Characteristics of non-melanoma skin cancers in Native American patients treated with Mohs micrographic surgery.

Despite the lower incidence of non-melanoma skin cancers in skin of color populations, greater morbidity and mortality have been reported. Literature describing non-melanoma skin cancers in Native Americans is scarce. We designed a retrospective review study aimed to evaluate the characteristics of non-melanoma skin cancers (basal cell carcinoma and squamous cell carcinoma) in Native American patients treated with Mohs micrographic surgery between January 2015 and August 2020, at a single academic center. Twenty-six patients with 28 tumors were identified; 12 squamous cell carcinomas (92% well-differentiated) and 16 basal cell carcinomas (94% nodular). Most tumors were on the head and neck, with mean size of 563mm2 (squamous cell carcinomas) and 350mm2 (basal cell carcinomas). Tumor clearance was achieved in one stage for 75% of tumors. Recurrence was seen in two patients with squamous cell carcinoma. No mortality reported, although follow up was limited. Few Native Americans patients underwent Mohs micrographic surgery for non-melanoma skin cancers. Squamous cell cancers were larger, lower risk while basal cell carcinomas were predominantly nodular. Average time from biopsy to Mohs micrographic surgery was three months. Further studies are needed to better characterize non-melanoma skin cancers in Native Americans and to identify barriers to prompt care.

Undermining during cutaneous wound closure for wounds less than 3 cm in diameter: a randomized split wound comparative effectiveness trial.

Undermining is thought to improve wound outcomes; however, randomized controlled data regarding its efficacy are lacking in humans. The objective of this randomized clinical trial was to determine whether undermining low to moderate tension wounds improves scar cosmesis compared to wound closure without undermining. Fifty-four patients, 18 years or older, undergoing primary linear closure of a cutaneous defect with predicted postoperative closure length of ≥ 3 cm on any anatomic site were screened. Four patients were excluded, 50 patients were enrolled, and 48 patients were seen in follow-up. Wounds were divided in half and one side was randomized to receive either no undermining or 2 cm of undermining. The other side received the unselected intervention. Three months, patients and 2 masked observers evaluated each scar using the Patient and Observer Scar Assessment Scale (POSAS). A total of 50 patients [mean (SD) age, 67.6 (11.5) years; 31 (64.6%) male; 48 (100%) white] were enrolled in the study. The mean (SD) sum of the POSAS observer component scores was 12.0 (6.05) for the undermined side and 11.1 (4.68) for the non-undermined side (P = .60). No statistically significant difference was found in the mean (SD) sum of the patient component for the POSAS score between the undermined side [15.9 (9.07)] and the non-undermined side [13.33 (6.20)] at 3 months. For wounds under low to moderate perceived tension, no statistically significant differences in scar outcome or total complications were noted between undermined wound halves and non-undermined halves.Trail Registry: Clinical trials.gov Identifier NCT02289859. https://clinicaltrials.gov/ct2/show/NCT02289859 .

Surgical Margin Mapping of Melanoma In Situ Using In Vivo Reflectance Confocal Microscopy Mosaics.

BACKGROUND: Melanoma in situ (MIS) can have poorly defined borders and subclinical extension that makes margin control challenging. Reflectance confocal microscopy (RCM) is a promising noninvasive technique that can be used to assess subclinical spread. OBJECTIVE: To optimize surgical margins of histology-proven MIS using RCM mosaics. MATERIALS AND METHODS: Prospective review of 22 patients with histology-proven MIS who underwent RCM margin mapping prior to staged excision, between August 1, 2018, and August 13, 2020, at the Department of Dermatology, University of New Mexico, School of Medicine. RESULTS: Twenty patients (91%) had tumor clearance on the first stage using a 3-mm surgical margin after confocal margin mapping. CONCLUSION: Reflectance confocal microscopy margin mapping using the mosaic device tends to clear MIS in one stage, and the use of the handheld device may improve the accuracy for difficult anatomic areas. Current Procedural Terminology codes for RCM do not reflect the time required and complexity of the procedure. Reflectance confocal microscopy margin mapping prior to excision has the potential to decrease the number of stages needed for melanoma removal, reduce treatment time, and cost.

BRAF inhibitor and hairy cell leukemia-related transient acantholytic dermatosis.

Grover disease (GD) is an acquired, nonfamilial, nonimmune mediated, transient or persistent acantholytic dermatosis. Herein, we present a 72-year-old man who had clinical and histopathologic findings of GD following two weeks of treatment with vemurafenib without MEK inhibitor. The patient was successfully treated with topical emollients and a high-potency corticosteroid. Meanwhile, vemurafenib was temporarily discontinued. Drug-induced GD has increasingly been reported in patients on BRAF inhibitor monotherapy as an immune-related adverse event. The cutaneous side effects seem to arise secondary to a paradoxical activation of the mitogen-activated protein kinase signaling of BRAF inhibitor treatment, leading to keratinocyte proliferation. Although the pathogenesis of GD has not been delineated, there is suggestion of activation of T lymphocytes, particularly helper cells under the action of pro-inflammatory cytokines, resulting in proliferation of keratinocytes. Combination therapy with a MEK inhibitor appears to prevent BRAF-induced GD. Given that there is a higher prevalence of GD in patients with hematologic malignancy, a direct causal relationship between the initiation of vemurafenib therapy and development of GD in this case may be difficult to establish.

Absorption and Safety of Topically Applied Timolol for Treatment of Chronic Cutaneous Wounds.

Objective: There are no safety or absorption studies to guide topical timolol therapy for treatment of chronic wounds. This study was undertaken to address this gap. Approach: A prospective, observational, cross-sectional comparative study of timolol plasma levels in patients after topical administration to a chronic wound, compared with levels in patients after timolol ocular administration for the indication of glaucoma. Results: There was no statistically significant difference in the average plasma level of timolol in wound as compared with glaucoma patients. No bradycardia or wheezing was observed after administration. Innovation: We determined the single time point concentration of timolol in plasma 1 h after application of timolol 0.5% gel-forming solution to debrided chronic wounds, providing insight as to the safety of this emerging off-label treatment. Conclusion: The topical application of timolol for chronic wounds shares the same safety profile as the widely used application of ocular administration for glaucoma.

Limb salvage of the foot with Lisfranc amputation following squamous cell carcinoma.

The indolent character of squamous cell carcinoma of the foot can be misleading and might result in unwarranted excisions or delayed treatment.

Cellular versus acellular matrix devices in the treatment of diabetic foot ulcers: Interim results of a comparative efficacy randomized controlled trial.

Healing of diabetic foot ulcers is a major challenge. Despite adhering to optimal standard of care (SOC), less than 30% of wounds heal after 20 weeks. Advanced cellular tissue-based products have shown better healing over SOC, albeit with great cost and modest improvement. We hypothesized no difference in healing effected by either cellular (Dermagraft), noncellular (Oasis) devices, relative to SOC in treating diabetic foot ulcer in a randomized controlled trial. The primary and secondary outcomes were the percentage of subjects that achieved complete wound closure by study endpoint (12 weeks of treatment) and study completion, respectively. During the 2-week screening phase with SOC, subjects with 40% change in ulcer size were excluded. After randomization, 56 patients entered an active treatment phase (8 weeks) followed by a maintenance phase (4-week SOC), with endpoint at visit 15, and 4 monthly follow-up visits. There was equal distribution of demographic data (p>.05) and no difference in initial wound characteristics (p>.05) between all groups. No differences were observed in complete wound closure by 12 and 28 weeks of treatment, nor were there any difference in percentage area reduction from treatment weeks 1 to 12 and from treatment weeks 1 to 28 between the groups. Each of the treatment arms showed statistically significant reduction in wound area from treatment weeks 1 to 28 (p<.05). This exploratory analysis suggests that the outcomes of treatment with either Dermagraft or Oasis matrix are comparable. We have completed enrollment, and the final data analysis is underway to make definitive conclusions.

Ulcerated Basal Cell Carcinomas Masquerading as Venous Leg Ulcers.

BACKGROUND: Nonmelanoma skin cancers rarely arise from venous leg ulcers (VLUs). Although basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer, its association with lower-extremity ulcers is not as frequently reported as other malignancies. OBJECTIVE: To report a case series of biopsy-proven BCC from lower-extremity ulcers of patients who presented at a multispecialty wound clinic. METHODS: Four male patients (mean age, 82.75 years) with 4 chronic VLUs (duration ranging from 2 months to 10 years) underwent a biopsy of their ulcerative lesions. RESULTS: Histologic examination of the specimens revealed 4 cases of BCC. All of the lesions were surgically excised, followed by split-thickness skin graft (n = 2) or healing by secondary intention (n = 2). All of the patients remained healed at follow-up ranging from 15 to 27 months, except for 1 patient who opted for conservative management and had not completely healed at 14 months' follow-up. CONCLUSIONS: Biopsies are warranted for any VLU with documented stalled healing following 3 months of standard of care. One biopsy is performed at the periphery of the ulcer and another at the base in order to rule out the presence of malignant transformation because of BCC, squamous cell carcinoma, sarcoma, melanoma, lymphoma, or metastases.

Combination therapy of autologous adipose mesenchymal stem cell-enriched, high-density lipoaspirate and topical timolol for healing chronic wounds.

Chronic venous leg ulcers are profoundly debilitating and result in billions in health care expenditure. Thus, there is a quest for engineered and innovative approaches. Herein we present a 63-year-old patient with a 30 year history of venous stasis and left lower extremity ulcers, which have been refractory to standard of care, anticoagulation and venous stripping. The medial ulcer was treated with transplantation of autologous adipose mesenchymal stem cell (AMSC)-enriched, high-density lipoaspirate (HDL) on OASIS wound matrix and compression therapy. The lateral ulcer was treated as a control with standard debridement and compression therapy. Four weeks later, both ulcers received daily topical timolol. Three months later, the test ulcer was completely epithelized and remains healed for over 15 months. However, the control showed minimal signs of improvement. In companion studies in our laboratory, human AMSC were cultured in Minimum Essential Medium Eagle Alpha Modifications (MEMα) with fetal bovine serum (FBS). Timolol was administered to AMSC prior to treatment with epinephrine and 104 bacteria/ml heat-killed Staphylococcus aureus. The MEMα with FBS devoid of AMSC served as a background control. After 24 h, cell culture supernatants and protein lysates were collected to determine cytokine production. There was a statistical significant decrease in pro-inflammatory interleukin-6 and -8 induced by the bacteria (to model the wound environment) in AMSC in the presence of timolol compared with control (p < 0.5). This is the first case of a successful combination of autologous AMSC-enriched, HDL with topical timolol for the healing of chronic venous leg ulcers. Copyright © 2016 John Wiley & Sons, Ltd.

Reclaiming Autologous Amputated Tissue for Limb Salvage of a Diabetic Foot Burn with Underlying Critical Limb Ischemia.

BACKGROUND: Diabetes mellitus is a worldwide pandemic that impacts more than 387 million people, with 29 million individuals affected in the United States alone. Diabetic patients have a 25% lifetime risk of developing a diabetic foot ulcer (DFU). Having a DFU is associated with a risk of recurrence approaching 70%. In addition, 1 in 6 patients with DFU will have a lower-limb amputation, with an associated increase in mortality ranging from 47% to 70%. Therefore, limb salvage is critical in patients with DFU. CASE STUDY: This article describes the case of a 70-year-old man with diabetes mellitus, end-stage renal disease, and peripheral arterial occlusive disease who presented with a 1.5% total-body-surface-area, third-degree burn to the left hallux with dry gangrene extending to the midfoot. Ankle brachial indexes were 0.66 on the left and 0.64 on the right. Toe pressures on the left were absent because of extensive dry gangrene. His right foot had a prior transmetatarsal amputation. Using a retrograde pedal approach, a chronic total occlusion of the left posterior tibial artery was recanalized with balloon angioplasty. He then underwent a transmetatarsal amputation with closure, except that the plantar medial side could not be closed without tension. Therefore, an autologous full-thickness skin graft, from the amputation specimen, was used to bridge the defect. DISCUSSION: At 32-week follow-up, the wound was healed, the graft had fully incorporated, and the patient was ambulating well using custom orthotic footwear. The creative use of amputated tissue to assist with wound coverage has not been well described in the literature.

Radioprotection With Amifostine Enhances Bone Strength and Regeneration and Bony Union in a Rat Model of Mandibular Distraction Osteogenesis.

BACKGROUND: Using distraction osteogenesis (DO) to regenerate robust endogenous bone could greatly enhance postoncologic reconstruction of head and neck cancer. However, radiation (XRT) corrosive effects still preclude DO's immense potential. We posit that adjunctive pretreatment with the radioprotectant amifostine (AMF) can optimize wound healing and allow for successful DO with quantifiable enhancements in bony union and strength despite previous surgical bed irradiation. METHODS: Two groups of murine left hemimandibles were exposed to a human equivalent radiation dosage fractionated over 5 daily doses of 7 Gy. AMF-XRT-DO (n = 30) received AMF before radiation, whereas XRT-DO (n = 22) was untreated. All animals underwent left hemimandibular osteotomy and external fixator placement, followed by distraction to a 5.1-mm gap. Left hemimandibles were harvested and mechanically tested for parameters of strength, yield, and breaking load. RESULTS: Radiation-related complications such as severe alopecia were significantly increased in XRT-DO compared with the AMF-treated group (P = 0.001), whereas infection and death were comparable (P = 0.318). Upon dissection, bony defects were grossly visible in XRT-DO distraction gap compared with AMF-XRT-DO, which exhibited significantly more complete unions (P = 0.004). Those results were significantly increased in the specimens prophylactically treated with AMF (yield: 39.41 N vs 21.78 N, P = 0.023; breaking load: 61.74 N vs 34.77 N, P = 0.044; respectively). CONCLUSIONS: Our study revealed that AMF enhances biomechanical strength, regeneration, and bony union after radiation in a murine model of DO. The use of prophylactic AMF in combination with DO offers the promise of an alternative reconstructive option for patients afflicted with head and neck cancer.

A systematic review on the use of cryotherapy versus other treatments for basal cell carcinoma.

BACKGROUND: Cryotherapy is a commonly discussed method for treatment of basal cell carcinoma skin cancer. Some uncertainty remains about its efficacy relative to other modalities. OBJECTIVE: To determine the efficacy and adverse events profile of cryotherapy for the treatment of basal cell carcinoma compared to other therapeutic options or non-intervention. METHODS: We systematically searched PubMed, OVID, Cochrane Library, EMBASE, CINHAL, and CANCERLIT databases for the following terms: "cryotherapy", AND "basal cell carcinoma", OR "cryosurgery" OR "cryoablation" up to April 2018. Two independent reviewers screened the results and extracted the data. Study endpoints included basal cell carcinoma recurrence, cosmetic outcome, and healing time. Study quality was assessed using the Jadad scale. RESULTS: Six clinical studies met our inclusion criteria. The efficacy and safety of cryotherapy alone or with curettage in the treatment of primary superficial and nodular basal cell carcinoma was comparable to photodynamic therapy and surgery, respectively. Cryotherapy was inferior to radiation in terms of recurrence rate. Most patients had better cosmetic outcomes with photodynamic therapy and surgery compared to cryotherapy alone, and cryotherapy with curettage. CONCLUSION: Current available data suggests equivalent efficacy of cryotherapy alone compared to photodynamic therapy or surgery, but inferior to radiotherapy. More studies are necessary to draw definitive conclusions.

Cellular versus acellular grafts for diabetic foot ulcers: altering the protocol to improve recruitment to a comparative efficacy trial.

Diabetic foot ulcers (DFUs) have a substantial impact on public health. The standard of care (SOC) for DFUs consists of a multidisciplinary approach involving glycemic control, wound care with debridement of necrotic tissue, application of a moist dressing, infection control, use of off-loading devices, and patient education. New therapeutic devices aim to target the extracellular matrix (ECM) that is impaired in DFU; however, there is insufficient data on the effectiveness of such therapies along with lack of evidence on their long-term effectiveness. We hypothesized that there is no difference in healing between the cellular matrix and an acellular matrix relative to SOC. To test this hypothesis, we conducted a randomized, single-blind clinical trial in patients with nonhealing DFUs that included 3 treatment arms: (1) SOC, (2) SOC plus a bioengineered ECM with living fibroblasts, and (3) SOC plus a bioengineered ECM devoid of cells. Our trial currently is closed for enrollment, as we have reached our target population size. Amendments to the protocol were made to help reach this threshold.

Significant Differences in the Bone of an Isogenic Inbred Versus Nonisogenic Outbred Murine Mandible: A Study in Rigor and Reproducibility.

Inattention to differences between animal strains is a potential cause of irreproducibility of basic science investigations. Accordingly, the authors' laboratory sought to ensure that cross-comparisons of results generated from studies of mandibular physiology utilizing the Sprague Dawley and Lewis rat strains are valid. The authors specifically investigated baseline histomorphometrics, bone mineral density, and biomechanical strength of the unaltered endogenous mandibles of the inbred, isogenic Lewis rat, and the outbred, nonisogenic Sprague Dawley rat to determine if they are indeed equal. The authors hypothesized that little difference would be found within these metrics.The authors' study utilized 20 male Lewis and Sprague Dawley rats, which underwent no manipulation other than final dissection and analysis. Ten rats from each strain underwent bone mineral density and biomechanical strength analysis. The remaining rats underwent histological analysis. Descriptive and bivariate statistics were computed and the P value was set at 0.05.Lewis rats had a significantly greater number of empty lacunae. Sprague Dawley rats exhibited a significantly greater ratio of bone volume-to-total volume, bone mineral density, tissue mineral density, bone volume fraction, and total mineral content. No differences were found during biomechanical testing.This study demonstrates that differences exist between the Lewis and Sprague Dawley rat within unaltered baseline mandibular tissue. However, these differences appear to have limited functional impact, as demonstrated by similar biomechanical strength metrics. Other specific differences not addressed in this manuscript may exist. However, the authors believe that researchers may confidently cross-compare results between the 2 strains, while taking into account the differences found within this study.

Fluoroscopy-induced radionecrosis.

Complications from radiation exposure during fluoroscopic guidance of cardiac catheterization may occur. With repeated procedures, the risk for cutaneous injuries increases. Herein, we describe a 59-year-old man with extensive coronary artery disease, who had undergone multiple revascularization procedures and developed a non-healing ulcer on his left inferior scapula. The patient's medical history, physical exam findings, and histopathology gave clues to a case of radiation-induced dermatitis and necrosis.