M J Barysch

University of Zurich, Zürich, Zurich, Switzerland

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Publications (5)8.54 Total impact

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    ABSTRACT: Background: Congenital melanocytic nevi (CMNs) are melanocytic neoplasms that can transform into melanoma. However, this development is impeded in the majority of cases and mostly affects patients with large or giant CMNs. Methods: To elucidate mechanisms that keep CMNs from malignant transformation, CMN tissue biopsies were investigated for p-ERK and senescence markers by immunohistochemistry and for SOX10/CD271 (p75<sup>NTR</sup>) by immunofluorescence. CMN cells were cultivated, and MTT assays were performed for evaluating cell viability. Mutation status for NRAS and BRAF was performed by real-time PCR. Results: 13 CMNs (from patients aged 0.5-11.8 years, mean: 2.7) showed immunoreactivity for SOX10/CD271 (p75<sup>NTR</sup>) in 34.2%. p-ERK was immunoreactive in 80% (4/5); β-galactosidase was significantly stronger expressed in CMNs compared to melanocytic nevi of patients over 70 years (p = 0.0085). The 5 CMN cultures were immunoreactive for SOX10/CD271 (p75<sup>NTR</sup>) in 36.7%. By silencing SOX10 by siRNA in 2 CMN cell cultures, cell viability decreased significantly. NRAS<sup>Q61K</sup> mutation was found in 91.7% (11/12) and BRAF<sup>V600E</sup> in 6.3% of all analyzable CMNs (1/16). Conclusions: Oncogene-induced senescence might prevent malignant transformation through activation of the mitogen-activated protein kinase pathway. SOX10 is necessary for the viability of human CMN cell cultures and may be responsible for clinical changes during aging. © 2014 S. Karger AG, Basel
    Dermatopathology. 01/2014; 1(1):35-46.
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    ABSTRACT: Introduction: Basal cell carcinoma (BCC) is the most frequent cancer with increasing incidence over the last decades. Standard of care is surgical excision, upon which complete tumour clearance is achieved in most cases. However, a small subgroup of patients will have remnants of disease post-excision and require further treatment options. Over 90% of all BCCs carry a mutation in PTCH 1 or SMO, two conducting proteins of the Hedgehog pathway (Hh). Therefore, inhibition of the Hh pathway is a promising option for systemic first-line therapy. Vismodegib was the first developed of these small molecules, which was approved by the FDA in January 2012. Areas covered: The authors review current treatment modalities for BCC and discuss current developments in pharmacological therapy. The current literature including meta-analyses, the Cochrane database and registered as well as completed randomized controlled trials. Expert opinion: Hh inhibitors are a new promising treatment option for patients with advanced or metastatic BCC. Phase I and II clinical trials with the Hh inhibitor, vismodegib, showed a significant reduction in tumour size and appearance of new tumours with relatively good tolerability. Nevertheless, further investigation on new molecules and the effectiveness of an intermittent dosing regimen is necessary.
    Expert Opinion on Pharmacotherapy 05/2013; · 2.86 Impact Factor
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    ABSTRACT: Dermatofibrosarcoma protuberans (DFSP) in childhood is a rare tumor with high recurrence rates. Wide local excision can result in disfiguring mutilation, whereas Mohs micrographic surgery (MMS) reduces surgical margins. MMS in children is not performed routinely, as the required infrastructures such as a histopathology lab in close proximity to the operating room is often lacking. We retrospectively reviewed children diagnosed with DFSP treated at our hospital over 2 years. We recorded surgical treatment details, including margins, duration of inpatient stay, outcome, follow-up, and molecular genetic tumor tissue analysis. Four children with a median age of 6.8 years (range 6.0-8.8 years) were identified who had a diagnostic delay of a median of 2.5 years (range 0.5-4.0 years); all underwent complete tumor excision using the slow MMS technique using vacuum-assisted closure systems between repeated excisions and before wound closure. The median maximal safety margins were 1.5 cm (range 1.0-3.0 cm). By using vacuum-assisted closure systems, no dressing changes were needed, pain was limited, and full mobility was maintained in all children. The median total time in the hospital was 11 days (range 10-14 days). No relapses occurred during a median follow-up of 25.8 months (range 11.3-32.6 months). Collagen 1A1/platelet-derived growth factor B (COL1A1/PDGFB) translocation on chromosomes 17 and 22 was detected in all three analyzable specimens. Lesions suspected of being DFSP warrant prompt histologic evaluation; interdisciplinary management is mandatory in particular for children. Micrographic surgery allows smaller surgical margins than wide excision and should be considered as the treatment of choice in children with DFSP. The interim usage of vacuum-assisted closure systems increases patient comfort. Translocations in the COL1A1/PDGFB gene imply susceptibility to targeted treatment modalities for therapy-resistant cases.
    Pediatric Dermatology 02/2013; · 1.04 Impact Factor
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    ABSTRACT: Melasma treatment remains challenging despite various laser systems available, because of potential side-effects and high recurrence rates. Non-ablative fractionated photothermolysis (FP) is a promising therapeutic method, long-time results comparing treated vs. non-treated site are lacking. A total of 14 patients were treated with FP in a split-face mode with standardized adjustments in three sessions (weeks 0, 3-4, 6-8, follow-up: 26-28). At each consultation, improvement was evaluated by patients and physicians. Objective assessment was performed using digital photographs and the pigment imaging tool SIAscope(®). Melasma improvement was registered in 83% and 75% of the cases 26-28 weeks after the first treatment based on two evaluations: by patient and by physician, respectively. Digital photography and SIAscope(®) revealed improvement in 54% and 85% after the first, 61% and 85% after the second, 41% and 58% after the third treatment, accordingly, mostly due to reduction of the outline sharpness. Patients with lighter skin complexions revealed significant improvement ranged from slight to moderate (P=0.03). Postinflammatory hyperpigmentation occurred in two cases with skin types III and IV. Non-ablative FP can be considered as a valuable treatment option with short-term improvement in terms of mild reduction and softening the edges of melasma in patients with skin types I/II, if prior topical therapies failed. Treatment of patients with skin types III+ should be critically questioned.
    Journal of the European Academy of Dermatology and Venereology 04/2011; 26(4):423-30. · 2.69 Impact Factor
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    ABSTRACT: Today skin cancer is mainly treated by surgical interventions. New findings concerning molecular biology and the signaling pathways in epithelial skin cancers such as basal cell carcinoma, squamous cell carcinoma or melanoma, and mesenchymal skin cancers such as angiosarcoma and dermatofibrosarcoma protuberans (DFSP) have identified new molecular targets for a systemic or local treatment approach. For DFSP there is an opportunity already today to reduce the intensity of surgical procedures by pretreatment with targeted therapy. This article highlights important aspects in several skin cancer types.
    Pathobiology 01/2011; 78(2):61-75. · 1.95 Impact Factor