Comparing Line-Field Confocal Optical Coherence Tomography and Reflectance Confocal Microscopy on the In Vivo Healing Process of Lesions Induced by Fractional Photothermolysis.

Background: The advent of ablative fractional photothermolysis has revolutionized laser dermatology by providing a method to produce well-standardized, precise, and repeatable microscopic lesions. These wounds typically heal within 1-3 weeks, depending on the body site, with a minimal risk of permanent scarring. This positions ablative fractional photothermolysis as an exemplary in vivo model for studying the skin's wound healing processes.

[Screening for cutaneous melanoma: little impact, major challenges].

Routine screening for melanoma has never been shown to be effective. Here, we revisit this debate and the preconceived notion that the increased detection of early-stage melanoma should necessarily be followed within the same population by a reduction in the incidence of advanced stages, which is not supported by any evidence. The issue of overdiagnosis, which has been debated for several decades, is discussed in the light of screening practices.

The human antigen R as an actionable super-hub within the network of cancer cell persistency and plasticity.

In this perspective article, a clinically inspired phenotype-driven experimental approach is put forward to address the challenge of the adaptive response of solid cancers to small-molecule targeted therapies. A list of conditions is derived, including an experimental quantitative assessment of cell plasticity and an information theory-based detection of in vivo dependencies, for the discovery of post-transcriptional druggable mechanisms capable of preventing at multiple levels the emergence of plastic dedifferentiated slow-proliferating cells. The approach is illustrated by the author's own work in the example case of the adaptive response of BRAFV600-melanoma to BRAF inhibition.

Multistage Reconstruction of Large Arm Defect Using Keystone Type I Flap and Temporary Synthetic Skin Substitute.

Large arm defects remain a challenge to the reconstructive surgeon, as local and regional flaps are limited regarding size and free flaps have disadvantages such as poor color match, technical complexity, prolonged operative time, and the risk of total flap loss. Keystone flaps are fascia-based flaps and combine perforator-based vascularity with relative simplicity of nonmicrosurgical techniques and do not distort local anatomy in cases of malignant excision with wide defects. This article highlights the approach of a multistaged procedure to reconstruct a large arm defect using a keystone type I flap and a temporary synthetic skin substitute for closure in a patient referred to our department for wide resection of a large melanoma in situ on the posterior aspect of the left arm.

Swiss Recommendations for Cutaneous Basal Cell Carcinoma.

Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer in Switzerland and worldwide. Most BCCs can be treated in a curative setting. However, patients can develop locally destructive and, rarely, metastatic tumors that require a different treatment approach.

Inhibition of the DAPKs-L13a axis prevents a GAIT-like motif-mediated HuR insufficiency in melanoma cells.

We previously showed that the adaptive response of BRAFV600-mutated melanoma cells to BRAF inhibition emerges from a subpopulation of cells expressing an intermittent lower level of the mRNA-binding protein HuR. In this study, following initial overexpression experiments in which we confirm our previous results, we use wild-type and mutants HuR full-length mRNA constructs and in vivo-interacting assays and demonstrate that a highly conserved interferon-γ-activated inhibitor of translation (GAIT)-like motif located upstream of the GU-rich elements of HuR major polyadenylation site (PAS2), interacts with constituents of the GAIT complex and affects HuR post-transcriptional expression regulation. Knockdown of the ribosomal protein L13a or the inhibition of the DAPK1-ZIPK axis involved in L13a phosphorylation, reduces the proportion of HuR cells at steady-state and attenuates the adaptive response of the whole melanoma-cell population to BRAF inhibition.

Rintala Flap and Posterior Perichondrial Cutaneous Graft: A Combined Approach for Nasal Tip Reconstruction.

Nasal tip reconstruction requires a meticulous approach due to the complexity of the nasal anatomy and its aesthetic importance. Many procedures have been described to restore this aesthetic unit, including the paramedian forehead flap, which is one of the workhorse flaps. However, despite excellent final outcomes, this procedure may be refused by patients, due to its temporary conspicuous appearance possibly associated with serious psychological implications, and the need of multiple interventions.

Head and Neck Porocarcinoma: SEER Analysis of Epidemiology and Survival.

Unlabelled: Porocarcinoma is a rare malignant adnexal tumor. Little is known about the location of the disease in the head and neck. Our aim is to offer the largest analysis of demographic, pathological, and treatment patterns of head and neck porocarcinoma in comparison with other locations of the neoplasm from an epidemiologically representative cohort.

[BRAF inhibitors-induced paradoxical reactions and oncogenesis].

Paradoxical oncogenesis and benign paradoxical proliferations occur in off-target rapidly regenerating labile tissues of patients treated for malignancies with small-molecule inhibitors of cell-signaling such as kinase inhibitors. These paradoxical proliferations, particularly well listed in patients treated with selective BRAF inhibitors carrying BRAF-mutated solid malignancies, have had their incidence reduced upon the advent of BRAF/MEK double blockade therapies. Mechanistically, the underlying molecular events involved in paradoxical proliferations in off-target tissues could prove to be as complex as those involved in the adaptive resistance of malignant cells to targeted therapies.

Survival outcomes and epidemiology of Merkel cell carcinoma of the lower limb and hip: A Surveillance, Epidemiology, and End Results analysis 2000-2018.

Background: Merkel cell carcinoma of lower limb and hip skin is a rare skin tumor that has a high recurrence rate.

Objective: To assess epidemiology and survival outcomes of the lower limb and hip Merkel cell carcinoma, which are less addressed in the literature.

Methods: The Surveillance, Epidemiology, and End Results database was searched for all cases of skin Merkel cell carcinoma between 2000 and 2018.

A mutual information-based in vivo monitoring of adaptive response to targeted therapies in melanoma.

The mechanisms of adaptive resistance to genetic-based targeted therapies of solid malignancies have been the subject of intense research. These studies hold great promise for finding co-targetable hub/pathways which in turn would control the downstream non-genetic mechanisms of adaptive resistance. Many such mechanisms have been described in the paradigmatic BRAF-mutated melanoma model of adaptive response to BRAF inhibition.

Anti-PD-1-Induced Hidradenitis Suppurativa.

Mucocutaneous adverse events are commonly observed under immune checkpoint inhibitors (ICIs) therapy. Here, we report the case of a 43-year-old male patient with a stage IIIC melanoma disease who developed hidradenitis suppurativa (HS) three months after the beginning of an anti-PD-1 (nivolumab) adjuvant therapy. The patient had no comorbidities other than obesity and severe acne during adolescence.

Skin cancer screening in Switzerland: Cross-sectional trends (1997-2012) in socioeconomic inequalities.

Introduction: Skin cancer is one of the most common malignancies. Despite controversy over its efficacy, skin cancer screening has become widespread although socioeconomic screening inequalities have been documented. Switzerland has the highest rate of melanoma in Europe but Swiss trends in skin cancer screening and social disparities have not been investigated.

Drug-induced expression of the RNA-binding protein HuR attenuates the adaptive response to BRAF inhibition in melanoma.

Strategies that aim to limit the adaptive response to pathway inhibition in BRAF-mutated melanoma face the inherent limit of signaling redundancy and multiplicity of possible bypass mechanisms. Drug-induced expression of selected RNA-binding proteins, like the ubiquitously expressed HuR, has the potential to differentially stabilize the expression of many genes involved in the compensatory mechanisms of adaptive response. Here, we detect in BRAF-mutated melanoma cell lines having a higher propensity for adaptive response and in non-responding melanoma tumors, a larger proportion of HuR cells in the expression distribution of HuR.

[Recent advances in the adjuvant treatment of high-risk melanoma].

Despite tremendous therapeutic innovations during the last decade, the prognosis of metastatic melanoma remains uncertain. Adjuvant therapy following resection of high-risk melanoma is currently under intense investigation. Both small-molecules targeted therapy and immune checkpoint inhibitor therapy, initially developed for metastatic disease, have proven to be efficient in the adjuvant setting in phase 3 trials.

Recognition of early melanoma: a monocentric dermoscopy follow-up study comparing de novo melanoma with nevus-associated melanoma.

Background: The earlier detection of melanomas occurring within preexisting nevi is theoretically possible using sequential dermoscopy. Characterizing the early follow-up changes of nevus-associated melanomas (NAMs) and differentiating them from those observed in de novo melanomas (DNMs) may help the earlier recognition of NAMs.

Methods: Using descriptive dermoscopic features to detect focal changes, we blindly evaluated retrospectively the baseline and follow-up images of 32 melanomas that were subsequently classified as histopathologically defined NAMs or DNMs.

Hu antigen R (HuR) heterogeneous expression quantification as a prognostic marker of melanoma.

Background: Prognostic markers for melanoma, particularly for stage II disease, are needed for the risk-benefit evaluation of future adjuvant therapies. The mainly nuclear RNA-binding protein human antigen R (HuR) regulates the protein expression of thousands of mRNAs, its own heterogeneous expression could therefore reflect tumor heterogeneity and plasticity. Here, we evaluate its quantification in primary melanoma as a marker of metastatic outcome.

Evaluation of the National Swiss Skin Cancer Screening Campaign 2013: Do We Do the Right Thing.

Background: Skin cancer prevention and screening programs are performed in many countries. Their benefit is discussed controversially.

Objective: Our aim is to evaluate the Skin Cancer Screening Program 2013 in Switzerland by following up screenees upon interventions.

Overexpression of the human antigen R suppresses the immediate paradoxical proliferation of melanoma cell subpopulations in response to suboptimal BRAF inhibition.

Tumor plasticity and the heterogeneous response of melanoma cells to targeted therapies are major limits for the long-term efficacy of this line of therapy. Targeting tumor plasticity is theoretically possible through the modulation of the expression of RNA-binding proteins which can affect many different compensatory mechanisms of the adaptive response of malignant cells to targeted therapies. Human antigen R (HuR) is a modulator of gene expression and a transacting factor in the mRNA-processing machinery used in the cell stress response, and is a potential target for reducing tumor plasticity.

In vivo reflectance confocal microscopy: a useful non-invasive tool to assess the response to isolated limb perfusion for superficial pigmented melanoma in-transit metastatic disease. Report of a case.

Complete response can be difficult to assess after isolated limb perfusion (ILP) for metastatic in-transit melanoma, especially when numerous and unresectable post-necrotic persisting pigmented lesions occur. These residual lesions are mainly seen in the more superficial and pigmented types of metastatic disease and correspond to the residual melanophage granuloma that persists after tumor tissues undergo complete necrosis. Reflectance confocal microscopy (RCM) is a non-invasive technique that allows the exploration of the superficial dermis.

Psammomatous Melanotic Schwannoma: A Challenging Histological Diagnosis.

Psammomatous melanotic schwannoma (PMS) is a rare pigmented tumor that can be part of the Carney complex. Here, we describe the case of a 35-year-old female patient presenting an isolated subcutaneous PMS. Histopathological analysis could not formally exclude the malignant nature of the tumor.