The Impact of Scars After DIEP-Flap Breast Reconstruction on Satisfaction and HR-QoL: A Cross-Sectional Study Comparing BREAST-Q Scores.

Background: Although deep inferior epigastric perforator (DIEP) flap breast reconstruction is the most widely used technique for autologous breast reconstruction, this technique leads to large scars in visible areas on breast and abdomen. So far, limited studies have thoroughly addressed the impact of breast and abdominal scars on satisfaction and Health-related Quality of Life (HR-QoL).

Objectives: This research aimed to determine whether women with no/minor scar symptoms after undergoing DIEP-flap breast reconstruction differ in satisfaction and perceived HR-QoL from women with symptomatic scars.

Microneedling in Abdominal Scarring after DIEP-flap Breast Reconstruction to Improve Scar Quality: A Randomized Controlled Split Scar Trial.

Background: Deep inferior epigastric perforator (DIEP) flap breast reconstruction leads to large scars in the breast and abdominal region. Common symptoms related to abdominal scarring include changes in color, stiffness, thickness, and irregularity of the skin. The aim of this study was to examine whether microneedling improves the abdominal scar quality after DIEP-flap breast reconstruction.

The association between acne care provision and quality of life: A cross-sectional survey.

Background And Aims: It has been suggested that professional acne care can be effective not only in reducing clinical signs but also in improving quality of life (QOL). This study aims to reach a better understanding of the association between QOL and professional acne care. The study also investigates other factors that might influence QOL such as age, gender, and acne severity.

IFN-γ-induced PD-L1 expression on human melanocytes is impaired in vitiligo.

Mounting evidence shows that the PD-1/PD-L1 axis is involved in tumor immune evasion. This is demonstrated by anti-PD-1 antibodies that can reverse tumor-associated PD-L1 to functionally suppress anti-tumor T-cell responses. Since type I and II interferons are key regulators of PD-L1 expression in melanoma cells and IFN-γ-producing CD8 T cells and IFN-α-producing dendritic cells are abundant in vitiligo skin, we aimed to study the role of PD-1/PD-L1 signalling in melanocyte destruction in vitiligo.

Reallocations in acne healthcare: exploring the possible roles and added value of non-physicians by a mixed-methods study design.

Background: A highly promoted opportunity for optimizing healthcare services is to expand the role of non-physician care providers by care reallocation. Reallocating care from physicians to non-physicians can play an important role in solving systemic healthcare problems such as care delays, hospital overcrowding, long waiting lists, high work pressure and expanding healthcare costs. Dermatological healthcare services, such as the acne care provision, are well suited for exploring the opportunities for care reallocation as many different types of care professionals are involved in the care process.

Exploring patient journeys through acne healthcare: a patient perspective.

Background: Despite the large availability of caregivers, there are no standardized care pathways for patients with acne. This increases the risk of ineffective care and unnecessary medicalizing. To better understand how to provide effective, efficient, and patient-satisfying care, it is necessary to gain insights into the patient journey through acne healthcare services.

The impact of scars on health-related quality of life after breast surgery: a qualitative exploration.

Purpose: The purpose of this research was to explore women's experiences after breast surgery with scar characteristics and symptoms, and its impact on their health-related quality of life (HRQOL).

Material And Methods: A qualitative study using semi-structured face-to-face interviews was conducted among women following prophylactic, oncologic, or reconstructive breast surgery in the Netherlands. A directed content analysis was performed using guiding themes.

Anti-Melanoma immunity and local regression of cutaneous metastases in melanoma patients treated with monobenzone and imiquimod; a phase 2 a trial.

Vitiligo development in melanoma patients during immunotherapy is a favorable prognostic sign and indicates breakage of tolerance against melanocytic/melanoma antigens. We investigated a novel immunotherapeutic approach of the skin-depigmenting compound monobenzone synergizing with imiquimod in inducing antimelanoma immunity and melanoma regression. Stage III-IV melanoma patients with non-resectable cutaneous melanoma metastases were treated with monobenzone and imiquimod (MI) therapy applied locally to cutaneous metastases and adjacent skin during 12 weeks, or longer.

Tumor-infiltrating T-cells: important players in clinical outcome of advanced melanoma patients.

Immune escape mechanisms are prevalent in tumors, while their influence on the potency of antitumor immunotherapy has yet to be distinguished. We recently showed that increased numbers of intratumoral T cells rather than immune-escape-mechanisms significantly correlated with clinical outcome of advanced melanoma patients to subsequent autologous tumor cell vaccination. Our data emphasize the therapeutic relevance of tumor-infiltrating T cells for the clinical outcome.

The antibody response against MART-1 differs in patients with melanoma-associated leucoderma and vitiligo.

Patients with melanoma may develop skin depigmentation spontaneously or following therapy, referred to as melanoma-associated leucoderma (MAL). As clinical presentation of MAL may precede primary/metastatic melanoma detection, recognition of MAL is important to prevent its misdiagnosis as vitiligo and the subsequent application of immunosuppressive treatment. To reveal the immunity involved in MAL development, we investigated the presence of antibody and T-cell immune responses directed against the melanocyte-differentiation-antigens MART-1 (Melan-A), tyrosinase and gp100 in patients with MAL, as compared to patients with vitiligo.

Immune-escape markers in relation to clinical outcome of advanced melanoma patients following immunotherapy.

In this study, we investigated a large series of immune (escape) markers, relevant to T-cell function, as potential biomarkers for clinical outcome following immunotherapy. We retrospectively studied the expression of immune (escape) markers in metastatic melanoma tissues of 27 patients before autologous tumor cell vaccination, and 16 patients who were intended to treat but were not vaccinated because of rapid disease progression. Immunohistochemical data of infiltrating (suppressive) cells, such as T cells, regulatory T cells, myeloid-derived suppressor cells, and mast cells, or the expression of T-cell inhibitory factors (PD-1/PD-L1, IDO, and galectins), cytotoxic molecules (granzyme-B), melanocyte differentiation antigens, HLA class-I and tolerogenic cytokines [interleukin (IL)-1, IL-6, IL-10, TNF-α, and TGF-β] were correlated statistically to clinical outcome and overall survival (OS).

Melanocyte-specific immune response in a patient with multiple regressing nevi and a history of melanoma.

Background/aim: Regressing nevi are considered an example of an efficient early antitumoral response preventing the development of neoplasia. The underlying mechanism has not been elucidated, although an immune-based destruction of melanocytes is supposed. The aim of this study was to provide evidence of an effective immunosurveillance of pigment lesions in a patient at high risk of melanoma.

In vivo vitiligo induction and therapy model: double-blind, randomized clinical trial.

In this study, we developed an in vivo vitiligo induction model to explore the underlying mechanisms leading to Koebner's phenomenon and to evaluate the efficacy of therapeutic strategies. The model consisted of 12 pigmented test regions on the back of generalized vitiligo patients that were exposed to three Koebner induction methods: cryotherapy, 755 nm laser therapy, and epidermal abrasion. In addition, four cream treatments (pimecrolimus, tacrolimus, steroid and placebo) were randomly applied.

T-cell immune function in tumor, skin, and peripheral blood of advanced stage melanoma patients: implications for immunotherapy.

Purpose: To predict the potential antitumor effect of antigen-specific T cells in melanoma patients, we investigated T-cell effector function in relation to tumor-escape mechanisms.

Experimental Design: CD8(+) T cells isolated from tumor, adjacent normal skin, and peripheral blood of 17 HLA-A2(+) patients with advanced-stage melanoma were analyzed for their antigen specificity and effector function against melanocyte differentiation antigens MART-1, gp100, and tyrosinase by using HLA-A2/peptide tetramers and functional assays. In addition, the presence of tumor-escape mechanisms PD-L1/PD-1 pathway, FoxP3 and loss of HLA or melanocyte differentiation antigens, both required for tumor cell recognition and killing, were studied.

The HGF/MET pathway as target for the treatment of multiple myeloma and B-cell lymphomas.

Hepatocyte growth factor (HGF) and its receptor MET are essential during embryonic development and throughout postnatal life. However, aberrant MET activation, due to overexpression, mutations, or autocrine ligand production, contributes to the development and progression of a variety of human cancers, often being associated with poor clinical outcome and drug resistance. B cell malignancies arise from B cells that are clonally expanded at different stages of differentiation.

Effective melanoma immunotherapy in mice by the skin-depigmenting agent monobenzone and the adjuvants imiquimod and CpG.

Background: Presently melanoma still lacks adequate treatment options for metastatic disease. While melanoma is exceptionally challenging to standard regimens, it is suited for treatment with immunotherapy based on its immunogenicity. Since treatment-related skin depigmentation is considered a favourable prognostic sign during melanoma intervention, we here aimed at the reverse approach of directly inducing vitiligo as a shortcut to effective anti-melanoma immunity.

First histopathological and immunophenotypic analysis of early dynamic events in a patient with segmental vitiligo associated with halo nevi.

Segmental vitiligo is often ascribed to the neurogenic theory of melanocyte destruction, although data about the initial etiopathological events are scarce. Clinical, histopathological and T-cell phenotypic analyses were performed during the early onset of a segmental vitiligo lesion in a patient with associated halo nevi. Histopathological analysis revealed a lymphocytic infiltrate, mainly composed of CD8+ T-cells and some CD4(+) T-cells around the dermo-epidermal junction.

Functional analysis of HGF/MET signaling and aberrant HGF-activator expression in diffuse large B-cell lymphoma.

Inappropriate activation of MET, the receptor tyrosine kinase for hepatocyte growth factor (HGF), has been implicated in tumorigenesis. Although we have previously shown that HGF/MET signaling controls survival and proliferation of multiple myeloma (MM), its role in the pathogenesis of other B-cell malignancies has remained largely unexplored. Here, we have examined a panel of 110 B-cell malignancies for MET expression, which, apart from MM (48%), was found to be largely confined to diffuse large B-cell lymphomas (DLBCLs) (30%).

Follicular dendritic cells catalyze hepatocyte growth factor (HGF) activation in the germinal center microenvironment by secreting the serine protease HGF activator.

Ag-specific B cell differentiation, the process that gives rise to plasma cells and memory B cells, involves the formation of germinal centers (GC). Within the GC microenvironment, multiple steps of B cell proliferation, selection, and maturation take place, which are controlled by the BCR in concert with cytokines and contact-dependent signals from follicular dendritic cells (FDCs) and T cells. Signaling by the multifunctional cytokine hepatocyte growth factor (HGF) and its receptor MET has been shown to induce integrin-mediated adhesion of B cells to VCAM-1, which is expressed by FDCs.

Multiple myeloma cells catalyze hepatocyte growth factor (HGF) activation by secreting the serine protease HGF-activator.

Multiple myeloma (MM) is a common hematologic neoplasm consisting of malignant plasma cells, which expand in the bone marrow. A potential key signal in the evolution of MM is hepatocyte growth factor (HGF), which acts as a potent paracrine and/or autocrine growth factor and survival factor for MM cells. Proteolytic conversion of HGF into its active form is a critical limiting step in HGF/MET signaling.

Illegitimate WNT signaling promotes proliferation of multiple myeloma cells.

The unrestrained growth of tumor cells is generally attributed to mutations in essential growth control genes, but tumor cells are also influenced by signals from the environment. In multiple myeloma (MM), the factors and signals coming from the bone marrow microenvironment are possibly even essential for the growth of the tumor cells. As targets for intervention, these signals may be equally important as mutated oncogenes.

c-Cbl is involved in Met signaling in B cells and mediates hepatocyte growth factor-induced receptor ubiquitination.

Hepatocyte growth factor/scatter factor (HGF) and its receptor tyrosine kinase Met are key regulators of epithelial motility and morphogenesis. Recent studies indicate that the HGF/Met pathway also plays a role in B cell differentiation, whereas uncontrolled Met signaling may lead to B cell neoplasia. These observations prompted us to explore HGF/Met signaling in B cells.