A case of markedly impaired wound repair with angiostatic pazopanib in a patient who had Mohs surgery for a basal cell carcinoma.

This case report highlights the adverse effects of pazopanib, a vascular endothelial growth factor receptor inhibitor, on wound healing after Mohs surgery. A 79-year-old male with metastatic renal cell carcinoma of the lung, on 600 mg daily pazopanib, underwent Mohs surgery for a nodular basal cell carcinoma on his right leg. Despite multiple wound care strategies, his wound deteriorated over 4 months. Discontinuing pazopanib resulted in rapid wound closure within 2 months. However, metastatic lung nodules grew, prompting treatment with immune checkpoint inhibitors, nivolumab, and ipilimumab, which were discontinued due to complications. Near-complete wound healing was observed prior to reintroducing pazopanib (6 months after initial discontinuation), which again led to wound deterioration. Pazopanib negatively impacts wound repair by inhibiting cell proliferation and angiogenesis. Depending on the malignancy or tumor, cessation of pazopanib, or switching to a course of immune checkpoint inhibitors may be warranted perioperatively.

MOC-31 Antibody Immunolabeling During Mohs Surgery.

BACKGROUND: Ber-EP4 is an antibody that labels basal cell carcinoma (BCC) by targeting epithelial cell adhesion molecule (Ep-CAM). MOC-31, a monoclonal mouse antibody, also targets Ep-CAM and is currently used to differentiate several extracutaneous epithelial tumors. However, the utility of MOC-31 has not been fully described in cutaneous tumors and in Mohs micrographic surgery (MMS). OBJECTIVE: To evaluate MOC-31 labeling in BCC and other cutaneous tumors and to compare immunolabeling intensity of MOC-31 and Ber-EP4 in BCCs. MATERIALS AND METHODS: Nineteen permanently fixed and 29 frozen BCC specimens and 23 other cutaneous tumors were labeled with MOC-31; labeling intensity of tumors, epidermis, and adnexal structures were recorded. In a separate study, a blinded dermatopathologist compared labeling intensities of 8 BCC specimens, each labeled with MOC-31 and Ber-EP4.4. RESULTS: MOC-31 labeled all BCCs. Eccrine coils and follicular bulbs did label variably, although this did not detract utility of MOC-31. Five of thirteen cutaneous squamous cell carcinomas and one of two Merkel cell carcinomas demonstrated MOC-31 positivity. MOC-31 and Ber-EP4 labeled BCCs similarly. CONCLUSION: MOC-31, an antibody directed against Ep-CAM, is sensitive for BCCs in frozen specimens encountered in MMS and permanently fixed specimen. In addition, MOC-31 demonstrated comparable immunolabeling characteristics with Ber-EP4 for BCCs.

A novel specialized suture and inserting device for the resuspension of ptotic facial tissues: early results.

BACKGROUND: In the past decade, the popularity of minimally invasive procedures for facial rejuvenation has increased. OBJECTIVE: To describe a new specialized suture, and its associated technique, used to elevate sagging tissues of the face and neck. METHODS: A detailed description of the technique and the results obtained in 20 patients in whom we have used this novel approach. Attention was given to appropriate patient selection. The primary focus was on the correction of the jowl, jawline, and neck subunits. It involves the percutaneous introduction of a novel 3-0 polypropylene suture that has 10 absorbable hollow cones along its axis that are equally interspersed with knots. Once the absorbable cones are resorbed into the surrounding tissues, the non-absorbable suture component can be removed without compromising the aesthetic outcome. RESULTS: All patients demonstrated improvement in these areas, with minimal complications. One patient required resuspension using the open technique. (Excessive ptotic tissue was later excised for an optimal cosmetic result.) CONCLUSION: The suture and technique described in this article provide a major contribution to the correction of ptosis of facial tissues. When done in conjunction with other procedures, such as neck and jowl microliposuction, this technique has proven to be a useful addition to facial rejuvenation.

Wound bed score and its correlation with healing of chronic wounds.

Adequate wound bed preparation is essential for healing of leg ulcers, and consists of controlling exudate and edema, decreasing the bacterial burden, promoting healthy granulation tissue, and removing necrotic tissue. Currently, there is no classification system for wound bed preparation that has predictive value. Based on past work and the authors' experience, we have now developed and tested a new classification system that scores the following parameters: healing edges (wound edge effect), presence of eschar, greatest wound depth/granulation tissue, amount of exudate amount, edema, peri-wound dermatitis, peri-wound callus and or fibrosis, and a pink/red wound bed. Each parameter receives a score from 0 (worst score) to 2 (best score), and all the parameter scores are added for a total score. Each wound can have a maximum score of 16 (the best score possible), to a minimum score of 0 (the worst score possible). We used this wound bed score (WBS) system in a study of 177 patients with venous ulcers who had been prospectively treated with and randomized to either conventional therapy (compression alone) or a living bilayered skin construct (BSC). We evaluated serial photographs at baseline to determine whether the results would be predictive of complete wound closure and could validate the WBS. We found that wounds that ultimately achieved full closure had a statistically significant higher WBS than those that did not heal (p = 0.0012). This was also true when separating wounds by treatment modality: standard therapy (p = 0.044) and treatment with a BSC (p = 0.011). When dividing the WBS in the following quartile groups: scores 4-10, 10-12, 12-13, and 13-16, the percentage of healed wounds correlated with the WBS (p = 0.0008). For all wounds, a one unit increase in total WBS resulted on average in a 22.8% increase in odds of healing (OR = 1.228). This WBS seems to have validity in predicting complete wound closure in wounds treated with either standard therapy or advanced modalities, such as BSC. If confirmed and widely adopted in this and other types of wounds, it could be a useful tool in both the clinical and research setting.

Safety and efficacy of a bilayered skin construct in full-thickness surgical wounds.

This was a prospective, randomized, controlled clinical trial assessing the safety and efficacy of a living bilayered skin construct (BSC; Organogenesis, Canton, MA) in treating full-thickness surgical excision wounds. We enrolled 31 patients needing excision of a non-melanoma skin cancer. The patients consisted of 18 females and 13 males, with an average age of 67 years (range: 44 to 84 years). Patients were randomized to either receive a single application of BSC or to heal by secondary intention. Endpoints to assess efficacy included time to complete wound closure, intensity and duration of post-operative pain, cosmetic appearance, patient satisfaction, and quality of the healed wound. Endpoints to assess safety included infection at the wound site and rejection of the BSC. Findings indicate that BSC is safe in the post-operative treatment of acute surgical wounds for removal of non-melanoma skin cancer. The data also suggest that BSC may facilitate management by decreasing post-operative pain. It is unclear whether or not BSC decreases healing time of acute wounds or results in a better cosmetic outcome.

Contact sensitivity in patients with leg ulcerations: a North American study.

OBJECTIVES: (1) To determine the prevalence of allergen sensitivity in patients with past or present leg ulcers in 2 North American study centers vs European study findings and the North American Contact Dermatitis Group (NACDG) database and (2) to delineate a standard battery of allergens for patch testing in North American patients that is representative of the newer dressings and wound care products. DESIGN: Fifty-four patients, with or without dermatitis, were prospectively entered in the study. The patients were patch tested to the NACDG standard series and a comprehensive supplemental series of 52 allergens. SETTING: Wound healing clinics at Boston University Roger Williams Medical Center and University of Ottawa. RESULTS: Sixty-three percent (n = 34) of patients had 1 or multiple positive patch test results, and 37% (n = 20) had no positive patch test result. The most common allergens were Myroxylon pereirae (balsam of Peru) (30% [16/54]), bacitracin (24% [13/54]), fragrance mix (20% [11/54]), wood tar mix (20% [11/54]), propylene glycol (14% [7/52]), neomycin sulfate (13% [7/54]), benzalkonium chloride (13% [7/54]), carba mix (11% [6/54]), nickel sulfate (11% [6/54]), and control gel hydrocolloid (11% [6/54]). CONCLUSIONS: Comparable to European study findings, there is a high incidence of positive patch test results in patients with past or present leg ulcerations. The incidences of the most common allergens in our patient population were higher than those seen in the NACDG, except for nickel. Using a modified leg ulcer series along with the standard NACDG series is important in evaluating patients with leg ulcers.

Clinical classification of bioengineered skin use and its correlation with healing of diabetic and venous ulcers.

BACKGROUND: Chronic wounds are being treated with bioengineering skin constructs. Yet, there is no standard way of assessing these wounds. We developed a classification system to evaluate wounds after construct application. The classification system evaluates the early clinical effect of bioengineered skin and early construct appearance giving a total score named the skin substitute score. OBJECTIVE: Apply classification system to both venous and diabetic foot ulcers and determine whether classification system has validity and predictability for healing. METHODS: Evaluated serial photographs in 83 and 78 patients with diabetic foot ulcers and in 84 and 83 patients with venous ulcer on Days 7 and 14, respectively, treated with a bilayered bioengineered skin construct. Applied the classification system and determined the percentages of healed patients. RESULTS: There was a significant correlation between better skin substitute score and complete wound closure for both venous ulcers p=0.002 on Day 7 and p=0.01 on Day 14) and diabetic foot ulcers p=0.0005 on Day 7 and p<0.0001 on Day 14). CONCLUSION: Optimal clinical effect was associated with complete wound closure. As the clinical effect becomes less than optimal continued clinical persistence of the construct becomes important. This classification system seems to have validity in predicting complete wound closure in wounds treated with a bilayered bioengineered skin construct.

Debridement performance index and its correlation with complete closure of diabetic foot ulcers.

In recent years there has been wider acceptance of aggressive surgical debridement as a means to accelerate closure of diabetic foot ulcers. In a clinical trial by Steed et al.1 involving the use of a topically applied growth factor, thorough surgical debridement of surrounding callus, necrotic ulcer bed, and undermined ulcers' edges was associated with greater incidence of healing and effectiveness of the therapeutic agent. However, at present there is no established way to judge the appropriate extent of debridement and its performance. Here we describe a scoring system to assess whether debridement has been performed adequately. Our scoring system consists of the following three categories: debridement of a) callus; b) ulcer's edge undermining; and c) wound bed necrotic tissue. We assigned a score of 0-2 to each of these categories using the following criteria: 0 = debridement needed but not done, 1 = debridement needed and done, and 2 = debridement not needed. These three scores are then added to give a total ranging from 0 to 6, with the highest number being the optimal score. This instrument, the Debridement Performance Index, evaluates both the adequacy of debridement and whether the ulcer has been or is being properly debrided. To initiate the validation of this scoring system and determine its predictive value for wound closure by week 12, we applied it to 143 patients with diabetic foot ulcers who had been treated in a clinical trial involving either standard therapy (n = 65) or the application of a bioengineered skin construct (n = 78). We blindly evaluated sequential digital photographs of each diabetic foot ulcer and applied the Debridement Performance Index score at day 0, before initiation of either treatment. We found that the lower the baseline Debridement Performance Index the lower the incidence of ultimate wound closure by week 12 ( p = 0.0276). Patients with a Debridement Performance Index between 3 and 6 were 2.4 times more likely to heal than those with a score of 0-2. After controlling for treatment, the Debridement Performance Index was found to be an independent predictor of wound closure (odds ratio = 2.4 95% confidence interval = 1.0-5.6). In conclusion, this novel scoring system for debridement performance appears to be very promising as a predictive tool for determining outcome in clinical trials and, most likely, in clinical practice.