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.

Complete response of Merkel cell carcinoma with talimogene laherparepvec (TVEC) monotherapy.

Merkel cell carcinoma (MCC) is a rare neuroendocrine neoplasm, warranting surgical excision with sentinel lymph node biopsy. In later stages, adjuvant chemotherapy and radiation are required owing to its aggressive malignant behavior. We describe a 62-year-old woman who presented with multifocal recurrence of MCC and was not a candidate for immunotherapy or surgery. The patient underwent four treatments of intratumoral talimogene laherparepvec (TVEC) and demonstrated a complete response with no histologic evidence of remaining MCC on four scouting biopsies. Although TVEC therapy is currently approved for the treatment of advanced stage melanoma, it is still being investigated in MCC. This case supports the use of TVEC as monotherapy in select patients with locally advanced MCC who are not candidates for surgery or systemic immunotherapy.

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.

Repurposing Ophthalmologic Timolol for Dermatologic Use: Caveats and Historical Review of Adverse Events.

Ophthalmic timolol solution is increasingly being repurposed as a topical therapeutic for a variety of dermatologic diseases, including pyogenic granulomas, infantile hemangiomas, and chronic wounds. There are no published guidelines or protocols for use in these indications in adults, and the dermatologic community may not be familiar with adverse events that have been extensively documented relating to its ophthalmic use. We review the evidence available relating to adverse events to topical timolol use to evaluate its safety in dermatologic applications and to alert clinicians to screening and monitoring that is needed when repurposing this drug for dermatologic use. The majority of serious adverse events associated with ophthalmic timolol were reported in the first 7 years of use, between 1978 and 1985, of which most common were cardiovascular and respiratory events, but also included 32 deaths. The available evidence suggests that ophthalmic timolol safety profiling may have been incomplete prior to widespread use. Recent clinical trials for dermatologic indications have focused on documenting efficacy and have not had rigorous monitoring for potential adverse events. Topical timolol may be safe and effective for the treatment of various dermatologic conditions in patients whose medical histories have been carefully reviewed for evidence of pre-existing cardiac or pulmonary disease and are monitored for potential adverse events. Despite the wide use of timolol in ophthalmologic practice, safe dermatologic repurposing requires recognition of the potential for facilitated systemic absorption though the skin and appreciation of its history of adverse events.

Use of Topical Timolol Maleate as Re-Epithelialization Agent for Treatment of Recalcitrant Wounds of Varying Etiologies.

Background: Chronic wounds remain a challenge for the clinician and healthcare system. It is therefore vital for additional therapies that target steps involved in wound recalcitrance. Recently, topical timolol has shown promising results for use in wound healing. Objective: The goal of this study was to assess timolol's effectiveness in healing wounds of varying etiologies. Methods: This multi-center series took place from 2016¬­2019 at the wound healing centers at the University of Miami Health System and the Veterans Affairs Northern California Healthcare. We identified all wound patients who received treatment with topical timolol maleate 0.5% for at least 4 weeks after failing previous treatments. Timolol drops at a dose of 1 drop per cm2 of wound area were instilled with dressing changes twice a day, once a day, every other day, or continuous application. Once they began the study, they stopped all concurrent therapies aside from standard of care. Healing outcomes were classified into 3 categories: healed, defined as complete re-epithelialization of the wound and closure, improved, defined as decreasing wound size area (WSA), and worsening, defined as increasing WSA. Results: We identified 39 patients, 32 males and 7 females that had a total of 55 chronic wounds of varying etiologies. Thirty-four of the wounds had completely healed, 15 wounds improved in WSA, 4 wounds were unchanged in WSA, and 2 wounds worsened in WSA. Conclusions: In line with our previous experience, we found topical timolol to be a safe, cost-effective, and efficacious treatment for recalcitrant wounds of varying etiologies.

Beta-adrenergic antagonist for the healing of chronic diabetic foot ulcers: study protocol for a prospective, randomized, double-blinded, controlled and parallel-group study.

BACKGROUND: Diabetic foot ulcers (DFUs) are the most common cause of leg amputations and their management is extremely challenging. Despite many advances and expensive therapies, there has been little success in improving outcomes of DFUs. In prior work our laboratory has examined the effects of beta-adrenergic antagonists (ßAAs) on skin and skin-derived cells. We have shown that ßAAs enhance the rate of keratinocyte migration, promote angiogenesis, and hasten wound healing in scratch wounds in vitro, in animal wound models, and in anecdotally reported cases of chronic wounds that healed successfully after topical application of the ßAA timolol. Thus, we propose to test timolol directly on DFUs to determine if it improves healing above the current standard of care (SOC). This study will examine the efficacy and safety of topically applied beta-antagonist Timoptic-XE® (timolol maleate ophthalmic gel forming solution) in subjects with DFUs. METHODS/DESIGN: This is a phase two, randomized, double-blinded, controlled, and parallel-group clinical trial with two treatment arms, SOC plus topical Timoptic-XE® and SOC plus a non-biologically active gel (hydrogel, as placebo drug). Study subjects with a DFU will be selected from the Veterans Affairs Northern California Health Care System (VANCHCS). Study duration is up to 31 weeks, with three phases (screening phase for two weeks, active phase for up to 12 weeks, with an additional second consecutive confirmatory visit after 2 weeks, and follow-up phase comprising monthly visits for 4 months). Subjects will apply daily either the topical study drug or the placebo on the foot ulcer for 12 weeks or until healed, whichever comes first. Measurements of wound size and other data will be collected at baseline, followed by weekly visits for 12 weeks, and then a monthly follow-up period. DISCUSSION: This is a clinical translation study, moving the investigators' pre-clinical laboratory research into a translational study in which we will analyze clinical outcomes to assess for safety and estimate the efficacy of a topical beta-antagonist in healing of DFUs. The results from this trial may establish new treatment paradigms and safety profile for DFU treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03282981. Registered on June 14th, 2018.

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.

Dermal suture only versus layered closure: A randomized, split wound comparative effectiveness trial.

BACKGROUND: Layered closure of cutaneous wounds is a commonly used surgical practice. However, there are studies that suggest the additional layer of epidermal sutures might not be necessary. OBJECTIVE: To compare scar outcomes between the single-layer deep-dermal suture technique and the conventional layered suture technique for primary closure of cutaneous wounds. METHODS: A total of 49 patients were enrolled in a prospective, randomized, evaluator-blinded, split scar study to compare the conventional bilayered closure technique with the single-layer deep-dermal suturing technique for primary closure of wounds. The primary outcome measure was mean sum Patient and Observer Scar Assessment Scale (POSAS) score at 3 and 12 months. RESULTS: At the 3-month follow-up, there was a statistically significant difference in the mean total POSAS scores for both the blinded observer and patients, indicating a preference for the side with the standard layered closure. However, at the 12-month follow-up, this difference was lost, with the exception of scar color, which was significantly more noticeable on the wound side closed with only dermal sutures. LIMITATION: Single-center study. CONCLUSION: Three months after surgery, the layered closure technique resulted in a slightly better scar outcome than the single-layered closure containing only dermal sutures. At 12-months' follow-up, this difference diminished, with scars for both sides appearing similar.

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.