Picosecond lasers in cosmetic dermatology: where are we now? An overview of types and indications.

Q-switched lasers have undeniably revolutionized the field of laser dermatology since four decades ago. Just as the first-generation laser emits its photonic signal in a few nanoseconds, the picosecond laser delivers pulse widths of at least ten times shorter. These devices offer a powerful tool for treating a wide range of skin conditions with a minimal downtime for visible improvement. For the current study, a literature research was performed on the dermatological applications of picosecond laser. The literature searched on this topic between 1999 and 2023 accessible through various platforms produce a result of 62 articles. The included studies have discussed the application of picosecond laser technology in tattoo removal, treatment of epidermal and dermal pigmentation, and collagen remodeling. After sifting the data from the articles into tables, the results were discussed in detail. The study shows a lot of evidence towards the efficacy of picosecond laser, yet it draws attention to its downsides.

Photodynamic therapy for actinic keratosis of the forehead and scalp with the Aktilite CL 128: Is there a cut-off value for PpIX-weighted irradiance for effective treatment?

BACKGROUND/PURPOSE: Photodynamic therapy (PDT) is an established treatment for actinic keratosis (AK). Among the approved protocols in Europe, the most widely used involves irradiation with the Aktilite CL 128 (C-PDT). We aimed to assess the heterogeneity of irradiance over the treatment area when using C-PDT. We also investigated whether there is a cut-off value for protoporphyrin IX (PpIX)-weighted irradiance that may predict the treatment outcome of C-PDT. METHODS: An Ophir PD300 photodiode sensor connected to an Ophir Laser Star power meter was used to measure the irradiance delivered to 114 AKs of the scalp and forehead of 19 patients treated with C-PDT. The PpIX-weighted irradiances were deduced and cross-referenced with the complete responses at 3 months. RESULTS: From the measured irradiances ranging from 0.25 to 60 mW/cm2 (average: 31.94 mW/cm2 ), a standard deviation of 17.17 mW/cm2 was computed. Irradiance heterogeneity over the treatment area during C-PDT was demonstrated. The 66/114 AKs with a complete response at 3 months (57.89%) received a mean PpIX-weighted irradiance of 0.52 mW/cm2 vs 0.56 mW/cm2 for the resistant 48/114 AKs (42.11%). No significant effect of PpIX-weighted irradiance on the complete response at 3 months was found (odds ratio for a 0.1-unit change, 0.96; 95% confidence interval, 0.83 to 1.10; P = 0.53). Therefore, no cut-off value for PpIX-weighted irradiance that predicts treatment outcome could be identified. CONCLUSIONS: A device enabling homogeneous irradiation at a lower irradiance than the Aktilite CL 128 may therefore be suitable. This lower irradiance may further increase the treatment tolerance by patients.

[Diagnosis of melanoma]. / Diagnostic du mélanome.

Melanoma is a rare cancer but it is the cancer with the biggest increase of incidence, especially in caucasian populations. UV exposure and genetic predisposition are the two main risk factors. The diagnosis is often clinically suspected with the "ABCDE" rule. However, there are some diagnostic traps. Histological exam of the whole lesion will confirm diagnosis and guide the management. In case of localised melanoma, Breslow index is the best prognostic index. In case of metastatic melanoma, prognostic is dark. The AJCC classification stages patients in 4 groups according to their global survival.

Oral metronomic cyclophosphamide in elderly with metastatic melanoma.

INTRODUCTION: In Western countries, the number of frail elderly people with metastatic melanoma (MM) keeps increasing. Conventional chemotherapy frequently induces imbalance in frail physiological cases. We propose to treat these patients with oral metronomic cyclophosphamide. PATIENTS AND METHODS: This retrospective study analyses the data of patients with unresectable MM who received 50 to 100 mg of cyclophosphamide a day, 3 weeks out of 4. Main evaluation criterion was safety. Secondary evaluation criteria were objective response rate and overall survival. RESULTS: Thirteen patients were included (median age: 80, 5 AJCC stage III and 8 AJCC stage IV). Clinical and biological safety were good, leading to long home staying and rare treatment discontinuations. Main toxicity observed was lymphopenia; no opportunist infection occurred. The control rate was 46%: one partial response and five stable diseases (median: 10 months). Survival after beginning of treatment ranged from 4 to 37 months (median: 8 months). DISCUSSION: Literature about MM in frail elderly is limited. Still, specific treatment is necessary. Cyclophosphamide in metronomic schema was well tolerated. The response rate was difficult to assess (small population) but several patients presented with long lasting stabilisation. The mechanisms of action of this treatment are original, associating antiangiogenic action and immunomodulation. CONCLUSION: Cyclophosphamide in metronomic schema showed good safety results for this frail population. Oral treatment enabled patients to stay at home longer and limited hospitalisation time. A larger controlled study will be necessary to confirm these encouraging results in elderly with MM, a classical chemoresistant tumor.

Photodynamic Therapy Using a New Painless Light-Emitting Fabrics Device in the Treatment of Extramammary Paget Disease of the Vulva (the PAGETEX Study): Protocol for an Interventional Efficacy and Safety Trial.

BACKGROUND: Extramammary Paget disease of the vulva (EMPV) is a rare skin disorder commonly seen in postmenopausal Caucasian females that appears clinically as red, eczematous, pruriginous, and sometimes painful lesions. Although most cases are noninvasive, EMPV may be associated with an underlying or distant adenocarcinoma. EMPV has a chronic and relapsing course. The reference treatment is based on local surgical excision with negative margins. However, disease frequently extends far from the visible lesion, and surgical margins are frequently positive. Topical photodynamic therapy (PDT) is an established treatment modality for various dermatooncologic conditions. For example, red light irradiation with the Aktilite CL 128 and Metvixia (Galderma SA) as a photosensitizing molecule is a conventional protocol approved and widely used in Europe for PDT treatment of actinic keratosis, but this treatment is not yet widely used for EMPV because it has never clearly been demonstrated and is very painful. OBJECTIVE: The aim of the study is to investigate the efficacy and safety relating to the medical device PAGETEX as a new painless PDT device using Metvixia in the treatment of vulvar Paget disease. The primary end point is the disease control rate at 3 months in 30% of the patients included, defined as stability, partial response, or total response, considering the extent of the lesion. Secondary end points are the disease control rate at 6 months, patient quality of life, level of pain experienced by the patient at each PDT session, severity of erythema, presence of protoporphyrin IX in Paget cells after each PDT session, and overall satisfaction level of the patient. METHODS: The trial is an interventional, exploratory, simple group, nonrandomized, and single center (Lille University Hospital) study. Twenty-four patients will be included according to Simon's optimal plan. Therapeutic procedure is based on a cycle of two PDT sessions with the PAGETEX medical device at 15-day intervals (Metvixia incubation during 30 minutes and 635 nm red light illumination with a low irradiance for 2 hours and 30 minutes for a total fluence of 12 J/cm²). At the assessment session, 3 months after inclusion, if the control of the disease is partial or null, the patient will complete another cycle of two PDT sessions. A final evaluation will be performed in all patients at 6 months. Analyses will be performed using SAS version 9.4 software (SAS Institute Inc). The characteristics of the patients at baseline will be described; qualitative variables will be described by numbers and percentages, and quantitative variables will be described either by the mean and standard deviation for Gaussian distribution or by the median and interquartile range (ie, 25th and 75th percentiles). The normality of the distributions will be tested by a Shapiro-Wilk test and checked graphically by histograms. RESULTS: First patient was included in September 2019 and clinical investigations are planned until August 2022. The final results of this study are expected to be available in January 2023. CONCLUSIONS: This clinical trial aims to evaluate the efficacy and safety of a new PDT protocol for the treatment of EMPV. The PAGETEX device could become the treatment of choice if it is effective, painless, and easy to implement and use in hospitals. TRIAL REGISTRATION: ClinicalTrials.gov NCT03713203; https://clinicaltrials.gov/ct2/show/NCT03713203. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/15026.

Can daylight-PDT be performed indoor?

Natural DayLight-mediated PhotoDynamic Therapy (NDL-PDT) is an efficacious treatment option for thin actinic keratosis that offers advantages over conventional PDT in terms of tolerability and cost. It is now accepted that the minimum criteria required for effective NDL-PDT is a dose of 4 J/cm² with a treatment time of 2 hours and a minimum temperature of 10 °C, corresponding to a minimum illuminance of 11,000 lux. This value is easily achievable: 20,000 lux can be obtained during a typical overcast day at midday. It can reach 110,000 lux with a bright sunlight. However, it is limited to certain times of the year at our latitude. However rain and cold temperatures appear the main limitations of NDL-PDT. Greenhouses make possible to perform the illumination even in harsh weather conditions. Furthermore, it is difficult to install a greenhouse everywhere. Several solutions are now proposed to carry out indoor illumination so-called artificial white light or simulated daylight (SDL-PDT). Illumination sources installed at the ceiling of the treatment room is one option. Several lamp pairs can be combined to illuminate groups of patients simultaneously. A surgical theatre light can be used or dedicated systems using white LEDs can be used to deliver the required illumination dose. In conclusion, Indoor lightning (or simulated daylight: SDL-PDT or Artificial White Light: AWL) could offer an interesting alternative to NDL-PDT.

Afro-Caribbean pemphigus: epidemiological data from a 5-year prospective study on the island of Guadeloupe (French West Indies).

BACKGROUND: There are no reported epidemiological data regarding autoimmune pemphigus in the Afro-Caribbean population. OBJECTIVES: To present the epidemiology of autoimmune pemphigus on the island of Guadeloupe (French West Indies, 400,736 inhabitants, mostly black Caribbean of African European descent). MATERIALS AND METHODS: Five-year prospective study. Inclusion of the incident cases when directly referred to the Dermatology Department or secondarily referred by their private practice dermatologist once identified by the computerized databases of the Guadeloupian pathology laboratories. RESULTS: World-population-standardized incidence was 6.96 (95% CI: 3.41-10.52) for pemphigus vulgaris and 3.75 (95% CI: 1.12-6.39) for pemphigus foliaceus. Patients usually live in the rural countryside, whereas 75% of the population of Guadeloupe Island live in an urban environment. CONCLUSION: We report a high incidence of autoimmune pemphigus in Guadeloupe, especially for the foliaceus type, and the existence of particular epidemiological features such as the rural countryside habitat.

Inactivation of the HIF-1α/PDK3 signaling axis drives melanoma toward mitochondrial oxidative metabolism and potentiates the therapeutic activity of pro-oxidants.

Cancer cells can undergo a metabolic reprogramming from oxidative phosphorylation to glycolysis that allows them to adapt to nutrient-poor microenvironments, thereby imposing a selection for aggressive variants. However, the mechanisms underlying this reprogramming are not fully understood. Using complementary approaches in validated cell lines and freshly obtained human specimens, we report here that mitochondrial respiration and oxidative phosphorylation are slowed in metastatic melanomas, even under normoxic conditions due to the persistence of a high nuclear expression of hypoxia-inducible factor-1α (HIF-1α). Pharmacologic or genetic blockades of the HIF-1α pathway decreased glycolysis and promoted mitochondrial respiration via specific reduction in the expression of pyruvate dehydrogenase kinase-3 (PDK3). Inhibiting PDK3 activity by dichloroacetate (DCA) or siRNA-mediated attenuation was sufficient to increase pyruvate dehydrogenase activity, oxidative phosphorylation, and mitochondrial reactive oxygen species generation. Notably, DCA potentiated the antitumor effects of elesclomol, a pro-oxidative drug currently in clinical development, both by limiting cell proliferation and promoting cell death. Interestingly, this combination was also effective against BRAF V600E-mutant melanoma cells that were resistant to the BRAF inhibitor vemurafenib. Cotreatment of melanomas with DCA and elesclomol in vivo achieved a more durable response than single agent alone. Our findings offer a preclinical validation of the HIF-1/PDK3 bioenergetic pathway as a new target for therapeutic intervention in metastatic melanoma, opening the door to innovative combinations that might eradicate this disease.