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.

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 Fiber Optic Sensor for Monitoring the Spectral Alterations and Depth in Ex Vivo and In Vivo Cryosurgery.

This article discusses how to monitor the freezing depth during cryotherapy using a fiber optic array sensor. The sensor was used to measure the backscattered and transmitted light from frozen and unfrozen ex vivo porcine tissue and in vivo human skin tissue (finger). The technique exploited the variations in optical diffusion properties of the frozen and unfrozen tissues to determine the extent of freezing. Ex vivo and in vivo measurements yielded comparable results, despite spectral variations attributable to the hemoglobin absorption peak in the human frozen and unfrozen tissues. However, because the spectral fingerprints of the freeze-thaw process in the ex vivo and in vivo experiments were similar, we could extrapolate the maximum depth of freezing. Therefore, this sensor has the potential to be utilized for monitoring cryosurgery in real time.

Flagellate dermatitis in a patient with testicular germ cell neoplasia on bleomycin.

Bleomycin, an antineoplastic antibiotic that inhibits DNA synthesis, is used to treat various malignant tumors such as Hodgkin's lymphoma, squamous cell carcinoma, and germ cell tumors. Flagellate erythema is a rare rash with a linear pattern that has been observed in association with bleomycin treatment. Herein, we present a 43-year-old patient with metastatic testicular cell neoplasms who developed a whiplash rash during treatment with a chemotherapy regimen that included bleomycin. A typical case of bleomycin-related flagellate dermatitis has been diagnosed and the main features of this characteristic adverse drug event are briefly discussed.

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.

Paraneoplastic Syndromes in Patients with Keratinocyte Skin Cancer.

A variety of well-characterized cutaneous paraneoplastic syndromes (PNS) are diagnosed during internal malignancies; however, the spectrum of keratinocyte skin neoplasms (KSC) related to PNS is still obscure. The aim of the present review is to compile and evaluate the literature data on PNS associated with a keratinocyte skin neoplasm (KSC). Employing Pubmed, MEDLINE was searched for KSC-associated PNS reports. Forty relevant entries were assembled, reporting a total of 41 PNS cases associated with a KSC (34 male). No review paper compiling this topic was found. Six distinct PNS entities were identified, and malignancy associated hypercalcemia (MAH; 78%), anemia (10%) and Bazex syndrome (5%) were the most frequently reported among them. 85% of the PNS were reported in association with SCC, 10% with BCC, and the rest with adnexal tumors. The median age of the patients at the time of PNS diagnosis was 58 years (range: five-83 years). In most cases the PNS was diagnosed either concurrently or after the KSC diagnosis. KSC predisposing conditions, as scars (22%) or hidradenitis suppurativa (20%), were reported in >70% of the PNS cases. Most PNS resolved after KSC treatment. In conclusion, PNS of a rather limited spectrum of entities are reported in association with KSC. They also seem to be rare, possibly reflecting a limited capacity of KSC to provoke overt PNS.

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.

A Guttate Psoriasis That Tends to Spare Three Tattoos: A Macrophage Liaison.

Induction of new psoriasis sites was reported in only a small amount of psoriasis patients undergoing tattooing, despite the intuitive belief that tattoo trauma might awaken the disease due to the isomorphic phenomenon of Koebner. In this case report, we discuss a patient who presented with a remarkable sparing of his three tattoo sites during a guttate psoriasis flare-up that was unrelated to tattooing. The spatial concordance of tattoo and psoriasis lesions was analyzed on clinical pictures of tattoo sites taken during the psoriasis episode. For the quantification of the spatial distribution of the psoriasis lesions, Voronoi diagrams were generated, and coefficients of variation and the two-sample t-test were employed to compare the distributions of Voronoi patch sizes in different settings. Compared to skin areas without tattoos, a tattoo introduced a higher variation in the sizes of the Voronoi patches centered around psoriasis lesions. Based on our findings, we would like to discuss the possible role of macrophages as the key cellular link in the complex pathophysiologic relationship between tattooing/tattoo and psoriasis. Taking into account the relationship of autophagy and psoriasis lesions, we propose the hypothesis that tattoos represent a "psoriasis-hostile" tissue environment pertained by a population of LAP active M2-polarized macrophages. Further clinical studies of the relationship of psoriasis lesions to the tattooed skin are needed and may provide important insights into the role of macrophages in the pathogenesis of psoriasis.

Single photon emission computed tomography myocardial perfusion imaging in patients with moderate to severe psoriosissis.

BACKGROUND: Psoriasis is a chronic inflammatory disorder with an increased risk for coronary artery disease (CAD). This retrospective study aimed to evaluate the rate of myocardial ischaemia in patients with psoriasis subjected to myocardial perfusion imaging (MPI). MATERIAL AND METHODS: Twelve patients with moderate to severe psoriasis that had MPI were compared to 395 MPIs randomly retrieved from our MPIs pool data. All patients had a [99mTc]tetrofosmin stress - rest single-photon emission computer tomography ([99mTc]SPECT). Summed difference scores (SDS) were calculated for stress (SSS), rest (SRS) and their difference (SDS = SSS - SRS). RESULTS: There was no significant difference in the frequency of abnormal MPI SPECT outcomes between patients with vs. without psoriasis (6/12 vs 214/395 respectively; p = 0.778). From the evaluation of SSS, SRS and SDS, only the SDS scores of inadequately compensated resting perfusion defects were significantly lower in patients with psoriasis (p = 0.012). CONCLUSIONS: Patients with moderate-to-severe psoriasis had a similar rate of abnormal SSS scans compared to control patients. However, the SDS scans were significantly lower in patients with psoriasis indicating compromised reversibility of resting perfusion defects. Larger controlled studies are needed to verify these observations.