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1.
Pharmacopsychiatry ; 56(2): 64-72, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36944329

RESUMEN

INTRODUCTION: Precision medicine in psychiatry is still in its infancy. To establish patient-tailored treatment, adequate indicators predicting treatment response are required. Electroconvulsive therapy (ECT) is considered one of the most effective options for pharmacoresistant major depressive disorder (MDD), yet remission rates were reported to be below 50%. METHODS: Since epigenetics of the stress response system seem to play a role in MDD, we analyzed the DNA methylation (DNAm) of genes encoding the glucocorticoid receptor (NR3C1) and proopiomelanocortin (POMC) through Sanger Sequencing. For analysis, blood was taken before and after the first and last ECT from MDD patients (n=31), unmedicated depressed controls (UDC; n=19, baseline), and healthy controls (HC; n=20, baseline). RESULTS: Baseline DNAm in NR3C1 was significantly lower in UDCs compared to both other groups (UDC: 0.014(±0.002), ECT: 0.031(±0.001), HC: 0.024(±0.002); p<0.001), whereas regarding POMC, ECT patients had the highest DNAm levels (ECT: 0.252(±0.013), UDC: 0.156(±0.015), HC: 0.162(±0.014); p<0.001). NR3C1m and POMCm decreased after the first ECT (NR3C1: p<0.001; POMC: p=0.001), and responders were less methylated compared to non-responders in NR3C1(p<0.001). DISCUSSION: Our findings indicate that both genes might play a role in the chronification of depression and NR3C1 may be relevant for ECT response prediction.


Asunto(s)
Trastorno Depresivo Mayor , Terapia Electroconvulsiva , Humanos , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/terapia , Proopiomelanocortina/genética , Metilación de ADN/genética , Epigénesis Genética , Resultado del Tratamiento , Receptores de Glucocorticoides/genética
2.
J Dtsch Dermatol Ges ; 16(4): 426-434, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29645369

RESUMEN

HINTERGRUND: Nach Tumoroperationen erfolgt ein Defektverschluss mit den für den individuellen Fall optimalen chirurgischen Methoden. Besonders im Kopf-Hals--Bereich ist das Ergebnis sehr wichtig. Ziel der retrospektiven Studie war es, Rekonstruktionsmethoden von Defekten entsprechend Alter, Lokalisation und Größe nach funktionellen und ästhetischen Gesichtspunkten zu vergleichen. PATIENTEN UND METHODIK: Die betroffenen Patienten wurden mittels Fragebögen angeschrieben. 1827 Patienten (Alter von 18 bis 92 Jahren, Median: 56 Jahre) beurteilten postoperative Probleme, ästhetisches sowie funktionelles Ergebnis und das Gesamtresultat. Aus der Patientenakte wurden Größe und Lokalisation des Defektes sowie die Art des Verschlusses dokumentiert. ERGEBNISSE: Die Dehnungslappenplastik erhielt bezüglich des Gesamtresultats mit einer sehr guten oder guten Bewertung (86 %) das beste Ergebnis. Lappenplastiken und Hauttransplantate wurden schlechter beurteilt. Postoperative Beschwerden traten signifikant häufiger nach lokalen Lappenplastiken auf. Die Sichtbarkeit der Narbe wurde von älteren Patienten bei allen Defektgrößen (< 150 mm2 , 150-300 mm2 , > 300 mm2 ) geringer beurteilt als von jüngeren. Narben in der zentralen Gesichtspartie wurden als sichtbarer wahrgenommen. Geschlecht und Rauchen hatten keinen Einfluss. SCHLUSSFOLGERUNGEN: Narben in zentralen Gesichtsregionen werden stärker wahrgenommen. Ältere Patienten beurteilten die Narbenbildung insgesamt als unauffälliger. Dehnungslappenplastiken, auch unter Wundrandspannung, führen zu sehr guten Ergebnissen und einer hohen Patientenzufriedenheit.

3.
J Dtsch Dermatol Ges ; 16(4): 426-433, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29645392

RESUMEN

BACKGROUND: Defect coverage following tumor excision requires a case-by-case decision as regards the optimal reconstruction technique. In the head and neck region in particular, the cosmetic outcome is of major importance. The objective of the present study was to compare various reconstruction methods in terms of their functional and aesthetic outcome based on patient age, defect size and site. PATIENTS AND METHODS: Overall, 1,827 patients (age: 18-92 years, median age: 56 years) were contacted. Using a standardized questionnaire, they were asked to assess postoperative complications, cosmetic and functional outcome, and the overall result of the surgical procedure. In addition, patient records were used to collect data on defect size and site as well as the type of surgical procedure employed. RESULTS: Rated as very good or good (86 %), defect closure by advancement flaps received the highest scores in terms of overall result. Other flaps and skin grafts were rated less favorably. Postoperative complications were significantly more common after local flaps. Irrespective of defect size (< 150 mm2 , 150-300 mm2 , > 300 mm2 ), older patients considered the visibility of the scar to be less prominent than younger individuals. Scars in the central facial region were perceived to be more visible. Gender and smoking habits had no impact on the results of the survey. CONCLUSIONS: Scars in the central facial region were perceived to be more prominent. Overall, older individuals considered their scars to be less conspicuous. Even though they are initially associated with greater tension, advancement flaps resulted in very good aesthetic and functional results and a high level of patient satisfaction.


Asunto(s)
Neoplasias Faciales/cirugía , Satisfacción del Paciente , Procedimientos de Cirugía Plástica/métodos , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Cicatriz/psicología , Estética , Neoplasias Faciales/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/psicología , Procedimientos de Cirugía Plástica/psicología , Colgajos Quirúrgicos/trasplante , Encuestas y Cuestionarios , Carga Tumoral , Cicatrización de Heridas , Adulto Joven
4.
J Dtsch Dermatol Ges ; 16(12): 1434-1442, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30537312

RESUMEN

BACKGROUND: Cutaneous sarcomas are rare and characterized by pathogenetic heterogeneity. Knowledge about local infiltration patterns and recurrence rates may be useful in improving patient care and outcomes. The objective of the present study was to compare these two characteristics in sarcomas that had been treated using the identical surgical procedure. PATIENTS AND METHODS: Between 2006-2010, 84 patients with various types of sarcoma underwent surgery followed by three-dimensional histology. Tumor entities included dermatofibrosarcoma protuberans (DFSP, 54 patients), leiomyosarcoma (ten patients), rhabdomyosarcoma (one patient), angiosarcoma (seven patients) as well as atypical fibroxanthoma (AFX, three patients) and cutaneous undifferentiated pleomorphic sarcoma (UPS, nine patients). Median follow-up was four years (range: 2-6 years). RESULTS: Local recurrence rates among patients with primary DFSP were 2.2 %. All patients undergoing re-excision were subsequently tumor free. Patients with leiomyosarcoma, rhabdomyosarcoma, AFX, and cutaneous UPS experienced no local recurrence; however, one individual developed in-transit metastasis (UPS) (8.3 %). Three patients with angiosarcoma developed local recurrence (43 %), two of whom remained tumor free following re-excision. Two angiosarcoma patients died from distant metastases (29 %). Both DFSP and especially angiosarcoma lesions exhibited extensive subclinical growth. CONCLUSIONS: Recurrence rates of cutaneous sarcomas following three-dimensional histology are low. Local recurrences are readily manageable by re-excision. Angiosarcoma is characterized by extensive superficial growth, aggressive biological behavior, and predominantly hematogenous spread.


Asunto(s)
Dermatofibrosarcoma , Hemangiosarcoma , Histiocitoma Fibroso Maligno , Sarcoma , Neoplasias Cutáneas , Dermatofibrosarcoma/diagnóstico , Dermatofibrosarcoma/cirugía , Hemangiosarcoma/diagnóstico , Hemangiosarcoma/terapia , Histiocitoma Fibroso Maligno/diagnóstico , Histiocitoma Fibroso Maligno/cirugía , Humanos , Recurrencia Local de Neoplasia , Sarcoma/cirugía , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/cirugía
5.
J Dtsch Dermatol Ges ; 15(3): 319-324, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28252849

RESUMEN

HINTERGRUND UND ZIEL: Die intraläsionale Gabe von Anti-CD20-Antikörpern (Rituximab) wurde als effektive Therapieoption für Patienten mit niedrig malignen primär kutanen B-Zell-Lymphomen beschrieben. Bis heute wurden allerdings keine Parameter identifiziert, welche reproduzierbar ein gutes klinisches Ansprechen dieser Therapie vorhersagen. Ziel dieser Studie ist, sowohl das klinische Ansprechen und die unerwünschten Nebenwirkungen als auch die Patientenwahrnehmung hinsichtlich intraläsionaler Injektionen von anti-CD20-Antikörpern zur Behandlung indolenter primär kutaner B-Zell-Lymphome im Vergleich mit anderen Therapien zu evaluieren. PATIENTEN UND METHODIK: Elf Patienten mit einem primär kutanen B-Zell-Lymphom, namentlich primär kutanes Keimzentrumslymphom (n = 9) und primär kutanes Marginalzonenlymphom (n = 2), welche mittels intraläsionalem Anti-CD20-Antikörper behandelt wurden, wurden retrospektiv evaluiert hinsichtlich der Ansprechrate und unerwünschter Nebenwirkungen sowie in Bezug auf deren Selbsteinschätzung dieser und anderer Therapien des primär kutanen B-Zell-Lymphoms. ERGEBNISSE: Patienten, deren primär kutanes B-Zell-Lymphom mittels intraläsionaler Gabe von Anti-CD20-Antikörper behandelt wurde, zeigten ein komplettes oder partielles Ansprechen in 45 % beziehungsweise 27 % aller Patienten. Speziell Patienten mit grippeähnlichen Symptomen nach erfolgter Injektion zeigten ein gutes Ansprechen. Die Mehrheit der Patienten empfand die Therapie mit Rituximab als die beste Therapie im Vergleich zu anderen Therapien wie beispielsweise chirurgische Exzision oder Radiotherapie. FAZIT: Intraläsionales Rituximab ist eine effektive Therapie mit hoher Patientenzufriedenheit. Starke therapiebedingte Nebenwirkungen wie Fieber, Schüttelfrost und Kopfschmerzen nach Gabe von Rituximab könnten als Indikator für gute Wirksamkeit dienen.

6.
J Dtsch Dermatol Ges ; 15(3): 319-323, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28177583

RESUMEN

BACKGROUND AND OBJECTIVES: Intralesional injection of anti-CD20 antibody (rituximab) has been described as effective therapeutic option for patients with indolent primary cutaneous B-cell lymphoma (PCBL). To date, no parameters that reproducibly predict favorable clinical outcome of this treatment have been identified. The study aims to evaluate the clinical response and adverse effects as well as patients' self-perception of intralesional injection of anti-CD20 antibody for treatment of indolent PCBL compared to other treatment modalities. PATIENTS AND METHODS: Eleven patients with PCBL, namely primary cutaneous follicle center lymphoma (n = 9) and primary cutaneous marginal zone lymphoma (n = 2), treated with intralesional anti-CD20 antibody were retrospectively evaluated for response rate and adverse events as well as their self-perception of anti-CD20 antibody therapy and other therapies of PCBL. RESULTS: Patients treated with intralesional anti-CD20 antibody for PCBL showed complete response or partial response in 45 % or 27 % of patients, respectively. Particularly, patients with marked flu-like symptoms after intralesional injection of rituximab responded very well to rituximab. The majority of patients considered rituximab as best therapy compared to other therapies such as excision or radiotherapy. CONCLUSIONS: Intralesional rituximab is an effective therapy with high patient satisfaction. Strong therapy induced side effects of fever, chills and headache after administration of rituximab might be used as indicator for favorable response.


Asunto(s)
Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Gastrointestinales/diagnóstico , Cefalea/inducido químicamente , Linfoma de Células B/tratamiento farmacológico , Rituximab/administración & dosificación , Rituximab/efectos adversos , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Escalofríos/inducido químicamente , Escalofríos/diagnóstico , Escalofríos/prevención & control , Femenino , Enfermedades Gastrointestinales/prevención & control , Cefalea/diagnóstico , Cefalea/prevención & control , Humanos , Inyecciones Intralesiones , Linfoma de Células B/inmunología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Neoplasias Cutáneas/inmunología , Estadística como Asunto , Resultado del Tratamiento
7.
Blood ; 121(10): 1795-804, 2013 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-23305738

RESUMEN

Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) rarely express T-cell-associated antigens (TCA), but the clinical significance of this finding is uncertain. Fifty cHLs expressing any TCA on the HRS cells (TCA-cHL) were identified in two cohorts (National Cancer Institute, n = 38; Basel, n = 12). Diagnostic pathology data were examined in all cases with additional T-cell receptor γ rearrangements (TRG@) polymerase chain reaction (PCR) in a subset of cases. The outcome data were compared with a cohort of cHLs negative for TCA (n = 272). Primary end points examined were event-free survival (EFS) and overall survival (OS). The median age in the TCA-cHL group was 40 years (range, 10-85 years). Seventy percent presented in low stage (stage I/II) at presentation with nodular sclerosis (NS) histology predominating in 80% of cases. Among the TCA, CD4 and CD2 were most commonly expressed, seen in 80.4% and 77.4% of cases, respectively. TRG@ PCR was negative for clonal rearrangements in 29 of 31 cases. During a median follow up of 113 months, TCA expression predicted shorter OS (adjusted hazard ratio [HRadj] = 3.32 [95% confidence interval (CI): 1.61, 6.84]; P = .001) and EFS (HRadj = 2.55 [95% CI: 1.45, 4.49]; P = .001). TCA-cHL often display NS histology, lack T-cell genotype, and are independently associated with significantly shorter OS and EFS compared with TCA-negative cHLs.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Enfermedad de Hodgkin/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Receptores de Antígenos de Linfocitos T/metabolismo , Células de Reed-Sternberg/metabolismo , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Niño , Estudios de Cohortes , ADN de Neoplasias/genética , Femenino , Estudios de Seguimiento , Reordenamiento Génico , Genes de las Cadenas Pesadas de las Inmunoglobulinas/genética , Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/metabolismo , Humanos , Técnicas para Inmunoenzimas , Hibridación in Situ , Captura por Microdisección con Láser , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/metabolismo , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , Pronóstico , Receptores de Antígenos de Linfocitos T/genética , Tasa de Supervivencia , Adulto Joven
8.
Haematologica ; 99(3): 481-8, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24162788

RESUMEN

The pathogenesis of follicular lymphoma is a multi-hit process progressing over many years through the accumulation of numerous genetic alterations. Besides the hallmark t(14;18), it is still unclear which other oncogenic hits contribute to the early steps of transformation and in which precursor stages these occur. To address this issue, we performed high-resolution comparative genomic hybridization microarrays on laser-capture micro-dissected cases of follicular lymphoma in situ (n=4), partial involvement by follicular lymphoma (n=4), and duodenal follicular lymphoma (n=4), assumed to represent, potentially, the earliest stages in the evolution of follicular lymphoma. Cases of reactive follicular hyperplasia (n=2), uninvolved areas from follicular lymphoma in situ lymph nodes, follicular lymphoma grade 1-2 (n=5) and follicular lymphoma grade 3A (n=5) were used as controls. Surprisingly, alterations involving several relevant (onco)genes were found in all entities, but at significantly lower proportions than in overt follicular lymphoma. While the number of alterations clearly assigns all these entities as precursors, the pattern of partial involvement by follicular lymphoma alterations was quantitatively and qualitatively closer to that of follicular lymphoma, indicating significant selective pressure in line with its faster rate of progression. Among the most notable alterations, we observed and validated deletions of 1p36 and gains of the 7p and 12q chromosomes and related oncogenes, which include some of the most recurrent oncogenic alterations in overt follicular lymphoma (TNFRSF14, EZH2, MLL2). By further delineating distinctive and hierarchical molecular and genetic features of early follicular lymphoma entities, our analysis underlines the importance of applying appropriate criteria for the differential diagnosis. It also provides a first set of candidates likely to be involved in the cascade of hits that pave the path of the various progression phases to follicular lymphoma development.


Asunto(s)
Transformación Celular Neoplásica/genética , Linfoma Folicular/genética , Linfoma Folicular/patología , Carcinoma in Situ/genética , Carcinoma in Situ/patología , Hibridación Genómica Comparativa , Progresión de la Enfermedad , Inestabilidad Genómica , Centro Germinal/patología , Humanos , Clasificación del Tumor , Estadificación de Neoplasias
9.
J Dtsch Dermatol Ges ; 12(11): 1028-35, 2014 Nov.
Artículo en Inglés, Alemán | MEDLINE | ID: mdl-25354011

RESUMEN

BACKGROUND: The continuous evaluation of the edges of a tumor by means of three-dimensional (3D) histology often appears complicated and require the surgeon and dermatopathologist to work together closely. We present clear rules that allow communication between all parties involved and then verify their application in daily routine. METHODS: Tissue processing, interpretation of results, as well as communication between the surgeon and the dermatopathologist are based on an algorithm with the aid of exact times and embedding cassettes, which allow precise topographic orientation. We evaluated the use of this method in daily clinic practice, taking into account 947 operated basal cell carcinomas in regard to the development of recurrent tumors. RESULTS: At a median follow-up of 47 months, 10 of the 947 operated basal cell carcinomas (1.1 %) recurred. Sclerodermiform basal cell carcinomas and basal cell carcinomas which could not be curatively resected (R0 resection) during the initial surgery showed a significantly higher recurrence rate (p < 0.05 and p < 0.001). CONCLUSIONS: Standardized rules for dealing with excised tissue allow an effective application of 3D histology in daily clinical practice. 3D histology results in low recurrence rates. Sclerodermiform basal cell carcinomas which could not be curatively resected (R0 resection) were identified as a risk group for the development of recurrent tumors.


Asunto(s)
Biopsia/normas , Carcinoma Basocelular/patología , Dermoscopía/normas , Imagenología Tridimensional/normas , Neoplasias Cutáneas/patología , Manejo de Especímenes/normas , Anciano , Algoritmos , Femenino , Alemania , Humanos , Masculino , Microscopía/normas , Guías de Práctica Clínica como Asunto , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
10.
Blood ; 118(11): 2976-84, 2011 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-21768298

RESUMEN

Follicular lymphoma in situ (FLIS) was first described nearly a decade ago, but its clinical significance remains uncertain. We reevaluated our original series and more recently diagnosed cases to develop criteria for the distinction of FLIS from partial involvement by follicular lymphoma (PFL). A total of 34 cases of FLIS were identified, most often as an incidental finding in a reactive lymph node. Six of 34 patients had prior or concurrent FL, and 5 of 34 had FLIS composite with another lymphoma. Of patients with negative staging at diagnosis and available follow-up (21 patients), only one (5%) developed FL (follow-up: median, 41 months; range, 10-118 months). Follow-up was not available in 2 cases. Fluorescence in situ hybridization for BCL2 gene rearrangement was positive in all 17 cases tested. PFL patients were more likely to develop FL, diagnosed in 9 of 17 (53%) who were untreated. Six patients with PFL were treated with local radiation therapy (4) or rituximab (2) and remained with no evidence of disease. FLIS can be reliably distinguished from PFL and has a very low rate of progression to clinically significant FL. FLIS may represent the tissue counterpart of circulating t(14;18)-positive B cells.


Asunto(s)
Linfoma Folicular/diagnóstico , Linfoma Folicular/patología , Adulto , Anciano , Cromosomas Humanos Par 14 , Cromosomas Humanos Par 18 , Estudios de Cohortes , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/genética , Masculino , Persona de Mediana Edad , Mutación/fisiología , Estadificación de Neoplasias/métodos , Proteínas Proto-Oncogénicas c-bcl-2/genética , Translocación Genética
11.
Bioessays ; 33(7): 490-8, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21590787

RESUMEN

The integration of pathology with molecular biology is vital if we are to enhance the translational value of cancer research. Pathology represents a bridge between medicine and basic biology, it remains the gold standard for cancer diagnosis, and it plays an important role in discovery studies. In the past, pathology and cancer research were closely associated; however, the molecular biology revolution has shifted the focus of investigators toward the molecular alterations of tumors. The reductionist approach taken in molecular studies is producing great insight into the inner workings of neoplasia, but it can also minimize the importance of histopathology and of understanding the disease as a whole. In turn, pathologists can underestimate the role of molecular studies in developing new ancillary techniques for clinical diagnosis. A multidisciplinary approach that integrates pathology and molecular biology within a translational research system is needed. This process will require overcoming cultural barriers and can be achieved through education, a more effective incorporation of pathology into biological research, and conversely an integration of biological research into the pathology laboratory.


Asunto(s)
Neoplasias/metabolismo , Neoplasias/patología , Patología/métodos , Animales , Humanos , Biología Molecular , Neoplasias/genética , Biología de Sistemas , Investigación Biomédica Traslacional
13.
Mod Pathol ; 24(12): 1586-97, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21822207

RESUMEN

The term gray zone lymphoma has been applied to tumors that demonstrate transitional morphologic and immunophenotypic features between classical Hodgkin's lymphoma and diffuse large B-cell lymphoma, especially primary mediastinal large B-cell lymphoma. Histopathological and genetic data are limited for these unusual cases. We analyzed cases of gray zone lymphoma (n=27), mediastinal composite lymphoma (n=3) and mediastinal synchronous/metachronous lymphoma (n=3) by morphology, immunophenotyping and fluorescence in situ hybridization. Mediastinal involvement was assured in 24/33 patients (73%). The patient cohort showed a male predominance (M:F ratio; 20:13) and a median age of 32 years (range, 16-91 years). Patients with mediastinal disease were significantly younger (median age: 29.5 years) than patients presenting without evident mediastinal disease (median age: 55 years). Gains including amplifications in 2p16.1 (REL/BCL11A locus) were observed in 33% of all patients, whereas alterations affecting the JAK2/PDL2 locus in 9p24.1 were present in 55%. Further studies revealed rearrangement of the CIITA locus at 16p13.13 in 8/30 cases (27%) and 7/26 cases (27%) demonstrated gains of 8q24 (MYC). Genetic aberrations involving 2p16.1, 9p24.1 and 8q24 showed a higher incidence in cases with evident mediastinal involvement. However, this was not statistically significant when compared with cases without known mediastinal involvement. Twelve of the 27 cases of gray zone lymphoma were morphologically more reminiscent of classical Hodgkin's lymphoma, whereas the other gray zone lymphomas presented with morphological features more closely resembling large B-cell lymphoma. Both morphological groups of gray zone lymphoma were similarly positive for Cyclin E (75 and 93%) and p63 (50 and 53%, respectively) expression. These findings further support a close relationship between gray zone lymphoma, classical Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma, and suggest that some cases of gray zone lymphoma without mediastinal disease may share similar genetic alterations.


Asunto(s)
Biomarcadores de Tumor/análisis , Aberraciones Cromosómicas , Enfermedad de Hodgkin/genética , Linfoma de Células B Grandes Difuso/genética , Linfoma/genética , Neoplasias del Mediastino/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Regulación Neoplásica de la Expresión Génica , Enfermedad de Hodgkin/clasificación , Enfermedad de Hodgkin/inmunología , Enfermedad de Hodgkin/patología , Humanos , Inmunohistoquímica , Inmunofenotipificación , Hibridación Fluorescente in Situ , Linfoma/clasificación , Linfoma/inmunología , Linfoma/patología , Linfoma de Células B Grandes Difuso/clasificación , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/patología , Masculino , Neoplasias del Mediastino/clasificación , Neoplasias del Mediastino/inmunología , Neoplasias del Mediastino/patología , Persona de Mediana Edad , Pronóstico , Adulto Joven
14.
Haematologica ; 96(4): 558-66, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21454882

RESUMEN

BACKGROUND: Mediastinal gray zone lymphoma is a newly recognized entity with transitional morphological and immunophenotypic features between the nodular sclerosis subtype of Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma. Diagnostic criteria for mediastinal gray zone lymphoma are still challenging, and the optimal therapy is as yet undetermined. Epigenetic changes have been implicated in the loss of the B-cell program in classical Hodgkin's lymphoma, and might provide a basis for the immunophenotypic alterations seen in mediastinal gray zone lymphoma. DESIGN AND METHODS: We performed a large-scale DNA methylation analysis of microdissected tumor cells to investigate the biological underpinnings of mediastinal gray zone lymphoma and its association with the related entities classical Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma, making comparisons with the presumptively less related diffuse large B-cell lymphoma. RESULTS: Principal component analysis demonstrated that mediastinal gray zone lymphoma has a distinct epigenetic profile intermediate between classical Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma but remarkably different from that of diffuse large B-cell lymphoma. Analysis of common hypo- and hypermethylated CpG targets in mediastinal gray zone lymphoma, classical Hodgkin's lymphoma, primary mediastinal large B-cell lymphoma and diffuse large B-cell lymphoma was performed and confirmed the findings of the principal component analysis. Based on the epigenetic profiles we were able to establish class prediction models utilizing genes such as HOXA5, MMP9, EPHA7 and DAPK1 which could distinguish between mediastinal gray zone lymphoma, classical Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma with a final combined prediction of 100%. CONCLUSIONS: Our data confirm a close relationship between mediastinal gray zone lymphoma and both classical Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma. However, important differences were observed as well, allowing a clear distinction from both parent entities. Thus, mediastinal gray zone lymphoma cannot be assigned to either classical Hodgkin's lymphoma or primary mediastinal large B-cell lymphoma, validating the decision to create an intermediate category in the World Health Organization classification.


Asunto(s)
Metilación de ADN/genética , Epigenómica , Linfoma/genética , Linfoma/fisiopatología , Neoplasias del Mediastino/genética , Neoplasias del Mediastino/fisiopatología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Análisis por Conglomerados , Islas de CpG/genética , Femenino , Humanos , Linfoma/diagnóstico , Masculino , Persona de Mediana Edad , Modelos Genéticos , Proteínas del Grupo Polycomb , Proteínas Represoras/metabolismo , Reproducibilidad de los Resultados , Adulto Joven
15.
Eur J Dermatol ; 20(3): 381-5, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20299310

RESUMEN

Lichenoid graft-versus-host disease (GVHD) is commonly observed in patients who have received donor lymphocyte infusions or allogeneic bone marrow transplantation (BMT). Here we report a striking case of lichenoid GVH-like exanthema in a young woman without any history of blood transfusions or BMT. A polymorphous, multiforme-like exanthema was observed after systemic antibiotic therapy of bronchitis and was initially diagnosed as drug eruption. Later on, disseminated lichenoid papules were noticed on the trunk and extremities with all histologic and clinical characteristics of lichenoid GVHD. Cutaneous GVH-like disease developed, as did obstructive lung disease. Pulmonary as well as skin disease were both refractory to various immunosuppressive therapies. The immune pathogenesis that caused the skin and lung disease in this patient remains unclear. Multiple pregnancies with two abortions with the potential induction of microchimerism may play a role in the disease pathogenesis.


Asunto(s)
Exantema/etiología , Enfermedad Injerto contra Huésped/diagnóstico , Erupciones Liquenoides/etiología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Piel/patología , Adulto , Biopsia , Diagnóstico Diferencial , Exantema/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Erupciones Liquenoides/diagnóstico
16.
Clin Epigenetics ; 12(1): 114, 2020 07 29.
Artículo en Inglés | MEDLINE | ID: mdl-32727556

RESUMEN

BACKGROUND: Major depressive disorder (MDD) represents a serious global health concern. The urge for efficient MDD treatment strategies is presently hindered by the incomplete knowledge of its underlying pathomechanism. Despite recent progress (highlighting both genetics and the environment, and thus DNA methylation, to be relevant for its development), 30-50% of MDD patients still fail to reach remission with standard treatment approaches. Electroconvulsive therapy (ECT) is one of the most powerful options for the treatment of pharmacoresistant depression; nevertheless, ECT remission rates barely reach 50% in large-scale naturalistic population-based studies. To optimize MDD treatment strategies and enable personalized medicine in the long- term, prospective indicators of ECT response are thus in great need. Because recent target-driven analyses revealed DNA methylation baseline differences between ECT responder groups, we analyzed the DNA methylome of depressed ECT patients using next-generation sequencing. In this pilot study, we did not only aim to find novel targets for ECT response prediction but also to get a deeper insight into its possible mechanism of action. RESULTS: Longitudinal DNA methylation analysis of peripheral blood mononuclear cells isolated from a cohort of treatment-resistant MDD patients (n = 12; time points: before and after 1st and last ECT, respectively) using a TruSeq-Methyl Capture EPIC Kit for library preparation, led to the following results: (1) The global DNA methylation differed neither between the four measured time points nor between ECT responders (n = 8) and non-responders (n = 4). (2) Analyzing the DNA methylation variance for every probe (=1476812 single CpG sites) revealed eight novel candidate genes to be implicated in ECT response (protein-coding genes: RNF175, RNF213, TBC1D14, TMC5, WSCD1; genes encoding for putative long non-coding RNA transcripts: AC018685.2, AC098617.1, CLCN3P1). (3) In addition, DNA methylation of two CpG sites (located within AQP10 and TRERF1) was found to change during the treatment course. CONCLUSIONS: We suggest ten novel candidate genes to be implicated in either ECT response or its possible mechanism. Because of the small sample size of our pilot study, our findings must be regarded as preliminary.


Asunto(s)
Metilación de ADN , Trastorno Depresivo Mayor/terapia , Terapia Electroconvulsiva/métodos , Adulto , Anciano , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Proyectos Piloto , Resultado del Tratamiento , Adulto Joven
17.
Eur J Dermatol ; 29(1): 67-74, 2019 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-30827943

RESUMEN

Daylight photodynamic therapy (DL-PDT) is an effective and convenient treatment for multiple actinic keratosis (AKs). There are limited tools to evaluate the outcome of AK treatment. Recently, the actinic keratosis area and severity index (AKASI) has been proposed as a quantitative tool for assessing AK severity. To investigate patient satisfaction and efficacy of DL-PDT for severe AKs and to validate AKASI scoring as a quantitative tool for assessing the outcome of DL-PDT treatment. In this prospective single-centre study, we analysed the results of patients treated with one or two cycles of DL-PDT for severe AKs in the facial or scalp area. Forty patients (37 male and three female) with a mean age of 74 years (range: 56-87 years) were included and received either one (n = 20) or two (n = 20) cycles of DL-PDT. At baseline, most patients (95%) had 20 or more lesions. Patients treated with one cycle of DL-PDT showed a mean AKASI reduction of 45.5% (p < 0.001). Patients eligible for two cycles of DL-PDT demonstrated a mean AKASI reduction of 23.7% (p < 0.05) after one and 48.2% (p < 0.001) after two cycles. Patients participating in this study were either very satisfied (67.5%) or satisfied (32.5%). Almost all patients (97.5%) would recommend DL-PDT to other patients. DL-PDT is a well-tolerated, safe and efficient treatment option for field cancerisation in the facial and scalp area with high patient satisfaction. AKASI scoring has proven useful as a quantitative tool for assessing the outcome of DL-PDT treatment.


Asunto(s)
Ácido Aminolevulínico/administración & dosificación , Dermatosis Facial/tratamiento farmacológico , Queratosis Actínica/tratamiento farmacológico , Fotoquimioterapia/métodos , Dermatosis del Cuero Cabelludo/tratamiento farmacológico , Protectores Solares/administración & dosificación , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad
19.
Eur J Dermatol ; 28(1): 3-12, 2018 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-29336324

RESUMEN

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disease of the skin requiring skin and serum tests for a precise diagnosis. OBJECTIVES: We analysed the sensitivity and specificity of BP-relevant parameters and the value of autoantibody titres during follow-up of BP patients. MATERIALS & METHODS: In a retrospective single-centre study, we included 200 consecutive patients with BP and 400 non-BP patients, and evaluated the test results of patients' serum and skin. In addition, we followed patients' autoantibody titres and clinical characteristics. RESULTS: BP180-ELISA revealed the highest sensitivity (85.0%; specificity: 93.9%), while BP230-ELISA demonstrated the lowest sensitivity (55.5%; specificity: 92.9%). Direct and indirect immunofluorescence showed comparable results for sensitivity (77.2%/72.7%) and specificity (94.9%/93.7%). The sensitivity for skin histology was 76.3% (specificity: 81.3%). Longitudinal analysis showed significant changes in autoantibody titres. CONCLUSIONS: BP diagnostics should include serum tests for BP autoantibodies and skin immunofluorescence. Skin histology is supportive for diagnosis. Autoantibody titres are markers for disease activity.


Asunto(s)
Autoantígenos/análisis , Distonina/análisis , Colágenos no Fibrilares/análisis , Penfigoide Ampolloso/inmunología , Anciano , Ensayo de Inmunoadsorción Enzimática , Eosinófilos/citología , Femenino , Técnica del Anticuerpo Fluorescente Directa , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Recuento de Leucocitos , Masculino , Penfigoide Ampolloso/diagnóstico , Estudios Retrospectivos , Sensibilidad y Especificidad , Colágeno Tipo XVII
20.
Eur J Dermatol ; 27(3): 281-285, 2017 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-28524054

RESUMEN

Rhinophyma is a deforming soft tissue hyperplasia of the nose and surgical removal represents the treatment of choice. Comprehensive data on surgical therapy and the impact of rhinophyma on patient quality of life are lacking. Patients who received surgery for rhinophyma between 2006 and 2015 were retrospectively evaluated for postoperative complications, clinical outcome, recurrence of rhinophyma, and the impact of rhinophyma on daily life. A total of 143 patients were treated with superficial tumour decortication by scalpel under tumescent anaesthesia. Outcomes were determined by clinical review, clinical files, and a patient questionnaire. Of 143 patients, 70 answered the questionnaire and were included in this study with a mean follow-up time of 54 months. Cosmetic results were evaluated as very good or good in 77% of patients. The majority of patients (87%) were very satisfied or satisfied with the postoperative result. Surgical treatment of rhinophyma improved patients' quality of life in 67% of patients. Recurrence of rhinophyma was detected in 38% of patients. Surgery is an effective therapy for rhinophyma with excellent outcome.


Asunto(s)
Calidad de Vida , Rinofima/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Estética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Complicaciones Posoperatorias , Recurrencia , Estudios Retrospectivos , Encuestas y Cuestionarios
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