Dermoscopy key points: recommendations from the international dermoscopy society.
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Biomedical subjects
Publications and source records attributed to H Kittler.
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Sentinel lymph node biopsy (SLNB) has become a widely accepted standard procedure in the staging of patients with cutaneous melanoma and absence of clinical lymph node metastases, although there is no final proof that SLNB influences overall survival in these patients. This study investigated the accuracy of SLNB and the clinical outcome of patients after a mean follow-up of 22 months. Between 1998 and 2003, SLNB was performed in 309 consecutive patients. Patients with one or more positive sentinel lymph nodes (SLNs) were subjected to selective lymphadenectomy (SL). Survival analyses were performed using the Kaplan-Meier approach. A Cox proportional-hazard analysis was used for univariate and multivariate analysis to explore the effect of variables on survival. Sentinel lymph nodes were identified in 299 of 309 patients (success rate: 96.8%). Of these, 69 (23%) had a positive SLN. The false-negative rate was 9.2%. Recurrence of disease to the regional lymph node basin (3.0%) and to the locoregional skin (2.6%) was rare in SLN-negative patients in contrast to SLN-positive patients (7.2 and 17.4%, respectively). The 3-year overall survival was 93 and 83% for SLN-negative and SLN-positive patients, respectively. Upon multivariate analysis, SLN status (P<0.001), Breslow thickness (P<0.02) and ulceration (P<0.026) were all found to be independent prognostic factors with respect to disease-free survival, whereas Breslow thickness proved to be the only significant factor with respect to overall survival.
Few data on the influence of lymphatic microvessel density (LMVD) on survival in patients with melanoma are available. The aim of this study was to assess LMVD and blood microvessel density (MVD) in tissue samples from 120 patients with melanoma. LMVD was stained with an antibody staining for podoplanin, and blood MVD was assessed by CD31 (PECAM-1)-immunostaining. Survival was determined using univariate and multivariate analysis. A significant association between a high CD31 MVD (but not LMVD) and the presence of lymph node metastases (P=0.007) was observed. Patients with a high LMVD had a significant shorter overall (OS) (P=0.0436) and disease-free survival (DFS) (P=0.0249) in univariate analysis. The survival analysis showed CD31 MVD was a strong prognostic factor for OS and DFS in both uni-and multivariate analyses. Our results demonstrate LMVD as a prognostic factor in malignant melanoma, although its prognostic relevance is much smaller compared with blood MVD.
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The accuracy of the dinical diagnosis of cutaneous melanoma with the unaided eye is only about 60%. Dermoscopy, a non-invasive, in vivo technique for the microscopic examination of pigmented skin lesions, has the potential to improve the diagnostic accuracy. Our objectives were to review previous publications, to compare the accuracy of melanoma diagnosis with and without dermoscopy, and to assess the influence of study characteristics on the diagnostic accuracy. We searched for publications between 1987 and 2000 and identified 27 studies eligible for meta-analysis. The diagnostic accuracy for melanoma was significantly higher with dermoscopy than without this technique (log odds ratio 4.0 [95% CI 3.0 to 5.1] versus 2.7 [1.9 to 3.4]; an improvement of 49%, p = 0.001). The diagnostic accuracy of dermoscopy significantly depended on the degree of experience of the examiners. Dermoscopy by untrained or less experienced examiners was no better than clinical inspection without dermoscopy. The diagnostic performance of dermoscopy improved when the diagnosis was made by a group of examiners in consensus and diminished as the prevalence of melanoma increased. A comparison of various diagnostic algorithms for dermoscopy showed no significant differences in their diagnostic performance. A thorough appraisal of the study characteristics showed that most of the studies were potentially influenced by verification bias. In conclusion, dermoscopy improves the diagnostic accuracy for melanoma in comparison with inspection by the unaided eye, but only for experienced examiners.
BACKGROUND: The aim of the study is to provide recent demographic data on cutaneous melanoma in Austria. PATIENTS AND METHODS: Patients with primary cutaneous melanoma diagnosed between January 1, 1990 and December 31, 1999 were included in the analysis. Data were retrieved from the melanoma registry of the University Department of Dermatology in Vienna. RESULTS: In the observation period, 2501 cutaneous melanomas were diagnosed in 2427 patients (mean age: 55.4 yrs; 51.2% females). A total of 267 (10.7%) cutaneous melanomas were in situ, and 2234 (89.3%) were invasive. The median invasion thickness according to Breslow for invasive melanomas was 0.98 mm (25%-75% percentiles: 0.55-2.00 mm). We observed a significant trend towards thicker tumors with increasing age (p < 0.001). In patients less than fifty years of age, a significantly higher Breslow thickness was observed in men than in women (0.90 mm versus 0.80 mm, p = 0.03). The median Breslow thickness of invasive melanoma decreased from 1.20 mm in 1990 to 0.92 mm in 1999 (p for trend, < 0.001). Compared to women, men had melanomas more frequently on the back (43.8% versus 24.4%, p < 0.001). In women, melanomas were more frequently found on the lower legs than in males (21.5% versus 6.7%, p < 0.001). In a multivariate model, invasion thickness according to Breslow was the single most important predictor of survival. CONCLUSION: Our data confirm recent reports from other European countries with regard to the decline in tumor thickness of cutaneous melanoma. Our data also demonstrate a need for improving early diagnosis, particularly in certain subgroups of patients.
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OBJECTIVE: To evaluate the utility of sequential imaging of melanocytic skin lesions. DESIGN: With the use of a computerized test environment, digital images of 80 melanocytic skin lesions (including 10 early melanomas) were presented to 24 dermatologists with different levels of experience in 3 sessions. The 3 sessions were designed to simulate the decision-making process (1) without the possibility of follow-up, (2) with the possibility of follow-up, and (3) after presentation of follow-up images. MAIN OUTCOME MEASURES: Diagnostic performance in terms of sensitivity, specificity, accuracy, treatment threshold, and utility. RESULTS: The possibility of follow-up increased the treatment threshold in all groups of dermatologists compared with decision making without the possibility of follow-up. The increase of the treatment threshold was accompanied by a loss of sensitivity and a gain in specificity. The overall diagnostic accuracy remained unchanged. After presentation of follow-up images, the diagnostic accuracy improved significantly. The sensitivity improved for all readers, but the specificity improved only for the most experienced readers. The utility of sequential imaging depended on the compliance of patients with follow-up. Under the assumption that all patients are compliant with follow-up, the utility of sequential imaging was superior to decision making without follow-up over a broad range of benefit-risk ratios. CONCLUSIONS: Sequential imaging of melanocytic skin lesions is a useful procedure for patients with multiple atypical nevi. Uncritical use of sequential imaging cannot be recommended, because the utility of this technique depends on the experience in the interpretation of follow-up images and on the patient's compliance with follow-up.
We analyze the discriminatory power of k-nearest neighbors, logistic regression, artificial neural networks (ANNs), decision tress, and support vector machines (SVMs) on the task of classifying pigmented skin lesions as common nevi, dysplastic nevi, or melanoma. Three different classification tasks were used as benchmarks: the dichotomous problem of distinguishing common nevi from dysplastic nevi and melanoma, the dichotomous problem of distinguishing melanoma from common and dysplastic nevi, and the trichotomous problem of correctly distinguishing all three classes. Using ROC analysis to measure the discriminatory power of the methods shows that excellent results for specific classification problems in the domain of pigmented skin lesions can be achieved with machine-learning methods. On both dichotomous and trichotomous tasks, logistic regression, ANNs, and SVMs performed on about the same level, with k-nearest neighbors and decision trees performing worse.
OBJECTIVE: To evaluate the effects of basic life support, time to first defibrillation and emergency medical service arrival time on neurologic outcome and expenses for hospital care in patients after cardiac arrest. SETTING: Large urban emergency medical services system and emergency department in a 2000-bed university hospital. DESIGN: Outcome and cost benefit analysis of patients admitted to the hospital after witnessed, out-of-hospital, ventricular fibrillation cardiac arrest from October 1, 1991, until December 31, 1997. PATIENTS: Out of 1054 patients with out-of-hospital cardiac arrest, 276 were eligible. MEASUREMENTS AND RESULTS: The effects of basic and advanced life support measures on neurologic outcome and hospital expenses were evaluated. In contrast to intubation (odds ratio 1.08; 95% CI: 0.51-2.31; p=0.84), basic life support (odds ratio 0.44; 95% CI: 0.24-0.77; p=0.004) and time to first defibrillation (odds ratio 1.08; 95% CI: 1.03-1.13; p=0.001) were significantly correlated with good neurologic outcome. Among the patients who did not receive basic life support, the average cost per patient with good neurologic outcome significantly increased with the delay of the first defibrillation (p<0.001). CONCLUSIONS: In contrast to intubation, bystander basic life support and time to first defibrillation were significantly associated with good neurologic outcome and resulted in fewer expenses spent on in-hospital efforts.
The aim of this study was to report on the compliance with follow-up among patients with thin melanomas. We also examined the prognosis of patients with recurrent disease and whether there were any differences in prognosis associated with the time between the last follow-up examination and the onset of recurrence. A retrospective analysis of the records of 513 consecutive patients (50.3% males, mean age: 52.8+/-16.9 years) with thin melanomas (<1.5 mm Breslow thickness) was carried out. The estimated cumulative proportion of patients who still continued their follow-up examinations 5 years after diagnosis of the primary tumour was 55.3% (95% Confidence Interval (CI): 50.4--60.2%). The mean annual drop-out rate was 11.2%. The drop-out rate was similar for males and females and was not influenced by the patients' age or the tumour thickness. Among 263 patients who continued follow-up, 50.2% (n=132) were not compliant with the time schedule. 20 patients presented with recurrent disease after a median of 35.9 months (25--75% percentiles: 16.7--46.5 months). Six patients who did not have a follow-up examination within 1 year before the onset of recurrence presented with more advanced disease and had a worse prognosis (median survival: 12.5 months, hazard ratio: 3.5, 95% CI: 1.1--17.1, P=0.04), than those patients, who had a recent follow-up examination before the onset of recurrence (n=14, median survival: 22.3+ months). In the majority of recurrent cases with good prognosis, metastatic disease was confined to the regional lymph nodes and the presumptive diagnosis of metastatic disease was either made by palpation or by sonography of the regional lymph nodes. The observed drop-out rate of patients during the first 5 years of follow-up is substantial and does not depend on the patients' age, sex or on the tumour thickness. Although the frequency of recurrences among patients with thin melanomas is low, regular follow-up examinations including physical examination, as well as palpation and sonography of the regional lymph nodes, are essential.
BACKGROUND: The blocking action of botulinum toxin type A (BTX-A) on cholinergically innervated sweat glands has been used successfully to treat patients with focal hyperhidrosis. OBJECTIVES: To investigate the long-term efficacy and safety of intradermal injections of BTX-A. METHODS: We performed an open-label study in 61 patients treated over a period of 3 years for axillary or palmar hyperhidrosis. A total dose of 400 mU BTX-A (Dysport) was injected into both axillae or 460 mU BTX-A (Dysport) into both palms. The injections were repeated after relapse. Objective quantification of sweat production was performed using digitized ninhydrin-stained sheets. RESULTS: Four weeks after BTX-A treatment the median reduction in sweat production was 71% compared with baseline (P < 0.001) in the axillary group and 42% (P = 0.005) in the palmar group. Subjective assessment of sweat production by the patients using a visual analogue scale (0, no sweating; 100, the most severe sweating) showed a significant reduction in both the axillary (P < 0.001) and palmar groups (P < 0.001). Secondary disturbances due to focal hyperhidrosis interfering with daily activities were markedly improved in both groups. The median time interval between the sets of injections was 34 weeks for axillary hyperhidrosis and 25 weeks for palmar hyperhidrosis. The treatment of palmar hyperhidrosis was complicated by transient but not disabling weakness of the small hand muscles in nine of 21 patients. CONCLUSIONS: Repeated intradermal injections of BTX-A in patients with axillary and palmar hyperhidrosis are as effective as first treatments.
Dermatoscopes are directly placed on the skin of patients and therefore may harbour potentially pathogenic bacteria. In this study we assessed bacterial contamination of dermatoscopes during routine use and examined the effectiveness of isopropyl alcohol and disposable lens covers. Aerobic bacterial cultures were performed on randomly selected dermatoscopes after examination of 39 patients. In addition, bacterial contamination of dermatoscopes after cleaning with 70% isopropyl alcohol and after using a disposable transparent lens cover was tested. Bacteria such as Staphylococcus epidermidis, Micrococcus species and Corynebacterium species, which are usually present on the skin, were repeatedly identified. In addition, rare bacteria such as Moraxella species were found. Known nosocomial micro-organisms such as Staphylococcus aureus were recovered from hospitalized patients. Disinfection with 70% isopropyl alcohol and the use of a disposable lens cover significantly reduced the number of bacteria. Image quality was identical with and without the use of a transparent lens cover. Dermatoscopes harbour potential pathogens and may be a source of bacterial transmission. Isopropyl alcohol is an effective cleaning agent for dermatoscopes. Disposable lens covers completely prevented bacterial transmission and are therefore recommended for routine dermatoscopy, especially in hospitalized patients.
High-dose cisplatin regimens have been shown to be highly active in advanced melanoma patients but are associated with unacceptable side effects. In order to increase the platinum dose but avoid severe side effects, we treated 15 dacarbazine (DTIC)-resistant metastatic melanoma patients with a combination regimen of cisplatin (100 mg/m2) and carboplatin (200 mg/m2), two platinum analogues with a similar mode of action but a different toxicity pattern. After a mean follow-up period of 10.7 months (range 4-18 months), two patients (13.3%) achieved complete remission and two patients (13.3%) showed partial remission, giving an overall response rate of 26.4% (95% confidence interval [CI] 4.2-49%). Furthermore, three patients (20%; 95% CI 0-40.2%) experienced stable disease. The median duration of response was 7.1 months (95% CI 4.2-10.0 months), and the median overall survival was 12.5 months (95% CI 5.8-19.2 months), with eight patients still alive. The main side effects were haematological (leukopenia/thrombocytopenia World Health Organization [WHO] grade I-IV; anaemia WHO grade I-III), gastrointestinal (WHO grade I-III), neurological (WHO grade I-II) and renal (WHO grade I) toxicity. Nevertheless, except in one patient, side effects did not result in discontinuation of therapy. Despite the small number of patients treated in this preliminary study, we believe that combining cisplatin and carboplatin represents a novel, active and well-tolerated therapeutic option as second-line chemotherapy in DTIC-resistant advanced melanoma patients.
The use of tyrosinase-based polymerase chain reaction (PCR) tests for the detection of circulating tumour cells in the blood of melanoma patients has led to highly controversial results. We here report on the analysis of 120 blood samples from 76 stage I to IV melanoma patients using a new MART-1/Melan-A PCR system in conjunction with the tyrosinase-specific assay reported in the literature. While there were no positive results in localized disease (stages I and II), identification of specific PCR products in stage III melanoma patients was restricted to the MART-1/Melan-A tests, with positive results in 11% (two out of 19) of the blood specimens analysed. Stage IV melanoma patients presented with the highest incidence of detectable mRNA levels, with positive results for tyrosinase in 38% (12 out of 32) and for MART-1/Melan-A in 22% (seven out of 32). By delineating 64 follow-up specimens covering sampling periods of up to 33 weeks, stable mRNA expression profiles were identified in nearly 95%. Four patients, however, showed PCR changes towards positive MART-1/Melan-A expression that were linked to metastatic melanoma progression. Taken together, PCR tests for tyrosinase and MART-1/Melan-A seem to lack sufficient detection frequencies for the routine monitoring of melanoma disease. Regarding the link between MART-1/Melan-A seroconversion and the development of metastatic disease, further studies are needed to clarify the clinical value of this observation.
A system for the computerized analysis of images obtained from ELM has been developed to enhance the early recognition of malignant melanoma. As an initial step, the binary mask of the skin lesion is determined by several basic segmentation algorithms together with a fusion strategy. A set of features containing shape and radiometric features as well as local and global parameters is calculated to describe the malignancy of a lesion. Significant features are then selected from this set by application of statistical feature subset selection methods. The final kNN classification delivers a sensitivity of 87% with a specificity of 92%.
INTRODUCTION: Botulinum A toxin (BTX-A) acts primarily at peripheral cholinergic synapses, inhibiting the release of acetylcholine. Initially it has been used to block the neuromuscular junction in focal dystonic and spastic syndromes. Recently there has been suggestions for potential clinical indications in non-muscular diseases where cholinergic terminals play a role. GUSTATORY SWEATING: In 1995 physicians reported a long-lasting anhidrotic effect of intracutaneous BTX-A injections in patients suffering from gustatory sweating (Frey's syndrome). Consequently, a number of clinical studies demonstrated good efficacy of intradermal injections of botulinumtoxin in patients with focal hyperhidrosis. FOCAL HYPERHIDROSIS OF THE PALMS AND AXILLAE: Focal hyperhidrosis is usually confined to the palms and axillae. Excessive sweating may be a social handicap and an occupational hazard. The management of focal hyperhidrosis remains controversial. Topical antiperspirants are only effective in very mild cases. Iontophoresis with tap water or anticholinergic drugs is messy and time consuming with only short-lived effect. Sympathectomy, the cornerstone of surgical management, is usually effective in palmar hyperhidrosis. Complications of this technique include surgical risks, postoperative and cosmetic problems and compensatory hyperhidrosis. AXILLARY HYPERHIDROSIS: Several studies confirmed that intracutaneous injections of botulinum toxin are useful in the majority of patients with axillary hyperhidrosis resistant to conventional treatment. In axillary hyperhidrosis total doses are ranging from 200-400 mU Dysport or from 80 to 130 mU Botox to reach a good clinical response. Injections are usually well tolerated and no serious side-effects have been observed. The mean duration of anhidrotic effect ranges between 3 and 9 weeks. PALMAR HYPERHIDROSIS: The use of botulinumtoxin in patients with palmar hyperhidrosis is rather difficult. The therapeutic window is smaller because injections are complicated by transient weakness of the small hand-muscles. Furthermore the injections at the palms are painful which can be overcomed by application of local anaesthetics or the blockade of the ulnar and median nerves. The duration of anhidrotic effect ranges from 20 to 50 weeks. CONCLUSION: Intracutaneous injections of botulinum-toxin should be offered to patients with focal hyperhidrosis of the palms and axillae causing serious social, psychologic and occupational problems, resistant to other conventional treatment options.
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