symptoms during a phone interview 3 months following the conclusion of treatment.

Many advances have been made in the treatment of challenging, nonhealing wounds in recent years.⁶ Dehydrated human amnion/chorion membrane grafting is a technology that has been proven in numerous trials to promote wound healing in certain settings.⁶ The biologic activity of amniotic membrane is due to the presence of regenerative growth factors, cytokines, and chemokines, all of which work together to create a balanced healing environment.⁶

Hyperbaric oxygen therapy is a proven treatment adjunct in the setting of chronic wounds associated with irradiated skin and failed skin grafts.⁹ Given the impaired angiogenesis of irradiated skin, HBOT is able to improve wound healing by decreasing tissue edema, increasing oxygen delivery, reducing reactive oxygen species, and stimulating macrophage-derived angiogenesis factor and macrophage-derived growth factor.¹⁰

The combination of HBOT and application of dHACM was shown to be beneficial with regards to wound healing and resolution of symptoms in this particular patient. 

The combination of HBOT and dHACM discussed here may prove to be a worthwhile treatment modality for improving healing times and overall outcomes in patients with similar presentations. A conservative, nonsurgical approach utilizing these methods may afford a desirable outcome with overall lower risk compared with extensive flap reconstruction.