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1.
J Eur Acad Dermatol Venereol ; 34(7): 1489-1495, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31955469

RESUMEN

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive type of haematologic precursor malignancy primarily often manifesting in the skin. We sought to provide a thorough clinical characterization and report our experience on therapeutic approaches to BPDCN. METHODS: In the present multicentric retrospective study, we collected all BPDCN cases occurring between 05/1999 and 03/2018 in 10 secondary care centres of the German-Swiss-Austrian cutaneous lymphoma working group. RESULTS: A total of 37 BPDCN cases were identified and included. Almost 90% of the patients had systemic manifestations (bone marrow, lymph nodes, peripheral blood) in addition to skin involvement. The latter presented with various types of cutaneous lesions: nodular (in more than 2/3) and bruise-like (in 1/3) skin lesions, but also maculopapular exanthema (in circa 1/6). Therapeutically, 22 patients received diverse combinations of chemotherapeutic regimens and/or radiotherapy. Despite initial responses, all of them ultimately relapsed and died from progressive disease. Eleven patients underwent haematopoietic stem cell transplantation (HSCT; autologous HSCT n = 3, allo-HSCT n = 8). The mortality rate among HSCT patients was only 33.33% with a median survival time of 60.5 months. CONCLUSION: Our study demonstrates the clinical diversity of cutaneous BPDCN manifestations and the positive development observed after the introduction of HSCT.


Asunto(s)
Neoplasias Hematológicas , Neoplasias Cutáneas , Austria , Células Dendríticas , Neoplasias Hematológicas/terapia , Humanos , Estudios Retrospectivos , Neoplasias Cutáneas/terapia
2.
Hautarzt ; 69(12): 1014-1020, 2018 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-29881891

RESUMEN

BACKGROUND: In addition to a broad and clinically diverse spectrum of known primary cutaneous lymphomas, for which an incidence of 1-3:100,000 is postulated, each year further entities are specified and defined. The goal is the presentation of a case series from daily clinical routine. METHODS: Over a period of 6 years and 2 months, patients consulting the Department of Dermatology, Medical Center University of Freiburg, were registered. Subsequently, collectives of mycosis fungoides (MF), Sezary syndrome (SS), CD30+ lymphoproliferative diseases, single cases with rare primary cutaneous lymphomas, and subcollectives of B­cell lymphomas were examined. The high number of MF cases allowed the additional quantitative analyses of the types of therapies used in this group. RESULTS: Yearly 16-25 new diagnoses of primary cutaneous lymphoma are made. The evaluation of 163 primary cutaneous lymphoma revealed 111 cases with MF (68.1%), including 9 particular variants, 15 primary cutaneous CD30+ lymphoproliferative diseases (9.2%) dominated by 10 lymphomatoid papulosis (LyP), in addition to 5 primary cutaneous anaplastic large cell lymphoma (PCALCL), 6 SS (3.68%), and 24 cutaneous B­cell lymphomas (14-72%). Three cases with rare primary cutaneous T/NK cell lymphomas are addressed in detail. In all, 82% of MF cases were stage IA and IB. The descending use of therapies for stage I-III included steroids and diverse UV therapies followed by bexarotene, interferon-α, methotrexate, and extracorporal photophoresis. CONCLUSIONS: Diagnoses of cutaneous lymphomas belong to a vast spectrum of differential diagnoses. This registry describes frequent findings and shows rare variants. You can only diagnose what you know; accordingly, a collection of case reports, which we wish to encourage, can help in processing and specification of entities.


Asunto(s)
Linfoma Cutáneo de Células T/clasificación , Linfoma Cutáneo de Células T/epidemiología , Papulosis Linfomatoide/epidemiología , Micosis Fungoide/epidemiología , Neoplasias Cutáneas/clasificación , Neoplasias Cutáneas/epidemiología , Alemania/epidemiología , Humanos , Antígeno Ki-1 , Papulosis Linfomatoide/patología , Micosis Fungoide/patología
4.
J Eur Acad Dermatol Venereol ; 34(1): e1-e3, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31374134
6.
Recent Results Cancer Res ; 201: 405-17, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24756807

RESUMEN

Vismodegib (GDC-0449, Erivedge®) is a novel small molecule antagonist of the hedgehog (Hh) pathway that binds to smoothened (SMO) and leads to inhibition of an aberrant activation of the Hh pathway. Dysregulated Hh signaling results in uncontrolled proliferation in basal cell carcinoma (BCC) and has also been found present in medulloblastoma, and many other cancers such as those of gastrointestinal tract, brain, lung, breast, and prostate. In January 2012, vismodegib became the first agent to target the Hh pathway to receive approval by the United States Food and Drug Administration (FDA) and in July 2013 approval by the European Medicines Agency (EMA) followed for the treatment of adult patients with symptomatic metastatic BCC, or locally advanced BCC inappropriate for surgery or radiotherapy. At the moment, many trials are ongoing to further investigate the role of vismodegib in other malignancies than BCC.


Asunto(s)
Anilidas/uso terapéutico , Antineoplásicos/uso terapéutico , Carcinoma Basocelular/tratamiento farmacológico , Proteínas Hedgehog/antagonistas & inhibidores , Piridinas/uso terapéutico , Transducción de Señal/efectos de los fármacos , Animales , Humanos , Neoplasias/tratamiento farmacológico
7.
Hautarzt ; 64(12): 927-30, 2013 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-24132612

RESUMEN

Offering psycho-oncological care is an essential, guideline-based component of comprehensive care in skin cancer centers. This paper describes the development, implementation and utilization of a specific psycho-oncologic care concept for melanoma patients in the University Dermatology Clinic Freiburg. Based on the stepped-care principle, the concept is composed of interdisciplinary group sessions for patients and their relatives offered every 4-6 weeks addressing medical and psycho-oncological topics related to treatment of malignant melanoma and then individual psycho-oncological sessions modified for the patient's treatment needs. Between April 2010 and July 2012, 67 % of the melanoma patients treated in the Freiburg Skin Cancer Center were reached by the program. A stepped-care concept with a routinely initiated first contact and low-threshold patient education group sessions is a reliable approach to reach patients and inform them about further psycho-oncological care. The advantages justify the allocation of resources and the approach proved successful for routine clinical practice.


Asunto(s)
Oncología Médica/organización & administración , Melanoma/psicología , Melanoma/terapia , Educación del Paciente como Asunto/métodos , Psicoterapia/organización & administración , Neoplasias Cutáneas/psicología , Neoplasias Cutáneas/terapia , Dermatología/organización & administración , Alemania , Humanos , Melanoma Cutáneo Maligno
8.
J Cancer Res Clin Oncol ; 149(13): 11705-11718, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37405475

RESUMEN

PURPOSE: Adjuvant treatment with immune checkpoint inhibitors like PD1-antibodies (ICI) ± CTLA4-antibodies (cICI) or targeted therapy with BRAF/MEK inhibitors (TT) in high-risk melanoma patients demonstrate a significant improvement in disease-free survival (DFS). Due to specific side effects, the choice of treatment is very often driven by the risk for toxicity. This study addressed for the first time in a multicenter setting the attitudes and preferences of melanoma patients for adjuvant treatment with (c)ICI and TT. METHODS: In this study ("GERMELATOX-A"), 136 low-risk melanoma patients from 11 skin cancer centers were asked to rate side effect scenarios typical for each (c)ICI and TT with mild-to-moderate or severe toxicity and melanoma recurrence leading to cancer death. We asked patients about the reduction in melanoma relapse and the survival increase at 5 years they would require to tolerate defined side-effects. RESULTS: By VAS, patients on average valued melanoma relapse worse than all scenarios of side-effects during treatment with (c)ICI or TT. In case of severe side effects, patients required a 15% higher rate of DFS at 5 years for (c)ICI (80%) compared to TT (65%). For survival, patients required an increase of 5-10% for melanoma survival during (c)ICI (85%/80%) compared to TT (75%). CONCLUSION: Our study demonstrated a pronounced variation of patient preferences for toxicity and outcomes and a clear preference for TT. As adjuvant melanoma treatment with (c)ICI and TT will be increasingly implemented in earlier stages, precise knowledge of the patient perspective can be helpful for decision making.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Suiza/epidemiología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Melanoma/terapia , Piel , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos
10.
Hautarzt ; 61(8): 691-3, 2010 Aug.
Artículo en Alemán | MEDLINE | ID: mdl-19953217

RESUMEN

Cheilitis granulomatosa (CG) can be associated with many different disorders. A 37-year-old male patient presented with CG as an early manifestation of Crohn's disease. Patients suffering from CG need a thorough diagnostic work-up for associated or underlying diseases. Clinical follow-up examinations are necessary as CG can precede the causative diseases.


Asunto(s)
Enfermedad de Crohn/diagnóstico , Síndrome de Melkersson-Rosenthal/diagnóstico , Adulto , Antiinfecciosos/uso terapéutico , Antiinflamatorios/uso terapéutico , Biopsia , Colonoscopía , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/patología , Dapsona/uso terapéutico , Diagnóstico Diferencial , Quimioterapia Combinada , Histiocitos/patología , Humanos , Mucosa Intestinal/patología , Labio/patología , Masculino , Síndrome de Melkersson-Rosenthal/tratamiento farmacológico , Síndrome de Melkersson-Rosenthal/patología , Triamcinolona Acetonida/uso terapéutico
12.
Eur J Cancer ; 109: 137-153, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30721788

RESUMEN

INTRODUCTION: Treatment of patients with metastatic melanoma is hampered by drug-resistance and often requires combination with radiotherapy as last-resort option. However, also after radiotherapy, clinical relapses are common. METHODS & RESULTS: Our preclinical models indicated a higher rate of tumour relapse when melanoma cells were first treated with BRAFV600E inhibition (BRAFi) followed by radiotherapy as compared to the reverse sequence. Accordingly, retrospective follow-up data from 65 stage-IV melanoma patients with irradiated melanoma brain metastases confirmed a shortened duration of local response of mitogen-activated protein kinase (MAPK)-inhibitor-pretreated compared with MAPK-inhibitor-naïve intracranial metastases. On the molecular level, we identified JARID1B/KDM5B as a cellular marker for cross-resistance between BRAFi and radiotherapy. JARID1Bhigh cells appeared more frequently under upfront BRAFi as compared with upfront radiation. JARID1B favours cell survival by transcriptional regulation of genes controlling cell cycle, DNA repair and cell death. CONCLUSION: The level of cross-resistance between combined MAPK inhibition and radiotherapy is dependent on the treatment sequence. JARID1B may represent a novel therapy-overarching resistance marker.


Asunto(s)
Neoplasias Encefálicas/terapia , Resistencia a Antineoplásicos , Melanoma/terapia , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Tolerancia a Radiación , Radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundario , Ciclo Celular , Movimiento Celular , Proliferación Celular , Quimioradioterapia , Femenino , Estudios de Seguimiento , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Melanoma/genética , Melanoma/patología , Persona de Mediana Edad , Mutación , Pronóstico , Proteínas Proto-Oncogénicas B-raf/genética , Estudios Retrospectivos , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
15.
Eur J Cancer ; 51(5): 653-67, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25638778

RESUMEN

BACKGROUND: Patient numbers requiring long-term melanoma surveillance are constantly rising. Surveillance is costly and guideline recommendations vary substantially. METHODS: In this German nationwide study, information on surveillance and treatment of patients diagnosed with melanoma and melanoma in situ (MMis) between April and June 2008 was prospectively collected over four years. Additionally, patient self-report questionnaires were evaluated to assess anxiety, depression, health-related quality of life, socio-demographic information and use of disease specific health information sources at year 4 after primary diagnosis. RESULTS: Complete data was available for 668 patients from 67 centres, of whom 96.0% were in regular melanoma surveillance. In year 3-4 of surveillance, only 55.6% of locoregionary metastases were detected during surveillance visits. Only 33.3% were self-detected by the patient even though 69.4% were documented as being clinically visible or palpable. Costs of 4year surveillance of 550 patients without tumour recurrence (stage I-IIC and MMis) accumulated to 228,155.75 €. Guideline-adherence for follow-up frequency, lymph node ultrasound, S100 serum level tests and diagnostic imaging recommendations was approximately 60% in year 3-4 of surveillance. Multivariate regression analysis showed that certain patient/tumour characteristics and regional differences were significantly associated with guideline deviations. The percentage of patients who exceeded published cut-off scores indicating clinically relevant symptoms of anxiety and depression were significantly increased. Patients frequently reported lack of psychosocial support and education but ascribed great importance to these. CONCLUSIONS: We recommend further reduction of melanoma follow-up in low-risk melanoma patients and improvement of psycho-social support and patient education for all melanoma patients.


Asunto(s)
Cuidados a Largo Plazo , Oncología Médica , Melanoma/diagnóstico , Melanoma/terapia , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/terapia , Adulto , Anciano , Progresión de la Enfermedad , Detección Precoz del Cáncer , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Adhesión a Directriz , Conocimientos, Actitudes y Práctica en Salud , Disparidades en Atención de Salud , Humanos , Cuidados a Largo Plazo/normas , Estudios Longitudinales , Masculino , Oncología Médica/normas , Melanoma/epidemiología , Melanoma/psicología , Melanoma/secundario , Persona de Mediana Edad , Educación del Paciente como Asunto , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina , Valor Predictivo de las Pruebas , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Autoexamen , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/psicología , Apoyo Social , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento
16.
Aliment Pharmacol Ther ; 17(12): 1559-62, 2003 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-12823160

RESUMEN

BACKGROUND: Hypoxia may contribute to impairment of liver function and thus interfere with results of liver tests. In patients with cirrhosis, cytochrome P-450 mediated metabolism of substrates is facilitated in the presence of supplemental oxygen. It has not been studied how this relates to liver function and haemoglobin content. AIM: We questioned how oxygen supplementation would influence the hepatic microsomal function as assessed by the 13C-methacetin breath test in patients with cirrhosis of different severity and different degrees of anaemia. METHODS: 13C/12C ratios in exhaled breath assessed by non-dispersive infrared spectrometry were studied in 34 patients with cirrhosis (Child A/B/C 9/17/8) after administration of 75 mg 13C-methacetin p.o. with and without oxygen inhalation (4 L/min). RESULTS: In patients breathing room air the total amount of 13C exhaled weakly correlated both with the Child-Pugh score (r = - 0.41, P < 0.02) and haemoglobin concentrations (r = 0.46; p = 0.006). Oxygen supplementation increased the total amount of 13C exhaled by 68 +/- 90% (P < 0.001). This effect was similar in Child-Pugh classes A (43 +/- 55%), B (83 +/- 80%) and C (66 +/- 123%) and not related to the Child-Pugh score. CONCLUSIONS: Our results suggest that tests of microsomal liver function are independently influenced both by oxygen delivery and the Child-Pugh score.


Asunto(s)
Acetamidas/metabolismo , Cirrosis Hepática/metabolismo , Oxígeno/uso terapéutico , Pruebas Respiratorias , Femenino , Hemoglobinas/análisis , Humanos , Hipoxia/complicaciones , Hipoxia/fisiopatología , Hígado/irrigación sanguínea , Cirrosis Hepática/fisiopatología , Masculino , Persona de Mediana Edad
18.
Hautarzt ; 58(4): 338-42, 2007 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-16874534

RESUMEN

Steroid-induced erythema in rosacea is a therapeutic challenge because of its tendency to rebound and the local characteristics of the facial skin. We describe 3 cases of steroid-induced rosacea with the typical history of steroid abuse with tachyphylaxis. Steroids with increasing potency had to be used with increasing frequency in the course of treatment in order to achieve a response. Acute exacerbations followed any attempt at withdrawal. The steroid treatment was discontinued and therapy with pimecrolimus cream 1% twice daily initiated. This brought rapid and marked improvement within a few days. The cases show that the calcineurin antagonist pimecrolimus offers an effective and well-tolerated therapy option in the acute therapy of steroid-aggravated facial dermatoses.


Asunto(s)
Rosácea/inducido químicamente , Rosácea/tratamiento farmacológico , Esteroides/efectos adversos , Tacrolimus/análogos & derivados , Anciano , Antiinflamatorios no Esteroideos/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Esteroides/uso terapéutico , Tacrolimus/uso terapéutico , Resultado del Tratamiento
19.
Hautarzt ; 58(2): 142-5, 2007 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-16525742

RESUMEN

High-dose steroids in combination with other immunosuppressant substances, usually azathioprine, are the therapy of choice in pemphigus vulgaris. Complete remission can be difficult to achieve, with mucosal lesions often recalcitrant. We describe two patients in whom gold in the form of sodium aurothiomalate was effective in resolving mucosal lesions. Initially both patients were treated with high-dose corticosteroids, one in combination with mycophenolate mofetil. Their oral lesions proved to be stubborn but responded well to intramuscular gold, which also showed a steroid-sparing effect, so that the dosage of corticosteroids could be reduced to a minimum. Sodium aurothiomalate was continued until both patients were in remission without any side effects.


Asunto(s)
Antirreumáticos/uso terapéutico , Tiomalato Sódico de Oro/uso terapéutico , Pénfigo/tratamiento farmacológico , Estomatitis/tratamiento farmacológico , Adulto , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Resistencia a Medicamentos , Femenino , Humanos , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Pénfigo/diagnóstico , Estomatitis/diagnóstico
20.
Dtsch Med Wochenschr ; 118(21): 769-74, 1993 May 28.
Artículo en Alemán | MEDLINE | ID: mdl-8504712

RESUMEN

The effect of transdermal oestrogen replacement therapy on prevention of osteoporosis was investigated in a controlled randomized study of 38 healthy women (mean age 49.6 [45-54] years) in the early postmenopausal period (< or = 3 years). 19 women (hormone group) continuously used oestrogen patches with a mean daily estradiol delivery of 0.05 mg with addition of medroxyprogesterone acetate, 5 mg orally, for 14 days per month. The other 19 women (calcium group), whose baseline levels were identical, took 500 mg calcium daily. Climacteric symptoms improved significantly in the hormone group, and serum and urinary calcium levels and total serum cholesterol all declined, while the HDL cholesterol levels increased slightly. Bone density was measured by single photon absorptiometry at two points (1/3 and 1/10 of the forearm length from the distal end of the radius). After 6 and 12 months, the values at the proximal site (1/3) had risen in the hormone group by 1.1% and 0.46% and had fallen in the calcium group by 1.96% and 2.42% respectively (both P < 0.05 vs hormone group). At the distal radial site (1/10), the values increased by 2.14% and 5.3% in the same period and fell by 3.59% and 5.67% in the calcium group. The overall difference after 12 months was 11% (P < 0.01). Transdermal oestrogen appears to be as effective as oral oestrogen replacement for prevention of osteoporosis, and should help to prevent vertebral and limb fractures in the elderly.


Asunto(s)
Estradiol/administración & dosificación , Terapia de Reemplazo de Estrógeno/métodos , Acetato de Medroxiprogesterona/administración & dosificación , Osteoporosis Posmenopáusica/prevención & control , Absorciometría de Fotón , Administración Cutánea , Administración Oral , Densidad Ósea/efectos de los fármacos , Quimioterapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/metabolismo , Factores de Tiempo
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