Should dermatologists go public? A skin cancer screening campaign at recreation centers.
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Biomedical subjects
Publications and source records attributed to J Smolle.
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BACKGROUND AND OBJECTIVE: A complicated course of erysipelas is not uncommon. Bullous, haemorrhagic, necrotic and purulent lesions may be encountered. Today no reliable data exist as to which constitutional factors renders a patient at risk for developing complicated erysipelas though several risk factors, particularly diabetes mellitus, are often suggested. Based on the analysis of patients with erysipelas at the Department of Dermatology in Graz, factors determining the risk for complicated erysipelas should be identified. PATIENTS/METHODS: In a retrospective case-control study clinical data sheets of 766 in- patients treated at the department were evaluated with respect to the course of the erysipelas and with respect to potential risk factors. RESULTS: General risk factors for local complications were location at the lower extremities, pre-existing hepatic or renal disease, hyperuricaemia, and diabetes mellitus. Hepatic and renal disease and - to a lesser extent - diabetes particularly predisposed for bullous and haemorrhagic lesions, while vascular occlusive disease enhanced the risk for necrotic lesions. CONCLUSIONS: Location and hepatic and renal disease are the most important risk factors, while diabetes is probably of less significance than previously suggested.
BACKGROUND: We wanted to determine the role of photodynamic therapy in a multimodal approach for the treatment of patients with advanced cancer of the esophagus. METHODS: We reviewed the cases of 119 patients with nonresectable esophageal carcinoma who underwent endoluminal palliation. Twenty-one patients required initial dilation and tumor obliteration with a neodymium: yttrium-aluminum-garnet laser prior to therapy. Forty-four patients received photodynamic therapy followed by brachyradiotherapy, and 75 patients were treated with brachyradiotherapy. In both groups, some patients also received external-beam irradiation. RESULTS: Photodynamic therapy produced a significant difference in relieving stenosis caused by tumor stenosis (mean, 6.6 mm; p = 0.0000). The dysphagia score improved by one to three levels in all patients, with a significant difference in favor of PDT (p = 0.0003). The mean number of overall treatment sessions was four (range, one to seven). The rate of major complications was 9.2%. Four esophageal perforations occurred, three after intervention and one spontaneously 5 months later. Four esophagorespiratory tract fistulas developed several months after combined PDT and irradiation. The mean overall survival was 7.7 months, and analysis of variance revealed a significant difference in favor of PDT and external-beam irradiation (p = 0.0129 and p = 0.0001, respectively). CONCLUSIONS: Photodynamic therapy has been shown to be an effective palliative treatment of advanced esophageal cancer. However, proper patient selection is necessary to prevent serious complications.
Exposing human skin to ultraviolet radiation causes DNA damage, sunburn, immune alterations, and eventually, skin cancer. We wished to determine whether liposomes containing a DNA repair enzyme could prevent any of the acute effects of irradiation when applied after ultraviolet exposure. Fifteen human patients with a prior history of skin cancer were exposed to two minimal erythema doses of ultraviolet radiation on their buttock skin. Liposomes containing T4 endonuclease V or heat-inactivated enzyme were applied immediately and at 2, 4, and 5 h after ultraviolet irradiation. Transmission electron microscopy after anti-T4 endonuclease V-staining and immunogold labeling on biopsies taken at 6 h after ultraviolet exposure revealed that the enzyme was present within cells in the skin. Immunohistochemical DNA damage studies suggested a trend toward improved DNA repair at the active T4 endonuclease V liposome-treated test sites. Although the active T4 endonuclease V liposomes did not significantly affect the ultraviolet-induced erythema response and microscopic sunburn cell formation, they nearly completely prevented ultraviolet-induced upregulation of interleukin-10 and tumor necrosis factor-alpha RNA message and of interleukin-10 protein. These studies demonstrate that liposomes can be used for topical intracellular delivery of small proteins to human skin and suggest that liposomes containing DNA repair enzymes may provide a new avenue for photoprotection against some forms of ultraviolet-induced skin damage.
We performed a multicentre study to evaluate the agreement between the direct clinical diagnosis and the telediagnosis of 43 cutaneous pigmented lesions. Digital clinical and dermoscopic images of the 43 pigmented skin lesions (11 melanomas, 23 melanocytic naevi, three basal cell carcinomas, three lentigines, two seborrhoeic keratoses and one angiokeratoma) were sent by email to 11 colleagues (six dermatologists, two residents in dermatology, one oncologist, one specialist in internal medicine and one general practitioner) in 10 centres. These 11 colleagues had different degrees of experience in dermoscopy. With histopathology as the gold standard, an average of 85% of the telediagnoses were correct, with results varying from 77% to 95%, whereas face-to-face diagnosis by an expert dermatologist was correct in 91% of cases. The kappa value for all participants ranged from 0.35 to 0.87. The results confirm that teledermoscopy can be a reliable technique for the diagnosis of pigmented skin lesions but one that will depend on the expertise of the observer.
BACKGROUND: Teledermoscopy uses telecommunication technologies to transfer images of pigmented skin lesions, including clinical and anamnestic data, via e-mail to specialized centers for teleconsultation. DESIGN: Sixty-six pigmented skin lesions examined on a face-to-face basis in a skin lesion clinic in L'Aquila, Italy, were sent via e-mail on a standard-resolution color monitor for consultation at a university dermatology department in Graz, Austria. INTERVENTION: Digital photographs of the clinical and dermoscopic images of all pigmented tumors were taken with a stereomicroscope connected to a high-resolution video camera in Truevision advanced graphic array (Targa) format file and converted successively into a Joint Photographic Expert Group (PEG) format file. All lesions were excised surgically and diagnosed histopathologically. MAIN OUTCOME MEASURE: Diagnostic concordance between face-to-face diagnosis and telediagnosis. RESULTS: The diagnostic concordance was 60 (91%) of 66 cases. The number of correct telediagnoses was lower, but the difference was not statistically significant (Wilcoxon test, P = .10). The accuracy of the telediagnoses was not related to the quality of the images, but highly depended on the level of diagnostic difficulty of a given pigmented skin tumor (Spearman correlation, P= .01). CONCLUSION: Teleconsultation of clinical and dermoscopic images of skin tumors via e-mail provides a similar degree of diagnostic accuracy as face-to-face diagnosis.
Previous studies have shown that congenital as well as acquired melanocytic naevi indicate an increased risk for developing melanoma in individual patients. Most studies stress the importance of melanocytic naevi as melanoma markers, while in some studies they are considered to be direct melanoma precursors. The latter opinion is favoured by the common co-occurrence of melanoma and naevus within one biopsy. The present study examines the question of whether the co-occurrence of melanoma and naevus is a random event or whether melanomas significantly co-localize with pre-existent naevi, which would suggest a precursor role for these naevi. Seven hundred biopsies of primary melanoma were examined for the presence of congenital or acquired naevi according to standard histological criteria. A naevus was found in 143 of the 700 biopsies (20.4%), of which 90 were acquired (12.9%) and 53 were congenital (7.6%). Within each biopsy the exact location of the melanoma and the naevus was determined using an ocular micrometer at a final magnification of 20 x. From these data the frequency of finding a naevus with increasing distance from the melanoma margin was calculated. The frequency of finding a naevus decreased from 2.6% immediately at the melanoma border to 0.3% at a distance of 4.5 mm and 0% at a distance of 5.0 mm. This decrease was statistically highly significant (P<0.001). Similar results were obtained when congenital and acquired naevi were evaluated separately. These data strongly indicate that melanoma and naevi are non-randomly distributed and that both congenital and acquired naevi may be precursors of melanoma.
OBJECTIVE: To use scientific methods to evaluate 2 claims made by practitioners of alternative medicine. DESIGN: A placebo-controlled, double-blind study of homeopathy in children with warts, and a cohort study of the influence of lunar phases on postoperative outcome in surgical patients. SETTING: Outpatients of a dermatology department (homeopathy study) and inpatients evaluated at an anesthesiology department (lunar phases). SUBJECTS: Sixty volunteers for the homeopathy study and 14,970 consecutive patients undergoing surgery under general anesthesia for the lunar phase study. INTERVENTIONS: Treatment of children with warts with individually selected homeopathic preparations (homeopathic study); surgical procedures including abdominal, vascular, cardiac, thoracic, plastic, and orthopedic operations and assessment of the lunar phase at the time of operation (lunar phase study). MAIN OUTCOME MEASURES: Reduction of area occupied by warts by at least 50% within 8 weeks; death from any cause within 30 days after surgery. RESULTS: Nine of 30 subjects in the homeopathy group and 7 of 30 subjects in the placebo group experienced at least 50% reduction in area occupied by warts (chi 2 = 0.34; P = .56); the mortality rate was 1.20% in patients operated on during waxing moon and 1.33% in patients operated on during waning moon (chi 2 = 0.49; P = .50). CONCLUSIONS: Statements and methods of alternative medicine--as far as they concern observable clinical phenomena--can be tested by scientific methods. When such tests yield negative results, as in the studies presented herein the particular method or statement should be abandoned. Otherwise one would run the risk of supporting superstition and quackery.
BACKGROUND: UV radiation can lead to clinical, histological, and ultrastructural changes in melanocytic nevi. In this study, we investigated whether exposure to 2 minimal erythema doses of UV radiation induces changes in the dermoscopic image of acquired melanocytic nevi. OBSERVATIONS: Fifteen melanocytic nevi were exposed to 2 minimal erythema doses of UV radiation. Differences in dermoscopic parameters (asymmetry, border, erythema, and telangiectasias in the nevus; pigmentation; hypopigmented areas; presence, regularity, and sharpness of pigment network; and brown-black globules) in digital dermoscopic images taken before and 3, 7, 14, and 28 days after UV irradiation were scored. Three days after UV irradiation, the borders of nevi were more faded (P<.02), the nevi were darker brown (P<.02), the hypopigmented areas were smaller (P<.02), and the pigment network structures were more faded (P<.007) and less prominent (P<.02) than before UV irradiation. Seven days after UV irradiation, pigmented globules have also grown (P<.05). After 28 days, all parameters, except hypopigmented areas, were essentially the same as before UV irradiation. CONCLUSION: UV irradiation of melanocytic nevi with 2 minimal erythema doses induces transient changes in their dermoscopic appearance that are sometimes suggestive of malignant melanoma.
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An important property of dendritic cells (DC), which contributes crucially to their strong immunogenic function, is their capacity to migrate from sites of antigen capture to the draining lymphoid organs. Here we studied in detail the migratory pathway and the differentiation of DC during migration in a skin organ culture model and, for comparison, in the conventional contact hypersensitivity system. We report several observations on the capacity of cutaneous DC to migrate in mouse ear skin. (i) Upon application of contact allergens in vivo the density of Langerhans cells in epidermal sheets decreased, as determined by immunostaining for major histocompatibility complex class II, ADPase, F4/80, CD11b, CD32, NLDC-145/DEC-205, and the cytoskeleton protein vimentin. Evaluation was performed by computer assisted morphometry. (ii) Chemically related nonsensitizing or tolerizing compounds left the density of Langerhans cells unchanged. (iii) Immunohistochemical double-staining of dermal sheets from skin organ cultures for major histocompatibility complex class II and CD54 excluded blood vessels as a cutaneous pathway of DC migration. (iv) Electron microscopy of organ cultures revealed dermal accumulations of DC (including Birbeck granule containing Langerhans cells) within typical lymphatic vessels. (v) Populations of migrating DC in organ cultures upregulated markers of maturity (the antigen recognized by monoclonal antibody 2A1, CD86), but retained indicators of immaturity (invariant chain, residual antigen processing function). These data provide additional evidence that during both the induction of contact hypersensitivity and in skin organ culture, Langerhans cells physically leave the epidermis. Both Langerhans cells and dermal DC enter lymphatic vessels. DC mature while they migrate through the skin.
The object of this study was to evaluate the prognostic impact of a cross-sectional area measured in routinely stained slides of cutaneous melanoma using fully automated image analysis. Hematoxylin-eosin stained slides of 238 specimens of primary cutaneous melanoma with Clark levels III to V were evaluated by digital image analysis using color video images, a scanning stage, and autofocus equipment. The cross-sectional area was significantly related to metastasis-free survival. Lesions with a cross-sectional area < or = 12 mm2 showed a 2-year metastasis-free survival rate of 92+/-2% compared with 41+/-8% in lesions with a cross-sectional area > 12 mm2 (log rank test: z = 71, p < 0.0001). The same was true for overall survival (98+/-1% compared with 82+/-6%; z = 42.12, p < 0.0001). In multivariate analysis, the cross-sectional area seems to provide prognostic information in addition to that provided by Breslow's index. In cases with regression and in small melanomas with vertical growth, however, metastatic spread may occur in lesions with a small cross-sectional area. It was concluded that automated measurement of the cross-sectional area may be helpful in assessing prognosis in cutaneous melanoma.
The presence of asymmetry is a major diagnostic criterion for the differentiation of melanoma from benign melanocytic proliferations. It is helpful in both clinical and histological evaluation. The underlying biological features that determine asymmetry have not yet been evaluated. Using computer simulation of the growth of neoplasms, we demonstrate that a functionally homogeneous cell population can give rise to asymmetric lesions when the cells respond to autocrine growth signals. In contrast, neoplastic cells that depend on paracrine stimuli tend to form symmetric lesions. Since the progression of melanocytic neoplasms has been demonstrated to be accompanied by increasing independence of paracrine growth signals and the development of autocrine loops, autocrine growth stimulation has to be considered as a potential source of asymmetry in melanoma.
The importance of tumor-stroma interaction in many solid tumors of the skin has been demonstrated in recent years. Invasion and metastasis require multiple interactions of the tumor cells with the surrounding stroma. In malignant melanoma most studies concerning tumor-stroma interaction focus on the peritumoral infiltrate, whereas other aspects of tumor-stroma interactions have not been considered. We investigated two morphologic criteria of tumor-stroma interaction in melanocytic skin tumors. Simple infiltration into the surrounding dermis or subcutis without evident stromal reaction (DERMSIMPLE) and the existence of morphologically intact collagen bundles of the reticular dermis within the tumor bulk (PRECOLL) were examined in 373 benign common nevi, 239 dysplastic nevi, 322 Spitz nevi, 368 primary malignant melanomas, and 344 melanoma lesions metastatic to the skin. Our results showed that there is a highly significant difference in the expression of DERMSIMPLE and PRECOLL between benign and malignant melanocytic skin tumors. Concerning DERMSIMPLE, 13.3% of benign skin lesions compared with 28.2% of malignant lesions were positive for this feature; PRECOLL was found in 13.8% benign and 37.1% malignant lesions (chi-squared test; p = 0.0001 for both features). Furthermore, it could be demonstrated that simple infiltration into the surrounding stroma as well as the existence of morphologically intact collagen bundles of the reticular dermis within the tumor bulk increases with tumor progression; between primary malignant melanoma and melanoma metastatic to the skin, for example, there was a highly significant difference for DERMSIMPLE, as well as for PRECOLL (chi-squared test; p = 0.00001). These data indicate that morphologic aspects of tumor-stroma interactions in different benign and malignant melanocytic skin lesions may reflect biological behavior of tumor cells. The analysis of further aspects of tumor-stroma interaction and the relation to the patient's outcome may lead to the development of further prognostic parameters in malignant melanoma.
In a previous qualitative study it has been shown that the incorporation of pre-existing collagen bundles from the reticular dermis into the bulk of melanoma lesions metastatic to the skin indicates rapid systemic spread. In the present study the amount of pre-existing dermal collagen in the bulk of the melanoma lesions in 267 cases of primary melanoma of the skin with a Clark level of at least III was quantitatively assessed using automated image analysis based on RGB (red, green and blue) colour images of sections stained with haematoxylin and eosin. There was a weak correlation between the amount of pre-existing collagen and the Clark level and the Breslow index. With regard to prognosis, a large amount of pre-existing collagen (> 0.13 mm2 per index slide) was significantly associated with a particularly poor outcome (24-month survival rate: 71 +/- 17% compared with 96 +/- 2%; log rank test: P < 0.001). It is clear that a large amount of pre-existing collagen bundles occurring as a particular feature of tumour-stroma interaction indicates high metastatic capacity in primary malignant melanoma.
Accurate clinical diagnosis of malignant melanoma is of great importance for early detection and further treatment. The purpose of this retrospective study was to evaluate the accuracy of clinical diagnosis by using different clinical and histopathological parameters. Calculations are based on a total of 44,258 histopathologically examined skin neoplasms, including 529 melanomas, which were recorded in the histological database of the Department of Dermatology, University of Graz during a 2 year period. The clinical diagnosis of the referring physicians was compared statistically with the final histopathological interpretation. Clinical diagnosis of melanoma showed a sensitivity of 70.1%, a specificity of 99.4%, and a positive predictive value of 60.7%. One hundred and fifty eight melanomas (29.9%) could not be diagnosed clinically. The age-dependent sensitivity was 47.6% in patients <40 years, whereas for patients >80 years the value was 90.2%. Remarkably, the sensitivity in melanomas >4 mm thickness (64.8%) was lower than in 'melanoma in situ' (72.6%). Our findings underline the importance of further development of clinical examination techniques such as dermoscopy and digital epiluminescence microscopy.
BACKGROUND: The decision "patient unfit for anaesthesia and operation" is likely to cause a delay of the scheduled operation. This retrospective evaluation was done: 1) to determine the correctness of preoperative tentative diagnoses of coexisting diseases making anaesthesia and operation excessively risky in relation to the physician's training status; 2) to examine the question of whether preoperative medical management modified according to the anaesthesiologist's suggestions had a positive impact on the perioperative course. METHODS: The medical records of patients scheduled for elective non-cardiac surgery who were rated "unfit for operation and anaesthesia" were evaluated. The accuracy of the tentative diagnoses was examined for relation to the training status of the anaesthesiologists. The preoperative management was tested for its impact on postoperative outcome. RESULTS: During the observation period 16,122 patients underwent preoperative anaesthesiological assessment; 1021 (6.3%) were initially considered to be unfit for operation and anaesthesia. The records of 807 patients were available for review. The accuracy of the tentative diagnoses was 70%, and was not significantly affected by the training status of the physicians (P = 0.022). Four hundred and seventeen patients were excluded from the second part of the investigation (discharged without operation, underwent operation using local anaesthesia or tentative diagnosis not confirmed). Three hundred and ninety patients were operated under general anaesthesia. Group I (n = 216) was managed according to the anaesthesiologist's suggestions and was found to have a significantly lower complication rate (18.1%) than group II (n = 174) in which the suggestions from the preoperative assessment were ignored (32.2%; P < 0.05). The perioperative mortality rate in group I was 2.3% compared with 5.2% in group II (n.s.; P > 0.05). CONCLUSIONS: We conclude that the anaesthesiology decision "patient unfit for operation and anaesthesia" has a high accuracy, independent of the anaesthesiologist's training status, and that preoperative medical management significantly reduces complications.
Expression of cell surface molecules that mediate cell-matrix and cell-cell interactions largely contributes to the ability of melanoma cells to migrate and spread beyond the primary site of the tumor. CD44, the principal cell-surface receptor for hyaluronate, and its numerous splice variants have been reported to play a crucial role in invasion and the metastatic process of different human neoplasms, including primary malignant melanoma (PMM). The aim of this study was to clarify which isoforms of CD44 (standard CD44 and CD44 variants) are distributed in PMM with a vertical tumor thickness of >1.4 mm. Staining of CD44 standard (CD44s) and splice variants was further examined for diagnostic and prognostic relevance in a panel of melanocytic skin lesions. Ten cases of PMM with Breslow >1.4 mm were analysed by immunohistochemistry using monoclonal antibodies specific for CD44s and the splice variants v3, v5, v6, v7, v7-8, and v10. In addition, using anti-CD44s, v5, and v6 antibodies, 55 melanocytic lesions, including dermal nevi (n=12), Clark nevi (dysplastic nevi) (CN; n=11), melanoma in situ (Mis; n=8), PMM (n=18), and cutaneous metastasis of malignant melanoma (cMMM; n=6) were assessed. Staining intensities were scored visually and evaluated by means of a staining index. In ten cases of PMM with a Breslow index >1.4 mm positive staining was ascertained for CD44s, v5 and for v6 in three cases. No staining was found for v3, v7, v7-8, and v10. Examination of CD44s, v5, and v6 in 55 melanocytic skin lesions revealed a high index for CD44s in all specimens and a weak staining of v5 in Mis; dermal nevi and CN did not stain for v5. However, in PMM and cMMM we found v5 to be strongly positive. The isoform v6 showed a variable index only in PMM, but without connection to established prognostic criteria. We conclude that CD44s and splice variants can not be regarded as indicators for tumor progression in malignant melanomas. However, v5 may potentially serve as a diagnostic marker for melanocytic skin lesions.