Factors Influencing Margin Clearance and the Number of Stages of Mohs Micrographic Surgery in Basal Cell Carcinoma: A Retrospective Chart Review.

How patient and tumor factors influence clearance margins and the number of Mohs Micrographic Surgery (MMS) stages when treating basal cell carcinoma (BCC) remains widely uncharacterized. It is important to elucidate these relationships, as surgical outcomes may be compared nationally between colleagues. Our objective is to evaluate the relationships between defect size and patient demographics, as well as between BCC subtypes and the number of MMS stages. Our second objective is to compare practice patterns and characteristics of patients requiring MMS at academic centers and private practices. A retrospective chart review was performed using data collected at academic centers (2015-2018) and private practices (2011-2018) of BCC patients older than 18 years old who underwent MMS. In total, 7651 patients with BCC requiring MMS were identified. Academic center adjusted analyses demonstrated clearance margins 0.1 mm higher for every year's increase in age (p < 0.0001) and 0.25 increase in MMS stages for high-risk BCC (p < 0.0001). Private practice adjusted analyses demonstrated clearance margins 0.04 mm higher for every year's increase in age (p < 0.0001). Clearance margins correlate with older age, and additional MMS stages correlate with high-risk BCC, suggesting the role patient and tumor factors may play in predicting tumor clearance and MMS stages.

Lesional CD8+ T-Cell Number Predicts Surgical Outcomes of Melanocyte-Keratinocyte Transplantation Surgery for Vitiligo.

The melanocyte-keratinocyte transplantation procedure (MKTP) treats stable and recalcitrant vitiligo. Despite careful selection of candidates based on clinical stability, the success of the procedure is unpredictable. The aim of our study was to define the immunological profile of stable vitiligo lesions undergoing MKTP and correlate them with clinical outcomes. We included 20 MKTP candidates with vitiligo and a patient with piebaldism as a control. Prior to MKTP, T-cell subsets and chemokines in the recipient skin were measured by flow cytometry and ELISA. During MKTP, melanocytes in the donor skin were quantified by flow cytometry. After MKTP, patients were followed for 12 months and repigmentation was assessed clinically and by ImageJ analysis of clinical photographs. Baseline immunologic biomarkers, duration of clinical stability, and transplanted melanocyte number were correlated to postsurgical repigmentation scores. CD8+ T cells were elevated in 43% of the clinically stable vitiligo lesions. CD8+ T-cell number negatively correlated with postsurgical repigmentation scores (r = -0.635, P = 0.002). Duration of clinical stability, skin chemokines, and transplanted melanocyte number did not influence postsurgical repigmentation. This study demonstrates that CD8+ T-cell number correlates negatively with success of postsurgical repigmentation and can be a biomarker to identify ideal surgical candidates.

Wound Care Adherence in Mohs Micrographic Surgery: A Prospective Cohort Study.

BACKGROUND: Patients undergoing Mohs micrographic surgery (MMS) are given detailed wound care instructions to prevent postoperative complications. Previous studies have revealed low treatment adherence in general dermatology, but adherence to postoperative wound care and its potential association with poor surgical outcomes remain largely unstudied. OBJECTIVE: To determine the frequency and causes of wound care nonadherence in patients who underwent MMS. MATERIALS AND METHODS: A questionnaire containing a modified Eight-Item Morisky Medication Adherence Measure Scale was administered to Mohs patients at their 1 to 2 weeks postoperative visit. RESULTS: Sixty-three patients were solicited and consented to completing the questionnaire. The average modified Eight-Item Morisky Medication Adherence Measure Scale score was 7.4 of 8, indicating high adherence. Old age and wound care assistance were associated with increased adherence. Factors contributing to nonadherence included feeling well, being too busy, wound care causing discomfort, and being with friends or family. One patient (1.6%) with high adherence developed an epidermal inclusion cyst within the scar. No other complications were observed. CONCLUSION: Most MMS patients demonstrated high adherence to wound care instructions, and nonadherence was not associated with postoperative complications.

Results of a National Survey on the Definition of Surgical Site Infections After Mohs Micrographic Surgery.

BACKGROUND: There is no standardized definition of surgical site infections (SSI) after Mohs micrographic surgery (MMS) used in the clinical or research settings, which may contribute to heterogeneity in the differences in infection rates reported. OBJECTIVE: To use an electronic survey of Mohs surgeons across the country to better understand how Mohs surgeons define SSI after MMS. METHODS: A web-based survey was developed and distributed to Mohs surgeons. Respondents were asked to respond to several different scenarios that could represent SSI after MMS. RESULTS: Of potential 1,500 respondents, 79 (5.3%) responded to the survey. Presentation of a surgical site with warmth, swelling, erythema, and pain at 7 days postoperatively resulted in 79.7% consensus of SSI. Surgical sites that were cultured and found to be Staphylococcus aureus-positive resulted in 100% agreement of SSI. There was no consensus regarding timing after MMS. CONCLUSION: There is consensus on numerous aspects of SSI after MMS among Mohs surgeons, which may allow for development of standardized definition in the future.

CXCL9 Links Skin Inflammation and Fibrosis through CXCR3-Dependent Upregulation of Col1a1 in Fibroblasts.

Morphea is characterized by initial inflammation followed by fibrosis of the skin and soft tissue. Despite its substantial morbidity, the pathogenesis of morphea is poorly studied. Previous work showed that CXCR3 ligands CXCL9 and CXCL10 are highly upregulated in the sera and lesional skin of patients with morphea. We found that an early inflammatory subcutaneous bleomycin mouse model of dermal fibrosis mirrors the clinical, histological, and immune dysregulation observed in human morphea. We used this model to examine the role of the CXCR3 chemokine axis in the pathogenesis of cutaneous fibrosis. Using the REX3 (Reporting the Expression of CXCR3 ligands) mice, we characterized which cells produce CXCR3 ligands over time. We found that fibroblasts contribute the bulk of CXCL9-RFP and CXCL10-BFP by percentage, whereas macrophages produce high amounts on a per-cell basis. To determine whether these chemokines are mechanistically involved in pathogenesis, we treated Cxcl9-, Cxcl10-, or Cxcr3-deficient mice with bleomycin and found that fibrosis is dependent on CXCL9 and CXCR3. Addition of recombinant CXCL9 but not CXCL10 to cultured mouse fibroblasts induced Col1a1 mRNA expression, indicating that the chemokine itself contributes to fibrosis. Taken together, our studies provide evidence that CXCL9 and its receptor CXCR3 are functionally required for inflammatory fibrosis.

Design and Validation of a Handheld Optical Polarization Imager for Preoperative Delineation of Basal Cell Carcinoma.

BACKGROUND: Accurate removal of basal cell carcinoma (BCC) is challenging due to the subtle contrast between cancerous and normal skin. A method aiding with preoperative delineation of BCC margins would be valuable. The aim of this study was to implement and clinically validate a novel handheld optical polarization imaging (OPI) device for rapid, noninvasive, in vivo assessment of skin cancer margins. METHODS: The handheld imager was designed, built, and tested. For clinical validation, 10 subjects with biopsy-confirmed BCC were imaged. Presumable cancer margins were marked by the study surgeon. The optical images were spectrally encoded to mitigate the impact of endogenous skin chromophores. The results of OPI and of the surgeon's preoperative visual assessment were compared to clinical intraoperative histopathology. RESULTS: As compared to the previous prototype, the handheld imager incorporates automated image processing and has 10-times shorter acquisition times. It is twice as light and provides twice as large a field of view. Clinical validation demonstrated that margin assessments using OPI were more accurate than visual assessment by the surgeon. The images were in good correlation with histology in 9 out of 10 cases. CONCLUSIONS: Handheld OPI could improve the outcomes of skin cancer treatments without impairing clinical workflows.

Recurrence and Mortality of Melanoma In Situ of the Trunk or Extremities: A Surveillance, Epidemiology, and End Results Analysis.

BACKGROUND: Recent studies demonstrate comparable outcomes of Mohs micrographic surgery (MMS) versus local excision (LE) for melanoma in situ. These studies are limited by their focus on the head and neck. OBJECTIVE: The primary objective was to compare 5-year overall and melanoma-specific mortality among patients with melanoma in situ of the trunk or extremities who undergo MMS versus LE. The secondary objective was to compare 5-year local recurrence among the same cohort of patients who undergo MMS versus LE. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (2000-2015) was queried to identify patients who underwent MMS versus LE for melanoma in situ of the trunk, upper extremities, or lower extremities. Outcomes were 5-year recurrence, melanoma-specific mortality, and overall mortality. Multivariable regression analyses were performed. RESULTS: Thirty three thousand nine hundred eighty-three patients underwent surgical treatment (MMS 3%; LE 97%). In adjusted analyses, there was no difference in local recurrence (hazard ratio [HR] 1.00, 95% confidence interval [CI] 0.56-1.78), melanoma-specific mortality (HR 0.89, 95% CI 0.12-6.47), nor overall mortality (HR 1.10, 95% CI 0.82-1.48) between MMS versus LE. CONCLUSION: There is no difference of 5-year local recurrence, melanoma-specific mortality, nor overall mortality associated with MMS versus LE for melanoma in situ of the trunk or extremities.

Consensus for Nonmelanoma Skin Cancer Treatment, Part II: Squamous Cell Carcinoma, Including a Cost Analysis of Treatment Methods.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in the United States. Cutaneous squamous cell carcinoma has an estimated incidence of more than 700,000 new cases per year and a 5% risk of metastasis. OBJECTIVE: To provide clinicians with guidelines for the management of cSCC based on evidence from a comprehensive literature review and consensus among the authors. MATERIALS AND METHODS: The authors conducted an extensive review of the medical literature on treatment methods for cSCC, taking into consideration cure rates, recurrence and metastatic rates, aesthetic and functional outcomes, and cost effectiveness of the procedures. RESULTS: Surgical treatments provide the best outcomes for cSCC. Mohs micrographic surgery is a cost-effective procedure that affords the highest cure rate, maximal tissue preservation, and superior cosmetic outcomes. Nonsurgical methods may be used as a primary treatment for low-risk squamous cell carcinomas, but the cure rates are lower. CONCLUSION: The cure rate remains the most important consideration in choosing the treatment method, but additional factors, such as the patient's general medical condition, psychosocial circumstances, the location of the tumor and cost effectiveness of the therapy should be considered. Mohs micrographic surgery remains the preferred treatment for high-risk tumors and tumors located in cosmetically sensitive areas.

Prospective randomized controlled study to determine the effect of topical application of botulinum toxin A for crow's feet after treatment with ablative fractional CO2 laser.

BACKGROUND: Botulinum toxin Type A (BoNT A) for the treatment of facial wrinkles is delivered through local injection. We previously demonstrated that topical surface application of BoNT A has negligible cutaneous bioavailability and is not effective in treating wrinkles. OBJECTIVE: To determine the effect of BoNT A solution applied topically on the skin surface immediately after ablative fractional CO2 laser treatment. METHODS: We conducted a randomized controlled trial for patients with periorbital wrinkles (crow's feet) (n = 10). Treatment was performed on both sides of the face with fractional ablative CO2 laser followed by the application of topical solutions of BoNT A on one side and normal saline as control on the other side. Pretreatment assessment was performed, and at 1 and 4 weeks after treatment. RESULTS: There was a clinically significant greater degree of improvement in wrinkles after treatment with CO2 laser, on the topically applied BoNT A side. Also, the difference between the 2 treatment types (laser followed by topical BoNT A vs laser followed by saline) at 1 week and at 1 month was statistically significant. CONCLUSION: Topically, noninjectable form of BoNT A applied on the surface of the skin after ablative fractional CO2 laser is effective in the treatment of lateral periorbital wrinkles.

Evaluation of orbicularis oculi muscle stripping on the cosmetic outcome of upper lid blepharoplasty: a randomized, controlled study.

BACKGROUND: Many variations in the surgical treatment of upper eyelid blepharoplasty have been described, including orbicularis oculi muscle stripping. There is no evidence in the literature to support the efficacy of this technique in improving the aesthetic results of the procedure. OBJECTIVES: To conduct a single-blind, randomized, controlled, split-face pilot study to evaluate the effects of orbicularis oculi muscle stripping on upper lid blepharoplasty. METHODS: Ten subjects were randomized to receive upper lid blepharoplasty with orbicularis oculi muscle stripping on one side and skin-only blepharoplasty on the other. Patients and two blinded physicians evaluated the aesthetics of the eyelids at 1-, 3-, and 17-month follow-up visits. RESULTS: Blinded physician evaluation failed to show a difference in the overall cosmetic appearance of the eyelids between the control and treatment sides at any time point. Analysis of the composite of all patient scores showed a trend favoring the control side at 3 months (p = .28) and the treatment side at 17 months (p = .50), but neither difference was significant. CONCLUSION: Based on the data from this pilot study, orbicularis oculi muscle stripping appears to have no affect on the aesthetic outcome of upper lid blepharoplasty.

Bendamustine-induced "flagellate dermatitis".

BACKGROUND: The term "flagellate erythema" after bleomycin therapy was described as bleomycin-induced linear hyperpigmentation. Since then, this pattern has not been related to any other chemotherapeutic regimen. OBSERVATION: We report a rare patient with chronic lymphocytic leukemia who developed "flagellate dermatitis" induced by bendamustine. CONCLUSION: Chemotherapy induced "Flagellate Dermatitis" is a rare finding reported only after bleomycin therapy. We describe the first case with this characteristic eruption pattern after administration of bendamustine.

Quantitative skin color measurements in acanthosis nigricans patients: colorimetry and diffuse reflectance spectroscopy.

Tristimulus colorimetry and diffuse reflectance spectroscopy (DRS) are white-light skin reflectance techniques used to measure the intensity of skin pigmentation. The tristimulus colorimeter is an instrument that measures a perceived color and the DRS instrument measures biological chromophores of the skin, including oxy- and deoxyhemoglobin, melanin and scattering. Data gathered from these tools can be used to understand morphological changes induced in skin chromophores due to conditions of the skin or their treatments. The purpose of this study was to evaluate the use of these two instruments in color measurements of acanthosis nigricans (AN) lesions. Eight patients with hyperinsulinemia and clinically diagnosable AN were seen monthly. Skin pigmentation was measured at three sites: the inner forearm, the medial aspect of the posterior neck, and anterior neck unaffected by AN. Of the three, measured tristimulus L*a*b* color parameters, the luminosity parameter L* was found to most reliably distinguish lesion from normally pigmented skin. The DRS instrument was able to characterize a lesion on the basis of the calculated melanin concentration, though melanin is a weak indicator of skin change and not a reliable measure to be used independently. Calculated oxyhemoglobin and deoxyhemoglobin concentrations were not found to be reliable indicators of AN. Tristimulus colorimetry may provide reliable methods for respectively quantifying and characterizing the objective color change in AN, while DRS may be useful in characterizing changes in skin melanin content associated with this skin condition.

Systemic analyses of immunophenotypes of peripheral T cells in non-segmental vitiligo: implication of defective natural killer T cells.

Although it is widely believed that non-segmental vitiligo (NSV) results from the autoimmune destruction of melanocytes, a clear understanding of defects in immune tolerance, which mediate this uncontrolled self-reactivity, is still lacking. In the present study, we systemically evaluated circulating regulatory T (Treg) cells, including CD4(+) CD25(+) FoxP3(+) Treg cells and invariant natural killer T (iNKT) cells, as well as naïve and memory CD4(+) and CD8(+) T cells and their cytokine production, in a cohort of 43 progressive NSV patients with race-, gender-, and age-matched healthy controls. We found that the general immunophenotypes of CD4(+) and CD8(+) T cells and the percentage of CD4(+) CD25(+) FoxP3(+) Tregs were comparable between NSV and healthy controls. However, percentages of peripheral iNKT cells were significantly decreased in NSV patients compared to that in healthy controls. Our data confirm the previous notion that the percentage of peripheral CD4(+) CD25(+) FoxP3(+) Tregs remains unaltered in NSV and suggests the involvement of defective iNKT cells in the pathogenesis of NSV.

Subcuticular incision versus naturally sourced porcine collagen filler for acne scars: a randomized split-face comparison.

BACKGROUND: Subcuticular incision is performed to release fibrotic bands beneath acne scars and to stimulate neocollagenesis. Naturally sourced porcine collagen has been approved for filling moderate to deep facial wrinkles and nasolabial folds. To our knowledge, naturally sourced porcine collagen filler has not yet been tried as a treatment for correcting atrophic acne scars. OBJECTIVE: To objectively assess and directly compare the efficacy and safety of subcuticular incision versus naturally sourced porcine collagen dermal filler in correcting atrophic and rolling acne scars. MATERIALS AND METHODS: We performed a prospective, randomized, split-face, single-blind study to evaluate intermediate long-term efficacy of subcision and collagen dermal filler on 20 unilateral faces. Patients and blinded physicians evaluated results. RESULTS: Patients rated subcision as superior to collagen dermal filler at 3 months (p=.03). At 6 months, subcision had a slightly higher rating than collagen dermal filler (p=.12). Blinded evaluators leaned toward subcision at 3 months (p=.12) and at 6 months showed no preference (p=.69). CONCLUSION: Subcuticular incision and naturally sourced porcine collagen dermal filler appear to be efficacious for improving atrophic and rolling acne scars. Patients may prefer subcuticular incision over collagen dermal filler. Blinded evaluators found no significant difference between the treatments.

Optimizing closure materials for upper lid blepharoplasty: a randomized, controlled trial.

BACKGROUND: Although upper eyelid blepharoplasty is a common procedure, subtleties in surgical technique can affect cosmetic outcomes. Suture materials commonly used include polypropylene, monofilament nylon, fast-absorbing gut, and ethylcyanoacrylate (ECA) tissue adhesive. OBJECTIVE: To assess upper lid blepharoplasty scars in participants whose incision had been closed with 6-0 polypropylene sutures, 6-0 fast-absorbing gut sutures, or ECA. MATERIALS AND METHODS: A randomized, split-eyelid, single-blind, prospective study of the short- (1 month) and intermediate-term (3 months) efficacy of polypropylene, fast-absorbing gut, and ECA on 36 consecutive upper lid blepharoplasties. Participants and a blinded physician evaluator evaluated cosmetic outcome 1 and 3 months after the procedure. RESULTS: Three subgroups tested were ECA versus fast-absorbing gut, ECA versus polypropylene, and fast-absorbing gut versus polypropylene. At 1 month, ECA was superior to fast-absorbing gut (p=.03) and had a marginally better outcome than polypropylene (p=.25), and polypropylene had an equivalent outcome to fast-absorbing gut (p=.46). At 3-month follow-up, ECA remained superior to fast-absorbing gut (p=.03). CONCLUSION: Although sutured epidermal closure and tissue adhesive are highly efficacious for upper eyelid blepharoplasty, physicians and participants felt that cosmesis with ECA was superior to that with fast-absorbing gut.