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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

A systematic review of low-level light therapy for treatment of diabetic foot ulcer.

Diabetes mellitus (DM) is a significant international health concern affecting more than 387 million individuals. A diabetic person has a 25% lifetime risk of developing a diabetic foot ulcer (DFU), leading to limb amputation in up to one in six DFU patients. Low-level light therapy (LLLT) uses low-power lasers or light-emitting diodes to alter cellular function and molecular pathways, and may be a promising treatment for DFU. The goal of this systematic review is to examine whether the clinical use of LLLT is effective in the healing of DFU at 12 and 20 weeks in comparison with the standard of care, and to provide evidence-based recommendation and future clinical guidelines for the treatment of DFU using LLLT. On September 30, 2015, we searched PubMed, EMBASE, CINAHL, and Web of Science databases using the following terms: "diabetic foot" AND "low level light therapy," OR "light emitting diode," OR "phototherapy," OR "laser." The relevant articles that met the following criteria were selected for inclusion: randomized control trials (RCTs) that investigated the use of LLLT for treatment of DFU. Four RCTs involving 131 participants were suitable for inclusion based upon our criteria. The clinical trials used sham irriadiation, low dose, or nontherapeutic LLLT as placebo or control in comparison to LLLT. The endpoints included ulcer size and time to complete healing with follow-up ranging from 2 to 16 weeks. Each article was assigned a level of evidence (LOE) and graded according to the Oxford Center for Evidence-based Medicine Levels of Evidence Grades of Recommendation criteria. Limitations of reviewed RCTs include a small sample size (N < 100), unclear allocation concealment, lack of screening phase to exclude rapid healers, unclear inclusion/exclusion criteria, short (<30 days) follow-up period, and unclear treatment settings (wavelength and treatment time). However, all reviewed RCTs demonstrated therapeutic outcomes with no adverse events using LLLT for treatment of DFU. This systematic review reports that LLLT has significant potential to become a portable, minimally invasive, easy-to-use, and cost effective modality for treatment of DFU. To enthusiastically recommend LLLT for treatment of DFU, additional studies with comparable laser parameters, screening period to exclude rapid healers, larger sample sizes and longer follow-up periods are required. We envision future stringent RCTs may validate LLLT for treatment of DFU. Systematic review registration number: PROSPERO CRD42015029825.

Low-level Light Therapy for Treatment of Diabetic Foot Ulcer: A Review of Clinical Experiences.

BACKGROUND: Diabetic foot ulcers (DFU) represent a significant complication of diabetes mellitus (DM). DFU affect one in four patients with DM and treatments of DFU are limited and challenging. The management of DFU remains a significant healthcare and socioeconomic burden ($245 billion). There is a wide range of advanced therapies for DFU, but these are costly and have demonstrated only minimal efficacy in limited published studies. An emerging treatment modality to improve DFU and optimize wound healing is the use of low-level light therapy (LLLT). LLLT involves the use of light in the form of low-level or low-power laser or light emitting diodes to alter biochemical pathways, which may result in changes to cell shape, cell migration, and cell signaling.
OBJECTIVE: To review published clinical experiences (case series and case reports) using LLLT for treatment of DFU, and provide evidence-based recommendations and future directions on the potential of LLLT as a therapeutic modality for DFU.
METHODS AND MATERIALS: On January 16, 2016 we searched the published literature using databases: PubMed, EMBASE, CINAHL, and Web of Science with key terms: "diabetic foot" AND ("low level laser therapy" OR "low level light therapy" OR "LLLT" OR "light emitting diode" OR "phototherapy" OR "laser").
RESULTS: After screening of titles, abstracts and/or full-text, 7 original articles were suitable in our review. Our review contains 5 case series and 2 case reports that evaluated LLLT for treatment of DFU, and all reviewed studies have shown positive improvement of DFU using LLLT with no adverse events, albeit with limitations that may be minimized with future RCTs.
CONCLUSIONS: LLLT is an emerging and promising treatment modality to current alternatives that are costly and have shown limited success. Based upon the published evidence, we envision additional research may allow for stronger recommendation with LLLT for treatment of DFU.

J Drugs Dermatol. 2016;15(7):843-848.

A Comparison of Vascularity, Bone Mineral Density Distribution, and Histomorphometrics in an Isogenic Versus an Outbred Murine Model of Mandibular Distraction Osteogenesis.

PURPOSE: The vascularity, bone mineral density distribution, and histomorphometric data between the inbred, isogenic Lewis rat and the outbred, nonisogenic Sprague Dawley rat within mandibular distraction osteogenesis (MDO) were evaluated to allow future researchers to compare the results generated from these 2 animals. We hypothesized that little difference would be found between the 2 strains within these metrics. MATERIALS AND METHODS: We implemented a comparative study between the Lewis and Sprague Dawley rat strains within MDO. The sample was composed of 17 male Lewis and 17 male Sprague Dawley rats that underwent surgical external fixation and distraction. The rats' hemimandibles were distracted to a total distance of 5.1 mm. After 28 days of consolidation, 9 rats from each group underwent bone mineral density distribution analysis. The remaining rats from each group were analyzed for the vascular and histologic metrics. Descriptive and bivariate statistics were computed, and the P value was set at .05. RESULTS: We demonstrated successful MDO in all the rats, with no significant difference found in the histologic or bone mineral density distribution metrics. No significant differences were found in any of the vascular metrics, with the exception of vascular separation, which was not normalized to the mandibular volume (P = .048). CONCLUSIONS: The results of the present study have demonstrated that little dissimilarity exists between the isogenic Lewis and outbred Sprague Dawley models of MDO. Thus, researchers can confidently compare the gross results between the 2 strains, with consideration of the very small differences between the 2 models. For studies that require an isogenic strain, the Lewis rat is an apt surrogate for the Sprague Dawley strain.

Amifostine Treatment Mitigates the Damaging Effects of Radiation on Distraction Osteogenesis in the Murine Mandible.

According to the American Society of Clinical Oncology, in 2012, more than 53,000 new cases of head and neck cancers (HNCs) were reported in the United States alone and nearly 12,000 deaths occurred relating to HNC. Although radiotherapy (XRT) has increased survival, the adverse effects can be unrelenting and their management is rarely remedial. Current treatment dictates surgical mandibular reconstruction using free tissue transfer. These complex operations entail extended hospitalizations and attendant complications often lead to delays in initiation of adjuvant therapy, jeopardizing prognosis as well as quality of life. The creation of new bone by distraction osteogenesis (DO) generates a replacement of deficient tissue from local substrate and could have immense potential therapeutic ramifications. Radiotherapy drastically impairs bone healing, precluding its use as a reconstructive method for HNC. We posit that the deleterious effects of XRT on bone formation could be pharmacologically mitigated. To test this hypothesis, we used a rodent model of DO and treated with amifostine, a radioprotectant, to assuage the XRT-induced injury on new bone formation. Amifostine had a profound salutary effect on bone regeneration, allowing the successful implementation of DO as a reconstructive technique. The optimization of bone regeneration in the irradiated mandible has immense potential for translation from the bench to the bedside, providing improved therapeutic options for patients subjected to XRT.

Fluoroscopy induced chronic radiation dermatitis should be included in the differential diagnosis of notalgia paresthetica.

We report a patient with radiation (fluoroscopic)-induced dermatitis that produced symptoms similar to notalgia paresthetica.

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.

Raman spectroscopy delineates radiation-induced injury and partial rescue by amifostine in bone: a murine mandibular model.

Despite its therapeutic role in head and neck cancer, radiation administration degrades the biomechanical properties of bone and can lead to pathologic fracture and osteoradionecrosis. Our laboratories have previously demonstrated that prophylactic amifostine administration preserves the biomechanical properties of irradiated bone and that Raman spectroscopy accurately evaluates bone composition ex vivo. As such, we hypothesize that Raman spectroscopy can offer insight into the temporal and mechanical effects of both irradiation and amifostine administration on bone to potentially predict and even prevent radiation-induced injury. Male Sprague-Dawley rats (350-400 g) were randomized into control, radiation exposure (XRT), and amifostine pre-treatment/radiation exposure groups (AMF-XRT). Irradiated animals received fractionated 70 Gy radiation to the left hemi-mandible, while AMF-XRT animals received amifostine just prior to radiation. Hemi-mandibles were harvested at 18 weeks after radiation, analyzed via Raman spectroscopy, and compared with specimens previously harvested at 8 weeks after radiation. Mineral (ρ958) and collagen (ρ1665) depolarization ratios were significantly lower in XRT specimens than in AMF-XRT and control specimens at both 8 and 18 weeks. amifostine administration resulted in a full return of mineral and collagen depolarization ratios to normal levels at 18 weeks. Raman spectroscopy demonstrates radiation-induced damage to the chemical composition and ultrastructure of bone while amifostine prophylaxis results in a recovery towards normal, native mineral and collagen composition and orientation. These findings have the potential to impact on clinical evaluations and interventions by preventing or detecting radiation-induced injury in patients requiring radiotherapy as part of a treatment regimen.