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1.
J Eur Acad Dermatol Venereol ; 38(1): 205-213, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37669834

RESUMO

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease that is highly correlated with obesity. Haptoglobin serum levels have recently been recognized as an important biomarker linking obesity with chronic inflammation. OBJECTIVE: To compare haptoglobin with previously proposed serum biomarkers for the determination of disease severity in HS patients. For this purpose, disease severity of HS patients was determined by a panel of clinical scores as well as several risk factors, such as weight and smoking habits. METHODS: A prospective, diagnostic accuracy study was performed at the International Centre for Hidradenitis suppurativa/Acne inversa Bochum (ICH). The study included a total of 263 patients, including 131 who had a confirmed diagnosis of HS in Hurley I (n = 16), II (n = 56) and III (n = 59) HS, and 132 healthy controls. The main outcome was to identify serological inflammatory markers for HS disease severity [severe (III) vs. moderate/mild (II/I)] as assessed by Hurley classification. RESULTS: The serum levels of acute phase proteins haptoglobin and CRP, as well as the number of neutrophils in peripheral blood, number of monocytes, the systemic immune-inflammation index and the pan-immune-inflammatory value correlated with disease severity according to established clinical scores (mHSS, SAHS, Hurley, DLQI). HS patients had significantly higher haptologlobin levels compared to healthy controls. Logistic regression analysis revealed haptoglobin as the only independent marker predicting severe HS. CONCLUSION: In this prospective study, we discovered that the serum levels of the acute phase protein haptoglobin levels serve as an independent marker of disease severity in HS. While this presents the first study in the context of HS. Thus, the present data not only yield a highly promising serum marker to be further validated.


Assuntos
Hidradenite Supurativa , Serina , Humanos , Biomarcadores , Haptoglobinas , Hidradenite Supurativa/diagnóstico , Inflamação/complicações , Obesidade/complicações , Gravidade do Paciente , Estudos Prospectivos , Índice de Gravidade de Doença , Serina/deficiência , Progressão da Doença
2.
J Cancer Res Clin Oncol ; 147(9): 2759-2764, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33630139

RESUMO

PURPOSE: Nodular melanoma (NM) is associated with worse disease outcome when compared to superficial spreading melanoma (SSM). We aimed to perform a single-center analysis of prognostic factors in patients with NM and compare the data with SSM patients. METHODS: We studied 228 patients with NN and 396 patients with SSM. Patients with in situ melanomas or stage IV at diagnosis were not included in the study. Data were analyzed using the Mann-Whitney test, Chi-square test, Kaplan-Meier curves including the log-rank test, and logistic regression model. RESULTS: When compared to patients with SSM, patients with NM had less likely lower Clark level, higher tumor thickness, less likely tumor regression, more often ulcerated tumors, and less likely a history of precursor lesions such as a nevus. Within a 5-year follow-up we observed significantly more disease relapses and deaths in NM patients than in SSM patients. On multivariate analysis, disease relapse in NM patients was independently predicted by tumor thickness and positive SLNB, whereas melanoma-specific death of NM patients was independently predicted by male sex and tumor thickness. Histologic regression also remained in the logistic regression model as a significant independent negative predictor of NM death. CONCLUSIONS: We did not observe that NM subtype was per se a significant independent predictor for disease relapse or melanoma-specific death. Among the well-known prognostic factors such as tumor thickness and male sex, NM is also associated with other unfavorable factors such as absence of regression.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Melanoma/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Melanoma/classificação , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/classificação , Neoplasias Cutâneas/tratamento farmacológico , Taxa de Sobrevida , Adulto Jovem
3.
J Eur Acad Dermatol Venereol ; 35(1): 203-210, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32978818

RESUMO

BACKGROUND: In a small number of kindreds with familial hidradenitis suppurativa (HS) different mutations of NCSTN (nicastrin) have been identified. Blocking of NCSTN leads to impairment of the Notch and PI3K/AKT signalling pathway, which is assumed to play a pathogenic role in HS. However, very limited data are available concerning expression levels of these pathway components in HS skin. OBJECTIVES: To analyse the mRNA and protein expression of NCSTN, Notch1-3, PIK3R3 and AKT3 in HS. METHODS: Skin samples from healthy controls, lesional and perilesional skin of HS patients with and without a positive family history were analysed by quantitative real-time RT-PCR and immunohistochemistry. Univariate statistical analyses were conducted regarding association between expression levels and patient's characteristics. RESULTS: Expression levels of all investigated genes showed significantly higher levels in lesional HS skin compared with healthy controls. Univariate analysis showed no association between a positive family history and mRNA expression levels. Perilesional HS skin of patients with mild disease severity (Hurley I) showed significant higher mRNA expression levels of the investigated pathway components compared to moderate (Hurley II) and severe disease (Hurley III). CONCLUSION: We found no evidence for diminished expression levels of the Notch signalling. In contrast, the NCSTN, Notch and PI3K/AKT signalling components are overexpressed in HS. Future research is needed to investigate a possible pathogenetic role or to reveal a coactivation of these overexpressed components during inflammatory response in HS.


Assuntos
Hidradenite Supurativa , Hidradenite Supurativa/genética , Humanos , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais , Pele , Fatores de Transcrição
4.
Eur J Cancer ; 138: 30-40, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32836172

RESUMO

BACKGROUND: Electrochemotherapy (ECT) is a treatment for both primary and secondary cutaneous tumours. The international Network for sharing practices on ECT group investigates treatment outcomes after ECT using a common database with defined parameters. METHODS: Twenty-eight centres across Europe prospectively uploaded data over an 11-year period. Response rates were investigated in relation to primary diagnosis, tumour size, choice of electrode type, route of bleomycin administration, electrical parameters recorded and previous irradiation in the treated field. RESULTS: Nine hundred eighty-seven patients, with 2482 tumour lesions were included in analysis. The overall response (OR) rate was 85% (complete response [CR]: 70%, partial response rate: 15%, stable disease: 11%, and progressive disease: 2%). For different histologies, OR and CR rates for metastases of malignant melanoma were 82% and 64%, basal cell carcinoma were 96% and 85%, breast cancer metastases were 77% and 62%, squamous cell carcinoma were 80% and 63% as well as Kaposi's sarcoma were 98% and 91%, respectively. Variance was demonstrated across histotypes (p < 0.0001) and in accordance with size of lesion treated (dichotomised at diameter of 3 cm (p < 0.0001). Hexagonal electrodes were generally used for larger tumours, but for tumours up to 3 cm, linear array electrodes provided better tumour control than hexagonal electrodes (80%:74%, p < 0.003). For tumours more than 2 cm, intravenous administration was superior to intratumoural (IT) administration (p < 0.05). Current recorded varied across tumour histologies and size but did not influence response rate. In previously irradiated areas, responses were selectively lower for IT administration. CONCLUSIONS: These cumulative data endorse efficiency of ECT across a broad range of histotypes. Analysis of 2482 lesions details subgroup analysis on treatment response informing future treatment choices.


Assuntos
Eletroquimioterapia/métodos , Neoplasias Cutâneas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias Cutâneas/patologia , Adulto Jovem
5.
Clin Exp Dermatol ; 45(8): 1011-1018, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32422686

RESUMO

BACKGROUND: In patients with cutaneous melanoma (CM), the time span between resection of the primary tumour and sentinel lymph node biopsy (SLNB) as well as the subsequent interval between SLNB and complete lymph node dissection (CLND) varies greatly. AIM: To determine whether very early timing of SLNB after resection of the primary tumour, or timing of CLND after SLNB affect the clinical outcome of patients with CM, compared with longer time intervals. METHODS: We compared the time spans between complete resection of the primary tumour and SLNB, and the interval between SLNB and CLND in a cohort of 896 patients with melanoma who had undergone SLNB. An interval between primary resection and SLNB or between SLNB and CLND of up to 7 days was classified as very early (VE-SLNB and VE-CLND, respectively). This time span was compared with intervals of > 7 days. Univariate and multivariate statistics were performed. RESULTS: VE-SLNB was significantly associated with the presence of micrometastases. However, this was probably due to tumour thickness being significantly higher in patients with VE-SLNB compared with patients with later SLNB. Importantly, VE-SLNB was not significantly associated with disease relapse and VE-CLND was not associated with melanoma-specific death. CONCLUSIONS: VE-SLNB and VE-CLND neither improved nor worsened the clinical outcome of patients. Thus, timing of SLNB and CLND has no influence on the overall clinical outcome of patients with melanoma. Our findings support the rational planning of lymph node surgery after resection of the primary tumour and provide help for effective patient counselling.


Assuntos
Intervenção Médica Precoce/estatística & dados numéricos , Linfonodos/cirurgia , Melanoma/cirurgia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aconselhamento/métodos , Feminino , Humanos , Excisão de Linfonodo/métodos , Excisão de Linfonodo/estatística & dados numéricos , Linfonodos/patologia , Metástase Linfática/patologia , Masculino , Melanoma/diagnóstico , Pessoa de Meia-Idade , Biópsia de Linfonodo Sentinela/métodos , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/cirurgia , Fatores de Tempo , Resultado do Tratamento , Melanoma Maligno Cutâneo
6.
Hautarzt ; 71(4): 256-262, 2020 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-32077977

RESUMO

Hidradenitis suppurativa/acne inversa (HS/AI) is a chronic inflammatory skin disease. Several studies showed that perianal, perineal and gluteal involvement is more common in men. Axillary, submammary and inguinal localizations seem to be more prevalent in women. Involvement of the genitoanal region is associated with a higher reduced quality of live and sexual health compared to other locations. Moreover HS/AI in the genitoanal region can lead to serious complications. The knowledge of perianal fistula formation, pubogenital lymphedema and squamous cell carcinoma, which are three of the most severe complications, is critical for adequate treatment.


Assuntos
Neoplasias dos Genitais Masculinos , Hidradenite Supurativa , Linfedema , Fístula Retal , Canal Anal/patologia , Nádegas , Carcinoma de Células Escamosas/etiologia , Gerenciamento Clínico , Feminino , Virilha , Hidradenite Supurativa/diagnóstico , Hidradenite Supurativa/terapia , Humanos , Inflamação , Linfedema/complicações , Masculino , Prevalência , Qualidade de Vida , Resultado do Tratamento
7.
Clin Exp Dermatol ; 44(3): 300-303, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30264463

RESUMO

Recurrence rates of both lentigo maligna (LM) and lentigo maligna melanoma (LMM) following conventional surgery are usually relatively high. We aimed to assess the frequencies of melanocytes in tumour-free margins around LM/LMM using soluble adenylyl cyclase (sAC) immunohistochemistry, and to compare these with those of matched healthy contralateral skin. Using the primary mouse-anti-human sAC antibody R21, we evaluated pan-nuclear melanocytic R21 immunostaining, and found that it was significantly (P < 0.001) higher in peritumoural melanocytes (median 20%; range 0-100%) than in contralateral healthy skin (mean 0%; range 0-20%). Accordingly, there was no correlation between peritumoural and contralateral R21 immunoreactivity (r = 0.12; P = 0.18). In conclusion, melanocytic R21 immunoreactivity in melanocytes is higher in tumour-free margins around LM/LMM than in site-matched contralateral skin. This observation may indicate that the biology of 'healthy'-appearing melanocytes around LM/LMM might be different from that of truly benign melanocytes.


Assuntos
Adenilil Ciclases/metabolismo , Anticorpos Monoclonais/metabolismo , Sarda Melanótica de Hutchinson/cirurgia , Neoplasias Cutâneas/cirurgia , Regulação para Cima , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Sarda Melanótica de Hutchinson/enzimologia , Masculino , Margens de Excisão , Melanócitos/metabolismo , Pessoa de Meia-Idade , Neoplasias Cutâneas/enzimologia , Resultado do Tratamento , Microambiente Tumoral
8.
J Eur Acad Dermatol Venereol ; 33(1): 19-31, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30176066

RESUMO

Hidradenitis suppurativa (HS)/acne inversa is a debilitating chronic disease that remains poorly understood and difficult to manage. Clinical practice is variable, and there is a need for international, evidence-based and easily applicable consensus on HS management. We report here the findings of a systematic literature review, which were subsequently used as a basis for the development of international consensus recommendations for the management of patients with HS. A systematic literature review was performed for each of nine clinical questions in HS (defined by an expert steering committee), covering comorbidity assessment, therapy (medical, surgical and combinations) and response to treatment. Included articles underwent data extraction and were graded according to the Oxford Centre for Evidence-based Medicine criteria. Evidence-based recommendations were then drafted, refined and voted upon, using a modified Delphi process. Overall, 5310 articles were screened, 171 articles were analysed, and 65 were used to derive recommendations. These articles included six randomized controlled trials plus cohort studies and case series. The highest level of evidence concerned dosing recommendations for topical clindamycin in mild disease (with systemic tetracyclines for more frequent/widespread lesions) and biologic therapy (especially adalimumab) as second-line agents (following conventional therapy failure). Good-quality evidence was available for the hidradenitis suppurativa clinical response (HiSCR) as a dichotomous outcome measure in inflammatory areas under treatment. Lower-level evidence supported recommendations for topical triclosan and oral zinc in mild-to-moderate HS, systemic clindamycin and rifampicin in moderate HS and intravenous ertapenem in selected patients with more severe disease. Intralesional or systemic steroids may also be considered. Local surgical excision is suggested for mild-to-moderate HS, with wide excision for more extensive disease. Despite a paucity of good-quality data on management decisions in HS, this systematic review has enabled the development of robust and easily applicable clinical recommendations for international physicians based on graded evidence.


Assuntos
Antibacterianos/uso terapêutico , Hidradenite Supurativa/tratamento farmacológico , Hidradenite Supurativa/epidemiologia , Fumar/epidemiologia , Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Produtos Biológicos/uso terapêutico , Comorbidade , Consenso , Técnica Delphi , Hidradenite Supurativa/cirurgia , Humanos , Guias de Prática Clínica como Assunto
9.
J Eur Acad Dermatol Venereol ; 32(9): 1485-1491, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29478287

RESUMO

BACKGROUND: Koebnerized non-melanoma skin cancer following skin trauma represents a rare and obscure event. OBJECTIVES: To study molecular pathological parameters in koebnerized squamous cell carcinomas (K-SCCs) occurring after complete tumour removal. METHODS: We assessed two patients with multiple sclerosis who were on treatment with dimethylfumarate (DMF) preceded by long-term azathioprine therapy. Both patients rapidly developed several K-SCCs following histopathologically proven complete excision of cutaneous SCCs. We performed immunohistochemistry for p53, p16, Ki-67, TET-2, IDH-2, 5-hmc and 5-mc. PCR was carried out for the detection of human papilloma viruses. Mutation analysis was performed for BRAF, K-RAS and EGFR. RESULTS: All lesions investigated were negative for HPV DNA. Mutations were not detected. Healthy appearing skin of both patients showed relatively high Ki-67, p16 and p53 expression which was comparable to the expression observed in primary SCCs as well as K-SCCs. Protein expression of Ki-67, p16 and mutant p53 was barely detected in the specimens of the healthy controls. A decreased protein expression of TET-2 enzyme was seen in all tumours and healthy appearing skin when compared to the skin of healthy controls. CONCLUSIONS: We observed two patients with K-SCCs developing under DMF treatment. In healthy appearing skin of patients with K-SCCs, wound healing processes, including induction of proliferation and growth factor release, might promote the growth of preneoplastic keratinocytes and cancer formation on the basis of pre-existing altered epigenetic pathways and cell cycle dysregulation. Although fumarates can reduce TET-2 expression, the role of DMF intake in the development of K-SCCs remains unclear.


Assuntos
Carcinoma de Células Escamosas/genética , Ciclo Celular , Epigênese Genética , Recidiva Local de Neoplasia/metabolismo , Neoplasias Cutâneas/genética , Fenômenos Fisiológicos da Pele , Pele/metabolismo , 5-Metilcitosina/metabolismo , Azatioprina/uso terapêutico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/cirurgia , Ciclo Celular/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Proteínas de Ligação a DNA/metabolismo , Desoxicitidina/análogos & derivados , Desoxicitidina/metabolismo , Fumarato de Dimetilo/uso terapêutico , Dioxigenases , Receptores ErbB/genética , Feminino , Humanos , Imunossupressores/uso terapêutico , Isocitrato Desidrogenase/metabolismo , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/cirurgia , Fenômenos Fisiológicos da Pele/genética , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
10.
Hautarzt ; 69(2): 149-161, 2018 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-29322225

RESUMO

Hidradenitis suppurativa/acne inversa (HS/AI) is a chronic inflammatory skin disease. Therapy consists of conservative and surgical treatment options. In Hurley stages II and III, surgical intervention is regarded as the method of choice for areas with irreversible tissue destruction. Resection techniques with different grades of invasiveness are described in the literature. Nevertheless, there is no generally accepted concept regarding resection and reconstruction techniques or specific postoperative care. Due to lack of definitions of recurrence after surgery and poor study quality, recurrence rates are difficult to determine.


Assuntos
Hidradenite Supurativa/cirurgia , Axila/cirurgia , Terapia Combinada , Curetagem , Drenagem , Feminino , Seguimentos , Doenças dos Genitais Femininos/diagnóstico , Doenças dos Genitais Femininos/cirurgia , Doenças dos Genitais Masculinos/diagnóstico , Doenças dos Genitais Masculinos/cirurgia , Hidradenite Supurativa/diagnóstico , Humanos , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos , Tratamento de Ferimentos com Pressão Negativa , Cuidados Pós-Operatórios , Recidiva , Retalhos Cirúrgicos/cirurgia , Ferida Cirúrgica , Cicatrização/fisiologia
11.
Arch Dermatol Res ; 310(2): 157-163, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29350263

RESUMO

Argon plasma coagulation (APC) is an electrosurgical technique which can be used to ablate skin lesions with limited invasion depth into dermal tissue. Hence, APC might be well suited for the removal of epithelial tumours. However, there are no data on the effects of APC on human skin tissue. Thus, the aim of this study was to determine the extent of epidermal and dermal damage after APC of human skin. We performed APC ex-vivo on 91 freshly resected human skin samples, which were obtained after reconstructive surgical closures in actinically damaged areas. Tissue effects were evaluated histologically and compared across different power settings. Using 15, 30, and 45 W, median (interquartile range; IQR) coagulation depths were 110.0 µm (91.7-130.0), 113.3 µm (85.8-135.0), and 130.0 µm (100.0-153.3.0), respectively. Median (IQR) thickness of necrosis zone was 30.0 µm (23.3-40.0) at 15 W, 26.7 µm (20.0-41.6) at 30 W, and 43.3 µm (30.8-57.5) at 45 W. The Kruskal-Wallis test showed significant differences between 15 and 30 W versus 45 W for coagulation depth (P = 0.0414), necrosis zone (P = 0.0017), and necrosis according to overlaying epidermal thickness (P = 0.0467). In summary, APC is a simple and controllable electrosurgical technique to remove epidermal tissue with limited penetration to the dermis. Thus, APC is particularly suited for the ablation of epithelial skin lesions and, therefore, may serve as possible treatment approach for intraepithelial neoplasms such as actinic keratosis.


Assuntos
Coagulação com Plasma de Argônio/efeitos adversos , Procedimentos Cirúrgicos Dermatológicos/efeitos adversos , Ceratose Actínica/cirurgia , Neoplasias Cutâneas/cirurgia , Pele/patologia , Idoso , Idoso de 80 Anos ou mais , Coagulação com Plasma de Argônio/métodos , Procedimentos Cirúrgicos Dermatológicos/métodos , Feminino , Humanos , Ceratose Actínica/etiologia , Masculino , Neoplasias Cutâneas/etiologia , Raios Ultravioleta/efeitos adversos
12.
Diabet Med ; 34(8): 1165-1168, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28523836

RESUMO

BACKGROUND: Diabetic foot ulcers are a common complication in the advanced stages of diabetes mellitus. Certain lesions may be refractory to usual treatments with prolonged healing. In these cases, differential diagnoses to classical ulcers should be considered. Although plantar warts are a common and easy-to-diagnose finding in the general population, diagnosis can be challenging in people with diabetic foot ulcers, as they mimic hyperkeratosis in these people. CASE REPORT: We report seven cases of people with diabetic foot ulcers and verrucae vulgares mimicking treatment-refractory hyperkeratosis, presenting to our centre between 2014 and 2016. Diagnosis was aided by the clinical presentation, followed by dermoscopy and punch biopsy. Treatment included topical application of 5-fluoruracil and salicylic acid (four people), cryotherapy (three people) and surgical excision (three people), all in combination with local pressure offloading. In five people, the verrucae were completely removed after a mean treatment period of 9.4 months; two individuals were lost to follow-up. CONCLUSION: Verrucae may be more common in people with diabetic foot lesions and polyneuropathy than generally assumed. Typical findings include small, pinhead-sized bleedings within and surrounding hyperkeratous lesions. These findings should alert the clinician for the potential presence of a verruca. In such cases, biopsy should be performed to enable specific diagnosis and treatment.


Assuntos
Pé Diabético/complicações , Verrugas/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biópsia , Terapia Combinada , Dermoscopia , Pé Diabético/fisiopatologia , Diagnóstico Diferencial , Feminino , , Alemanha , Hospitais Universitários , Humanos , Ceratodermia Palmar e Plantar/diagnóstico , Ceratodermia Palmar e Plantar/etiologia , Ceratodermia Palmar e Plantar/patologia , Ceratodermia Palmar e Plantar/terapia , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Polineuropatias/complicações , Polineuropatias/fisiopatologia , Resultado do Tratamento , Verrugas/complicações , Verrugas/patologia , Verrugas/terapia
13.
J Cancer Res Clin Oncol ; 143(2): 347-350, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27778198

RESUMO

BACKGROUND: Lateral distribution of cancer has been observed previously. Most evident is this laterality in ultraviolet (UV)-induced skin cancer, based on an unequally distributed UV exposure. OBJECTIVES: The aim of this study was to explore whether patients from Germany also show asymmetrical lateral distribution of Merkel cell carcinoma (MCC). METHODS: In total, 115 patients with MCC were studied for laterality of the primary tumour. Correlation of clinical variables with lateral distribution of MCC was investigated as well. RESULTS: In 64/115 (55.7%) patients, primary tumours were present on the left side, in 37/115 (32.2%) on the right side, and in 14/115 (12.2%) in the midline (P < 0.0001). Excluding the latter localization occurrence of left-sided MCCs (64 of 101/63.4%) was significantly (P = 0.0072) more often observed (1.73-fold) when compared to right-sided tumours (37 of 101/36.6%). The excess of left-sided tumours was found on the head with a left-right ratio of 1.8, trunk of 8, arm of 1.2, and leg of 1.8. There was no significant association between laterality and gender, age, MCPyV status, and anatomic localization of primary tumours including the occurrence in sun-exposed sites. CONCLUSIONS: Occurrence of left-sided MCCs was significantly more often observed when compared to right-sided tumours. Laterality was not associated with tumour presentation at chronically ultraviolet-exposed sites. Hence, the reason for laterality in MCC remains obscure, but likely goes beyond UV exposure.


Assuntos
Carcinoma de Célula de Merkel/patologia , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Célula de Merkel/epidemiologia , Feminino , Alemanha , Humanos , Masculino , Neoplasias Cutâneas/epidemiologia , Luz Solar/efeitos adversos
14.
J Eur Acad Dermatol Venereol ; 31(4): 724-731, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27976439

RESUMO

BACKGROUND: To date, there is still a debate how to deal with patients receiving antithrombotic agents prior to surgical procedures on the skin. OBJECTIVE: To prospectively assess complications after dermatosurgical interventions, especially bleeding, depending on anticoagulation therapy. METHODS: Patients underwent surgery consecutively as scheduled, without randomization, whether or not they were currently taking anticoagulants. Nine institutions of the DESSI (DErmatoSurgical Study Initiative) working group documented patient data prospectively on a standardized study sheet prior to and after 9154 dermatosurgical interventions. RESULTS: Bleeding complications were observed in 7.14% of cases (654/9154 surgeries). A severe bleed requiring intervention by a physician occurred in 83 surgeries (0.91%). In multivariate analysis, INR, length of the defect, perioperative antibiotic treatment, current treatment with anticoagulation therapy, age and surgery on hidradenitis suppurativa/acne inversa (HS/AI) were significant parameters independently influencing the risk of bleeding. Discontinuation of phenprocoumon therapy and subsequent switching to low molecular weight heparin was associated with the highest risk of bleeding (9.26%). CONCLUSION: Bleeding complications in skin surgery are generally rare. Even if slightly increased complication rates are found in patients taking anticoagulants during skin surgery, platelet inhibitors should not be stopped prior to surgery. If a surgical procedure in patients on a combination therapy of 2 or more antiplatelet cannot be postponed, it should be conducted with the patient remaining on combination therapy. Discontinuation of DOACs is recommended 24 h prior to surgery. Bridging of phenprocoumon should be terminated. In patients with a bleeding history, the INR value should be within the therapeutic range.


Assuntos
Anticoagulantes/efeitos adversos , Procedimentos Cirúrgicos Dermatológicos/efeitos adversos , Hemorragia Pós-Operatória/epidemiologia , Hemorragia Pós-Operatória/etiologia , Dermatopatias/cirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Feminino , Heparina/efeitos adversos , Hidradenite Supurativa/cirurgia , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Femprocumona/efeitos adversos , Hemorragia Pós-Operatória/terapia , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Ferida Cirúrgica/complicações
15.
J Cancer Res Clin Oncol ; 143(1): 43-49, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27624714

RESUMO

BACKGROUND: It has recently been reported that atonal homolog 1 (ATOH1) gene is down-regulated in Merkel cell carcinoma (MCC) and thus may represent a tumor suppressor gene. OBJECTIVES: We aimed to test for ATOH1 gene mutations and expression levels in MCC tissues and cell lines. METHODS: Genomic DNA isolation and amplification via PCR was successfully performed in 33 MCCs on formalin-fixed paraffin-embedded tissue and three MCC cell lines, followed by Sanger sequencing of the whole ATOH1 gene to detect genomic aberrations. ATOH1 mRNA levels were determined by RT-PCR. Immunohistochemistry of ATOH1 was performed to quantify protein expression in tumor samples and cell lines. RESULTS: Neither in any of the 33 MCC tissue samples nor in the three cell lines ATOH1 mutations were present. ATOH1 was expressed in all lesions, albeit at different expression levels. Univariate analysis revealed that the total immunohistology score significantly correlated with the occurrence of tumor relapse (r = 0.57; P = 0.0008). This notion was confirmed in multivariate analysis suggesting that ATOH1 expression is a potential independent predictor for tumor relapse in MCC patients (P = 0.028). MCC-related death also correlated with ATOH1 expression (r = 0.4; P = 0.025); however, ATOH1 expression did not retain its predictive value in the regression model. CONCLUSIONS: In contrast to anecdotal reports ATOH1 expression is not lost by genetic alterations in MCC. However, protein expression of ATOH1 is increased in advanced MCC indicating that ATOH1 is involved in MCC progression.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Célula de Merkel/metabolismo , Recidiva Local de Neoplasia/metabolismo , Neoplasias Cutâneas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Biomarcadores Tumorais/genética , Carcinoma de Célula de Merkel/virologia , Linhagem Celular Tumoral , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Poliomavírus das Células de Merkel/genética , Prognóstico , Neoplasias Cutâneas/virologia
16.
Eur J Surg Oncol ; 42(9): 1420-6, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27160354

RESUMO

BACKGROUND: The long-term outcome of patients with melanoma who had recurrence after negative sentinel lymph node (SLN) biopsy has rarely been evaluated systematically. METHODS: We searched our databases for melanoma patients with SLN biopsy from the end of 1999 and the beginning of 2011. Data was analyzed using uni- and multivariate statistics as well as Kaplan-Meier curves. RESULTS: Data of 651 patients with melanoma was available for statistics. We observed 451 (69.3%) patients with negative SLN who had no evidence of disease recurrence during follow-up. Recurrence in SLN negative patients was found in 50 (7.7%) cases. Tumor subtypes such as invasive lentigo maligna melanoma and acral melanoma (odds ratio 15.2, P = 0.015) and tumor thickness > 2 mm (odds ratio 3.1, P = 0.0017) were independent predictors for recurrence in patients with negative SLN. Patients with negative SLN and subsequent recurrence had a significantly (P = 0.036) reduced 5-year melanoma-specific survival (MSS) when compared with positive SLN patients. Recurrence of disease in positive SLN patients was observed after a median of 39 months when compared to patients with negative SLN and recurrence (28 months, P = 0.0079). Negative SLN with recurrence was an independent predictor for worse recurrence free and melanoma-related survival. CONCLUSIONS: Patients with negative SLN and recurrence experience earlier disease relapses and poorer MSS when compared to patients with positive SLN status implicating that more stringent follow-up procedures are warranted in patients with higher tumor thickness and invasive lentigo maligna and acral melanoma, despite a negative SLN.


Assuntos
Neoplasias de Cabeça e Pescoço/patologia , Melanoma/patologia , Recidiva Local de Neoplasia/epidemiologia , Linfonodo Sentinela/patologia , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Prognóstico , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/mortalidade , Úlcera Cutânea/epidemiologia , Carga Tumoral , Adulto Jovem
17.
Ann Oncol ; 27(2): 332-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26578727

RESUMO

BACKGROUND: MicroRNAs (miRNAs) have been identified as key players in posttranscriptional gene regulation and have a significant impact on basal cell carcinoma (BCC) development. The Sonic hedgehog pathway inhibitor vismodegib has been approved for oral therapy of metastatic or advanced BCC. Here, a high-throughput miRNA sequencing analysis was carried out to identify differentially expressed miRNAs and possible novel miRNA candidates in vismodegib-treated BCC tissue. Additionally, we described our surgical experience with neoadjuvant oral vismodegib therapy. PATIENTS AND METHODS: A punch biopsy (4 mm) from a patient with an extensive cranial BCC under oral vismodegib therapy and a corresponding nonlesional epithelial skin biopsy were harvested. Total RNA was isolated, after which a sequencing cDNA library was prepared, and cluster generation was carried out, which was followed by an ultra-high-throughput miRNA sequencing analysis to indicate the read number of miRNA expression based on miRBase 21. In addition to the identification of differentially expressed miRNAs from RNA sequencing data, additional novel miRNA candidates were determined with a tool for identifying new miRNA sequences (miRDeep2). RESULTS: We identified 33 up-regulated miRNAs (fold change ≥2) and 39 potentially new miRNA candidates (miRDeep scores 0-43.6). A manual sequence analysis of the miRNA candidates on the genomic locus of chromosome 1 with provisional IDs of chr1_1913 and chr1_421 was further carried out and rated as promising (chr1_1913) and borderline (chr1_421). Histopathology revealed skip lesions in clinically healthy appearing skin at the tumor margins, which were the cause of seven re-excisions by micrographic controlled surgery to achieve tumor-free margins. CONCLUSION: miRNA sequencing revealed novel miRNA candidates that need to be further confirmed in functional Dicer knockout studies. Clinically, on the basis of our surgical experience described here, neoadjuvant vismodegib therapy in BCC appears to impede histopathologic evaluations with effects on surgical therapy. Thus, larger studies are necessary, but are not preferable at this time if other options are available.


Assuntos
Carcinoma Basocelular/genética , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , Neoplasias Cutâneas/genética , Pele/patologia , Idoso , Anilidas/uso terapêutico , Antineoplásicos/uso terapêutico , Sequência de Bases , Biópsia , Carcinoma Basocelular/tratamento farmacológico , Carcinoma Basocelular/cirurgia , Feminino , Proteínas Hedgehog/antagonistas & inibidores , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Dados de Sequência Molecular , Piridinas/uso terapêutico , Análise de Sequência de RNA , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/cirurgia
18.
J Wound Care ; 24(3): 135; 138-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25764958

RESUMO

OBJECTIVE: Modified microscopically controlled surgery (MCS) is a staged and margin-controlled excision; after MCS, the selection of an appropriate initial wound dressing plays an important role in wound healing. A wide range of dressings is available for temporary wound coverage; however, data comparing different types of wound dressings after MCS are lacking. The aim of this study was to compare two commonly used and commercially available types of wound dressings. METHOD: We assessed pain levels, wound adherence, bleeding upon dressing removal and signs of infection, with chlorhexidine-impregnated tulle gras and a lipidocolloid dressing used for primary wound dressing following MCS. RESULTS: A total of 42 patients were included. Adherence of the dressing to the wound (p<0.001) and bleeding after removal (p=0.001) were significantly higher in the chlorhexidine-impregnated tulle gras dressing group. Pain during removal of wound dressing had a higher visual analogue scale score (1.9 ± 2.2) in the chlorhexidine-impregnated tulle gras dressing group compared to 0.7 ± 1.0 in the lipidocolloid dressing group (p=0.022). CONCLUSION: The results indicate that the lipidocolloid dressing, when compared with the chlorhexidine-impregnated tulle gras dressing, offers a significant benefit during removal in terms of less pain, less wound adherence and less wound bleeding. DECLARATION OF INTEREST: The authors have no conflict of interest to declare.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Bandagens , Clorexidina/administração & dosagem , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/cirurgia , Cicatrização/efeitos dos fármacos , Ferimentos Penetrantes/terapia , Administração Tópica , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Coloides/administração & dosagem , Feminino , Humanos , Lipídeos/administração & dosagem , Masculino , Microcirurgia/efeitos adversos , Pessoa de Meia-Idade , Estudos Prospectivos , Pele/lesões , Resultado do Tratamento , Ferimentos Penetrantes/etiologia
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