Dynamic optical coherence tomography unveils subclinical, vascular differences across actinic keratosis grades I-III.

Actinic keratosis (AK) classification relies on clinical characteristics limited to the skin's surface. Incorporating sub-surface evaluation may improve the link between clinical classification and the underlying pathology. We aimed to apply dynamic optical coherence tomography (D-OCT) to characterize microvessels in AK I-III and photodamaged (PD) skin, thereby exploring its utility in enhancing clinical and dermatoscopic AK evaluation. This explorative study assessed AK I-III and PD on face or scalp. AK were graded according to the Olsen scheme before assessment with dermatoscopy and D-OCT. On D-OCT, vessel shapes, -pattern and -direction were qualitatively evaluated at predefined depths, while density and diameter were quantified. D-OCT's ability to differentiate between AK grades was compared with dermatoscopy. Forty-seven patients with AK I-III (n = 207) and PD (n = 87) were included. Qualitative D-OCT evaluation revealed vascular differences between AK grades and PD, particularly at a depth of 300 µm. The arrangement of vessel shapes around follicles differentiated AK II from PD (OR = 4.75, p < 0.001). Vessel patterns varied among AK grades and PD, showing structured patterns in AK I and PD, non-specific in AK II (OR = 2.16,p = 0.03) and mottled in AK III (OR = 29.94, p < 0.001). Vessel direction changed in AK II-III, with central vessel accentuation and radiating vessels appearing most frequently in AK III. Quantified vessel density was higher in AK I-II than PD (p ≤ 0.025), whereas diameter remained constant. D-OCT combined with dermatoscopy enabled precise differentiation of AK III versus AK I (AUC = 0.908) and II (AUC = 0.833). The qualitative and quantitative evaluation of vessels on D-OCT consistently showed increased vascularization and vessel disorganization in AK lesions of higher grades.

Vascular feature identification in actinic keratosis grades I-III using dynamic optical coherence tomography with automated, quantitative analysis.

Clinical grading of actinic keratosis (AK) is based on skin surface features, while subclinical alterations are not taken into consideration. Dynamic optical coherence tomography (D-OCT) enables quantification of the skin´s vasculature, potentially helpful to improve the link between clinical and subclinical features. We aimed to compare microvascular characteristics across AK grades using D-OCT with automated vascular analysis. This explorative study examined AK and photodamaged skin (PD) on the face or scalp. AKs were clinically graded according to the Olsen Classification scheme before D-OCT assessment. Using an open-source software tool, the OCT angiographic analyzer (OCTAVA), we quantified vascular network features, including total and mean vessel length, mean vessel diameter, vessel area density (VAD), branchpoint density (BD), and mean tortuosity from enface maximum intensity projection images. Additionally, we performed subregional analyses on selected scans to overcome challenges associated with imaging through hyperkeratosis (each lesion group; n = 18). Our study included 45 patients with a total of 205 AKs; 93 grade I lesions, 65 grade II, 47 grade III and 89 areas with PD skin. We found that all AK grades were more extensively vascularized relative to PD, as shown by greater total vessel length and VAD (p ≤ 0.009). Moreover, AKs displayed a disorganized vascular network, with higher BD in AK I-II (p < 0.001), and mean tortuosity in AK II-III (p ≤ 0.001) than in PD. Vascularization also increased with AK grade, showing significantly greater total vessel length in AK III than AK I (p = 0.029). Microvascular quantification of AK unveiled subclinical, quantitative differences among AK grades I-III and PD skin. D-OCT-based microvascular assessment may serve as a supplement to clinical AK grading, potentially raising perspectives to improve management strategies.

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.

A one-time pneumatic jet-injection of 5-fluorouracil and triamcinolone acetonide for treatment of hypertrophic scars-A blinded randomized controlled trial.

BACKGROUND: Patients with hypertrophic scars (HTS) risk reduced quality of life due to itching, pain, poor cosmesis, and restriction of movement. Despite good clinical efficacy, patients are often reluctant to undergo repeated needle injections due to pain or needle phobia. OBJECTIVES: To evaluate the applicability of needle-free pneumatic jet injection (PJI) and assess changes in hypertrophic scars following a single PJI treatment with 5-fluorouracil (5-FU) and triamcinolone acetonide (TAC). METHODS: Twenty patients completed this blinded, randomized, controlled, split-scar trial. The intervention side of the HTS received a one-time treatment with PJIs containing a mixture of TAC + 5-FU injected at 5 mm intervals (mean 7 PJI per HTS); the control side received no treatment. Assessments were made at baseline and 4 weeks posttreatment. Outcome measures included change in (1) Vancouver Scar Scale (VSS) total score and subscores, (2) scar volume and surface area assessed by three-dimensional imaging, (3) skin microarchitecture measured by optical-coherence tomography (OCT), (4) photo-assessed scar cosmesis (0-100), (5) patient-reported pain and satisfaction (0-10), and (6) depiction of drug biodistribution after PJI. RESULTS: PJI with TAC + 5-FU significantly decreased both HTS height (-1 VSS; p = 0.01) and pliability (-1 VSS; p < 0.01) with a nonstatistically significant reduction of -1 in total VSS score (0 in control; p = 0.09). On 3D imaging, a 33% decrease in scar volume (p = 0.016) and a 37% decrease in surface area (p = 0.008) was observed. OCT indicated trends towards smoother scar surface (Ra 11.1-10.3; p = 0.61), normalized dermal microarchitecture (attenuation coefficient: 1.52-1.68; p = 0.44), and a reduction in blood flow between 9% and 17% (p = 0.50-0.79). Despite advances in VSS subscores and OCT, no improved photo-assessed cosmesis was found (-3.2 treatment vs. -1.4 control; p = 0.265). Patient-reported pain was low (2/10) and 90% of the patients that had previously received needle injections preferred PJI to needle injection. Depositions of TAC + FU were imaged reaching deep into the scar at levels corresponding to the reticular dermis. CONCLUSION: A single PJI injection containing 5-FU and TAC can significantly improve the height and pliability of HTS. PJI is favored by the patients and may serve as a complement to conventional needle injections, especially for patients with needle phobia.

Use of 5-Aminolevulinic Acid and Daylight Photodynamic Therapy for the Treatment of Actinic Keratoses.

BACKGROUND: Photodynamic therapy (PDT) is an effective modality for the treatment of actinic keratoses (AKs). The use of methyl aminolevulinate with daylight PDT (D-PDT) has quickly gained popularity internationally because of its tolerability and high levels of safety and efficacy. However, there is a paucity of studies on the use of D-PDT with 5-aminolevulinic acid (ALA). OBJECTIVE: To study the safety and efficacy of D-PDT in treating AKs on the face and scalp using ALA. MATERIALS AND METHODS: Thirty patients were recruited for this prospective, uncontrolled study. Patients were treated with topical ALA on either the scalp or face, incubated for 30 minutes, and then sat at home in a shady area for 2 hours. Weather conditions, lux measurements, and AK counts at 3 and 6 months were measured. RESULTS: Daylight PDT led to a median of 75% reduction in AK count at 6 months, with no significant adverse effects. Ninety-six percentage of patients were either moderately or very satisfied with the treatment, and the median peak pain score during treatment was 1. There was no correlation between weather or average lux received during treatment and 6-month outcomes. CONCLUSION: Daylight PDT with ALA is a safe and effective treatment modality for AKs on the head.

Pretreatment with 5-Fluorouracil Cream Enhances the Efficacy of Daylight-mediated Photodynamic Therapy for Actinic Keratosis.

The efficacy of photodynamic therapy (PDT) with methyl aminolevulinate is reduced when treating actinic keratosis (AK) on the extremities in comparison with the face and scalp. Studies indicate that PDT efficacy can be improved by combining PDT with other treatment modalities. This randomized intra-individual study investigated whether pretreatment with topical 5% 5-fluorouracil (5-FU) enhanced the treatment efficacy of daylight-mediated PDT in 24 patients with AKs on the hands. One hand of each patient was given 7 days of pretreatment with 5-FU twice daily before daylight-PDT, whereas the other hand was treated with daylight-PDT alone. At 3-month follow-up the overall lesion response rate was significantly higher for the combination of 5-FU and daylight-PDT (62.7%) than for daylight-PDT alone (51.8%) (p = 0.001). Furthermore, pain and erythema in relation to treatment were similar in the 2 groups (p = 1.0 and p = 0.2, respectively). Combination therapy is a safe and effective method to improve daylight-PDT for acral AKs.

Is the thin layer of methyl aminolevulinate used during photodynamic therapy sufficient?

BACKGROUND: If the recommended 1.0 mm layer of methyl aminolevulinate (MAL) is used during photodynamic therapy (PDT) of large areas with multiple actinic keratoses (AK) huge amounts of cream are needed. OBJECTIVES: To report the amount of MAL used for PDT of AK and basal cell carcinomas (BCC) in daily routine. The association of protoporphyrin IX (PpIX) fluorescence and thickness of MAL was investigated in a randomized paired study in healthy volunteers. METHODS: Amount of cream used per cm(2) during conventional and daylight PDT was recorded. In 16 healthy volunteers, 0.1 mm, 0.2 mm, 0.5 mm and 1.0 mm MAL cream were applied for 3 h on tape-stripped areas on each forearm randomized to light-permeable or light-impermeable occlusion. PpIX fluorescence was measured. RESULTS: Less than 0.4 mm MAL was used during PDT of BCC and 0.2 mm for AK. No difference in PpIX fluorescence was found between the different thicknesses of MAL using light-impermeable occlusion. CONCLUSION: In daily routine <0.4 mm MAL was used during PDT of BCC and 0.1-0.2 mm MAL during PDT of AK. The recommended 1.0 mm MAL did not result in a higher accumulation of PpIX compared to thinner MAL layers after light-impermeable occlusion for 3 h.

Skin pigmentation kinetics after exposure to ultraviolet A.

Multiple exposures to ultraviolet radiation (UVR) are the norm in nature and phototherapy. However, studies of the kinetics of pigmentation following UVA exposure have included only fair-skinned persons. The aim of this study was to investigate steady-state pigmentation and fading in 12 Scandinavians and 12 Indians/Pakistanis after 6 and 12 exposures on the back using broadband UVA and UVA1 with equal sub-minimal melanogenic doses (individually predetermined). Pigmentation was measured by skin reflectance at 555 and 660 nm. The UV dose to minimal pigmentation was higher in dark-skinned persons after a single broadband UVA exposure, but independent of pigmentation/skin type after single and multiple UVA1 exposures. To elicit minimal melanogenic doses after 6 and 12 exposures, every dose is lowered by a factor of 2 and 3, respectively, but the cumulative dose increases three- and four-fold, respectively. The absolute increase in pigmentation was independent of pre-exposure pigmentation; therefore the percentage increase in pigmentation was higher in fair-skinned subjects. The absolute increase in pigmentation was higher and it took 2-3 days longer to reach steady-state after 12 UV exposures compared with 6 UV exposures. Days to steady-state pigmentation and fading were independent of pre-exposure pigmentation, and fading took 5-6 months. Comparing data from a narrowband UVB source and a Solar Simulator, it was shown that pigmentation built up faster and increased more after 12 UVA exposures (16 days) than with the Solar Simulator (21 days).

Skin pigmentation kinetics after UVB exposure.

There have been few previous studies of the kinetics of pigmentation following ultraviolet B (UVB) exposure, and these have included only fair-skinned persons. The current study investigated pigmentation increase to steady state and fading in 12 Scandinavians and 12 Indians/Pakistanis. Over a period of 3 weeks the subjects were UV-irradiated 6 times on the right side of the back and 12 times on the left side using a Solar Simulator and narrowband UVB with equal sub-Minimal Melanogenesis Doses (individually predetermined). Pigmentation was measured from skin remittance at 555 nm and 660 nm (allowing correction for erythema). The absolute pigmentation increase was independent of pre-exposure pigmentation, therefore the percentage pigmentation increase was higher in fair-skinned volunteers. The UV dose to minimal pigmentation was higher in darker-skinned persons for single and multiple UV exposures for both UV sources. Going from a single exposure to 6 and 12 exposures, the required dose to minimal pigmentation was reduced by factors of 2 and 3, respectively, for both UV sources, thus reducing the risk of sunburn, but the cumulative dose increased 3- and 4-fold, respectively. This result was independent of skin type and pre-exposure pigmentation. Fading took 4-5 months and was not related to frequency of UV exposure or to ethnic origin.