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BACKGROUND: Metabolic reprogramming and altered gene expression mediated by hypoxia-inducible factors play crucial roles during tumour growth and progression. Nevertheless, studies analysing the expression of hypoxia-inducible factor-1α and its downstream targets in Merkel cell carcinoma (MCC) are lacking but are warranted to shed more light on MCC pathogenesis and to potentially provide new therapeutic options. OBJECTIVES: To analyse the immunohistochemical expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor-A (referred to as VEGF throughout the manuscript), VEGF receptor-2 (VEGFR-2), VEGF receptor-3 (VEGFR-3), glucose transporter-1 (Glut-1), monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CAIX) in primary cutaneous MCC. METHODS: The 16 paraffin-embedded primary cutaneous MCCs (Merkel cell polyomavirus (McPyV) positive/negative: 11/5) were analysed by immunohistochemistry, namely HIF-1α, VEGF, VEGFR-2 (KDR), VEGFR-3 (FLT4), Glut-1, MCT4 and CAIX. An established quantification score (QS) was applied to quantitate the protein expression by considering the percentage of positive tumour cells (0: 0%; 1: up to 1%; 2: 2-10%; 3: 11-50%; 4: >50%) in relation to the staining intensity (0: negative; 1: low; 2: medium; 3: strong). RESULTS: HIF-1α was expressed in all MCCs and predominantly found at the invading edges of tumour margins. The HIF-1α downstream factors Glut-1, MCT4 and CAIX were expressed in 13 of 16 MCC (81%), 14 of 16 MCC (88%) and 16 of 16 MCC (100%), respectively. Interestingly, VEGF and VEGFR-2 were not expressed in tumour cells, whereas VEGFR-3 was expressed in all MCCs. HIF-1α was expressed significantly stronger in McPyV+ tumours (QS: 10.36 ± 2.41) than in McPyV- tumours (QS: 5.40 ± 1.34; P = 0.002). Similarly, VEGFR-3 was also expressed significantly stronger in McPyV+ tumours (QS: 10.00 ± 2.52) than in McPyV- tumours (QS: 5.40 ± 3.43, P = 0.019). CONCLUSIONS: Our data provide first evidence for a role of HIF-1α in induced metabolic reprogramming contributing to MCC pathogenesis. The metabolic signatures of McPyV+ and McPyV- tumours seem to show relevant differences.
Assuntos
Carcinoma de Célula de Merkel , Subunidade alfa do Fator 1 Induzível por Hipóxia , Poliomavírus das Células de Merkel , Neoplasias Cutâneas , Fator A de Crescimento do Endotélio Vascular , HumanosRESUMO
BACKGROUND: Convolutional neural networks (CNNs) efficiently differentiate skin lesions by image analysis. Studies comparing a market-approved CNN in a broad range of diagnoses to dermatologists working under less artificial conditions are lacking. MATERIALS AND METHODS: One hundred cases of pigmented/non-pigmented skin cancers and benign lesions were used for a two-level reader study in 96 dermatologists (level I: dermoscopy only; level II: clinical close-up images, dermoscopy, and textual information). Additionally, dermoscopic images were classified by a CNN approved for the European market as a medical device (Moleanalyzer Pro, FotoFinder Systems, Bad Birnbach, Germany). Primary endpoints were the sensitivity and specificity of the CNN's dichotomous classification in comparison with the dermatologists' management decisions. Secondary endpoints included the dermatologists' diagnostic decisions, their performance according to their level of experience, and the CNN's area under the curve (AUC) of receiver operating characteristics (ROC). RESULTS: The CNN revealed a sensitivity, specificity, and ROC AUC with corresponding 95% confidence intervals (CI) of 95.0% (95% CI 83.5% to 98.6%), 76.7% (95% CI 64.6% to 85.6%), and 0.918 (95% CI 0.866-0.970), respectively. In level I, the dermatologists' management decisions showed a mean sensitivity and specificity of 89.0% (95% CI 87.4% to 90.6%) and 80.7% (95% CI 78.8% to 82.6%). With level II information, the sensitivity significantly improved to 94.1% (95% CI 93.1% to 95.1%; P < 0.001), while the specificity remained unchanged at 80.4% (95% CI 78.4% to 82.4%; P = 0.97). When fixing the CNN's specificity at the mean specificity of the dermatologists' management decision in level II (80.4%), the CNN's sensitivity was almost equal to that of human raters, at 95% (95% CI 83.5% to 98.6%) versus 94.1% (95% CI 93.1% to 95.1%); P = 0.1. In contrast, dermatologists were outperformed by the CNN in their level I management decisions and level I and II diagnostic decisions. More experienced dermatologists frequently surpassed the CNN's performance. CONCLUSIONS: Under less artificial conditions and in a broader spectrum of diagnoses, the CNN and most dermatologists performed on the same level. Dermatologists are trained to integrate information from a range of sources rendering comparative studies that are solely based on one single case image inadequate.
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Melanoma , Neoplasias Cutâneas , Dermatologistas , Dermoscopia , Alemanha , Humanos , Masculino , Melanoma/diagnóstico por imagem , Redes Neurais de ComputaçãoRESUMO
BACKGROUND: Deep learning convolutional neural networks (CNN) may assist physicians in the diagnosis of melanoma. The capacity of a CNN to differentiate melanomas from combined naevi, the latter representing well-known melanoma simulators, has not been investigated. OBJECTIVE: To assess the diagnostic performance of a CNN when used to differentiate melanomas from combined naevi in comparison with dermatologists. METHODS: In this study, a CNN with regulatory approval for the European market (Moleanalyzer-Pro, FotoFinder Systems GmbH, Bad Birnbach, Germany) was used. We attained a dichotomous classification (benign, malignant) in dermoscopic images of 36 combined naevi and 36 melanomas with a mean Breslow thickness of 1.3 mm. Primary outcome measures were the CNN's sensitivity, specificity and the diagnostic odds ratio (DOR) in comparison with 11 dermatologists with different levels of experience. RESULTS: The CNN revealed a sensitivity, specificity and DOR of 97.1% (95% CI [82.7-99.6]), 78.8% (95% CI [62.8-89.1.3]) and 34 (95% CI [4.8-239]), respectively. Dermatologists showed a lower mean sensitivity, specificity and DOR of 90.6% (95% CI [84.1-94.7]; P = 0.092), 71.0% (95% CI [62.6-78.1]; P = 0.256) and 24 (95% CI [11.6-48.4]; P = 0.1114). Under the assumption that dermatologists use the CNN to verify their (initial) melanoma diagnosis, dermatologists achieve an increased specificity of 90.3% (95% CI [79.8-95.6]) at an almost unchanged sensitivity. The largest benefit was observed in 'beginners', who performed worst without CNN verification (DOR = 12) but best with CNN verification (DOR = 98). CONCLUSION: The tested CNN more accurately classified combined naevi and melanomas in comparison with trained dermatologists. Their diagnostic performance could be improved if the CNN was used to confirm/overrule an initial melanoma diagnosis. Application of a CNN may therefore be of benefit to clinicians.
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Aprendizado Profundo , Dermatologistas , Diagnóstico por Computador/métodos , Melanoma/diagnóstico por imagem , Nevo Pigmentado/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Adulto , Idoso , Competência Clínica , Dermoscopia , Feminino , Humanos , Masculino , Melanócitos/patologia , Melanoma/patologia , Pessoa de Meia-Idade , Nevo Pigmentado/patologia , Sensibilidade e Especificidade , Neoplasias Cutâneas/patologia , Adulto JovemRESUMO
BACKGROUND: Since the establishment of dermoscopy as a routine examination procedure in dermatology, the spectrum of noninvasive, optical devices has further expanded. In difficult-to-diagnose clinical cases, these systems may support dermatologists to arrive at a correct diagnosis without the need for a surgical biopsy. OBJECTIVE: To give an overview about technical background, indications and diagnostic performance regarding four new optical procedures: reflectance confocal microscopy, in vivo multiphoton tomography, dermatofluoroscopy, and systems based on image analysis by artificial intelligence (AI). MATERIALS AND METHODS: This article is based on a selective review of the literature, as well as the authors' personal experience from clinical studies relevant for market approval of the devices. RESULTS: In contrast to standard histopathological slides with vertical cross sections, reflectance confocal microscopy and in vivo multiphoton tomography allow for "optical biopsies" with horizontal cross sections. Dermatofluoroscopy and AI-based image analyzers provide a numerical score, which helps to correctly classify a skin lesion. The presented new optical procedures may be applied for the diagnosis of skin cancer as well as inflammatory skin diseases. CONCLUSION: The presented optical procedures provide valuable additional information that supports dermatologists in making the correct diagnosis. However, a surgical biopsy followed by dermatohistopathological examination remains the diagnostic gold standard in dermatology.
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Dermatologia , Dermatopatias , Neoplasias Cutâneas , Dermoscopia , Humanos , Microscopia Confocal , Pele , Dermatopatias/diagnóstico , Neoplasias Cutâneas/diagnósticoRESUMO
ADVANTAGES OF ARTIFICIAL INTELLIGENCE (AI): With responsible, safe and successful use of artificial intelligence (AI), possible advantages in the field of dermato-oncology include the following: (1) medical work can focus on skin cancer patients, (2) patients can be more quickly and effectively treated despite the increasing incidence of skin cancer and the decreasing number of actively working dermatologists and (3) users can learn from the AI results. POTENTIAL DISADVANTAGES AND RISKS OF AI USE: (1) Lack of mutual trust can develop due to the decreased patient-physician contact, (2) additional time effort will be necessary to promptly evaluate the AI-classified benign lesions, (3) lack of adequate medical experience to recognize misclassified AI decisions and (4) recontacting a patient in due time in the case of incorrect AI classifications. Still problematic in the use of AI are the medicolegal situation and remuneration. Apps using AI currently cannot provide sufficient assistance based on clinical images of skin cancer. REQUIREMENTS AND POSSIBLE USE OF SMARTPHONE PROGRAM APPLICATIONS: Smartphone program applications (apps) can be implemented responsibly when the image quality is good, the patient's history can be entered easily, transmission of the image and results are assured and medicolegal aspects as well as remuneration are clarified. Apps can be used for disease-specific information material and can optimize patient care by using teledermatology.
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Inteligência Artificial , Dermatologia/métodos , Melanoma/diagnóstico por imagem , Aplicativos Móveis , Neoplasias Cutâneas/diagnóstico por imagem , Smartphone , Telemedicina/instrumentação , Humanos , Interpretação de Imagem Assistida por Computador , Oncologia , Melanoma/diagnóstico , Neoplasias Cutâneas/diagnósticoRESUMO
BACKGROUND: The Psoriasis Area and Severity Index (PASI) represents the gold standard for psoriasis severity assessments but is limited by its subjectivity and low intra- and inter-rater consistency. OBJECTIVES: To investigate the precision and reproducibility of automated, computer-guided PASI measurements (ACPMs) in comparison with three trained physicians. METHODS: This was a comparative observational study assessing ACPMs attained by automated total-body imaging and computerized digital image analysis in a cohort of 120 patients affected by plaque psoriasis of various severities. The level of agreement between ACPMs and physicians' PASI measurements was calculated by the intraclass correlation coefficient (ICC). The reproducibility of ACPMs in comparison with physicians' PASI measurements was investigated by performing two successive 'repeat PASI calculations' in the same patients. RESULTS: The agreement between ACPMs and physicians' PASI calculations in 120 fully evaluable patients was high (ICC 0·86, 95% confidence interval 0·80-0·90, mean absolute difference 2·5 PASI points). Repeat ACPMs to measure the reproducibility showed an excellent ICC of 0·99 (95% confidence interval 0·98-0·99) with a mean absolute difference of 0·5 PASI points. The ACPMs thus outperformed the three physicians for intrarater reliability (mean ICC 0·86). CONCLUSIONS: The results of this first clinical study investigating ACPMs in 120 patients with psoriasis indicate a similar precision and higher reproducibility in comparison with trained physicians. Limitations arise from poorly observable body sites and from patients unable to attain predefined postures during automated image acquisition.
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Interpretação de Imagem Assistida por Computador/métodos , Psoríase/diagnóstico , Índice de Gravidade de Doença , Adulto , Dermatologistas/estatística & dados numéricos , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/instrumentação , Interpretação de Imagem Assistida por Computador/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Fotografação , Reprodutibilidade dos Testes , Pele/diagnóstico por imagemRESUMO
The use of dermoscopy by dermatologists across Europe has become a standard examination for benign and malignant skin lesions and increasingly also for inflammatory skin diseases. However, based on the experience of the authors from numerous dermoscopy courses, knowledge about important dermoscopic features in special locations such as mucosa or nails is often limited. This may be explained by (1) a different anatomy of the skin and its adnexa in special locations in comparison to the remaining integument, (2) difficult technical access to special locations with a dermatoscope, and (3) a rather low incidence of malignant skin neoplasms in areas of special locations (with the exception of facial skin/scalp). This article aims at explaining dermoscopic characteristics and features of important benign and malignant lesions of nails, acral skin, face, and mucosa.
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Dermoscopia/métodos , Melanoma , Unhas , Neoplasias Cutâneas , Europa (Continente) , Humanos , MucosaRESUMO
Background: Deep learning convolutional neural networks (CNN) may facilitate melanoma detection, but data comparing a CNN's diagnostic performance to larger groups of dermatologists are lacking. Methods: Google's Inception v4 CNN architecture was trained and validated using dermoscopic images and corresponding diagnoses. In a comparative cross-sectional reader study a 100-image test-set was used (level-I: dermoscopy only; level-II: dermoscopy plus clinical information and images). Main outcome measures were sensitivity, specificity and area under the curve (AUC) of receiver operating characteristics (ROC) for diagnostic classification (dichotomous) of lesions by the CNN versus an international group of 58 dermatologists during level-I or -II of the reader study. Secondary end points included the dermatologists' diagnostic performance in their management decisions and differences in the diagnostic performance of dermatologists during level-I and -II of the reader study. Additionally, the CNN's performance was compared with the top-five algorithms of the 2016 International Symposium on Biomedical Imaging (ISBI) challenge. Results: In level-I dermatologists achieved a mean (±standard deviation) sensitivity and specificity for lesion classification of 86.6% (±9.3%) and 71.3% (±11.2%), respectively. More clinical information (level-II) improved the sensitivity to 88.9% (±9.6%, P = 0.19) and specificity to 75.7% (±11.7%, P < 0.05). The CNN ROC curve revealed a higher specificity of 82.5% when compared with dermatologists in level-I (71.3%, P < 0.01) and level-II (75.7%, P < 0.01) at their sensitivities of 86.6% and 88.9%, respectively. The CNN ROC AUC was greater than the mean ROC area of dermatologists (0.86 versus 0.79, P < 0.01). The CNN scored results close to the top three algorithms of the ISBI 2016 challenge. Conclusions: For the first time we compared a CNN's diagnostic performance with a large international group of 58 dermatologists, including 30 experts. Most dermatologists were outperformed by the CNN. Irrespective of any physicians' experience, they may benefit from assistance by a CNN's image classification. Clinical trial number: This study was registered at the German Clinical Trial Register (DRKS-Study-ID: DRKS00013570; https://www.drks.de/drks_web/).
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Aprendizado Profundo , Dermatologistas/estatística & dados numéricos , Processamento de Imagem Assistida por Computador/métodos , Melanoma/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Competência Clínica , Estudos Transversais , Dermoscopia , Humanos , Processamento de Imagem Assistida por Computador/estatística & dados numéricos , Cooperação Internacional , Curva ROC , Estudos Retrospectivos , Pele/diagnóstico por imagemRESUMO
BACKGROUND: Early detection is a key factor in improving survival from melanoma. Today, the clinical diagnosis of cutaneous melanoma is based mostly on visual inspection and dermoscopy. Preclinical studies in freshly excised or paraffin-embedded tissue have shown that the melanin fluorescence spectra after stepwise two-photon excitation, a process termed dermatofluoroscopy, differ between cutaneous melanoma and melanocytic naevi. However, confirmation from a larger prospective clinical study is lacking. OBJECTIVES: The primary end point of this study was to determine the diagnostic accuracy of dermatofluoroscopy in melanoma detection. Secondary end points included the collection of data for improving the computer algorithm that classifies skin lesions based on melanin fluorescence and the assessment of safety aspects. METHODS: This was a prospective, blinded, multicentre clinical study in patients with pigmented skin lesions (PSLs) indicated for excision either to rule out or to confirm cutaneous melanoma. All included lesions underwent dermoscopy and dermatofluoroscopy in vivo before lesions were excised and subjected to histopathological examination. RESULTS: In total, 369 patients and 476 PSLs were included in the final analysis. In 101 of 476 lesions (21·2%) histopathology revealed melanoma. The observed sensitivity of dermatofluoroscopy was 89·1% (90 of 101 melanomas identified), with an observed specificity of 44·8%. The positive and negative predictive values were 30·3% and 93·9%, respectively. No adverse events occurred. CONCLUSIONS: Dermatofluoroscopy is a safe and accurate diagnostic method to aid physicians in diagnosing cutaneous melanoma. Limitations arise from largely amelanotic or regressing lesions lacking sufficient melanin fluorescence.
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Dermoscopia/métodos , Detecção Precoce de Câncer/métodos , Melanoma/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Adulto , Idoso , Biópsia , Dermoscopia/efeitos adversos , Dermoscopia/instrumentação , Detecção Precoce de Câncer/efeitos adversos , Detecção Precoce de Câncer/instrumentação , Estudos de Viabilidade , Feminino , Fluoroscopia/efeitos adversos , Fluoroscopia/instrumentação , Fluoroscopia/métodos , Humanos , Melanoma/patologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Pele/diagnóstico por imagem , Pele/patologia , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: The Psoriasis Area and Severity Index (PASI) is the standard for psoriasis severity assessment. However, PASI measurement is complex and subjective, frequently leading to a high intra- and interobserver variability. To date, the precise extent of variability in PASI measurements and its underlying causes remain unknown. OBJECTIVE: To determine the inter- and intrarater variability of image-based PASI measurements by calculating Intra-Class-Correlation-Coefficients (ICCs) and to investigate the impact of the different PASI components and specific anatomic regions on the extent of variability. METHODS: First, the methodology of 'image-based' vs. commonly used 'live' PASI measurements was validated in a pilot study. Next, in an observational cohort study, PASI scores of 120 patients affected by plaque psoriasis were prospectively evaluated by three formally trained physicians by means of total body images (TBI). Each observer independently performed two rounds of image-based PASI calculations in all patients at two different time points. RESULTS: Overall, 720 image-based PASI scores were calculated with a mean PASI of 8.8 (range 0.7-34.8). An interrater variability with an ICC of 0.895 and mean absolute difference (MAD) of 3.3 PASI points were observed. Intrarater variability showed a mean ICC of 0.877 and a MAD of 2.2 points. When considering specific PASI components, the highest agreement was found for the assessment of the involved body surface area (BSA), while the lowest ICCs were calculated for severity scoring of 'scaling' and 'induration'. As BSA scores serve as a multiplier in the calculation of PASI, minor inaccuracies were capable of inducing a large share of variability. CONCLUSION: The overall inter- and intrarater reliability of image-based PASI measurements in this study was good. However, physicians were formally trained and experienced, which frequently is not the case in a real-life clinical setting. Therefore, new strategies for higher standardization and objectivity of PASI calculations are needed.
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Fotografação , Psoríase/diagnóstico por imagem , Índice de Gravidade de Doença , Superfície Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Projetos Piloto , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
BACKGROUND: While the excisional biopsy and histological examination of suspicious lesions remains the current gold standard for diagnosing cutaneous melanoma (CM), there is a demand for more objective and non-invasive examination methods that may support clinicians in their decision when to biopsy or not. METHODS: This review is based on publications and guidelines retrieved by a selective search in PubMed and MEDLINE and focused on non-invasive diagnostic strategies for detecting melanoma. RESULTS: Ten different non-invasive techniques were compared with regard to applicability, status of development, and resources necessary for introduction into clinical routine (dermoscopy, sequential digital dermoscopy, total body photography, computer-aided multispectral digital analysis, electrical impedance spectroscopy, Raman spectroscopy, reflectance confocal microscopy, multiphoton tomography, stepwise two-photon-laser spectroscopy, quantitative dynamic infrared imaging). In an effort to create a classification based on our analyses, we suggest to differentiate i) tools for screening of patients in daily clinical routine, ii) tools for examination of a restricted number of preselected lesions that produce an automated diagnostic score, iii) tools for examination of a restricted number of preselected lesions at specialized centers requiring extensive training, iv) devices at an experimental stage of development. CONCLUSION: None of the discussed examination techniques is able to provide a definite and final diagnosis or to completely replace the histopathological examination. Up to date, the need for fully automated devices offering a complete skin cancer screening has not been satisfied.
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Dermoscopia/métodos , Melanoma/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Adulto , Idoso , Biópsia/métodos , Diagnóstico por Computador/métodos , Diagnóstico Diferencial , Espectroscopia Dielétrica/instrumentação , Espectroscopia Dielétrica/métodos , Detecção Precoce de Câncer/instrumentação , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Incidência , Masculino , Melanoma/epidemiologia , Melanoma/patologia , Microscopia Confocal/métodos , Fotografação/métodos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Análise Espectral Raman/instrumentação , Análise Espectral Raman/métodos , Melanoma Maligno CutâneoRESUMO
BACKGROUND: What lesions to select for a most efficient dermatoscopic monitoring of patients with multiple nevi remains an unresolved issue. OBJECTIVE: To compare the grade of atypia of melanomas and nevi of the same patient at baseline. METHODS: Prospective observational study using 236 dermatoscopic baseline images (59 quartets from 59 patients, each including one melanoma detected during follow-up and three nevi). Dermatologists (n = 26) were asked to assess the 'grade of dermatoscopic atypia' on a numerical scale and to identify the melanomas. RESULTS: On average, each dermatologist identified 24 of 59 melanomas (40%, range: 11-37). The number of correct picks was greater for dermatologists with moderate (mean: 28) or high (mean: 28) experience compared to beginners (mean 17; P < 0.001). In three of the 59 sets, none of the 26 dermatologists identified the melanoma. The mean grade of dermatoscopic atypia was 2.5 for nevi (95% CI: 2.4-2.6) and 3.0 for melanomas (95% CI: 2.9-3.1, P < 0.001). LIMITATIONS: Rating dermatologists were informed that each quartet of images included one melanoma creating substantial deviation from a real-life situation. CONCLUSION: A significant proportion of melanomas detected during follow-up cannot be differentiated from nevi at baseline. This necessitates the additional inclusion of less atypical lesions for monitoring.
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Dermoscopia/métodos , Melanoma/patologia , Monitorização Fisiológica/métodos , Nevo/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Infantile haemangiomas (IH) are common benign tumours in infancy. Most IH resolve spontaneously, but some require treatment due to ulceration, functional impairment or cosmetic disfiguration. While systemic propranolol is effective in many cases, laser therapy may be a safe topical alternative. OBJECTIVE: To assess the efficacy of combined Nd:YAG/pulsed dye laser (PDL) or PDL alone for therapy of IH. PATIENTS AND METHODS: A total of 271 IH in 149 infants were treated with combined Nd:YAG/PDL or PDL alone. Based on photographs before and 4-6 weeks after the last treatment, the results were evaluated independently by three physicians. Remissions were categorized as 0-25% (I), 26-50% (II), 51-75% (III) and 76-100% (IV). RESULTS: In total, 472 laser treatments were performed. In 137 of 149 infants (91.9%) laser therapy was performed during a short sevoflurane mask anaesthesia, while 12 of 149 infants (8.1%) received topical anaesthetic gel. Combined Nd:YAG/PDL was applied in 187 of 271 IH (69.0%), while PDL alone in 84 of 271 IH (31.0%). On average, 1.74 treatments per IH were necessary (Nd:YAG/PDL: 1.95, PDL: 1.26). Moderate or strong (III/IV) improvement was observed in 92.4% of all IH treated. No serious adverse effects were observed. CONCLUSION: Combined Nd:YAG/PDL therapy is an effective and well-tolerated local treatment option for IH of any classification, in any phase of development and at any age. With regard to the systemic use of propranolol, combined Nd:YAG/PDL therapy seems a safe and promising alternative in many cases.
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Hemangioma/cirurgia , Lasers de Corante/uso terapêutico , Lasers de Estado Sólido/uso terapêutico , Neoplasias Cutâneas/cirurgia , Antagonistas Adrenérgicos beta/uso terapêutico , Criança , Terapia Combinada , Feminino , Hemangioma/tratamento farmacológico , Humanos , Lactente , Lasers de Corante/efeitos adversos , Lasers de Estado Sólido/efeitos adversos , Masculino , Propranolol/uso terapêutico , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Resultado do TratamentoRESUMO
Dermoscopy has a high diagnostic accuracy in pigmented and nonpigmented malignant and benign skin tumors. These microscopic in vivo examinations with polarized and nonpolarized light are effective in the early detection of malignant skin tumors and reduce the number of unnecessary excisions of benign skin tumors. The selection of the skin lesions is crucial for the diagnostic accuracy of the dermoscopic examination. Not only large pigmented skin lesions, but also small hypo-, de-, or nonpigmented skin lesions, should be examined dermatoscopically as well as skin lesions that have changed in shape and/or color. In clinical routine, research and teaching, the dermoscopic diagnosis should be performed by describing the visible structures, their distribution and colors by means of descriptive and/or metaphoric terminology. Optionally, a diagnostic algorithm can also be used. Especially in benign lesions, the dermatoscopic diagnosis should be uniform for the complete area. Comparison with other nearby skin tumors of the same patient (comparative approach) is helpful in the evaluation of numerous melanocytic skin tumors. If it is unclear whether the lesion is malignant, a biopsy or complete excision should be performed with subsequent histopathological examination.
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Dermoscopia/normas , Dermatopatias/patologia , Neoplasias Cutâneas/patologia , Terminologia como Assunto , Diagnóstico Diferencial , Humanos , Pele/patologiaRESUMO
The diagnosis of advanced cutaneous melanoma may easily be made by the unaided eye, followed by excisional biopsy and histopathological examination. However, in the setting of melanoma screening examinations in high-risk patients with many nevi, dermatologists are challenged with the differentiation of atypical but benign nevi and early invasive or in situ melanomas. In this situation, there is a real need for additional, noninvasive examination techniques that may serve as an aide to decide for or against an excisional biopsy. Conventional dermoscopy is a well-established examination procedure and an increase in sensitivity was confirmed by two independent meta-analyses. Moreover, dynamic changes or newly developed pigmented lesions may be detected by sequential digital dermoscopy or (automated) total body photography, respectively. Over the past years, a number of medicinal products gained market access after licensing by American and European agencies for the noninvasive diagnosis of cutaneous neoplasms. These devices are based on technologies including in vivo reflectance confocal microscopy, multispectral analysis, electrical impedance spectroscopy, or Raman spectroscopy. Other technologies are still on the verge of becoming less experimental but more clinically applicable for diagnosing melanoma (in vivo multiphoton tomography, stepwise two-photon laser spectroscopy, infrared thermal image analysis, epidermal genetic information retrieval). This review provides a concise overview of general principles and sheds light on indication and added value for dermatologists.
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Dermoscopia/métodos , Melanoma/diagnóstico , Microscopia Confocal/métodos , Neoplasias Cutâneas/diagnóstico , Análise Espectral Raman/métodos , Imagem Corporal Total/métodos , Diagnóstico por Computador/métodos , Diagnóstico Diferencial , Espectroscopia Dielétrica/métodos , Humanos , Melanoma/patologia , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: The nucleotide excision repair (NER) pathway repairs UV-induced DNA lesions in an accurate fashion and prevents UV-irradiated areas of the skin from tumour formation. The XPA protein plays a major role in DNA damage demarcation as well as stabilization of other NER factors and was found to be defective in xeroderma pigmentosum (XP) complementation group A patients. OBJECTIVE: Characterization of four new XP-A patients. METHODS: Genomic and cDNA sequencing, post-UV cell survival of living cells, host-cell reactivation of patients' fibroblasts and Western blotting. RESULTS: One of the four investigated patients shows a novel mutation leading to two different truncated protein variants. Three patients contain the already described p.R228X mutation. All patient cell lines exhibit a strong UVC sensitivity and reduced NER capability. In most of the cases stable protein expression was detected. CONCLUSION: We discovered four new XP-A patients and a novel XPA mutation resulting in two diverse patient alleles.
Assuntos
Reparo do DNA/genética , RNA Mensageiro/metabolismo , Proteína de Xeroderma Pigmentoso Grupo A/genética , Xeroderma Pigmentoso/genética , Adolescente , Adulto , Criança , Análise Mutacional de DNA , Fibroblastos , Humanos , Deficiência Intelectual/complicações , Deficiência Intelectual/genética , Masculino , Mutação , Fenótipo , Cultura Primária de Células , RNA Mensageiro/análise , Análise de Sequência de RNA , Distúrbios da Fala/complicações , Distúrbios da Fala/genética , Xeroderma Pigmentoso/complicações , Proteína de Xeroderma Pigmentoso Grupo A/química , Adulto JovemRESUMO
BACKGROUND: Factors associated with early vs. late diagnosis of cutaneous melanoma remain poorly understood. OBJECTIVE: To identify factors with a significant impact on melanoma thickness. METHODS: Patients with previous melanoma (n = 347, median age at diagnosis: 56.5 years, 44.7% female, 55.3% male) were recruited for this monocentre, non-randomized, observational study between April 2012 and March 2013. All patients were assessed by means of a structured interview and systematic clinical and dermoscopic full-body examination. Melanoma thickness in association with patients' characteristics, risk indicators and patterns of diagnosis was submitted to statistical analyses. RESULTS: Univariate analyses revealed associations between a statistically significant lower Breslow thickness and participation in specialized dermoscopic screening programs, personal history of more than one previous melanoma, diagnostic examination with a dermatoscope, diagnostic examination by board certified dermatologist, high number of common and/or atypical nevi, younger age at time of diagnosis, higher level of education, or superficial spreading or lentigo maligna melanoma subtype (all P ≤ 0.01). In a multivariate regression analysis only three of these criteria: (i) participation in specialized screening programs (P < 0.0001); (ii) melanoma subtype (P < 0.0001); and (iii) diagnostic examination with a dermatoscope (P = 0.040) and one interaction term ('younger age' x 'female sex', P < 0.0001) showed an independent influence on a significantly lower melanoma thickness. CONCLUSIONS: The screening of patients in specialized surveillance programs resulted in melanoma detection at significantly earlier stages. The use of dermoscopy, SSM or LMM histotype and younger age in connection with female sex were also characteristics that were independently associated with significantly thinner melanomas in multivariate analyses.
Assuntos
Dermoscopia , Detecção Precoce de Câncer , Melanoma/patologia , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Cold atmospheric plasma (CAP, i.e. ionized air) is an innovating promising tool in reducing bacteria. OBJECTIVE: We conducted the first clinical trial with the novel PlasmaDerm® VU-2010 device to assess safety and, as secondary endpoints, efficacy and applicability of 45 s/cm(2) cold atmospheric plasma as add-on therapy against chronic venous leg ulcers. METHODS: From April 2011 to April 2012, 14 patients were randomized to receive standardized modern wound care (n = 7) or plasma in addition to standard care (n = 7) 3× per week for 8 weeks. The ulcer size was determined weekly (Visitrak® , photodocumentation). Bacterial load (bacterial swabs, contact agar plates) and pain during and between treatments (visual analogue scales) were assessed. Patients and doctors rated the applicability of plasma (questionnaires). RESULTS: The plasma treatment was safe with 2 SAEs and 77 AEs approximately equally distributed among both groups (P = 0.77 and P = 1.0, Fisher's exact test). Two AEs probably related to plasma. Plasma treatment resulted in a significant reduction in lesional bacterial load (P = 0.04, Wilcoxon signed-rank test). A more than 50% ulcer size reduction was noted in 5/7 and 4/7 patients in the standard and plasma groups, respectively, and a greater size reduction occurred in the plasma group (plasma -5.3 cm(2) , standard: -3.4 cm(2) ) (non-significant, P = 0.42, log-rank test). The only ulcer that closed after 7 weeks received plasma. Patients in the plasma group quoted less pain compared to the control group. The plasma applicability was not rated inferior to standard wound care (P = 0.94, Wilcoxon-Mann-Whitney test). Physicians would recommend (P = 0.06, Wilcoxon-Mann-Whitney test) or repeat (P = 0.08, Wilcoxon-Mann-Whitney test) plasma treatment by trend. CONCLUSION: Cold atmospheric plasma displays favourable antibacterial effects. We demonstrated that plasma treatment with the PlasmaDerm® VU-2010 device is safe and effective in patients with chronic venous leg ulcers. Thus, larger controlled trials and the development of devices with larger application surfaces are warranted.