Efficacy and tolerability of tirbanibulin 1% ointment in the treatment of cancerization field: a real-life Italian multicenter observational study of 250 patients.

BACKGROUND: Tirbanibulin 1% ointment is approved for the field treatment of Olsen grade I actinic keratoses (AKs) of the face and scalp. METHODS: We performed a multicenter retrospective study involving 15 dermatologic units in Italy to investigate the efficacy and tolerability of tirbanibulin in a real-life setting. 250 patients were enrolled. Tirbanibulin, 1% ointment, was applied daily for five consecutive days. The efficacy of treatment was measured with modifications of the Actinic Keratosis Area and Severity Index (AKASI). A satisfactory response was defined by complete (100% reduction in the number of lesions) or partial clearance (75-99%) of treated AKs. RESULTS: Overall, the AKASI score was significantly reduced in the studied population (mean, from 4.1 ± 2.7 to 1.4 ± 1.5; P < 0.001). A satisfactory response was observed in 222 (88.8%) cases. The proportion of satisfactory responses was higher when follow-up was performed after 8 weeks (34/35, 97.1%). The reduction in AKASI was significant in patients with Olsen grade II or III lesions (from 5.3 ± 2.8 to 1.6 ± 1.6; P < 0.001). A satisfactory response was observed in 91/104 (87.5%) cases. AKASI reduction was also significant in patients with trunk or limb AKs (from 7.0 ± 1.3 to 2.0 ± 1.6; P = 0.018) since a satisfactory response was observed in 7/8 (87.5%) cases. Tirbanibulin was well tolerated; all adverse events (AEs) included transient local reactions at the site of treatment. Overall, 231 patients had at least one AE. Only 7 (2.8%) grade 4 AEs were recorded. CONCLUSION: Our retrospective study confirmed that tirbanibulin 1% ointment is effective and well tolerated in a real-life setting and is also promising for Olsen grade II and grade III AKs and AKs localized on difficult-to-treat areas.

Cumulative incidence and risk factors for cutaneous squamous cell carcinoma metastases in organ transplant recipients: The Skin Care in Organ Transplant Patients in Europe-International Transplant Skin Cancer Collaborative metastases study, a prospective multicenter study.

INTRODUCTION: Solid organ transplant recipients (SOTRs) are believed to have an increased risk of metastatic cutaneous squamous cell carcinoma (cSCC), but reliable data are lacking regarding the precise incidence and associated risk factors. METHODS: In a prospective cohort study, including 19 specialist dermatology outpatient clinics in 15 countries, patient and tumor characteristics were collected using standardized questionnaires when SOTRs presented with a new cSCC. After a minimum of 2 years of follow-up, relevant data for all SOTRs were collected. Cumulative incidence of metastases was calculated by the Aalen-Johansen estimator. Fine and Gray models were used to assess multiple risk factors for metastases. RESULTS: Of 514 SOTRs who presented with 623 primary cSCCs, metastases developed in 37 with a 2-year patient-based cumulative incidence of 6.2%. Risk factors for metastases included location in the head and neck area, local recurrence, size > 2 cm, clinical ulceration, poor differentiation grade, perineural invasion, and deep invasion. A high-stage tumor that is also ulcerated showed the highest risk of metastasis, with a 2-year cumulative incidence of 46.2% (31.9%-68.4%). CONCLUSIONS: SOTRs have a high risk of cSCC metastases and well-established clinical and histologic risk factors have been confirmed. High-stage, ulcerated cSCCs have the highest risk of metastasis.

Aquaporin 1, Aquaporin 8, and Aquaporin 9 Expressions in Malignant Melanoma: A Possible Correlation with Prognosis and Clinical Outcome.

Aquaporins (AQPs) are small transmembrane proteins able to facilitate the passive transport of water and small molecules throughout cells. Several studies have demonstrated that modulation of AQPs' expression contributes to cancer development and progression. However, to date, very little is known about their involvement in malignant melanoma (MM) progression. In this retrospective observational study, we evaluated the correlation between AQP1, -8, and -9 expression and the clinical outcomes of 58 patients diagnosed with MM from 2014 to 2016, of which 14 were diagnosed as nodular melanoma (NM) and 44 as superficial spreading melanoma (SSM). In general, we found that AQPs were more highly expressed in SSM than NM, suggesting a potential correlation with prognosis. While analyzing the expression of each AQP, we discovered that AQP1 was associated with a specific body site and low mitotic index, AQP8 with a negative sentinel lymph node, and AQP9 with the Breslow thickness and lack of ulcerations. Together with the survival analysis performed in this study, our results suggest that the expression of AQP1, -8, and -9 could be correlated with a better prognosis for malignant melanoma.

Impact of artificial intelligence-based color constancy on dermoscopical assessment of skin lesions: A comparative study.

BACKGROUND: The quality of dermoscopic images is affected by lighting conditions, operator experience, and device calibration. Color constancy algorithms reduce this variability by making images appear as if they were acquired under the same conditions, allowing artificial intelligence (AI)-based methods to achieve better results. The impact of color constancy algorithms has not yet been evaluated from a clinical dermatologist's workflow point of view. Here we propose an in-depth investigation of the impact of an AI-based color constancy algorithm, called DermoCC-GAN, on the skin lesion diagnostic routine. METHODS: Three dermatologists, with different experience levels, carried out two assignments. The clinical experts evaluated key parameters such as perceived image quality, lesion diagnosis, and diagnosis confidence. RESULTS: When the DermoCC-GAN color constancy algorithm was applied, the dermoscopic images were perceived to be of better quality overall. An increase in classification performance was observed, reaching a maximum accuracy of 74.67% for a six-class classification task. Finally, the use of normalized images results in an increase in the level of self-confidence in the qualitative diagnostic routine. CONCLUSIONS: From the conducted analysis, it is evident that the impact of AI-based color constancy algorithms, such as DermoCC-GAN, is positive and brings qualitative benefits to the clinical practitioner.

Epidemiology and risk factors for multiple squamous cell carcinomas in a cohort of organ transplant recipients from northern Italy: a single center study.

BACKGROUND: Keratinocyte cancers account for the most frequent oncological complication in organ transplant recipients. To date, many different risk factors have been reported, unless variability among the studies exist. We aimed to determine the incidence and risk factors for keratinocyte neoplasms in a cohort of kidney transplant and liver transplant recipients. METHODS: A cohort of 338 patients were included in this retrospective study and followed-up from transplantation until the end of December 2021, with a 2-year minimum transplant time. Each skin cancer was collected in a specific database, together with all the demographic data and dermatological history and feature of patients. RESULTS: In our cohort, liver transplant patients presented a higher keratinocyte cancer incidence compared to kidney transplant recipients. Regarding the risk factors for skin cancer in the entire group of patients, we observed a significant association with the detection of actinic keratosis and solar lentigo, and such relation was stronger when considering patients developing multiple skin cancers, in which fair skin types and occupational sun exposure were also associated. Furthermore, while actinic keratosis and a history of previous dialysis were significantly associated with the development of a least one squamous cell carcinoma, the presence of keratotic lesions and azathioprine intake resulted connected with the appearance of multiple squamous neoplasms. CONCLUSIONS: We report here that, in our cohort, factors potentially leading to immune dysfunction were found to play a causative role in the development of the more aggressive histotype of keratinocyte tumors, and such association seemed more convincing in case of multiple squamous cell carcinomas.

Role of the Microbiota in Skin Neoplasms: New Therapeutic Horizons.

The skin and the gut are regularly colonized by a variety of microorganisms capable of interacting with the immune system through their metabolites and influencing the balance between immune tolerance and inflammation. Alterations in the composition and diversity of the skin microbiota have been described in various cutaneous diseases, including skin cancer, and the actual function of the human microbiota in skin carcinogenesis, such as in progression and metastasis, is currently an active area of research. The role of Human Papilloma Virus (HPV) in the pathogenesis of squamous cell carcinoma is well consolidated, especially in chronically immunosuppressed patients. Furthermore, an imbalance between Staphylococcus spp., such as Staphylococcus epidermidis and aureus, has been found to be strongly related to the progression from actinic keratosis to squamous cell carcinoma and differently associated with various stages of the diseases in cutaneous T-cell lymphoma patients. Also, in melanoma patients, differences in microbiota have been related to dissimilar disease course and prognosis and may affect the effectiveness and tolerability of immune checkpoint inhibitors, which currently represent one of the best chances of a cure. From this point of view, acting on microbiota can be considered a possible therapeutic option for patients with advanced skin cancers, even if several issues are still open.

Temporal correlation between the first melanoma and the first noncutaneous tumor in CKDN2A genotyped patients.

CDKN2A pathogenic variants are well known to be associated with cutaneous melanoma and noncutaneous tumors (NCTs). Herein, we investigated the temporal correlation between the first cutaneous melanoma and NCT both in CDKN2A mutation carriers (MUT) and in wild-type melanoma patients, a poorly explored issue to date. Two hundred forty-five cutaneous melanoma patients were genotyped for the CDKN2A gene and divided into 51 MUT and 189 wild-type; the remaining five variant carriers were excluded from the analyses. MUT developed a significantly higher number of cutaneous melanoma than wild-type, while 13.7% in both genotyped groups received a diagnosis of at least one malignant NCT, without statistically significant differences. The onset of the first cutaneous melanoma preceded that of the first malignant or benign NCT in both MUT and wild-type patients by an average of 4.5 and 3.02 years, respectively. Considering only malignant tumors, the diagnosis of melanoma preceded that of the first NCT on an average of 8 and 4.34 years, in MUT and wild-type patients respectively. We emphasize the relevance to adopt a global vision for the primary and secondary surveillance of patients affected by cutaneous melanoma, not only limited to high-risk for multiple primary skin cancers but also to NCT that may develop several years after the diagnosis of the first cutaneous melanoma.

Decreased Gas6 and sAxl Plasma Levels Are Associated with Hair Loss in COVID-19 Survivors.

Post-acute conditions after coronavirus disease 2019 (COVID-19) are quite common, although the underlying pathogenetic mechanisms leading to these conditions are not yet completely understood. In this prospective observational study, we aimed to test the hypothesis that Growth Arrest-Specific 6 (Gas6) and its soluble receptors, Axl (sAxl) and MerTK (sMer), might be implicated. A total of 263 subjects underwent a structured clinical evaluation one year after their hospital discharge for COVID-19, and they consented to donate a blood sample to measure their circulating Gas6, sAxl, and sMer levels. A total of 98 (37.3%) post-COVID-19 subjects complained of at least one residual physical symptom one year after their hospital discharge. Univariate analysis revealed that sAxl was marginally associated with residual symptoms, but at the level of logistic regression analysis, only the diffusing capacity of the lungs for carbon monoxide (DLCO) (OR 0.98, CI 95%: 0.96-0.99; p = 0.007) and the female sex (OR 2.49, CI 95%: 1.45-4.28; p = 0.001) were independently associated with long-lasting symptoms. A total of 69 (26.2%) subjects had hair loss. At the level of univariate analysis, Gas6, sAxl, DLCO, and the female gender were associated with its development. In a logistic regression analysis model, Gas6 (OR 0.96, CI 95%: 0.92-0.99; p = 0.015) and sAxl (OR 0.98, CI 95%; 0.97-1.0; p = 0.014), along with the female sex (OR 6.58, CI 95%: 3.39-12.78; p = 0.0001), were independent predictors of hair loss. Decreased levels of Gas6 and sAxl were associated with a history of hair loss following COVID-19. This was resolved spontaneously in most patients, although 23.7% complained of persistent hair loss one year after hospital discharge.

Is There any Link between Madelung Disease and Ischemic Stroke? A Case Report.

A 70-year-old man presented to the Emergency Department with left hemiparesis, slurred speech, and elevated blood pressure. A brain computed tomography scan revealed an ischemic lesion in the right frontal and parietal lobes. At clinical examination bilateral pseudo gynecomastia was detected together with the presence of multiple elastic, adipose bulging masses on the neck, trunk, and upper limbs. A type I-II Lanois-Bensaude syndrome was diagnosed. Ultrasonography confirmed their adipose nature. Multiple symmetric lipomatosis, also known as Lanois-Bensaude syndrome or Madelung disease, is a very rare condition with extreme variability in its clinical presentation. The simultaneous occurrence of ischemic stroke and lipomatosis in the same patient might be due to a mitochondrial function impairment, which could lead to abnormal fat tissue distribution and defective cellular energy production, thus resulting in neuronal sufferance and death. The possibility that, in our case, lipomatosis could have represented a further risk factor in promoting the stroke occurrence is discussed. In our opinion, multiple symmetric lipomatosis must be carefully evaluated to improve the patients' quality of life.

AKASI and Near-Infrared Spectroscopy in the combined effectiveness evaluation of an actinic keratoses preventive product in immunocompetent and immunocompromised patients.

Introduction: The high incidence of actinic keratoses among both the elderly population and immunocompromised subjects and the considerable risk of progression from in situ to invasive neoplasms makes it essential to identify new prevention, treatment, and monitoring strategies. Objective: The aim of this study was to evaluate the efficacy on AKs of a topical product (®Rilastil AK Repair 100 +) containing high-protection sunscreens, a DNA Repair Complex with antioxidant and repairing action against UV-induced DNA damage, and nicotinamide, a water-soluble derivative of vitamin B3 that demonstrated several photoprotective effects both in vitro and in vivo. Methods: The study enrolled 74 Caucasian patients, which included 42 immunocompetent and 32 immunosuppressed subjects. The efficacy of the treatment has been evaluated through the clinical index AKASI score and the non-invasive Near-Infrared Spectroscopy method. Results: The AKASI score proved to be a valid tool to verify the efficacy of the product under study, highlighting an average percentage reduction at the end of treatment of 31.37% in immunocompetent patients and 22.76% in organ transplant recipients, in comparison to the initial values, with a statistically significant reduction also in the single time intervals (T0 vs. T1 and T1 vs. T2) in both groups. On the contrary, the Near-Infrared Spectroscopy (a non-invasive technique that evaluates hemoglobin relative concentration variations) did not find significant differences for O2Hb and HHb signals before and after the treatment, probably because the active ingredients of the product under study can repair the photo-induced cell damage, but do not significantly modify the vascularization of the treated areas. Conclusion: The results deriving from this study demonstrate the efficacy of the product under study, confirming the usefulness of the AKASI score in monitoring treated patients. Near-Infrared Spectroscopy could represent an interesting strategy for AK patients monitoring, even if further large-scale studies will be needed.

DermoCC-GAN: A new approach for standardizing dermatological images using generative adversarial networks.

BACKGROUND AND OBJECTIVE: Dermatological images are typically diagnosed based on visual analysis of the skin lesion acquired using a dermoscope. However, the final quality of the acquired image is highly dependent on the illumination conditions during the acquisition phase. This variability in the light source can affect the dermatologist's diagnosis and decrease the accuracy of computer-aided diagnosis systems. Color constancy algorithms have proven to be a powerful tool to address this issue by allowing the standardization of the image illumination source, but the most commonly used algorithms still present some inherent limitations due to assumptions made on the original image. In this work, we propose a novel Dermatological Color Constancy Generative Adversarial Network (DermoCC-GAN) algorithm to overcome the current limitations by formulating the color constancy task as an image-to-image translation problem. METHODS: A generative adversarial network was trained with a custom heuristic algorithm that performs well on the training set. The model hence learns the domain transfer task (from original to color standardized image) and is then able to accurately apply the color constancy on test images characterized by different illumination conditions. RESULTS: The proposed algorithm outperforms state-of-the-art color constancy algorithms for dermatological images in terms of normalized median intensity and when using the color-normalized images in a deep learning framework for lesion classification (accuracy of the seven-class classifier: 79.2%) and segmentation (dice score: 90.9%). In addition, we validated the proposed approach on two different external datasets with highly satisfactory results. CONCLUSIONS: The novel strategy presented here shows how it is possible to generalize a heuristic method for color constancy for dermatological image analysis by training a GAN. The overall approach presented here can be easily extended to numerous other applications.

Multiple Basal Cell Carcinomas in Immunocompetent Patients.

BACKGROUND: The onset of multiple BCCs is a relatively common condition, not only among patients undergoing chronic treatment with immunosuppressant drugs, but also in the general population, although specific risk factors for immunocompetent patients have not been identified. A putative role of somatic mutations in the hedgehog pathway should be considered. METHODS: This study is a retrospective observation of all patients diagnosed and surgically treated for BCCs during 5 years at our Dermatological Division. For these patients, we evaluated clinical and histopathological characteristics and data about possible risk factors for BCC. RESULTS: Five-hundred and six patients affected by multiple BCCs, accounting for the 24.2% of the entire sample, have been identified. In these patients, the total number of BCCs was 1516, ranging from 2 to 11. Subjects affected by multiple BCCs were more frequently males, with an older age at diagnosis; multiple BCCs developed mainly on the trunk and were often represented by a nodular histotype. The multivariate analysis highlighted that male gender, older age, nodular BCC, or face involvement at the first diagnosis are risk factors for the development of multiple BCCs. CONCLUSIONS: The frequency of multiple BCCs even among the non-immunocompromised population underlines the need to subject patients to a close surveillance program, to allow early diagnosis and treatment of additional cancers.

COVID-19 first lockdown and outpatient hospital setting: a single center, real life study focusing on pattern changes in patients' ethnicities and treated dermatoses.

BACKGROUND: During the first Italian lockdown period, the imponent amount of hospital COVID-19 patients forced the healthcare system to re-organize visits but no information are available on outpatient ethnical patterns. Here we evaluated healthcare management changes on dermatological outpatient non-surgical settings visits during the SARS-CoV-2 pandemic. METHODS: In this retrospective study we collected data of scheduled, performed and not-performed visits, together with patients' characteristics (i.e., age, gender) with a particular attention for ethnicities among the outpatients accessing during the first Italian lockdown (March 5-April 30, 2020). Then, we compared these data with the corresponding ones in 2019 (before COVID-19 pandemic). RESULTS: During the Italian lockdown the dermatological department registered a great decrement (-83.5%, P<0.001) in visits compared to the corresponding time period in 2019. Performed and scheduled visits to non-oncological stable patients together with emergency accesses to dermatology decreased. Non-Italian patients decreased accesses, especially the South East Asians (-70.4%) and North Africans (-90.0%). CONCLUSIONS: Hospitals policy and mass media deeply condition the public opinion, and this aspect may explain a different access to the hospital among non-Italian patients. Telemedicine should be promoted especially among non-Italian communities in Italy to overgo patients' skepticism and incentivize prevention and early treatment in dermatological conditions.

Teledermoscopy in the Diagnosis of Melanocytic and Non-Melanocytic Skin Lesions: NurugoTM Derma Smartphone Microscope as a Possible New Tool in Daily Clinical Practice.

Background: Due to the COVID-19 pandemic, teledermoscopy has been increasingly used in the remote diagnosis of skin cancers. In a study conducted in 2020, we demonstrated a potential role of an inexpensive device (NurugoTM Derma) as a first triage to select the skin lesions that require a face-to-face consultation with dermatologists. Herein, we report the results of a novel study that aimed to better investigate the performance of NurugoTM. Objectives: (i) verify whether the NurugoTM can be a communication tool between the general practitioner (GP) and dermatologist in the first assessment of skin lesions, (ii) analyze the degree of diagnostic-therapeutic agreement between dermatologists, (iii) estimate the number of potentially serious diagnostic errors. Methods: One hundred and forty-four images of skin lesions were collected at the Dermatology Outpatient Clinic in Novara using a conventional dermatoscope (instrument F), the NurugoTM (instrument N), and the latter with the interposition of a laboratory slide (instrument V). The images were evaluated in-blind by four dermatologists, and each was asked to make a diagnosis and to specify a possible treatment. Results: Our data show that F gave higher agreement values for all dermatologists, concerning the real clinical diagnosis. Nevertheless, a medium/moderate agreement value was obtained also for N and V instruments and that can be considered encouraging and indicate that all examined tools can potentially be used for the first screening of skin lesions. The total amount of misclassified lesions was limited (especially with the V tool), with up to nine malignant lesions wrongly classified as benign. Conclusions: NurugoTM, with adequate training, can be used to build a specific support network between GP and dermatologist or between dermatologists. Furthermore, its use could be extended to the diagnosis and follow-up of other skin diseases, especially for frail patients in emergencies, such as the current pandemic context.

Nicotinamide Attenuates UV-Induced Stress Damage in Human Primary Keratinocytes from Cancerization Fields.

UVB radiation directly damages DNA, increases ROS and nitric oxide (NO) release, and promotes inflammation leading to genomic instability and cell death. Nicotinamide (NAM) is the precursor of NAM adenine dinucleotide, essential for cell energy production and DNA damage repair. NAM protects HaCat cells from UV-induced impairment; however, little is known about its effects on human primary keratinocytes and those isolated from field cancerization (i.e., field cancerization human primary keratinocytes [FC-HPKs]). We examined the role of NAM against UV-induced oxidative stress damages in FC-HPKs, isolated from precancerous lesions and skin cancers, and in normal human epidermal keratinocytes. Cells were treated for 18, 24, and 48 hours with NAM (5, 25, and 50 µM, respectively) before UVB irradiation. FC-HPK showed four-fold higher basal ROS levels than normal human epidermal keratinocytes; NAM downregulated ROS production only in irradiated FC-HPKs, which showed a greater sensibility to UV rays. UV exposure increased OGG1, inducible nitric oxide synthase, and IL-1ß expression, an effect counteracted by NAM pretreatment. Intracellular nitric oxide production and DNA damages were inhibited by NAM exposure before irradiation. Collectively, our findings indicate that pretreatment with 25 µM NAM 24 hours before UVB irradiation effectively prevents oxidative stress formation, DNA damage, and inflammation in both normal human epidermal keratinocytes and FC-HPKs.

Alpha-Tocopherol Protects Human Dermal Fibroblasts by Modulating Nitric Oxide Release, Mitochondrial Function, Redox Status, and Inflammation.

BACKGROUND: The altered balance between oxidants/antioxidants and inflammation, changes in nitric oxide (NO) release, and mitochondrial function have a role in skin aging through fibroblast modulation. Tocopherol is promising in counteracting the abovementioned events, but the effective mechanism of action needs to be clarified. OBJECTIVE: The aim of this study was to examine the effects of α-tocopherol on cell viability/proliferation, NO release, mitochondrial function, oxidants/antioxidants, and inflammation in human dermal fibroblasts (HDF) subjected to oxidative stress. METHODS: HDF were treated with H2O2 in the presence or absence of 1-10 µM α-tocopherol. Cell viability, reactive oxygen species (ROS), NO release, and mitochondrial membrane potential were measured; glutathione (GSH), superoxide dismutase (SOD)-1 and -2, glutathione peroxidase-1 (GPX-1), inducible NO synthase (iNOS), and Ki-67 were evaluated by RT-PCR and immunofluorescence; cell cycle was analyzed using FACS. Pro- and anti-inflammatory cytokine gene expression was analyzed through qRT-PCR. RESULTS: α-Tocopherol counteracts H2O2, although it remains unclear whether this effect is dose dependent. Improvement of cell viability, mitochondrial membrane potential, Ki-67 expression, and G0/G1 and G2/M phases of the cell cycle was observed. These effects were accompanied by the increase of GSH content and the reduction of SOD-1 and -2, GPX-1, and ROS release. Also, iNOS expression and NO release were inhibited, and pro-inflammatory cytokine gene expression was decreased, confirming the putative role of α-tocopherol against inflammation. CONCLUSION: α-Tocopherol exerts protective effects in HDF which underwent oxidative stress by modulating the redox status, inflammation, iNOS-dependent NO release, and mitochondrial function. These observations have a potential role in the prevention and treatment of photoaging-related skin cancers.

Consensus-Based Recommendations on the Prevention of Squamous Cell Carcinoma in Solid Organ Transplant Recipients: A Delphi Consensus Statement.

IMPORTANCE: There is a paucity of evidence to guide physicians regarding prevention strategies for cutaneous squamous cell carcinoma (CSCC) in solid organ transplant recipients (SOTRs). OBJECTIVE: To examine the development and results of a Delphi process initiated to identify consensus-based medical management recommendations for prevention of CSCC in SOTRs. EVIDENCE REVIEW: Dermatologists with more than 5 years' experience treating SOTRs were invited to participate. A novel actinic damage and skin cancer index (AD-SCI), consisting of 6 ordinal stages corresponding to an increasing burden of actinic damage and CSCC, was used to guide survey design. Three sequential web-based surveys were administered from January 1, 2019, to December 31, 2020. Pursuant to Delphi principles, respondents thoroughly reviewed all peer responses between rounds. Supplemental questions were also asked to better understand panelists' rationale for their responses. FINDINGS: The Delphi panel comprised 48 dermatologists. Respondents represented 13 countries, with 27 (56%) from the US. Twenty-nine respondents (60%) were Mohs surgeons. Consensus was reached with 80% or higher concordance among respondents when presented with a statement, question, or management strategy pertaining to prevention of CSCC in SOTRs. A near-consensus category of 70% to less than 80% concordance was also defined. The AD-SCI stage-based recommendations were established if consensus or near-consensus was achieved. The panel was able to make recommendations for 5 of 6 AD-SCI stages. Key recommendations include the following: cryotherapy for scattered actinic keratosis (AK); field therapy for AK when grouped in 1 anatomical area, unless AKs are thick in which case field therapy and cryotherapy were recommended; combination lesion directed and field therapy with fluorouracil for field cancerized skin; and initiation of acitretin therapy and discussion of immunosuppression reduction or modification for patients who develop multiple skin cancers at a high rate (10 CSCCs per year) or develop high-risk CSCC (defined by a tumor with approximately ≥20% risk of nodal metastasis). No consensus recommendation was achieved for SOTRs with a first low risk CSCC. CONCLUSIONS AND RELEVANCE: Physicians may consider implementation of panel recommendations for prevention of CSCC in SOTRs while awaiting high-level-of-evidence data. Additional clinical trials are needed in areas where consensus was not reached.

The Role in Teledermoscopy of an Inexpensive and Easy-to-Use Smartphone Device for the Classification of Three Types of Skin Lesions Using Convolutional Neural Networks.

BACKGROUND: The use of teledermatology has spread over the last years, especially during the recent SARS-Cov-2 pandemic. Teledermoscopy, an extension of teledermatology, consists of consulting dermoscopic images, also transmitted through smartphones, to remotely diagnose skin tumors or other dermatological diseases. The purpose of this work was to verify the diagnostic validity of images acquired with an inexpensive smartphone microscope (NurugoTM), employing convolutional neural networks (CNN) to classify malignant melanoma (MM), melanocytic nevus (MN), and seborrheic keratosis (SK). METHODS: The CNN, trained with 600 dermatoscopic images from the ISIC (International Skin Imaging Collaboration) archive, was tested on three test sets: ISIC images, images acquired with the NurugoTM, and images acquired with a conventional dermatoscope. RESULTS: The results obtained, although with some limitations due to the smartphone device and small data set, were encouraging, showing comparable results to the clinical dermatoscope and up to 80% accuracy (out of 10 images, two were misclassified) using the NurugoTM demonstrating how an amateur device can be used with reasonable levels of diagnostic accuracy. CONCLUSION: Considering the low cost and the ease of use, the NurugoTM device could be a useful tool for general practitioners (GPs) to perform the first triage of skin lesions, aiding the selection of lesions that require a face-to-face consultation with dermatologists.

Rapid and exceptional response to Sonidegib in a patient with multiple locally advanced basal cell carcinomas.

Locally advanced basal cell carcinoma (laBCC) represents a rare but possible occurrence in the vast scenario of dermatological diseases. It is well known that most BCC has a pathological activation of the hedgehog pathway, making them susceptible to targeted therapy with selective inhibitors. Sonidegib, approved for the treatment of laBCC on the basis of the results of the basal cell carcinoma outcomes with LDE225 treatment study, demonstrated rapid efficacy and a manageable safety profile. Here, we describe the case of a patient affected by multiple laBCC treated with Sonidegib. The patient experienced an important regression of tumors after only 2 months of therapy, with few side effects. This result confirms the role of Sonidegib as a valid and well-tolerated therapeutic option for laBCC.

A PRISMA-compliant meta-analysis on association between X-ray repair cross complementing (XRCC1, XRCC2, and XRCC3) polymorphisms and oral cancer susceptibility.

BACKGROUND: Oral Cancer (OC) is one of the leading causes of death and the disease mainly occurs over 50 years of age. Herein, a meta-analysis aimed to assess the association between X-ray repair cross complementing (XRCC) polymorphisms and OC risk. METHODS: Four databases were searched extensively until June 5, 2020. Subgroup analysis, meta-regression, and funnel plots, as well as the quality assessment were estimated. RESULTS: Fifteen studies were entered to the analysis. With regards to allele, homozygote, heterozygote, recessive, and dominant models, the pooled ORs for XRCC1 rs1799782 polymorphism were 1.51 (P = 0.01), 1.45 (P = 0.11), 1.45 (P = 0.0003), 1.44 (P = 0.0002), and 1.29 (P = 0.26); for XRCC1 rs1799782 polymorphism were 1.65 (P = 0.11), 1.50 (P = 0.33), 1.06 (P = 0.83), 1.57 (P = 0.12), and 1.32 (P = 0.45); for XRCC1 rs25489 polymorphism were 0.01 (P = 0.19), 1.44 (P = 0.48), 1.21 (P = 0.72), 1.17 (P = 0.19), and 1.38 (P = 0.54); for XRCC2 rs2040639 polymorphism were 0.68 (P = 0.0002), 0.63 (P = 0.02), 0.95 (P = 0.92), 0.79 (P = 0.49), and 0.61 (P = 0.005); and for XRCC3 rs861539 polymorphism were 1.24 (P = 0.20), 1.28 (P = 0.48), 0.99 (P = 0.95), 1.15 (P = 0.46), and 1.52 (P = 0.15), respectively. CONCLUSIONS: The T allele and CT genotype of XRCC1 rs1799782 polymorphism had an elevated risk, whereas the G allele and GG genotype of XRCC2 rs2040639 polymorphism had a protective role in OC.