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Treatment-resistant actinic keratosis (AK) is of concern in clinical practice, often requiring retreatment. Microvascular assessments might help differentiate treatment-resistant from treatment-responsive AKs, enabling targeted treatment. Using dynamic optical coherence tomography, AK vascularization was investigated following daylight photodynamic therapy, comparing treatment-resistant with cleared AKs. AKs on face/scalp were graded according to the Olsen Classification Scheme and scanned with dynamic optical coherence tomography pre-treatment, and 3- and 12-months post-treatment. Employing dynamic optical coherence tomography, total vessel length, mean vessel length, mean vessel diameter, vessel area density, and branchpoint density were quantified. Thirty-eight patients with 62 AKs were enrolled, including 37 AK I, 18 AK II, and 7 AK III. Treatment-resistant AKs displayed a trend toward intensified vascularization compared with cleared AK at baseline (AKs I, II), suggested by higher total vessel length (median 144.0, IQR 104.3-186.6) and vessel area density (median 27.7, IQR 18.4-34.2) than in cleared AK (median 120.9, IQR 86.9-143.0 and median 22.9, IQR 17.3-26.8). Additionally, vascularization in treatment-resistant AK I-II appeared disorganized, with trends toward shorter mean vessel length (median 151.0, IQR 138.5-167.5) and increased branchpoint density (median 3.2, IQR 2.3-3.8) compared with cleared AK (median 160.0, IQR 152.0-169.3 and median 2.6, IQR 2.2-3.0). These findings suggest that dynamic optical coherence tomography holds potential to identify treatment-resistant AKs.

Keratinocyte-derived skin cancers comprise basal cell carcinoma, squamous cell carcinoma, its precursor actinic keratosis, and Bowen's disease. Historically, this group of neoplasms has been subsumed under the term non-melanoma skin cancer. However, the term non-melanoma skin cancer can be misleading and lacks precision. Therefore, more precise and reasonable terminology, valuing the relevance of keratinocyte-derived cancer, appears pertinent to meet its clinical and scientific significance. A group of experienced dermato-oncologists initiated a consensus approach to promote the use of the term "keratinocyte cancer" instead of "non-melanoma skin cancer" when referring to carcinomas and their precursors that are derived from keratinocytes. The vote among members of the consensus group indicated unanimous agreement on the consistent use of the term "keratinocyte cancer" instead of "non-melanoma skin cancer". International delegates also voted in favour of the revised terminology. The more precise and, by means of etiopathogenesis, correct term "keratinocyte cancer" should be consistently used for malignancies originated from keratinocytes. This is expected to have a positive impact on patient-physician communication and gives better justice to this important group of keratinocyte-derived cancers.

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.

Actinic keratoses are pre-malignant skin lesions that require personalized care, a lack of which may result in poor treatment adherence and suboptimal outcomes. Current guidance on personalizing care is limited, notably in terms of tailoring treatment to individual patient priorities and goals and supporting shared decision-making between healthcare professionals and patients. The aim of the Personalizing Actinic Keratosis Treatment panel, comprised of 12 dermatologists, was to identify current unmet needs in care and, using a modified Delphi approach, develop recommendations to support personalized, long-term management of actinic keratoses lesions. Panellists generated recommendations by voting on consensus statements. Voting was blinded and consensus was defined as ≥ 75% voting 'agree' or 'strongly agree'. Statements that reached consensus were used to develop a clinical tool, of which, the goal was to improve understanding of disease chronicity, and the need for long-term, repeated treatment cycles. The tool highlights key decision stages across the patient journey and captures the panellist's ratings of treatment options for attributes prioritized by patients. The expert recommendations and the clinical tool can be used to facilitate patient-centric management of actinic keratoses in daily practice, encompassing patient priorities and goals to set realistic treatment expectations and improve care outcomes.

Rapid diagnosis of suspicious pigmented skin lesions is imperative; however, current bedside skin imaging technologies are either limited in penetration depth or resolution. Combining imaging methods is therefore highly relevant for skin cancer diagnostics. This pilot study evaluated the ability of optical coherence tomography, reflectance confocal microscopy, photo-acoustic imaging and high-frequency ultrasound to differentiate malignant from benign pigmented skin lesions. A total of 41 pigmented skin tumours were scanned prior to excision. Morphological features and blood vessel characteristics were analysed with reflectance confocal microscopy, optical coherence tomography, high-frequency ultrasound and photoacoustic imaging images, and the diagnostic accuracy was assessed. Three novel photoacoustic imaging features, 7 reflectance confocal microscopy features, and 2 optical coherence tomography features were detected that had a high correlation with malignancy; diagnostic accuracy > 71%. No significant features were found in high-frequency ultrasound. In conclusion, optical coherence tomography, reflectance confocal microscopy and photoacoustic imaging in combination enable image-guided bedside evaluation of suspicious pigmented skin tumours. Combining these advanced techniques may enable more efficient diagnosis of skin cancer.

Pain is the main acute adverse event during photodynamic therapy of skin lesions. The objective of this randomized study was to evaluate the pain-relieving effect of pauses and cooling during illumination. Twenty-four patients with actinic keratoses were treated with photodynamic therapy in two symmetrical areas and cooled with either cold-water-spray or cold-water-pack (CoolPack). Treatment areas were cooled during either the first or second period of illumination, which were separated by a 3-min pause in illumination. Pain intensity was scored from 0 to 10. Water-spray reduced the mean pain score by 1.2 points (p=0.030) and CoolPack by 1.3 points (p=0.007) during the first half of the illumination. Pain intensity decreased during the pause by 3.7 points in water-spray patients (p<0.0001) and 3.0 points in CoolPack patients (p<0.0001). In conclusion, cooling resulted in a minor reduction in pain intensity, while adding the intermediate pause in illumination reduced the pain considerably. Use of pauses and cooling during illumination is an easy and inexpensive way to make photodynamic therapy more tolerable for the patient.

The aim of this study was to examine the effect of ultraviolet (UV) irradiation on human cutaneous cicatrices. In this randomized, controlled study, dermal punch biopsy wounds served as a wound healing model. Wounds healed by primary or second intention and were randomized to postoperative solar UV irradiation or to no UV exposure. Evaluations after 5 and 12 weeks included blinded clinical assessments, skin reflectance measurements, histology, immunohistochemistry, and biochemical analyses of the N-terminal propeptide from procollagen-1, hydroxyproline, hydroxylysine, and proline. Twelve weeks postoperatively, UV-irradiated cicatrices healing by second intention: (i) were significantly pointed out as the most disfiguring; (ii) obtained significantly higher scores of colour, infiltration and cicatrix area; and (iii) showed significantly higher increase in skin-reflectance measurements of skin-pigmentation vs. non-irradiated cicatrices. No histological, immunohistochemical or biochemical differences were found. In conclusion, postoperative UV exposure aggravates the clinical appearance of cicatrices in humans.

Onychomycosis among diabetic patients has been reported in some studies to be of high prevalence. This study aimed to investigate the prevalence of onychomycosis among diabetic patients at a Danish University Hospital. Clinical and mycological examinations were performed on type 1 and 2 diabetic patients from in- and out-patient clinics. A total of 271 patients were enrolled, 72% males, mean age 61.3 years, 26% of the patients had diabetes type 1. The prevalence of toe nail onychomycosis (positive culture and/or microscopy) was 22% (n = 59) of which 55 cases were caused by dermatophytes (93%) and 4 cases by yeasts (7%). A correlation was found between onychomycosis and age (p =0.02) and severity of nail changes (p <0.001), respectively. However, no significant correlation was found to gender, type of diabetes, lower extremity arterial disease, neuropathy, toe amputation or oedema. Onychomycosis occurred with a high prevalence in diabetic patients, especially among older patients and those with severe nail changes.

There is a demand for pain relief during photodynamic therapy. We therefore investigated the efficacy and side-effects of topical morphine gel 0.3% for pain relief during topical photodynamic therapy in a randomized, double-blind, placebo-controlled study. The study involved 28 patients with actinic keratoses or basal cell carcinomas. Each patient was treated with photodynamic therapy after superficial curettage of 2 treatment areas that were randomized to morphine gel or placebo gel. The gels were applied 15 min before illumination. Pain was assessed pre-illumination, during, and immediately after illumination, using a numeric rating scale. Skin redness was determined by reflectance spectrophotometry and the size of the treated area by protoporphyrin IX fluorescence. There were no differences between the areas according to accumulation of protoporphyrin IX (p =0.34), size of fluorescence areas (p =0.84), or skin redness (p =0.95). There was no significant pain relief of topical morphine gel compared with placebo gel (p >0.23). This negative result suggests that opioid receptors may not be involved in the pain induced by photodynamic therapy.

Onychomycosis among psoriasis patients is reported with varying prevalence. This prospective, controlled study investigates the occurrence of onychomycosis among inpatients with psoriasis versus inpatients with other skin diseases. The inclusion period was 15 months. Scrapings from clinically abnormal nails (both fingernails and toenails) were examined using microscopy and culture. The prevalence of onychomycosis in patients with psoriasis was 17/79 = 21.5% compared to 18/142 = 12.7% for patients with other skin diseases (p = 0.13). In 17 mycologically positive psoriasis patients, dermatophytes, yeasts and moulds were isolated in 8, 10 and 4 cases, respectively, and in 18 mycologically positive patients with other skin diseases in 12, 7 and 5, respectively. Onychomycosis occurred more frequently in men than in women (psoriasis patients (p = 0.02), patients with other skin diseases (p = 0.03)). Psoriasis patients had a higher frequency of abnormal nails (82.3%) compared to patients with other skin diseases (37.3%) (p < 0.01) and more severe affection of their toenails than patients with other skin diseases (p < 0.01). It is concluded that the frequency of onychomycosis among inpatients with psoriasis compared to inpatients with other skin diseases is not significantly different.

Promising clinical results have been obtained with the normal mode ruby laser for removal of unwanted hair. Melanin within the hair follicles is thought to act as target for the ruby laser pulses, whereas epidermal melanin is thought to be a competitive chromophore, responsible for potential side effects. This study aimed (i) to objectify postoperative changes in skin pigmentation and texture and (ii) to evaluate the importance of variations in preoperative skin pigmentation for the development of side effects 12 weeks after 1 treatment with the normal-mode ruby laser. A total of 17 volunteers (skin types I-IV) were laser-treated in the hairy pubic region (n = 51 test areas). A shaved test area served as control. Skin reflectance spectroscopical measurements, 3-dimensional surface contour analysis and ultrasonography objectified postoperative changes in skin pigmentation and texture. Blinded clinical assessments revealed postoperative hyperpigmentation (2% of test areas) and hypopigmentation (10%), whereas no textural changes were seen. Reflectance spectroscopically-determined pigmentary changes depended on the degree of preoperative skin pigmentation, fairly pigmented skin types experiencing subclinical hyperpigmentation and darkly pigmented skin types experiencing subclinical hypopigmentation. Three-dimensional surface profilometry documented similar pre- and postoperative surface contour parameters, indicating that the skin surface texture is preserved after laser exposure. Ultrasonography revealed similar skin thicknesses in laser-exposed and untreated control areas. It is concluded that normal-mode ruby laser treatment is safe for hair removal in skin types I-IV.

The pulsed dye laser is the treatment of choice for port-wine stains. In this study we evaluate the importance of preoperative skin pigmentation and skin redness for the development of side effects from one treatment with the pulsed dye laser. A risk assessment is performed and skin reflectance measurement objectifies postoperative pigmentary changes. Fourteen human volunteers (skin types I to V) were laser-treated on the inside of the proximal brachium. Photographic documentation was used for blinded, clinical evaluation of side effects 3 and 6 months postoperatively. Skin was artificially reddened using topical application of 10% nicotinic acid cream. The development of pigmentary alterations and texture changes depended on the preoperative pigmentation and redness degrees. The risk of inducing clinically visible pigmentary alterations and texture changes increased with higher preoperative skin pigmentation and redness degrees, and with the application of increasing laser doses. Pigmentary alterations were induced at a lower fluence level than texture changes. The risk of side effects was higher 3 months postoperatively than 6 months postoperatively, substantiating a gradual disappearance of side effects. Skin reflectance measurements documented postoperative hyperpigmentation that faded partially from 3 to 6 months postoperatively. This is the first human experimental model for port-wine stains which provides quantitative data on the relationship between preoperative skin colours and postoperative clinically disturbing side effects.