The association between rosacea and skin cancer remains inconclusive, with conflicting reports. The aim of this nationwide population-based cohort study was to determine the risk of skin cancer in ...patients with rosacea. A rosacea cohort (n = 11,420) was formulated and evaluated from 2010 to 2019. The incidence rate ratios of actinic keratosis, cutaneous melanoma, keratinocyte carcinoma and gastric, colorectal, and liver cancer were analysed in comparison with a matched control group, and multivariable stratified Cox proportional hazards model analysis was performed. The risk of actinic keratosis and keratinocyte carcinoma was increased in the rosacea group compared with the control group, with adjusted hazard ratios of 6.05 (95% confidence interval 3.63-10.09) and 2.66 (1.53-4.61), respectively. The risk of cutaneous melanoma and gastric, colorectal and liver cancer was not increased, with adjusted hazard ratios of 1.69 (0.25-11.37), 0.81 (0.59-1.10), 0.91 (0.69-1.18) and 1.32 (0.89-1.95), respectively. These results reveal an increased risk of actinic keratosis and keratinocyte carcinoma in patients with rosacea.
Objectives
To identify molecular characteristics of keratosis of unknown significance and to nominate pathways of molecular progression to oral cancer. Our work could provide a rationale for ...monitoring and treating these lesions definitively.
Methods
Patients with oral leukoplakia were eligible for our prospective observational study. We correlated alterations in cancer‐associated genes with clinical and histopathologic variables (keratosis of unknown significance vs. moderate‐to‐severe dysplasia) and compared these alterations to a previously molecularly characterized oral cancer population.
Results
Of 20 enrolled patients, 13 (65%) had evidence of keratosis of unknown significance, while seven (35%) had dysplasia. Nine patients (45%) developed oral cancer (4/13 with keratosis of unknown significance, 5/7 with dysplasia). At a median follow‐up of 67 (range 22–144) months, median overall survival was significantly shorter for patients with dysplasia (hazard ratio 0.11, p = .02). KMT2C and TP53 alterations were most frequent (75% and 35%, respectively). There were molecular similarities between keratosis of unknown significance and dysplasia patients, with no significant differences in mutational frequency among genes with ≥15% rate of alteration.
Conclusions
Among patients with leukoplakia, both patients with keratosis of unknown significance and patients with dysplasia developed oral cancer. Molecular alterations between these two groups were similar at this sample size.
Photodynamic therapy (PDT) is an effective intervention for actinic keratosis and field cancerization. Ablative fractional lasers may facilitate the delivery of photosensitizers and thereby improve ...the effects of PDT.
To summarize the current evidence on the efficacy and safety of laser-assisted PDT.
We performed a systematic literature research in Medline, Embase, and the Cochrane Central Register of Controlled Trials and hand-searched pertinent trial registers for eligible randomized controlled trials. Results from individual studies were pooled by using a random-effects model. The risk of bias was estimated with the Cochrane Risk of Bias Tool, and the quality of evidence of the outcomes was assessed with the Grading of Recommendations, Assessment, Development, and Evaluation approach.
Of 817 records initially identified, 7 randomized controlled trials were included in the qualitative analysis and 4 were included in the meta-analysis. Laser-assisted PDT showed significantly higher clearance rates than did PDT monotherapy (risk ratio, 1.33; 95% confidence interval, 1.24-1.42; I2 = 25%; P < .01). There was no difference in pain intensity between laser-assisted PDT and other interventions (mean difference, 0.31; 95% confidence interval, −0.12 to 0.74; I2 = 0%; P = .16). The included studies showed a high risk of bias.
The clinical heterogeneity of included studies.
Laser-assisted PDT is more efficient but not more painful than PDT or laser treatment only.
: Multiphoton tomography (MPT) is an in vivo imaging technique with very high spatial resolution and efforts are made to combine MPT with other non‐invasive imaging methods. The goals of the present ...study were the description of the features of different dermatological entities as seen in MPT and confocal laser scanning microscopy (CLSM) comparison of these two novel techniques and the ‘classical’ diagnostic measures visual inspection, dermoscopy and histology with respect to the strengths and weaknesses of the different methods and the potential benefit from their combined implementation. After study approval by the local Ethics Committee, 47 patients (31 male, 16 female, age range: 24–88 years) were recruited from the Department of Dermatology of the University Hospital Jena. In this work, we present an illustrative selection of eleven cases from a clinical study combining in vivo MPT with in vivo CLSM. The patients presented with a broad range of dermatological disorders including seborrheic keratoses, angioma, actinic keratoses, melanocytic nevi, malignant melanoma, psoriasis, pemphigus vulgaris and scarring. Both methods, CLSM and MPT, were found to be suitable for in vivo imaging of superficial skin layers and may therefore be useful in dermatological practice for the diagnosis of skin diseases. However, both methods differ in their technical and physical principles. Thus, despite of many similarities concerning the morphological presentation of cells and tissues, important differences are recognized. Synergies of the combination of CLSM and MPT may be obtained by combined implementation in order to benefit from the fast overview given by CLSM and the detailed imaging of skin structures by MPT.
Non-melanoma-skin cancer is an emerging clinical problem in the elderly, fair skinned population which predominantly affects patients aged older than 70 years. Its steady increase in incidence rates ...and morbidity is paralleled by related medical costs. Despite the fact that many elderly patients are in need of care and are living in nursing homes, specific data on the prevalence of skin cancer in home care and the institutional long-term care setting is currently lacking. A representative multicenter prevalence study was conducted in a random sample of ten institutional long-term care facilities in the federal state of Berlin, Germany. In total, n = 223 residents were included. Actinic keratoses, the precursor lesions of invasive cutaneous squamous cell carcinoma were the most common epithelial skin lesions (21.1%, 95% CI 16.2 to 26.9). Non-melanoma skin cancer was diagnosed in 16 residents (7.2%, 95% CI 4.5 to 11.3). None of the residents had a malignant melanoma. Only few bivariate associations were detected between non-melanoma skin cancer and demographic, biographic and functional characteristics. Male sex was significantly associated with actinic keratosis whereas female sex was associated with non-melanoma skin cancer. Smoking was associated with an increased occurrence of non-melanoma skin cancer. Regular dermatology check-ups in nursing homes would be needed but already now due to financial limitations, lack of time in daily clinical practice and limited number of practising dermatologists, it is not the current standard. With respect to the worldwide growing aging population new programs and decisions are required. Overall, primary health care professionals should play a more active role in early diagnosis of skin cancer in nursing home residents. Dermoscopy courses, web-based or smartphone-based applications and teledermatology may support health care professionals to provide elderly nursing home residents an early diagnosis of skin cancer.
: Actinic keratosis (AK) is a chronic disease which is mainly located across areas of sun-exposed skin. Clinical and subclinical lesions coexist across a large area resulting in a field ...cancerization. As these lesions have the potential to transform into invasive squamous cell carcinoma (iSCC), treatment is crucial. With global prevalence increasing, AK is expected to be the most common in situ carcinoma of the skin.
: In this article, we cover the established algorithm of treating AK and give an insight into the drugs under development. There are six compounds under development covering different treatment angles, from Sinecatechin a Polyphenon E which targets the link between HPV infection and development of AK, over Tirbanibulin which targets the SRC proto-oncogene and fast proliferating cells, to Tuvatexib a small-molecule dual VDAC/HK2 modulator that has shown that it can compete with the established therapies.
: These new treatment options are moving us further toward a more individually tailored treatment for each patient considering his abilities, the size and location of his lesions but also the genetic bases as well as individual risk of transforming into a iSCC and possibly other factors contributing to each patients individual AK lesions.
Actinic keratosis (AK) and cutaneous squamous cell carcinoma in situ (CIS) are two of the most common precursors of cutaneous squamous cell carcinoma (cSCC). However, the genomic landscape of AK/CIS ...and the drivers of cSCC progression remain to be elucidated. The aim of our study was to investigate the genomic alterations between AK/CIS and cSCC in terms of somatic mutations and copy number alterations (CNAs). We performed targeted deep sequencing of 160 cancer‐related genes with a median coverage of 515× for AK (N = 9), CIS (N = 9), cSCC lesions (N = 13), and matched germline controls from 17 patients. cSCC harboured higher abundance of total mutations, driver mutations and CNAs than AK/CIS. Driver mutations were found in TP53 (81%), NOTCH1 (32%), RB1 (26%) and CDKN2A (19%). All AK/CIS and cSCC lesions (93.5%), except two, harboured TP53 or NOTCH1 mutations, some of which were known oncogenic mutations or reported mutations in normal skin. RB1 driver mutations were found in CIS/cSCC (36.4%) but not in AK. CDKN2A driver mutations were found more frequently in cSCC (30.8%) than in AK/CIS (11.1%). Among recurrent (≥3 samples) CNAs (gain in MYC and PIK3CA/SOX2/TP63; loss in CDKN2A and RB1), MYC (8q) gain and CDKN2A (9p) loss were more frequently detected in cSCC (30.8%) than in AK/CIS (11.1%). Ultraviolet was responsible for the majority of somatic mutations in both AK/CIS and cSCC. Our study revealed that AK/CIS lesions harbour prevalent TP53 or NOTCH1 mutations and that additional somatic mutations and CNAs may lead to cSCC progression in AK/CIS lesions.
Actinic Keratosis (AK), is the most common precancerous skin lesion induced by the excessive Ultraviolet B (UVB) and is a significant threat to the public health. UVB exposure causes oxidative DNA ...damage and is considered to be a significant contributor to AK and subsequent development of skin cancer. Besides, activation of p38 MAPK also plays a significant role in the development of AK.
This study aimed at the development of a nature compound which can inhibit UVB-induced AK.
MTS Cell Proliferation Assay Kit was used to detect the toxicity of astragalin. HE-staining, Immunohistochemical, Western blot and Enzyme Linked Immunosorbent Assay were applied to examine the clinicopathologic feature of AK and the change of p38 MAPK signal pathway treated with astraglin under the condition of UVB in vitro and in vivo. Results：In our clinical findings revealed that p38 MAPK, phospho-MSK1, and γ -H2AX were significantly highly expressed in human AK tissue than the normal healthy skin tissue. Moreover, in vitro studies showed that UVB induced the phospho-MSK1 and γ-H2AX in a time- and dose-dependent manner in HaCaT cells. Further, in vitro kinase assay demonstrated that astragalin could directly bind to p38 MAPK and suppress p38 MAPK activity. Furthermore, astragalin exhibited no toxicity and suppressed the UVB-induced expression of phospho- MSK1 and γ -H2AX by suppressing p38 MAPK activity in a time-dependent and dose-dependent manner in HaCaT cells. The in vivo studies with animal UV model demonstrated that astragalin inhibited UVB-induced expression of phospho-MSK1 and γ-H2AX in Babl/c mice.
These results suggested that p38 MAPK is a direct valid molecular target of astragalin for the attenuation of UVB-induced AK. Furthermore, astragalin could be a potential promising novel natural therapeutic agent for the prevention and management of UVB-induced AK with high target specificity and low toxicity.
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