The Neutrophil-to-Lymphocyte Ratio as a Biomarker in Cutaneous Oncology: A Systematic Review of Evidence beyond Malignant Melanoma.

With the ongoing progress of basic research along with the introduction of new pharmaceutical options spanning almost all therapeutic areas, the need for biomarkers that will be implemented into the personalized medical approach is higher than ever. Their use can be incorporated into clinical practice and can be applied to the classification of disorders and the evaluation of disease severity but also to the monitoring of the progress of therapeutic/pharmaceutical interventions. This systematic review collects the findings of hematologic biomarkers in various cutaneous malignancies, excluding malignant melanoma, to support their potential use in the prognosis but also in the assessment of therapeutic strategies for the specific category of skin disorders.

BCC and Immunocryosurgery scar differentiation through computational resolution-enhanced OCT images and skin optical attenuation: A proof-of-concept study.

Monitoring medical therapy remains a challenging task across all non-surgical skin cancer treatment modalities. In addition, confirmation of residual tumours after treatment is essential for the early detection of potential relapses. Optical coherence tomography (OCT), a non-invasive method for real-time cross-sectional imaging of living tissue, is a promising imaging approach for assessing relatively flat, near-surface skin lesions, such as those that occur in most basal cell carcinomas (BCCs), at the time of diagnosis. However, the skin's inherent property of strong light scattering impedes the implementation of OCT in these cases due to the poor image quality. Furthermore, translating OCT's optical parameters into practical use in routine clinical settings is complicated due to substantial observer subjectivity. In this retrospective pilot study, we developed a workflow based on the upscale of the OCT images resolution using a deep generative adversarial network and the estimation of the skin optical attenuation coefficient. At the site of immunocryosurgery-treated BCC, the proposed methodology can extract optical parameters and discriminate objectively between tumour foci and scar tissue.

The Promise of Semantic Segmentation in Detecting Actinic Keratosis Using Clinical Photography in the Wild.

AK is a common precancerous skin condition that requires effective detection and treatment monitoring. To improve the monitoring of the AK burden in clinical settings with enhanced automation and precision, the present study evaluates the application of semantic segmentation based on the U-Net architecture (i.e., AKU-Net). AKU-Net employs transfer learning to compensate for the relatively small dataset of annotated images and integrates a recurrent process based on convLSTM to exploit contextual information and address the challenges related to the low contrast and ambiguous boundaries of AK-affected skin regions. We used an annotated dataset of 569 clinical photographs from 115 patients with actinic keratosis to train and evaluate the model. From each photograph, patches of 512 × 512 pixels were extracted using translation lesion boxes that encompassed lesions in different positions and captured different contexts of perilesional skin. In total, 16,488 translation-augmented crops were used for training the model, and 403 lesion center crops were used for testing. To demonstrate the improvements in AK detection, AKU-Net was compared with plain U-Net and U-Net++ architectures. The experimental results highlighted the effectiveness of AKU-Net, improving upon both automation and precision over existing approaches, paving the way for more effective and reliable evaluation of actinic keratosis in clinical settings.

Image Perceptual Similarity Metrics for the Assessment of Basal Cell Carcinoma.

Efficient management of basal cell carcinomas (BCC) requires reliable assessments of both tumors and post-treatment scars. We aimed to estimate image similarity metrics that account for BCC's perceptual color and texture deviation from perilesional skin. In total, 176 clinical photographs of BCC were assessed by six physicians using a visual deviation scale. Internal consistency and inter-rater agreement were estimated using Cronbach's α, weighted Gwet's AC2, and quadratic Cohen's kappa. The mean visual scores were used to validate a range of similarity metrics employing different color spaces, distances, and image embeddings from a pre-trained VGG16 neural network. The calculated similarities were transformed into discrete values using ordinal logistic regression models. The Bray-Curtis distance in the YIQ color model and rectified embeddings from the 'fc6' layer minimized the mean squared error and demonstrated strong performance in representing perceptual similarities. Box plot analysis and the Wilcoxon rank-sum test were used to visualize and compare the levels of agreement, conducted on a random validation round between the two groups: 'Human-System' and 'Human-Human.' The proposed metrics were comparable in terms of internal consistency and agreement with human raters. The findings suggest that the proposed metrics offer a robust and cost-effective approach to monitoring BCC treatment outcomes in clinical settings.

Treatment of nail clippings with ethyl alcohol improves the efficacy of Raman spectroscopy in the diagnosis of Trichophyton rubrum onychomycosis.

The purpose of this work was to enhance the diagnostic accuracy of nail Raman spectroscopy for fungal nail infections, specifically onychomycosis caused by Trichophyton rubrum. The study assessed the different ethyl alcohol retention rates between control and infected nails after soaking nail clippings in ethanolic solutions and drying. Results revealed that ethyl alcohol completely evaporated from infected nail samples, while significant amounts were still present in control samples. Principal component analysis (PCA) was applied to discriminate control from infected nails and showed superior group separation when nails were treated with ethyl alcohol. PCA loadings plot attributed the efficient classification to the νs (CCO) Raman vibrational mode of ethyl alcohol. As Raman spectroscopy can detect minute concentration changes of ethyl alcohol in nails and the deterioration caused by onychomycosis accelerates its evaporation, a simple and rapid method for detecting T. rubrum onychomycosis is proposed.

A Meta-Analysis on the Impact of the COVID-19 Pandemic on Cutaneous Melanoma Diagnosis in Europe.

The COVID-19 pandemic has been the epicenter of healthcare attention globally for the past two years, and large-scale adaptations in healthcare provision have been required. This study aimed to investigate the impact of the pandemic and the resulting lockdowns on cutaneous melanoma diagnosis and tumor burdens in Europe. A relevant literature search in electronic databases was conducted from inception to September 2022. The inclusion criteria were: controlled studies published in a peer-reviewed journal evaluating cutaneous melanoma in Europe and reporting data on melanoma characteristics from diagnoses. The quality of studies was evaluated using the Cochrane ROBINS-I tool for assessing bias in non-randomized studies. Meta-analysis was conducted utilizing a random effects model to synthesize the data. A total of 25 studies involving 32,231 patients were included in the data analysis models. Statistically significant increases in mean Breslow thickness (0.29 mm (0.03-0.55 mm)), ulceration rates (OR = 1.66 (1.29-2.13)), and resultant tumor staging were observed in the PostCovid group, with subgroup analysis revealing that lockdown-derived data were responsible for this trend. This meta-analysis reported on the impact of COVID-19 restrictions on melanoma diagnosis in Europe, emphasizing the higher tumor burden and disease progression state provoked by healthcare adaptations in the pandemic period.

The Feasibility of Immunocryosurgery in the Treatment of Non-Superficial, Facial Basal Cell Carcinoma That Relapsed after Standard Surgical Excision: An Experience Report from Two Centers.

In this retrospective, chart review study, we evaluated the feasibility of immunocryosurgery in facial, non-superficial basal cell carcinomas (BCC) that had relapsed after standard surgery. Inclusion criteria were (a) 'biopsy confirmed relapse of facial BCC', (b) known 'calendar year of surgical excision(s)', and (c) 'relapse within 10 years after the last surgical excision'. Tumors treated from 1 January 2011 to 31 December 2020 with a standard 5-week immunocryosurgery cycle (daily imiquimod application for 5 weeks and a cryosurgery session at day 14) were included. Descriptive statistics, Kaplan-Meier method, and Cox proportional hazards model were calculated with significance at p < 0.05. From the n = 27 BCC evaluated, n = 20 (74.1 ± 8.4%) cleared after one immunocryosurgery cycle. Two of the remaining cases cleared completely after a repeat cycle, one patient favored surgery, and four BCC did not clear despite additional immunocryosurgery cycles (feasibility 81.5 ± 7.5%). Of the 22 tumors with clinical outcome 'complete clearance with immunocryosurgery', three BCC relapsed at 9, 28, and 50 months. Overall, the 5-year treatment efficacy rate was 60.2 ± 13.4% (mean follow-up 94.6 ± 15.1 months). In total, 20/27 BCC relapses after surgery (74.1%) were tumor-free at the end of personalized follow-up times (66.7 ± 12.4% tumor free patients at 5-year follow-up). Number of tumor relapses before immunocryosurgery was the single predictor of tumor progression after immunocryosurgery (p = 0.012). Conclusively, immunocryosurgery could be further evaluated as an alternative, definitive treatment of selected facial BCC relapsing after surgery.

Methylprednisolone Plus Low-Dose Methotrexate for Bullous Pemphigoid-A Single Center Retrospective Analysis.

Monomodal systemic glucocorticoids remain the mainstay of treatment for bullous pemphigoid (BP). In this retrospective, single-arm study, we evaluated the feasibility (efficacy and tolerability) of the combination of methylprednisolone and low-dose (up to 12.5 mg/week) methotrexate (MP + MTX) for BP. At week 12, 53/55 (96.4%) patients initiated on MP + MTX during a five-year period (potential follow up time: ≥4 years) remained on treatment. At this time-point, BP remission was achieved in all compliant patients (including n = 24 cases of dipeptidyl peptidase-4 inhibitors-associated BP; 12-week remission rate: 100% [95% CI: 91.9-100.0%]; mean time to remission: 29.5 days, SEM: 2.3 days) at a mean cumulative MP dose to disease control of 678.4 mg (SEM = 49.4 mg). Eight patients relapsed during follow up (10.81 [95% CI: 5.16-21.72] relapses/100 person years, py), and seven manifested a severe adverse event (6.80 [95% CI: 3.00-14.28] severe adverse events/100 py); however, 73.4% (±7.9%) had suffered neither a relapse nor a SAE at the three-years follow up. Continuing low dose MP intake (≤8 mg/day) beyond week 12 in combination with MTX minimized the risk of a feasibility limiting event (p = 0.013). Conclusively, the combination of methylprednisolone with methotrexate is a promising, safe, and efficient modality for BP patients, which enables rapid glucocorticoid tapering.

Immunocryosurgery is a safe and feasible treatment for basal cell carcinoma and Bowen disease in renal transplant recipients.

Keratinocyte skin carcinomas (squamous cell carcinoma, basal cell carcinoma [BCC], Bowen disease [BD]) inflict significant morbidity and constitute a treatment challenge in renal transplant recipients (RTR). Immunocryosurgery has shown efficacy >95% in the treatment of BCC and BD in immunocompetent patients. The present study evaluated the safety, feasibility and efficacy, of immunocryosurgery in the treatment of BCC and BD in a series of RTR. During a 3-year period, biopsy-confirmed cases of BCC and BD were treated with a standard immunocryosurgery cycle (5 weeks daily imiquimod and a session of cryosurgery at day 14). Safety was evaluated by comparing graft function markers between immunocryosurgery treated RTR patients and matched controls. Ten BCC (8 nodular, 1 basosquamous, 1 superficial; diameter 6-14 mm; mean 9.2 mm) and nine BD disease lesions in nine patients (7 men, 2 women; age range: 54-70 years, mean: 62.1 years) were treated with immunocryosurgery and followed-up for two to 5 years. Five BCC were located on the "H area" of the face. No patient showed clinical or laboratory signs of transplant dysfunction during treatment or follow-up. Seven out of 10 BCC lesions cleared completely after one 5-week immunocryosurgery cycle, two cleared after repeat and intensified treatment cycles and one responded only partially (clearance rate: 90%). Seven out of nine BD lesions cleared after one 5-week immunocryosurgery cycle and one lesion after two cycles (clearance rate: 88.9%). In conclusion, immunocryosurgery is a safe, feasible and effective minimally invasive treatment alternative to standard surgical modalities for BCC and BD in RTR.

Application of a burn scar assessment tool for the evaluation of visual scarring following immunocryosurgery for facial basal cell carcinoma

Background: The therapeutic interventions for basal cell carcinoma (BCC) impact facial cosmesis. Objectives: Our aim was to assess the aesthetic burden of facial BCC treatment by evaluating the extent of the tumour site visually based on clinical images before and after immunocryosurgery; a minimally invasive combination treatment of topical imiquimod and cryosurgery. Materials & Methods: A three-item (texture, height, colour) burn scar scale was independently applied by four physicians (two dermatologists and two plastic surgeons) on archival semi-standardized clinical images of facial BCC before and one year after immunocryosurgery. The score assessments were compared using non-parametric statistical tests; internal consistency (reliability) and inter-rater agreement were assessed using Cronbach's α and Gwet's AC2, respectively. Results: Images (before and one year after treatment) of 27 BCCs from 26 patients (15 males) were analysed. The reliability was good (α>0.80) for all items before surgery and for colour after surgery. The inter-rater agreement was acceptable (AC2>0.70) for all items except for height pre-treatment (AC2 = 0.482). Based on averaging of all raters, cosmesis improved significantly after treatment at all tumour sites (p<0.001, Wilcoxon signed ranks test). The main limitations of the study are the inclusion of cases from a single centre and its retrospective nature. Conclusion: The evaluated burn scar scale can be reliably used to compare the extent of the BCC site visually before therapy and after resultant scars have formed. In this way, the impact of therapeutic interventions on cosmesis (from tumour to scar) can be evaluated, particularly for less aggressive facial skin tumours, such as most BCC.

A Review of Immunocryosurgery and a Practical Guide to Its Applications.

Immunocryosurgery is a minimally invasive combinational therapeutic procedure that has been designed, developed, and evaluated in the Dermatology Department of the University of Ioannina from 2004. In a fixed time protocol, this approach combines immune stimulatory therapy with imiquimod and cryosurgery, i.e., cryosurgery is applied during continuous imiquimod treatment. Laboratory findings in tissue and blood level credit the efficacy to the synergy of imiquimod and cryosurgery. The synergy has been established through clinical trials and the excellent feasibility and efficacy demonstrated in clinical practice. Immunocryosurgery has extensive proof of excellent efficacy, comparable to surgery, in the treatment of basal cell carcinoma. It has also been evaluated in cases of Bowen's disease, keratoacanthoma, Merkel cell carcinoma, lentigo maligna, and cutaneous squamous cell carcinoma with or without the addition of adjuvants. The aims of this review are to detail the immunocryosurgery protocol with the addition of daily practice clinical tips, compile data on the mechanism of action of immunocryosurgery, and delineate indications and possible future applications. Most of the available data originate from the treatment of BCC, of all histological types and localizations, and the principles reported mainly reflect on evidence related to the treatment of this common skin cancer.

Spirochetal uveitis: Spectrum of clinical manifestations, diagnostic and therapeutic approach, final outcome and epidemiological data.

PURPOSE: Analysis of cases with spirochetal uveitis related to spirochetes in a tertiary referral academic center. METHODS: Retrospective study of patients diagnosed with uveitis attributed to Treponema pallidum, Leptospira spp. and Borrelia burgdorferi from June 1991 until December 2019. RESULTS: A total of 57 cases of spirochetal uveitis (22 patients with T. pallidum, 26 with Leptospira spp., and 9 with B. burgdorferi) that consisted 1% of the overall number of uveitics were recorded. All these cases presented with a wide spectrum of clinical presentations (anterior uveitis, posterior uveitis, panuveitis, vasculitis, papillitis, and in some rare cases concomitant posterior scleritis). The treatment included mainly penicillin or doxycycline, while corticosteroids were administered systematically in some cases with Borrelia or Leptospira infection. The final visual outcome was favorable (> 6/10 in Snellen visual acuity) in approximately 76% of our patients. CONCLUSION: Despite being rare, spirochetal uveitis can be detrimental for the vision and must always be included in the differential diagnosis.

Aeromonas hydrophila Survives the Treatment of Posttraumatic Cellulitis in the Shelter of an Obscured Fish-Bone Fragment.

Fish bone and/or spine puncture injuries can result in infection of the upper extremities with aquatic bacterial pathogens. Additionally, in such injuries, the inoculation of foreign organic material is frequent and may further complicate the clinical presentation and course of the resulting infection. We describe the case of a 45-year-old female patient with a minimal fish rostrum puncture trauma acquired during preparation of fresh fish meal, which resulted in a galloping hand cellulitis. The alarming clinical presentation and the prompt response of the skin infection to clindamycin obscured the presence of inoculated fish rostrum remnants in the tissue that, three weeks later, gave rise to a foreign body granuloma, from which Aeromonas hydrophila was isolated. Final resolution was achieved with an additional two-week doxycycline treatment. In conclusion, the reported case highlights the potential of the accidentally implanted organic material, as are fish bones, not only to transfer uncommon pathogens but also to offer a sanctuary that favors microbial survival despite antibiotic therapy thus enabling latent or recurrent infections.

Cryosurgery, Intralesional Methotrexate and Imiquimod for Keratoacanthoma: Tuning the Combination.

Keratoacanthomas (KA) are self-regressing, destructively expanding keratinocyte skin neoplasms typically characterized by sudden onset of explosive growth followed by complete involution. Cryosurgery, intralesional methotrexate and imiquimod have been used alone or in combination of two for the treatment of KA. Presently 3 patients (49, 60, and 65 years old; two females, one suspected with Ferguson-Smith syndrome), with 5 KA (6-24 mm maximal diameter) were treated with the combination of cryosurgery (liquid N2, open spray, 2 cycles of 15 sec each) and intralesional methotrexate (2.5-30 mg cumulative dose) and subsequent daily application of imiquimod (14-35 days). Starting with 4 cryosurgery/intralesional methotrexate sessions and 5 weeks daily imiquimod, to document feasibility and efficacy we progressively reduced the intensity of the treatment to one cryosurgery/intralesional methotrexate (total dose: 5 mg) session and 14 days of daily imiquimod without compromising efficacy. KA stopped growing promptly with sustained clearance after 6-24 months follow up, implicating a huge potential of therapeutic synergy of the employed modalities in the management of KA. We suggest that, optimized, the present three modalities combination (one session mild cryosurgery/low dose, 5 mg intralesional methotrexate and 2 weeks once daily imiquimod) is a promising treatment for KA that merits evaluation in further studies.

The lipid profile of three Malassezia species assessed by Raman spectroscopy and discriminant analysis.

Malassezia yeasts constitute the major eukaryotic cutaneous flora of homoeothermic vertebrates. These lipophilic yeasts are able to cause, trigger, or aggravate common skin diseases under favorable conditions. Species identification and subspecies differentiation is currently based on morphological characteristics, lipid assimilation profile, and molecular tests. Mass spectrometry has been also reported as a reliable, yet costly and labor-intensive, method to classify Malassezia yeasts. Here, we introduce Raman spectroscopy as a new molecular technique able to differentiate three phylogenetically close Malassezia species (M.globosa, M.pachydermatis, and M.sympodialis) by examining their lipid metabolic profile. Using Raman spectroscopy, lipid fingerprints of Malassezia cultures on Leeming-Notman agar, were analyzed by spectral bands assignment and partial least squares discriminant analysis. Our results demonstrate differential utilization of lipid supplements among these three species and the ability of Raman spectroscopy to rapidly and accurately discriminate them by predictive modelling.