Abstract
Introduction
Definitive reconstruction after excision of cutaneous and soft tissue malignancies is sometimes limited due to lack of native tissue coverage options, patient comorbidities or pending permanent margin analysis. Acellular dermis (AlloDerm®) reconstruction offers an excellent coverage alternative to autologous reconstruction in these situations. We describe our experience using AlloDerm for coverage of skin and soft tissue defects.
Methods
An IRB approved review of patients undergoing skin and soft tissue reconstruction or coverage with AlloDerm from 2006-2012 was performed. Clinicopathologic variables, early post-operative findings and subjective final cosmetic outcome were analyzed.
Results
Sixty-seven patients underwent resection with AlloDerm reconstruction (median age 72 years (33-95 years). Melanoma (67%) was the most frequent diagnosis. The median defect size was 42 cm2 (2-340 cm2), involving the lower extremity in 45%, head & neck in 32%. AlloDerm was intended for use as a temporary biologic dressing in 64% (43/60) and permanent coverage in 24 (36%). Ten patients required re-excision for positive margins. Twenty-five (37%) underwent STSG or flap coverage after AlloDerm placement. Radiation was administered to 16 patients (24%) after AlloDerm reconstruction within a median of 53 days after surgery (range, 18-118 days). At first post-operative examination (median 11 days after surgery), 85% had evidence of healthy AlloDerm incorporation. Cellulitis was the most frequent complication (13%) all resolving with oral antibiotics.
Conclusions
AlloDerm reconstruction after skin and soft tissue resection offers a suitable coverage alternative and may serve as a bridge to permanent reconstruction or as a permanent biologic dressing of complex surgical defects. In situations where adjuvant radiation is needed, AlloDerm can be used without major complications.
Keywords: AlloDerm, acellular dermal matrix, reconstruction, skin graft, radiation
Introduction
Definitive reconstruction of skin and soft tissue defects is sometimes delayed while awaiting pathologic margin assessment for negative surgical margins. In other situations, lack of native tissue options, anatomical constraints or prohibitive medical comorbidities may limit or preclude immediate reconstruction. Skin grafting or myocutaneous flap coverage are excellent permanent coverage alternatives but potential donor site morbidity and the possible need for further resection of the tumor site (for positive margins) pose potential therapeutic challenges to the clinician. Biologic dressings, as temporary or permanent wound coverage substitutes or a bridge to definitive reconstruction, have been described as viable alternatives with favorable outcomes.[1]
AlloDerm® (Lifecell, Branchburg, NJ) is an FDA-approved, acellular dermal matrix derived from human cadaveric skin and has several surgical applications. Reconstruction of complex surgical defects using AlloDerm has been described for anastomotic esophageal leaks,[2] cleft palate repair,[3] meningeal/dural repair,[4] intraoral reconstruction,[5] complex burn contractures,[6] breast reconstruction,[7] abdominal hernia repair,[8] as well as a host of others. It consists of an extracellular matrix in which the cellular components have been removed, leaving the basement membrane intact with a scaffold that retains its collagen and elastic fiber content. These features allow native tissue ingrowth, revascularization, and remodeling.[9] Decellularization during processing renders AlloDerm immunologically inert and studies have demonstrated that AlloDerm can be applied without inciting a significant immune response.[9, 10] This is advantageous in situations where temporary or permanent coverage after skin and soft tissue resection are needed. AlloDerm can be easily removed and definitive reconstruction can subsequently be performed on a healthy bed of granulation tissue after negative pathologic margins are confirmed.
We herein describe our experience using AlloDerm as a temporary and definitive coverage alternative after skin and soft tissue resection. Early subjective post-operative physical examination findings and final outcome characteristics after AlloDerm reconstruction as a dermal substitute are detailed.
Methods
An IRB-approved, single institution, retrospective review was performed of patients treated at Moffitt Cancer Center, from 2006- 2011 who underwent skin and soft tissue resection with AlloDerm, skin graft or flap reconstruction of the defects. Patients who underwent reconstruction using AlloDerm were further analyzed. Indications for resection, time to definitive reconstruction and early post-operative outcomes were evaluated.
AlloDerm utilization was defined as permanent if utilized for definitive coverage or temporary if utilized as a biologic dressing as a bridge to definitive myocutaneous flap or skin graft coverage. The indications for AlloDerm use (temporary or definitive) were obtained from the pre-operative planning documentation and operative note. The area of AlloDerm coverage (cm2) was obtained from the operative note based on the intraoperative measurement of the surgical defect.
Subjective early post-operative examination findings were defined as: well healing (evidence of healthy incorporation), partial loss (less than 50% surface area non-incorporation), or complete loss (non-incorporation requiring removal). Time to definitive myocutaneous or skin graft coverage from temporary AlloDerm coverage was recorded in days. Descriptive statistics were measured using SPSS 19.0 software (Cary, NC).
Results
A total of 873 patients underwent skin and soft tissue resection with skin graft, flap or dermal matrix reconstruction at Moffitt Cancer Center from 2006 to 2011. Of the 873 patients, 67 (8%) patients had AlloDerm reconstruction and are further analyzed. Median patient age was 73 years (range, 33-95). Melanoma was the most frequent indication for resection (67%). Most tumors were located on the lower extremity (45%) followed by the head and neck (34%), upper extremity (13%) and trunk (8%). (Table 1)
Table 1. Clinicopathologic Variables.
| Variable | N (%) |
|---|---|
| Median Age (range in years) | 72.5 (33-95) |
| Gender | |
| Male | 50 (75) |
| Female | 17 (25) |
| Race | |
| Caucasian | 62 (92) |
| African American | 5 (8) |
| Location | |
| Head & Neck | 23 (34) |
| Trunk | 5 (8) |
| Lower Extremity | 30 (45) |
| Upper Extremity | 9 (13) |
| Disease | |
| Melanoma | 45 (67) |
| LMS | 6 (9) |
| Squamous Cell Carcinoma | 5 (8) |
| Merkel Cell Carcinoma | 4 (6) |
| Basal Cell Carcinoma | 3 (5) |
| Dermatofibrosarcoma Protuberans | 2 (3) |
| Adnexal Carcinoma | 2 (3) |
| Intended Initial Alloderm Usage | |
| Temporary | 43 (64) |
| Permanent | 24 (36) |
Operative Experience using AlloDerm
The initial intention for AlloDerm usage (based on review of pre-operative documentation from the operating surgeon) was temporary in 43 patients (64%) and permanent in 24 (36%). (Figure 1) The median surgical defect size in need of coverage was 42 cm2 (range 2-340 cm2). Three patients (4%) underwent multiple resections with AlloDerm coverage of multiple sites during the same procedure.
Figure 1.
Initial operative description for the 67 patients who underwent skin and soft tissue resection and temporary or permanent reconstruction with AlloDerm.
Twenty-five patients (40%) total underwent subsequent skin graft placement after initial intentional temporary AlloDerm coverage. (Table 2, Figure 1) The median time to skin grafting after AlloDerm graft placement was 11 days (range, 6-188). Five of the 25 patients underwent delayed-skin graft placement (30 days or greater) after AlloDerm coverage for the following reasons: XRT after AlloDerm placement before reconstruction (2), full AlloDerm loss (1), lymphadenectomy for nodal disease and replacement of AlloDerm at the same surgery (1), unknown (1).
Table 2. Operative and AlloDerm Usage Data.
| Variable | N (%) |
|---|---|
| Median Surgical Defect Size (range in cm2) | 42 (2-340) |
| Thickness of AlloDerm Utilized (mm) | |
| 0.39 | 14 (21) |
| 0.53 | 26 (39) |
| 0.79 | 19 (28) |
| 1.04 | 1 (2) |
| STSG after AlloDerm Graft Removal | 25 (37) |
| Median Time to STSG (range in days) | 11 (6-188) |
| Re-excision of (+) margin after AlloDerm | 10 (15) |
| Median Time to Re-excision (range in days) | 13.5 (6-54) |
| Wound Management after Re-excision | |
| STSG | 8 (80) |
| Digit Amputation | 1 (10) |
| Cosmatrix Application* | 1 (10) |
| 2nd AlloDerm Graft Placement | 3 (5) |
| Median Time to 2nd AlloDerm Graft (range in days) | 91 (28-112) |
Separate surgeon performed re-excision and graft placement
In 16 of the 43 patients who had AlloDerm placed initially as a temporary dressing, the graft was left in situ and managed expectantly because of surgeon/patient preference after favorable initial post-operative healing was observed. None of these 16 patients required further skin grafting or myocutaneous flap coverage.
Negative margins were obtained at the initial resection in a majority of patients (85%). Ten patients (15%) did require margin re-excision and extirpation of the AlloDerm graft for positive margins after initial resection. The median time to re-excision was 13.5 days (range, 6-54 days). Of these 10 requiring re-excision, 8/10 (80%) underwent skin graft placement after re-excision, 1 underwent distal digital amputation and the remaining patient underwent coverage with an alternative biologic dressing based on surgeon preference (different surgeon performed the re-excision).
Outcome Experience using AlloDerm
Early post-operative physical exam findings were favorable with 57 patients (85%) having evidence of healthy incorporation at initial examination. (Figure 2A & 2B, Table 3) Evidence of early incorporation was evident as early as the initial post-operative examination. For the patients who underwent subsequent skin grafting, at the time of AlloDerm removal for definitive reconstruction, evidence of incorporation with healthy granulation tissue present was often visible. AlloDerm use helped to foster native tissue ingrowth and helped to mature an ideal recipient site for skin grafting. Two patients (3%) had evidence of complete AlloDerm graft loss with associated cellulitis at initial examination. These two patients were managed with skin grafts (included in the 25 patients who had skin grafts after AlloDerm placement).
Figure 2.
A: Early post-operative (day 5) appearance of a forearm wide excision for melanoma with AlloDerm reconstruction.
B: Large surface area coverage with AlloDerm after resection of a locally advanced basal cell carcinoma of the anterior chest wall (day 10).
Table 3. Outcomes after AlloDerm Placement.
| Variable | N (%) |
|---|---|
| 1st Post-op Physical Exam Findings | |
| Healing with Early Incorporation | 57 (85) |
| Partial Loss | 7 (10) |
| Complete Loss | 2 (3) |
| Unknown | 1 (2) |
| Final AlloDerm Outcome | |
| Partial Loss | 12 (18) |
| Complete Loss | 12 (18) |
| Post-operative Complications | |
| Cellulitis Requiring Antibiotics | 9 (13) |
| Seroma | 7 (10) |
| Hematoma | 1 (2) |
| Post-op Radiation | 16 (24) |
| Final Actual AlloDerm Usage | |
| Temporary | 27 (40) |
| Permanent | 40 (60) |
| Median Follow Up (range in months) | 9 (0-37) |
Delayed subjective post-operative findings (generally 3-4 weeks post-operative) for those patients who did not go onto immediate skin graft placement were characterized by evidence of further ingrowth of the AlloDerm grafts and incorporation with the native tissue. Eschar formation as a stage of AlloDerm healing and eventual incorporation was present in some patients and is usually evident 3 to 4 weeks after initial AlloDerm placement. (Figure 3A) Eschar formation was more commonly identified when thicker sheets of AlloDerm were utilized. Six of the 12 patients with eschar formation present had AlloDerm grafts of 0.79 mm or thicker. Mild debridement was often performed in the clinic to maintain clean wound edges and help facilitate healthy wound contracture. Eschar formation did not appear to have a negative impact on wound healing or long-term cosmetic outcome as a majority (11 of the 12) were managed expectantly without further intervention. As eschar formation and AlloDerm incorporation progressed over time (generally 4-6 weeks), the AlloDerm grafts would more closely resembled native tissue. A healthy bed of granulation tissue would progressively decrease in size as wound contracture and neo-epithelialization increased and native tissue ingrowth predominated. The end result was often cosmetically acceptable and without any significant impairment to function. (Figure 3B)
Figure 3.
A: Eschar formation of a plantar graft after melanoma resection and AlloDerm reconstruction (3 weeks).
B: Final outcome in same patient with eschar formation of a plantar graft after melanoma resection and AlloDerm reconstruction (6 months).
Final AlloDerm usage was as a temporary biologic dressing in 27 (40%) and permanent biologic dressing in 40 (60%). The 40 patients includes all 24 patients who originally had AlloDerm placed as an intended permanent dressing as well as 16 additional patients who initially had AlloDerm placed as a temporary dressing. When we further reviewed our AlloDerm usage patterns over time, it was clear that surgeons at our institution became more comfortable using AlloDerm as a definitive reconstruction alternative. For instance, in 4 of the first 33 patients (12%) treated, AlloDerm was utilized as intended permanent coverage whereas 20 of the last 34 patients (59%) had AlloDerm grafts placed as intended definitive coverage. Post-operative complications were mild and generally self-limiting, the most frequent was cellulitis (13%).
Adjuvant Radiation Experience using AlloDerm
Adjuvant external beam irradiation was administered to 16 patients (24%) in the study at a median of 53 days (range, 8-118 days) after surgery. Two of the 10 patients who required re-excision for positive margins received adjuvant radiation. A majority of the patients tolerated adjuvant irradiation without difficulty, 12 of the 16 patients (75%) had no further sequelae from irradiation of the AlloDerm graft after placement. Four patients (4/16, 25%) developed complete AlloDerm graft loss after adjuvant irradiation, all of which were managed with healing by secondary intention.
Discussion
Since mid-2006, we have utilized AlloDerm as a temporary or permanent dermal substitute at Moffitt Cancer Center for patients undergoing reconstruction after skin and soft tissue resection. Our preference is to perform immediate autologous reconstruction at the time of skin and soft tissue resection when possible.[11] However, in some patients, proceeding with immediate reconstruction (skin grafting or myocutaneous flap coverage) may not be possible because of issues such as primary tumor location or anatomical constraints with limited reconstruction possibilities. In addition, we tend to place a temporary coverage on skin and soft tissue malignancy wounds with AlloDerm if there is a concern about pathology margins ie. when tumors are more extensive during surgery than originally thought, especially with certain histologies such as dermatofibrosarcoma protuberans, or extensive melanoma in situ/ lentigo in severely sun damaged skin where gross negative margins cannot be adequately assessed by physical exam. Other scenarios where AlloDerm might be are in elderly and infirm patients with multiple medical co-morbidities where we would like to avoid general anesthesia (required for larger flaps and grafts) and simple resection and coverage of the defect with AlloDerm is possible under local anesthesia and in those patients where immediate radiation to the resection bed might be needed and placing a skin graft over that site would preclude radiation for 4 to 6 weeks.
While our initial oncologic indications for AlloDerm use were primarily for patients in need of temporary coverage of skin and soft tissue defects while awaiting permanent pathologic margin assessment, it was apparent in reviewing this patient population that other factors were important when considering AlloDerm. Our patients tended to be older with more medical comorbidities and often had tumors located on distal extremities (or the scalp). The median tumor size resected was also moderately large at 42 cm2 with approximately 25% of patients having surgical defects larger than 100 cm2 in size. Others have also reported using AlloDerm for coverage of large surgical defects after Mohs excision in anatomically sensitive areas with favorable results.[12] For larger tumors located on the scalp, we tried to place AlloDerm on the periostium when possible to avoid direct placement onto the cranium. Nonetheless, others have reported acceptable outcomes when AlloDerm is placed directly onto the skull such as in cases of osteomyelitis or other trauma-associated scalp defects.[13-15]
Our initial experiences with AlloDerm were generally favorable when used for temporary reconstruction, allowing definitive reconstruction to be performed at a later date after pathologic margins were confirmed. We discovered that a large percentage of patients had excellent early post-operative outcomes and if no further resection were required the temporary AlloDerm graft would often go on to heal uneventfully if left undisturbed. Our increasing experience and comfort in using AlloDerm in this setting was most evident based on the observation that a majority of the patients treated later in the series had AlloDerm placed as intended definitive reconstruction. It is interesting to note that a majority of the patients in this series who had AlloDerm grafts placed required no further intervention. For these patients, the use of AlloDerm avoided the need for a second general anesthetic procedure or additional reconstruction with potential donor site morbidity. For the 10 patients who required re-excision for positive margins and the 27 patients who did undergo subsequent skin graft placement after Alloderm coverage, AlloDerm in these situations was able to be easily removed at the time of definitive reconstruction leaving underneath a healthy bed of granulation tissue and an ideal recipient site for grafting.
Early subjective post-operative physical examination results demonstrated healthy on initial inspection in a majority of patients. This was often evident as early as the first post-operative examination with complete native tissue ingrowth and cellularization often evident 4-6 weeks after placement. Eschar formation as a function of wound healing and AlloDerm incorporation was also an occasional finding on physical examination, especially with the later post-operative visits (at 3-4 weeks on average postoperatively). When present, bedside debridement was performed, and it did not have a negative impact on long-term cosmetic appearance or functional outcome (Figure 3B). AlloDerm graft loss was observed in a few patients and when it did occur was managed expectantly with supportive local wound care (silvadene, wet-to-dry dressing changes) without further morbidity or significant burden to the patient.
Given the aggressive nature and increased risk of local recurrence of certain high-risk skin and soft tissue tumors, adjuvant irradiation may be required in certain situations. The potential impact of adjuvant irradiation on AlloDerm graft outcome, especially in circumstances when AlloDerm is intended for definitive reconstruction, becomes a significant determinant of pre-operative reconstruction planning. When unfractionated irradiation is applied to skin grafts, for instance, ulceration and skin graft loss can be observed with doses of 25 Gy or greater.[16] Pre-clinical studies have demonstrated a negative impact of irradiation on AlloDerm graft recellularization but that radiation to the dermal matrix graft does not adversely affect graft survival.[17] In the current series, 24% of patients received adjuvant irradiation after AlloDerm graft placement, however, it was well tolerated by a majority of these patients without a significant impact on final outcome. Indeed, 12 patients (75%) required no further intervention after radiation was administered. The remainder developed loss of their AlloDerm grafts after irradiation but were able to be managed expectantly, healing by secondary intention. While these results are observational, they do suggests that even in the setting of irradiation a majority of patients with AlloDerm grafts will continue to heal uneventfully without the need for further intervention. Salvage skin grafting or flap coverage may be reserved for those with irradiation-associated graft loss or who develop chronic non-healing wounds.
Several limitations of this retrospective review warrant mentioning. The cosmetic outcome measures described were subjective and not based on a reproducible standardized objective scale. There was also a surgeon bias for which patients preferentially underwent AlloDerm placement versus other forms of temporary or definitive reconstruction after skin and soft tissue resection and no formal comparison was made using AlloDerm to other commercially available products.
In conclusion, AlloDerm offers suitable temporary coverage alternative of skin and soft tissue defects for large defects in anatomically sensitive locations, elderly patients with associated comorbidities or while awaiting pathologic margin assessment after resection. AlloDerm may serve as a bridge to permanent reconstruction with skin graft coverage or even as a permanent biologic dressing of complex surgical defects with favorable early cosmetic outcomes. In situations where adjuvant radiation is needed, AlloDerm may be safely used with acceptable outcomes and minimal morbidity.
Figure 4.
Final AlloDerm graft outcome description for the 67 patients who underwent skin and soft tissue resection and reconstruction.
Footnotes
Presented in part at the 2012 Society of Surgical Oncology Annual Meeting Orlando, FL, March 21-24, 2012
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