An Explorative Study on Calcium Electroporation for Low-risk Basal Cell Carcinoma.

In electrochemotherapy, permeabilization of the cell membrane by electric pulses increases the anti-tumour effect of chemotherapeutics. In calcium electroporation, chemotherapy is replaced by calcium chloride with obvious benefits. This study explores the effect and underlying mechanisms of calcium electroporation on basal cell carcinomas using either high- or low-frequency electroporation. Low-risk primary basal cell carcinomas were treated in local anaesthesia with intratumoral calcium chloride followed by electroporation with high (167 kHz) or low (5 kHz) frequencies. Non-complete responders were retreated after 3 months. The primary endpoint was tumour response 3 months after last calcium electroporation. Plasma membrane calcium ATPase was examined in various cell lines as plasma membrane calcium ATPase levels have been associated with calcium electroporation efficacy. Twenty-two out of 25 included patients complete the study and 7 of these (32%) achieved complete response at 3 months with no difference in efficacy between high- and low-frequency pulses. High-frequency calcium electroporation was significantly less painful (p=0.03). Plasma membrane calcium ATPase was increased 16-32-fold in basal cell carcinoma cell lines compared with 4 other cancer cell lines. Calcium electroporation for low-risk basal cell carcinomas does not fulfil the requirements of a new dermatological basal cell carcinoma treatment but may be useful as adjuvant treatment to surgery in more advanced basal cell carcinomas. The elevated PMCA levels in basal cell carcinomas may contribute to low efficacy.

Dermatologic Scar Assessment With Stereoscopic Imaging and Digital Three-Dimensional Models: A Validation Study.

BACKGROUND AND OBJECTIVE: We evaluated a new handheld stereoscopic imaging system capable of visualizing scars with digital three-dimensional (3D) models and providing automated morphometric estimates. The objective was to validate the repeatability and accuracy of intra- and inter-investigator scan results. STUDY DESIGN/MATERIALS AND METHODS: Engineered metal plates with depressed and elevated model scars (n = 72) were scanned six times by one investigator. In vivo hypertrophic and atrophic scars (n = 15) were scanned once by three investigators. The repeatability of morphometric estimates was assessed using coefficients of variation (CVs) to compare the variation among multiple scan results for both models and in vivo scars, with 0% reflecting a perfect match. Scar estimates from digital 3D reconstructions were compared with the known dimensions of physical model scars and with ruler measurements of in vivo scars. RESULTS: A total of 48 model scars and 12 in vivo scars were eligible for automated analyses with the imaging system's proprietary software. Intra-investigator scan results for the model scars were repeatable, with low variance for all parameters: volume, area, length, and depth/height (CV: 1.8-3.1%). By comparison, inter-investigator scans of real in vivo scars resulted in slightly higher median CVs (4.4-7.3%; P < 0.05). 3D model scar estimates correlated well with the known physical dimensions of model scars for all parameters (P < 0.001) and accurately reflected the measurements of in vivo scars (P < 0.001). The six in vivo scars situated on the chest and abdomen showed the highest inter-investigator variation, due to respiratory movement artifacts. CONCLUSION: Stereoscopic imaging of scars generates accurate and repeatable measurement estimates that show little intra- and inter-investigator-based assessment variation. The best results are achieved by minimizing subject movement. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

In Vivo Reflectance Confocal Microscopy of Gold Microparticles Deposited in the Skin. A Case Report on Cutaneous Chrysiasis.

Cutaneous chrysiasis is gold deposition in the dermis, described after parenteral administration of gold salts or after topical exposure to gold-containing materials. Gold microparticles (GMPs) have versatile therapeutic effects and are increasingly used in medicine. This case report describes the development of a blue-gray macule following the facial application of GMPs and laser treatment of acne vulgaris. Dermoscopy showed a nonspecific homogenous blue-gray pattern, gradually fading over an 8-month-period. Reflectance confocal microscopy (RCM) detected hyperreflective, subcellular particles in the papillary dermis, localized around hair follicles, eccrine glands, and inside macrophages. Histopathological evaluation, darkfield illumination with hyperspectral imaging, and neutron activation analysis confirmed the presence of GMPs in the dermis. RCM allowed non-invasive fast visualization of aggregates of hyperreflective particles in the dermis and can potentially be used for monitoring localized cutaneous chrysiasis and other metal deposition conditions over time. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Transfollicular delivery of gold microparticles in healthy skin and acne vulgaris, assessed by in vivo reflectance confocal microscopy and optical coherence tomography.

INTRODUCTION: Topical application of gold microparticles (GMPs) for selective photothermolysis is a recently FDA-cleared therapy for acne vulgaris. Current evidence indicates the potential of optical imaging to non-invasively visualize GMPs and describe photothermal tissue effects. OBJECTIVES: To qualitatively and quantitatively describe GMP delivery in vivo and visualize laser-mediated thermal effects of GMPs in facial skin of acne patients and healthy participants, using reflectance confocal microscopy (RCM) and optical coherence tomography (OCT). METHODS: Patients with facial acne (n = 14), and healthy participants (n = 7) were included. RCM and OCT images were acquired at baseline, after GMP application, and after diode laser exposure. All images were evaluated qualitatively and quantitatively with regards to GMP delivery in skin layers and morphological thermal effects. Lastly, skin biopsies were obtained to compare RCM and OCT findings to histology. RESULTS: GMPs were delivered equally in healthy participants and acne patients, and in lesional and non-lesional acne skin. In RCM images, GMPs appeared as hyperreflective aggregates inside hair follicles and eccrine ducts, corresponding to natural skin openings (NSOs). The fraction of NSOs with hyperreflective content increased significantly after GMP application compared to baseline (50-75% increase, P = 8.88 × 10-16 ). Similarly, in OCT images, GMPs appeared as hyperreflective columns inside hair follicles and were not detected in surrounding skin. GMPs reached a maximum depth of 920 µm (median 300 µm). After laser exposure, RCM and histology revealed selective perifollicular tissue changes around NSOs. CONCLUSION: Optical imaging visualizes GMP delivery and thermal tissue response following laser exposure and enables bedside monitoring of transfollicular microparticle delivery. Lasers Surg. Med. 51:430-438, 2019. © 2019 Wiley Periodicals, Inc.

Microneedle fractional radiofrequency-induced micropores evaluated by in vivo reflectance confocal microscopy, optical coherence tomography, and histology.

BACKGROUND: Microneedle fractional radiofrequency (MNRF) is a minimally invasive technique that delivers radiofrequency (RF) energy into the skin via microneedles. Reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) enable the characterization of device-tissue interactions in in vivo skin. The aim of this study is to describe MNRF-induced micropores using RCM and OCT imaging. MATERIALS AND METHODS: Five healthy participants were treated with a 7 × 7 array of 1500 µm microneedles on two adjacent areas of the right hip. One area received MNRF using high RF energy while the other underwent MNRF at low RF energy. Micropore morphology was evaluated qualitatively and quantitatively with RCM and OCT. To relate imaging with histology, one participant underwent punch biopsy in both areas. RESULTS: Reflectance confocal microscopy visualized shape, content, and thermal-induced coagulation zone (CZ) of MNRF micropores. At high RF energy, micropores showed concentric shape, contained hyperreflective granules, and coagulated tissue from epidermis to dermo-epidermal junction (diameter 63-85 µm). Micropores at low RF energy, presented with a stellate shape, no content and CZs that were visible only in epidermis (CZ thickness 9 µm, IQR 8-21 µm). Evaluating OCT, high RF energy showed deeper (150 µm), more easily identifiable micropores compared to low RF energy micropores (70 µm). Histology showed tissue coagulation to a depth of 1500 µm at high RF energy, while at low RF energy, disruption was only visible in epidermis. CONCLUSION: Microneedle fractional radiofrequency micropores show distinct characteristics in both RCM and OCT, depending on RF energy. These in vivo imaging modalities are complementary and allow combined, qualitative, and quantitative evaluation.

Acne vulgaris severity graded by in vivo reflectance confocal microscopy and optical coherence tomography.

INTRODUCTION: Acne is an inflammatory disease of the pilosebaceous unit, which can be investigated in vivo using reflectance confocal microscopy (RCM) and optical coherence tomography (OCT). OBJECTIVES: By means of RCM and OCT to identify morphological characteristics of acne that may be associated with clinical acne severity. METHODS: Patients with mild to moderate facial acne (n = 14, Investigators Global Assessment scale, IGA 1-3), and healthy participants (n = 7, IGA 0) were included in this explorative study. A total of 108 RCM image blocks and 54 OCT scans (each RCM and OCT image measuring 6 × 6 mm) were captured from lesional-, perilesional, and lesion-free skin areas. Acne lesions, infundibular regions of follicles and inflammation degree were compared in acne patients and healthy participants. RESULTS: Combined use of RCM and OCT demonstrated infundibular morphology, acne lesions, and blood flow. RCM images of perilesional- and lesion-free skin in acne patients revealed follicle infundibula with hyperkeratinized borders and abundant keratin plugs, contrasting skin of healthy participants. Higher acne severity related to increased number of follicles with hyperkeratotic borders (P = 0.04) and keratin plugs (P = 0.006), increased infundibulum diameter (P < 0.001), increased density of inflammatory cells (P < 0.001), and blood flow (P = 0.03). Acne lesion morphology was not associated with acne severity. CONCLUSION: Combined use of RCM and OCT elucidated distinctive follicle infundibulum characteristics and inflammation degree that were associated with acne severity. Future trials may apply imaging techniques to support clinical acne grading, and monitor treatment efficacy. Lasers Surg. Med. 51:104-113, 2019. © 2018 Wiley Periodicals, Inc.