The New American Joint Committee on Cancer staging system for cutaneous melanoma: a critical analysis based on data of the German Central Malignant Melanoma Registry.
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Biomedical subjects
Publications and source records attributed to Claus Garbe.
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There are no generally accepted guidelines for the follow-up of cutaneous melanoma (CM), and there is an ongoing debate about the value of follow-up examinations. Some authors doubt whether early detection has any beneficial effect on patient survival and suggest that it may only prolong the patient's period of suffering from the knowledge of having metastasis. A systematic review of the literature on early detection and resection of CM metastasis shows the following picture: (1) In in-transit metastasis and in regional node metastasis, the tumour volume of the metastatic nodules at the time of diagnosis is prognostically significant. Either the number of nodes involved in regional metastasis or the diameter of the largest node showed prognostic impact in different studies. Therefore, early detection seems to affect the cure rate in this stage of disease. (2) In distant metastasis, surgical resection of all recognisable metastases prolongs survival. This is true as long as only one organ system is involved and particularly if complete resection of all metastases can be achieved. Therefore, early detection contributes to prolongation of survival. We performed a follow-up study in 2008 prospectively documented consecutive patients with stage I-III cutaneous melanoma who presented for follow-up examination at the Department of Dermatology of the University of Tübingen from August 1996 to August 1998. Stage-appropriate follow-up examinations were carried out according to the German Society of Dermatology guidelines. A total of 3,800 clinical examinations and 12,398 imaging techniques were documented: 62 second primary melanomas were detected in 46 patients and 233 disease recurrences in 112 patients during this time. Physical examination was responsible for the discovery of 50% of all recurrences, with the patient initially detecting the metastasis on self-examination in 17% of these cases. Technical examinations were responsible for the detection of the remaining 50%. In the primary tumour stages, 21% of all recurrences were discovered by lymph node sonography, the majority being classified as early detection. Among the recurrences, 48% were classified as early detection, and these patients had a significantly more favourable probability of recurrence-free survival than those with recurrences classified as late detection. The results of our study suggest that a follow-up schedule elaborated for cutaneous melanoma is suitable for the early detection of second primary melanomas and of early recurrences in approximately 5% of patients during a 2-year follow-up period.
The eccrine gland is one of the major cutaneous appendages and secretes sweat. Its principal function is thermoregulation during exposure to a hot environment or physical exercise. In addition to this function, we show that LL-37, a member of cathelicidin family of anti-microbial peptides, is expressed in sweat. LL-37 protein and mRNA was seen in the eccrine structures of normal human skin by immunohistochemistry and in situ hybridization. LL-37 was localized to both the eccrine gland and sweat ductal epithelial cells, whereas dermcidin, a previously described natural antibiotic in sweat, was expressed only in the gland itself. The anti-microbial activity of LL-37 and dermcidin against various bacteria in the sweat ionic environment was demonstrated by solution colony forming assay using synthetic peptides, and in sweat obtained from normal volunteers. These results indicate that cathelicidin is secreted in human sweat, has potent anti-microbial activity against both gram-positive and gram-negative bacteria, and can, after processing from the preproform, provide a barrier for protection against infection. Thus, sweat represents a unique mode of delivery for potent innate immune effector molecules in the absence of inflammation.
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UNLABELLED: The term epidermolysis bullosa (EB) encompasses a heterogeneous group of genodermatoses, characterised by fragility and blistering of the skin, often associated with extracutaneous manifestations. The clinical picture comprises severe subtypes with lethal outcome in the first years of life as well as milder subtypes with localised blistering or minimal symptoms confined exclusively to nail or teeth abnormalities. We present the case of a male infant, who was born with a few bullae and rapidly developed extensive blistering of the skin. The disease was complicated by painful erosions of the oral mucosa, refused ingestion, and recurrent infections. The child died at the age of 4 months because of cardiac failure due to severe sepsis. Antigen mapping of a skin biopsy showed a split within the lamina lucida of the epidermal basement membrane zone and junctional epidermolysis bullosa (JEB) was diagnosed within the first 3 weeks of life. Markedly reduced staining for laminin 5 indicated the Herlitz type of JEB (OMIM 226700), which could be confirmed by mutation analysis in the LAMB3 gene, showing homozygous nonsense mutations. CONCLUSION: early antigen mapping using antibodies against the proteins affected in epidermolysis bullosa, is a useful tool providing early mutation analysis and valuable prognostic information needed for adequate therapeutic strategies. The recently published literature on current diagnostic procedures and the revised classification system for inherited epidermolysis bullosa aim towards a better understanding of the disease.
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Numerous laboratory tests and imaging methods are available that can be used in patients who are diagnosed with cutaneous melanoma. The downside risks related to testing are cost and patient anxiety. Therefore, it must be critically considered which examinations are useful and feasible. After a diagnosis of primary cutaneous melanoma, many physicians in Germany perform lymph node ultrasound to detect occult regional metastasis. Whole-body imaging techniques, except the physical examination, are unlikely to detect distant occult metastasis. In tumors that have an intermediate or high risk of recurrence (> 1 mm tumor thickness), baseline whole-body imaging may serve as a reference for ongoing evaluation. During follow-up care, physical examination alone is appropriate when there is a low risk for recurrence (up to 1-mm tumor thickness). In patients whose tumors are > 1 mm thickness, regular lymph node ultrasound examinations and determination of serum tumor marker S-100beta protein are commonly used by physicians in Germany. Whole-body imaging techniques are useful in patients who have locoregional and/or distant metastasis. For consideration of surgical resections in stage IV disease, more advanced examinations techniques such as positron emission tomography-computed tomography or whole body magnetic resonance imaging may be used. Early detection of limited disease using these methods may be helpful for patients who have locoregional metastases and for 10-20% of patients who have distant metastases and whose limited disease may be amenable to surgical resection.