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Actinic keratosis is a lesion that develops in sun-exposed areas of the skin and is considered to be a precancerous condition or an early in situ squamous cell carcinoma. Treatment of actinic keratosis is important for reducing skin cancer risk, with treatment choice based on patient-, lesion- and treatment-related considerations. Of the topical treatments used for field-directed therapy, those containing 5-fluorouracil are among the most effective and widely prescribed. The most recently developed topical 5-fluorouracil preparation (Tolak®; Pierre Fabre, France) contains 4% 5-fluorouracil in an aqueous cream. This narrative review discusses data on 4% 5-fluorouracil cream to treat actinic keratosis, and provides the authors’ expert opinion on issues associated with it use. The effect of the cream has been evaluated in phase 2 and 3 trials of adult patients with actinic keratosis on the face, ears or scalp. These trials included patients with severe baseline disease, defined by high lesion counts and large-size treatment fields, which possibly affected the proportion of patients who were able to achieve complete clearance. Other efficacy parameters (e.g. percentage change in lesion count, ≥ 75% clearance of lesions or clinically significant changes in validated severity scales) should also be assessed to fully evaluate 4% 5-fluorouracil treatment efficacy in these patients. Nevertheless, 4% 5-fluorouracil is associated with high efficacy, a low level of recurrence and a satisfactory safety profile.

Abstract Introduction Topical 5-fluorouracil (5-FU)-containing treatments are effective for actinic keratosis (AK); however, they frequently lead to transient local skin reactions (LSRs), which often result in treatment non-adherence. Methods The aim of this international, phase IV clinical trial was to investigate whether addition of an emollient to topical 4% 5-FU would reduce the frequency and severity of LSRs over 4 weeks of treatment (intervention group) compared with 4% 5-FU alone (control group) in patients with AK. The primary objective was to assess the severity of LSRs (i.e. erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation and erosion/ulceration) at week 4 of treatment (or before, in case of a major local reaction). Key secondary objectives were LSR total scores at weeks 2 and 8, the scores of individual LSR items at each visit, and the proportions of patients with 100% and ≥ 75% AK lesion clearance at week 8. Results In total, 141 patients were included in the efficacy analysis (71 in the intervention group and 70 in the control group). There were no statistically or clinically significant differences between the treatment groups in terms of LSR total score at week 4 (overall and by subgroups defined by the number of lesions and patient age at baseline), scores of individual LSR items at any time point, and AK lesion clearance rates at week 8. LSR scores with topical 4% 5-FU alone were lower than expected. Skin reactions were the most common treatment-emergent adverse events in both groups, leading to treatment discontinuation in nine patients (12.3%) in the intervention group and seven (9.9%) in the control group. No new safety signals were observed with the addition of an emollient to 4% 5-FU. Conclusions Daily emollient applications during the 4-week treatment course did not impact the safety and efficacy profile of 4% 5-FU.

Advanced cutaneous squamous cell carcinoma (cSCC) can be a life-threatening disease for which effective and safe treatment in advanced stages is very limited. GP-2250 has been recently proven to have—in vitro and in vivo—antineoplastic effects on cancer cells. This study aims to investigate the potential anti-neoplastic effects of GP-2250 on the cSCC cell lines SCC13 and A431 through dose finding assessments, MTT cytotoxicity assays, cell migration assays, BrdU proliferation assays and FCM analysis. Our preliminary results have shown for the first time evidence for anti-neoplastic effects of GP-2250 on cSCC cells, enhancing cytotoxicity, attenuating cancer cell proliferation, inducing apoptosis and reducing tumour cell migration. Further investigations evaluating the modes of action of GP-2250 on cSCC cell lines are warranted in order to justify the use in vivo studies.

Torsten Eggert, Hans Dorn, Heidi Danker-Hopfe Charité – Universitätsmedizin Berlin, Competence Centre of Sleep Medicine, Berlin, GermanyCorrespondence: Heidi Danker-Hopfe, Email heidi.danker-hopfe@charite.dePurpose: The quantitative sleep EEG has been considered as electroencephalographic “fingerprint”, ie, it is stable within but differs between individuals. So far, however, almost all studies addressing this aspect have been conducted in young men. It was therefore of interest to know whether the sleep EEG fingerprint concept holds true in older samples of both sexes.Patients and Methods: Data from three different subsamples of 30 healthy individuals each were reused for the present secondary analysis (young men (YM) = 25.6 ± 2.4 years, elderly men (EM) = 69.1 ± 5.5 years, elderly women (EW) = 67.8 ± 5.7 years). Individuals slept ten times in the sleep laboratory, resulting in a total of 900 study nights. However, to avoid misinterpretation due to intervention-related changes in sleep EEG power spectra, only the 3 sham nights without any intervention were included, reducing the datasets to 270. To determine stability of NREM sleep EEG power spectra between sham night pairs, within- and between-subject Manhattan distance measures were computed separately by sample.Results: Regardless of subsample and sham night pair, lowest distance measures, ie, largest similarity, were observed for within-subject power spectra comparisons (range of mean distance measures for EW from 3.82 to 4.06, for EM from 3.55 to 3.63, and for YM from 3.04 to 3.62). Moreover, intraindividual similarity did not differ substantially between samples. Between-subject power spectra distance measures were considerably larger (range of mean distance measures for EW from 12.95 to 13.15, for EM from 12.21 to 12.57, and for YM from 10.33 to 10.78) and varied significantly between young and elderly individuals.Conclusion: The present results support the view that the sleep EEG power spectrum is an individual trait-like characteristic that remains unique up until old age. This finding may help to increase the sensitivity in measuring intervention effects.Keywords: sleep EEG power spectra, aging and sleep, heritability of sleep EEG, electroencephalographic fingerprint, trait-like quantitative EEG characteristics, individuality of sleep EEG

Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline “actinic keratosis and cutaneous squamous cell carcinoma” was updated and expanded by the topics cutanepus squamous cell carcinoma in situ (Bowen’s disease) and actinic cheilitis. This guideline was developed at the highest evidence level (S3) and is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC.