Biomedical subjects

C Garbe

Publications and source records attributed to C Garbe.

At least 19 recordsLinked to original sources

PubMed2006

Dose-intensified bi-weekly temozolomide in patients with asymptomatic brain metastases from malignant melanoma: a phase II DeCOG/ADO study.

BACKGROUND: Temozolomide has shown some efficacy in metastatic melanoma and recently received extended approval to treat brain tumours. The purpose of this study was to test a dose-intensified regimen of temozolomide in melanoma patients with brain metastases in a prospective, open-label, multicentre phase II trial. PATIENTS AND METHODS: Forty-five patients with asymptomatic brain metastases from melanoma were stratified into arm A (no prior chemotherapy; n = 21) and arm B (previous chemotherapy; n = 24). Patients received oral temozolomide either 150 mg/m(2)/day (arm A) or 125 mg/m(2)/day (arm B), days 1-7 and 15-21, every 28 days. The primary study end point was objective response, and secondary end points were overall survival and safety. RESULTS: Two patients (4.4%) achieved a partial response (PR) in brain metastases (one in each arm), one of them (2.2%) also showing a PR in extracerebral disease. An additional five patients (11.1%; two in arm A, three in arm B) showed disease stabilisation (SD) in brain and other sites. However, 82% revealed progressive disease (PD) already evident 8 weeks after therapy initiation. Median survival time from therapy onset was 3.5 months (range 0.7-8.3; arm B) and 4.3 months (range 1.6-11.8; arm A), P = 0.43. Dose modifications and prolongations of therapy cycles due to toxicity were required in 20% of patients. Grade 3/4 toxicity was observed in one patient only (2.2%). CONCLUSIONS: Oral administration of temozolomide given bi-weekly is well-tolerated in melanoma patients with cerebral involvement. However, the efficacy is limited, with lower than 5% objective responses observed in brain and extracerebral metastases.

Adult↗

PubMed2006

Melanoma of the ear: prognostic factors and surgical strategies.

BACKGROUND: The ear's specific anatomical and lymphatic characteristics impose special requirements on the treatment of melanoma of the ear. OBJECTIVES: The aim of this prospective study was to define prognostic factors for melanoma of the ear and to evaluate surgical strategies for excision margins, histological evaluation and sentinel lymph node biopsy (SLNB) in order to achieve better cosmetic and functional results. PATIENTS AND METHODS: One-hundred and sixty-one patients with stage I/II melanoma of the external ear were treated in the Department of Dermatology, University of Tuebingen, from March 1976 to March 2004 (median follow-up 62 months). Malignant melanoma of the external ear represented 3% of the stage I/II cutaneous melanomas and 20% of the stage I/II head and neck melanomas recorded in the Melanoma Registry of the Department of Dermatology at the University of Tuebingen. Twenty of 42 lentigo maligna melanomas (LMM) underwent conventional histological evaluation, 22 underwent complete three-dimensional histology of excision margins (3D histology) in a paraffin-technique, i.e. micrographic surgery. SLNB was performed in 28 patients with melanomas thicker than 1.0 mm. Clinical, histological and surgical risk factors were evaluated by univariate and multivariate analysis. RESULTS: The median thickness of the tumours in the present study was 1.08 mm (mean 1.51 mm; range 0.18-8.50 mm), and the median excision margins were 11.0 mm (mean 12.61 mm; range 2.0-31.0 mm). The 3-year disease-specific survival rate was 98%, and the 3-year recurrence-free survival rate was 83%. Tumour thickness and invasion level were the only risk factors significant for disease-specific survival. Tumour thickness, location of the tumour and extent of excision margins were independently significant risk factors for recurrence-free survival. LMMs removed surgically with accompanying 3D histology were thicker than those examined by conventional histology (median 0.93 mm vs. 0.83 mm). The use of surgery with 3D histology, i.e. micrographic surgery, made it possible to reduce the excision margins (median 5 mm vs. 10 mm) without an increased risk of recurrence. Two of 29 SLNBs were positive (6.9%). There were six preregional recurrences after negative SLNB and one after positive SLNB. None of the patients who underwent SLNB died of melanoma-related causes during the observation period. CONCLUSIONS: This is the largest series of ear melanomas reported so far. The overall survival depended only on the tumour thickness and Clark level of invasion. Local recurrence was more frequent with smaller excision margins, but this did not influence the overall survival. Smaller excision margins under 3D-histological control did not carry an increased risk of local recurrence. Our results do not permit conclusions regarding the prognostic impact of SLNB for patients with melanoma of the ear.

Adult↗

PubMed2006

Conventional histology vs. three-dimensional histology in lentigo maligna melanoma.

BACKGROUND: Conventional surgery for lentigo maligna melanoma (LMM) is based on normal histological evaluation. However, such evaluation leaves diagnostic gaps. In contrast, complete three-dimensional (3D) histology of excision margins permits accurate detection of continuously spreading tumour strands like those of LMM. These can be specifically excised in tumour-positive areas with smaller excision margins, and better cosmesis and function. To date there have been no controlled studies of micrographic surgery of LMM. OBJECTIVES: Clinical parameters and surgical strategies influencing the prognosis of patients with LMM were evaluated in a prospective study of melanoma patients in the Department of Dermatology of the University of Tübingen (1980-99). METHODS: The 292 LMMs comprised 7.4% of 3960 primary stage I and II melanomas treated during this period. One hundred and thirty-six patients in this group (46.6%) underwent surgery on the basis of 3D histology. RESULTS: The geometric mean excision margins were significantly smaller in the 3D histology group (P < 0.0001). Patients with micrographic surgery had fewer recurrences. Multivariate analysis of clinical, histological and surgical variables was carried out, and tumour thickness and 3D histology proved to be independent, significant factors for the prognosis of recurrence-free survival (relative risk, RR 2.08, P < 0.0001 and RR 2.11, P = 0.0037, respectively). There were no melanoma-related deaths in the 3D histology group. All 16 melanoma-related deaths were observed among the 156 patients of the conventional histology group (10.3%). CONCLUSIONS: Excision of LMM using 3D histology resulted in a twofold lower probability of recurrence and twofold smaller excision margins. 3D histology is a valuable diagnostic tool and can be used in the management of LMM because of the latter's pattern of continuous tumour spread.

Disease-Free Survival↗

PubMed2006

Comparative analysis of incidence and clinical features of cutaneous malignant melanoma in Crete (Greece) and southern Germany (central Baden-Württemberg).

BACKGROUND: Comparative analysis of the incidence rates and epidemiological features of cutaneous malignant melanoma (CMM) between different ethnic groups exposed to varying environmental factors is critical for consideration of the causes of CMM but can also be utilized in a public health approach to control of the disease. OBJECTIVES: To compare incidence rates and clinical features of CMM in a Greek and a central European population (central Baden-Württemberg, Germany). METHODS: Incident cases of CMM were traced in all hospitals of the island of Crete for the period 1999-2002. Age-standardized incidence rates per 100 000 inhabitants per year for the European Standard Population were calculated based on the Cretan population statistics. A comparison was performed between the Cretan findings and those of southern Germany as registered by the hospital-based Central Malignant Melanoma Registry, which likewise documents more clinical features than normally recorded by population-based cancer registries. RESULTS: Mean incidence rates in Crete for 1999-2002 were 4.01 per 100 000 inhabitants per year for males and 4.05 for females as compared with 10.6 for males and 11.1 for females in southern Germany. There were striking differences in the clinical characteristics of CMMs, with significantly higher tumour thickness in Crete (median 1.4 mm vs. 0.7 mm in southern Germany). Correspondingly, significantly more nodular melanomas were observed in Crete (29%) as compared with southern Germany (11%). CONCLUSIONS: Incidence of CMM in Crete, with about four cases per 100 000 inhabitants per year, is clearly higher than previously estimated, and there is an urgent necessity for earlier recognition of CMM in Crete. However, the incidence of CMM in southern Germany is much higher.

Adult↗

PubMed2006

Basal cell carcinoma: histological classification and body-site distribution.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer worldwide in white-skinned populations. Recent studies suggest that BCC is not a single entity and that different histological subtypes show different clinical behaviour and might have different aetiology. OBJECTIVES: To provide information on the incidence of BCC by histopathological subtype and body site. METHODS: A case series of BCC from a prospective population-based register study collecting information on all excised and histologically confirmed skin cancers in Townsville, north Australia between 1997 and 1999. RESULTS: Age-standardized incidence rates for nodular BCC were 727.1 per 100 000 inhabitants per year for males and 411.8 for females, while rates for superficial BCC were 336.5 for males and 251.4 for females. Incidence rates for 'high risk' BCC were 261.3 for males, 146.5 for females with infiltrative, and 156.7 for males and 100.2 for females with micronodular types. Superficial BCC occurred at a younger age, particularly in female patients. For all histological subtypes and both genders relative tumour density was highest for the face, followed by the neck. An exception was superficial BCC in males, where the posterior trunk was second, followed by the neck. CONCLUSIONS: The study found a higher rate of superficial BCC than previous studies from less sun-exposed countries, and a more equal distribution of superficial BCC on face, trunk and limbs. These results seem to blur the difference between intermittent and continuous sun exposure as the causative environmental agents. The clinical implications of 'high risk' BCC rates are discussed.

Adult↗

PubMed2006

Correlation with digital dermoscopic images can help dermatopathologists to diagnose equivocal skin tumours.

BACKGROUND: A variety of pigmented skin tumours can lead to diagnostic difficulties in dermatopathology. OBJECTIVES: To investigate whether the interobserver agreement between histopathological diagnoses of equivocal pigmented tumours made by two referral centres can be improved by additional use of dermoscopic images. MATERIAL AND METHODS: Retrospective study using 160 tumours excised in the pigmented skin lesions clinic in Graz and 141 from Tübingen. Tumours were diagnosed in the referring centres using clinical data, histopathology and, if required, immunohistochemistry. The tumours were initially diagnosed as 74 melanomas, 218 melanocytic naevi and nine nonmelanocytic tumours. Haematoxylin and eosin sections, patients' age and sex, tumour localization and digital dermoscopic images were then exchanged between the participating centres. Then, diagnoses were made initially based solely on dermatopathology and clinical information. After a washout phase, the same sections were reevaluated with the additional use of dermoscopic images. The main outcome measures were the Cohen's kappa-coefficients of the initial diagnoses of the centre submitting the cases and the diagnoses of the other centre without and with dermoscopy. RESULTS: The kappa-coefficient between the initial diagnoses with those made by the second centre without dermoscopy was 0.90 in Graz, 0.73 in Tübingen, and 0.81 overall. With the additional use of dermoscopy the kappa-value was invariably high with 0.89 in Graz, and improved to 0.87 in Tübingen, and to 0.88 overall. CONCLUSIONS: The additional use of digital dermoscopic images further improved the overall very good agreement of histopathological diagnoses between two referral centres.

Adolescent↗

PubMed2006

Is head and neck melanoma a distinct entity? A clinical registry-based comparative study in 5702 patients with melanoma.

BACKGROUND: The head and neck region is more heavily exposed to ultraviolet (UV) radiation than any other body site. Therefore, cutaneous malignant melanoma (CMM) of the head and neck area is proposed to have notable differences from melanoma at other body sites regarding clinicopathological features and survival of patients. OBJECTIVES: The present retrospective study based on clinical registry data aims to compare clinical features and prognostic factors of head and neck melanoma (HNM) vs. melanoma at other anatomical regions (MOR) in order to detect differences which may be associated to the mode of sun exposure. METHODS: The clinical records and histopathological findings of 844 patients with clinical stage I and II invasive HNM were compared with the data of 4858 patients with MOR. Survival analysis was performed using the Kaplan-Meier estimate, and the multivariate Cox proportional hazard model was used to evaluate independent prognostic factors. RESULTS: Melanoma density was clearly higher for HNM than for MOR: this was particularly true for the face, where it was elevated by a factor of 2.6. There was a higher male/female ratio in patients with HNM and they were significantly older than patients with MOR (P < 0.0001). Breslow tumour thickness did not differ between HNM and MOR. However, CMMs at the scalp were significantly thicker and to a higher degree ulcerated. Concerning clinicopathological CMM subtypes, there was an increased proportion of lentigo maligna melanoma among HNM and of nodular melanoma in the scalp and neck regions. Excision margins were narrower and the rate of complete primary excision was lower in HNM than in MOR. Overall, there was no significant statistical difference in cumulative 10-year survival rates according to Kaplan-Meier estimates among patients with HNM (84.6%) and MOR (87.8%). Tumour thickness turned out to be the variable with the highest prognostic impact followed by ulceration in both HNM and MOR. CONCLUSIONS: In relation to the skin surface significantly more CMMs were found in the head and neck area than in other anatomical regions. This might indicate, but does not prove, that UV exposure promotes the development of CMM. Although HNM showed specific clinicopathological features, prognosis remained unaffected. Thus HNM seems not to be a distinct subtype of CMM.

Adolescent↗

PubMed2006

Naturally processed dermcidin-derived peptides do not permeabilize bacterial membranes and kill microorganisms irrespective of their charge.

Dermcidin (DCD) is a recently described antimicrobial peptide, which is constitutively expressed in eccrine sweat glands and transported via sweat to the epidermal surface. By postsecretory proteolytic processing in sweat the dermcidin protein gives rise to several truncated DCD peptides which differ in length and net charge. In order to understand the mechanism of antimicrobial activity, we analyzed the spectrum of activity of several naturally processed dermcidin-derived peptides, the secondary structure in different solvents, and the ability of these peptides to interact with or permeabilize the bacterial membrane. Interestingly, although all naturally processed DCD peptides can adopt an alpha-helical conformation in solvents, they have a diverse and partially overlapping spectrum of activity against gram-positive and gram-negative bacteria. This indicates that the net charge and the secondary structure of the peptides are not important for the toxic activity. Furthermore, using carboxyfluorescein-loaded liposomes, membrane permeability studies and electron microscopy we investigated whether DCD peptides are able to permeabilize bacterial membranes. The data convincingly show that irrespective of charge the different DCD peptides are not able to permeabilize bacterial membranes. However, bacterial mutants lacking specific cell envelope modifications exhibited different susceptibilities to killing by DCD peptides than wild-type bacterial strains. Finally, immunoelectron microscopy studies indicated that DCD peptides are able to bind to the bacterial surface; however, signs of membrane perturbation were not observed. These studies indicate that DCD peptides do not exert their activity by permeabilizing bacterial membranes.

Amino Acid Sequence↗

PubMed2005

Surveillance of patients at high risk for cutaneous malignant melanoma using digital dermoscopy.

BACKGROUND: Dermoscopy has improved the sensitivity and specificity of clinical diagnosis of melanoma from 60% to over 90%. However, in order not to miss melanoma a certain percentage of suspicious but benign lesions has to be excised. OBJECTIVES: To evaluate the dermoscopic changes and the rates of excision in benign melanocytic naevi and cutaneous malignant melanoma in long-term follow-up of high-risk patients using digital dermoscopy. METHODS: Digital dermoscopic images of 2015 atypical melanocytic naevi in 196 high-risk patients were analysed retrospectively. Among others, the following data were collected for each naevus: changes in surface area, overall architecture, dermoscopic patterns and distribution of pigmentation. All tumours suspicious for melanoma or showing asymmetrical changes were excised. RESULTS: During a median follow-up time of 25 months 128 (6.4%) of all naevi showed changes in size or architecture. Eighty-six per cent of all changes in patients who attended more than one visit were observed at the first follow-up visit. Thirty-three lesions showing changes were excised and two melanomas in situ and 31 melanocytic naevi were diagnosed. CONCLUSIONS: Follow-up examinations using digital dermoscopy revealed unchanged morphology in the large majority of melanocytic naevi. Excisions were only performed in cases of asymmetrical growth, asymmetrical changes of pigmentation, or development of dermoscopic features indicative of melanoma. The ratio of 33 lesions excised in order to identify two melanomas in situ seems reasonable and may be further reduced in future.

Adolescent↗

PubMed2005

Distribution and colocalization of markers for proliferation, invasion, motility and neoangiogenesis in benign melanocytic naevi and malignant melanomas.

BACKGROUND: Melanomas are heterogeneous tumours, and differentiation from other melanocytic lesions may cause problems. It may be possible that the distribution and/or colocalization pattern of different markers in the lesions can enable a more accurate diagnosis of melanocytic tumours. OBJECTIVES: To test this hypothesis, melanocytic naevi, primary melanomas and metastases were investigated. METHODS: The distribution and colocalization of markers for proliferation, invasion, angiogenesis and motility of the tumour cells were investigated using antibodies directed against actin, cathepsin B (CatB), transforming growth factor-beta, vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen/Ki-67 and basic fibroblast growth factor (FGF-2). In addition, melanoma markers (HMB-45 and Melan-A) and proteins unrelated to melanoma progression [epidermal growth factor (EGF) and cathepsin H] were investigated. RESULTS: Malignant melanomas tended to express more markers of malignancy compared with melanocytic naevi, and the differences were statistically significant for EGF and actin immunoreactivity: melanocytic naevi displayed clear EGF labelling more often (60% vs. 5%) and melanomas showed more intense actin labelling (70% vs. 0%). HMB-45+ cells to a large extent also stained with antibodies to CatB but not to EGF or actin; EGF-, FGF-2- and VEGF-immunoreactive cells were predominantly HMB-45-. Similar combinations were observed in melanocytic naevi and in melanomas. CONCLUSIONS: Labelling with EGF may improve the differential diagnosis of melanocytic neoplasias. However, we did not detect a clear-cut increase of markers of malignancy in melanoma. Cells expressing multiple malignancy markers were also found in some melanocytic naevi; this may confirm the dormant potential of melanocytic naevi for melanoma development.

Biomarkers, Tumor↗

PubMed2004

[Sentinel lymph node in melanoma].

The procedure of sentinel node biopsy (SNB) has emerged as an important advance especially with respect to staging of malignant melanoma. Elective (prophylactic) lymph node dissection that had been practiced in primary melanoma with a suspected increased risk of (clinically occult) lymphatic metastasis has been replaced by SNB. Patients with proven metastatic involvement of the sentinel node (12-25%) can be specifically selected for regional lymph node dissection. Metastatic involvement of the sentinel node (SN) is a significant independent prognostic factor. The value of detecting metastasis by highly sensitive diagnostic tools such as RT-PCR is just as uncertain as is the therapeutic benefit of operative or conservative therapies in sentinel node-positive patients with respect to improving prognosis and is currently under study.

Clinical Trials as Topic↗

PubMed2004

[Therapy of malignant melanoma at the stage of distant metastasis].

Treatment of melanoma in the stage of distant metastasis aims on palliation and achievement of durable tumor remission with prolongation of survival. As long as metastasis is confined to one organ system and is removable, surgery remains the treatment of first choice. In limited metastasis radiotherapy may likewise be indicated, particularly in bone and brain metastasis. More extensive metastasis should be treated by chemotherapy or chemoimmunotherapy. Monochemotherapy with dacarbazine, temozolomide, fotemustine and vindesine or its combinations with interferon-alpha are currently preferred. Polychemotherapy or its combinations with interferon-alpha and interleukin-2 are suitable to produce higher response rates but failed to prolong survival. As these treatments are associated with substantially higher toxicity they have been widely abandoned. Combined treatment with dacarbazine and interferon-alpha obtain tumor responses or stable disease in 40-50% and objective tumor remissions in 15-20% of patients. Effective cancer vaccination strategies and blockade of melanoma specific target molecules are currently developed as new treatment options.

Antineoplastic Agents↗

PubMed2004

Additional reverse transcription-polymerase chain reaction of peripheral slices is not superior to analysis of the central slice in sentinel lymph nodes from melanoma patients.

BACKGROUND: The status of the sentinel lymph node (SLN) is an important prognostic factor in patients with cutaneous melanoma. Reverse transcription-polymerase chain reaction (RT-PCR) has been used as a sensitive means of detecting tumour cells in SLNs. OBJECTIVES: To determine whether RT-PCR analysis of the SLN using both the central and the peripheral slices is more sensitive than molecular analysis of the central slice only. METHODS: Eighty-three SLNs from 59 patients with primary cutaneous melanoma were identified by SLN mapping. All SLNs were bisected along their longitudinal axis to produce two equal halves. One half was used for histology and immunohistochemistry, and the other was analysed by RT-PCR for tyrosinase and MelanA. Parallel to the longitudinal axis, one central slice (approximately 2 mm in thickness) was cut manually. This central slice was used for our standard RT-PCR protocol. In the current study, up to eight additional peripheral slices (each approximately 2 mm in thickness) were cut parallel to the existing cut surface. These peripheral slices were analysed by additional RT-PCR. RESULTS: Standard RT-PCR of the central slice yielded positive results in 34 of 59 patients (57%). Additional RT-PCR of peripheral slices demonstrated positive findings in six additional patients (10%) who were initially negative by standard RT-PCR of the central slice. In detail, seven of those 34 patients positive by standard RT-PCR of the central slice had positive histological findings. In each of these seven patients, RT-PCR was positive both in the central slice as well as in the peripheral slices. The remaining 27 patients with positive RT-PCR results of the central slice showed negative histological findings. Only nine (33%) of these 27 patients had a positive RT-PCR also in the peripheral slices. Finally, all 25 patients with negative RT-PCR results in the central slice showed negative histological findings. Six of these patients (24%) revealed positive RT-PCR results on the analysis of peripheral slices. However, three of these patients expressed only MelanA but not tyrosinase. Thirty lymph nodes from 24 nonmelanoma patients served as negative controls for RT-PCR. In three of these 24 patients (13%) expression of MelanA but not tyrosinase was detected by RT-PCR. CONCLUSIONS: Molecular analysis of peripheral slices yielded six additional patients (10%) positive by RT-PCR who were initially negative by standard RT-PCR of the central slice. However, three of these six patients were found to express only MelanA but not tyrosinase. As MelanA expression was also found in 13% of control lymph nodes, positive MelanA expression alone in SLNs of melanoma patients requires cautious interpretation in order to avoid false-positive findings. Thus, additional molecular processing of peripheral slices did not significantly increase the number of patients with RT-PCR-positive SLNs.

Adult↗

PubMed2004

Clinical risk factors and prognostic significance of local recurrence in cutaneous melanoma.

BACKGROUND: True local recurrence (LR) means clinically detectable regrowth of parts of the tumour which were not completely excised. In the literature the term 'LR' has been used in a vague and inconsistent manner that may include satellite and in-transit metastasis. OBJECTIVE: The aim of this study was to establish clinical, histological and surgical risk factors for the manifestation of LR and to evaluate the prognostic significance of LR. STUDY DESIGN: Data from 3960 Stage I and II melanoma patients who visited the melanoma clinic of the Department of Dermatology at the University of Tuebingen from 1980 to 1999 were documented in a prospective manner. A retrospective comparative analysis of patients with and without LR was performed. RESULTS: Of all patients 1.4% had a LR as a first recurrence and 1.7% had a LR in the course of the follow-up period. LR were most frequent after previous clinical or histological misdiagnosis and inadequate therapy. In the univariate analysis significant risk factors for LR-free survival were age, tumour surface area, locality, tumour thickness, level of invasion, histological type, associated naevus, surgery (one step vs. multiple steps) and compliance with recommended excision margins. In the multivarate analysis the factors locality (P < 0.0001), tumour thickness (P = 0.0086) and compliance with recommendations on excision margins (P = 0.014) were significant independent risk factors for the manifestation of LR. The overall survival of patients with LR as first progression did not significantly differ from the overall survival of the other patients with melanoma (P = 0.60). CONCLUSION: True LR is a rare event for which tumour locality, tumour thickness and surgery are independent risk factors. The occurrence of LR might not impair the prognosis of melanoma patients. However, in the published literature numerous definitions of 'LR', including lymphogenic metastasis, complicate comparison.

Female↗

PubMed2004

Dermcidin is constitutively produced by eccrine sweat glands and is not induced in epidermal cells under inflammatory skin conditions.

BACKGROUND: Antimicrobial peptides (AMPs) are important effector molecules of innate immunity, protecting epithelial surfaces of multicellular organisms. In human skin two classes of AMPs-the beta-defensins and the cathelicidins-are produced by keratinocytes primarily under inflammatory conditions. In contrast, dermcidin (DCD), a recently discovered AMP with broad-spectrum activity, is expressed in eccrine sweat glands and transported via sweat to the epidermal surface. OBJECTIVES: To investigate whether DCD expression is induced under inflammatory conditions in epidermal keratinocytes. METHODS: Lesional skin of the inflammatory skin diseases atopic dermatitis, psoriasis and lichen planus was analysed by immunohistochemistry using a polyclonal anti-DCD antiserum. We also examined whether DCD RNA expression is induced in cultured human keratinocytes, fibroblasts, melanocytes and melanoma cells. RESULTS: Whereas DCD was constitutively expressed in eccrine sweat glands of all skin biopsies, we found that, independent of the type of the inflammatory skin lesion, DCD protein expression was not induced in human epidermal keratinocytes. In contrast, beta-defensin 2 was expressed in epidermal keratinocytes of inflammatory human skin, but not in keratinocytes of healthy human skin. Upon stimulation of the cultured cells with 12-O-tetradecanoyl-phorbol-13-acetate, tumour necrosis factor-alpha, lipopolysaccharide or H2O2, DCD mRNA expression was not detected in primary keratinocytes, fibroblasts and melanocytes, but was detected in MeWo and SKMEL28 melanoma cells. CONCLUSIONS: These results indicate that, unlike human cathelicidins and beta-defensins which are inducible peptides that primarily function in response to injury and inflammation, DCD is exclusively part of the constitutive innate defence of human skin. By modulating surface colonization, DCD may help to prevent local and systemic invasion of pathogens.

Adult↗

PubMed2004

Digital image analysis for diagnosis of cutaneous melanoma. Development of a highly effective computer algorithm based on analysis of 837 melanocytic lesions.

BACKGROUND: Digital image analysis has been introduced into the diagnosis of skin lesions based on dermoscopic pictures. OBJECTIVES: To develop a computer algorithm for the diagnosis of melanocytic lesions and to compare its diagnostic accuracy with the results of established dermoscopic classification rules. METHODS: In the Department of Dermatology, University of Tuebingen, Germany, 837 melanocytic skin lesions were prospectively imaged by a dermoscopy video system in consecutive patients. Of these lesions, 269 were excised and examined by histopathology: 84 were classified as cutaneous melanomas and 185 as benign melanocytic naevi. The remaining 568 lesions were diagnosed by dermoscopy as benign. Digital image analysis was performed in all 837 benign and malignant melanocytic lesions using 64 different analytical parameters. RESULTS: For lesions imaged completely (diameter < or = 12 mm), three analytical parameters were found to distinguish clearly between benign and malignant lesions, while in incompletely imaged lesions six parameters enabled differentiation. Based on the respective parameters and logistic regression analysis, a diagnostic computer algorithm for melanocytic lesions was developed. Its diagnostic accuracy was 82% for completely imaged and 84% for partially imaged lesions. All 837 melanocytic lesions were classified by established dermoscopic algorithms and the diagnostic accuracy was found to be in the same range (ABCD rule 78%, Menzies' score 83%, seven-point checklist 88%, and seven features for melanoma 81%). CONCLUSIONS: A diagnostic algorithm for digital image analysis of melanocytic lesions can achieve the same range of diagnostic accuracy as the application of dermoscopic classification rules by experts. The present diagnostic algorithm, however, still requires a medical expert who is qualified to recognize cutaneous lesions as being of melanocytic origin.

Algorithms↗

PubMed2004

Value of the clinical history for different users of dermoscopy compared with results of digital image analysis.

BACKGROUND: The clinical history of a given pigmented lesion could influence the therapeutic decision. Teledermatology and automated image analysis also hold great potential for revolutionizing dermatology services. AIM: The aim of this retrospective study was to evaluate the diagnostic accuracy of users with different experiences in dermoscopy with and without information about patients and their history compared with classification by an automated analysing system. SETTING: One hundred and fifty-seven dermoscopic images of pigmented lesions, taken and proved by histopathology at the Pigmented Lesions Clinic of the Department of Dermatology of the University Tuebingen, Germany, were included. METHODS: All images were viewed by three investigators with different experience: excellent (A), average (B) and beginner (C). In the first dermoscopic classification, no information was available. After 3 months the same images were once more classified by the three investigators, now with the information about the patients and their history. The melanocytic lesions were tested by the Tuebinger Mole Analyser. RESULTS: For user A the sensitivity, specificity and diagnostic accuracy revealed no improvement on including the history (81.3% to 84.4%, 94.6% to 92.3% and 92.0% to 90.7%), whereas user B clearly improved his results (75.0% to 87.5%, 76.9% to 88.5% and 76.5% to 88.3%). No change in the sensitivity was seen by user C (84.4%), but there was a clear improvement in the specificity (69.2% to 87.7%) and diagnostic accuracy (72.2% to 87.0%). Using the computer algorithm, a sensitivity of 100%, a specificity of 76.9% and a diagnostic accuracy of 81.9% were achieved. CONCLUSIONS: The study revealed results relevant to the use of dermoscopy: (1) continuing dermoscopic education influences the diagnostic accuracy; (2) the history is helpful for averaged users and beginners in dermoscopy; (3) digital image analysis has the highest sensitivity, but a lower specificity compared to the clinicians; and (4) digital dermoscopy could be used for store-and-forward systems in teledermoscopy.

Adolescent↗

PubMed2004

Micrometastasis of a sentinel lymph node in cutaneous melanoma is a significant prognostic factor for disease-free survival, distant-metastasis-free survival, and overall survival.

OBJECTIVE: Sentinel lymph node biopsy (SLNB) has been proposed as a minimally invasive procedure for the histopathologic staging of the regional lymph node basin. The aim of this work was to investigate the prognostic value of detection of micrometastasis by SLNB. METHODS: In the period from January 1996 to March 2000, a sentinel lymph node (SLN) was identified in 283 patients at the Department Dermatology, University of Tuebingen. In the case of 38 patients (13.4%) histopathologic examination led to the detection of micrometastasis in at least one SLN. The median follow-up period was 29 months. RESULTS: Thirty-one of 245 patients (12.7%) suffered a tumor recurrence following a negative SLNB, and 19 of 38 patients (50%) following positive SLNB. In the case of disease-free survival the remaining significant independent prognostic factors of the multivariate analysis were tumor thickness (p=0.011), ulceration (p=0.026), and the detection of micrometastasis in SLNB (p=0.021). With respect to distant-metastasis-free survival the significant independent prognostic factors of the multivariate analysis were tumor thickness (p=0.0022) and the SLNB results (p=0.0068). For overall survival the tumor thickness (p=0.013) and the SLNB results (p=0.034) were significant independent prognostic parameters in the multivariate analysis. CONCLUSION: The study examined patients with melanomas of all tumor thicknesses and SLNB for which the prognostic significance of SLNB was tested. Recurrences were more frequent in patients with a micrometastatic SLN. Patients with a negative SNLB are still at risk for tumor recurrence. The histopathologic result of SLNB is, after tumor thickness, the most significant prognostic factor for disease-free survival, distant-metastasis-free survival, and overall survival.

Disease-Free Survival↗