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Biomedical subjects

C Garbe

Publications and source records attributed to C Garbe.

At least 91 records · Page 5Linked to original sources

RNA isolation from human skin tissues for colorimetric differential display.

High-quality RNA is essential when analyzing expression patterns of tissues by the differential display technique. However, the isolation of intact RNA can be very difficult when tissues are used that contain many RNAses or that are hard to homogenize (e.g. skin samples). We describe an improved protocol for the extraction of high-quality RNA of snap-frozen biopsies from skin tissues that works in a reproducible and reliable manner. In addition, we developed a simplified non-radioactive differential display technique using RNA from small amounts of skin samples.

Colorimetry↗

Molecular events in melanoma development and progression.

Based on clinical and histopathological features, five steps of melanoma progression have been proposed: common acquired and congenital nevi with structurally normal melanocytes, dysplastic nevus with structural and architectural atypia, early radial growth phase (RGP) primary melanoma, advanced vertical growth phase primary melanoma (VGP) with competence for metastasis, and metastatic melanoma. Despite a wealth of research resources (tissues, cell lines, and antibodies), the genetic alterations responsible for the development and stepwise progression of melanoma are still unclear. Cytogenetic analyses have failed to identify consistent gene deletions, mutations, translocations, or amplifications in sporadic cases. However, in vitro characterization of melanoma cells has revealed fundamental differences from normal melanocytes. Earlier work using monoclonal antibodies has defined a variety of melanoma-associated antigens that mediate cell-cell or cell-substratum adhesion, growth regulation, proteolysis, and modulation of immune responses. Functional studies of these individual candidate molecules will lead to a better understanding of the pathogenesis of melanoma and of potential targets for rational therapy.

Antigens, Neoplasm↗

Lymph node micrometastases of cutaneous melanoma: increased sensitivity of molecular diagnosis in comparison to immunohistochemistry.

The presence of regional lymph node metastases is one of the most significant prognostic factors for predicting survival in patients with clinical stage I or II cutaneous melanoma. For accurate staging of the primary tumor a sensitive technique is required to detect occult nodal micrometastases. This prospective diagnostic study was designed to evaluate the incidence of nodal micrometastases using nested reverse transcription-polymerase chain reaction (RT-PCR) for tyrosinase in comparison to immunohistochemical examination. Furthermore, the incidence of melanoma micrometastases detected by RT-PCR was analysed in correlation to major prognostic factors. A total of 466 regional lymph nodes from 79 patients with primary cutaneous melanoma (tumor thickness > 0.75 mm) were investigated. In 49 lymph nodes from 31 patients immunohistochemistry demonstrated melanoma metastases. Using tyrosinase RT-PCR, nodal micrometastases were detected in 136 lymph nodes from 52 patients including all lymph nodes positive by immunohistochemical examination. Out of the 417 lymph nodes negative by immunohistochemistry, 87 nodes (21%) were identified to express tyrosinase by the RT-PCR technique. Among the 48 patients negative by immunohistochemical assessment, 21 (44%) had nodal micrometastases (n = 40) using RT-PCR. All 68 lymph nodes from 46 non-melanoma patients serving as negative controls for tyrosinase RT-PCR were negative. The detection of melanocytic nodal micrometastases by tyrosinase RT-PCR is a highly specific method with a sensitivity significantly higher than that achieved by immunohistochemistry (p < 0.0001). Patients with nodal micrometastases identified exclusively by RT-PCR had significantly higher tumor thickness as compared to patients with negative results by RT-PCR (p < 0.01).

Biomarkers, Tumor↗

[Prevention of malignant melanoma].

Dermatologists and physicians of other specialties, as well as other health professionals have made tremendous efforts to improve the public education (primary prevention) and early detection (secondary prevention) of cutaneous malignant melanoma (CMM) especially during the last decade. In Australia, the country with the highest incidence of CMM in the world, the first public and effective campaigns were already carried out in the sixties. Through the public campaigns, the knowledge increased about skin cancer, and the attitude and behavior toward sun exposure changed in the population. In the USA and Great Britain too, effective public campaigns were carried out in great numbers and extensive experience was acquired. In Germany, prevention campaigns were first run in regional areas. In 1989, the Commission of Early Detection and Prevention of Melanoma of the German Dermatological Society launched nation-wide campaigns. These activities were complemented by regional campaigns in the 1990s. The analysis of previous campaigns demonstrates that single activities are less effective and repeated campaigns are necessary to increase knowledge about skin and to change attitudes and behavior towards UV-exposure. In addition, the development of sun protective clothing and structural changes, e.g. creation of shady places around open-air swimming pools, should be aimed for. Physicians of other specialties and other health professionals should also be included in prevention campaigns.

Cross-Cultural Comparison↗

Human papillomaviruses are commonly found in normal skin of immunocompetent hosts.

We have previously demonstrated, by the combined application of two degenerate polymerase chain reaction primer sets, the presence of human papillomavirus (HPV) DNA in 91% of cutaneous squamous cell cancers from renal allograft recipients, with multiple types being present in one-third of these tumors. Five HPV types--HPV 20, HPV 23, HPV 38, DL40, and DL267--accounted for 73% of positive results. These HPV types are all related to the epidermodysplasia verruciformis group, and HPV 38 was originally isolated from a melanoma. The aims of this study were to determine: (i) whether HPV DNA could readily be demonstrated in skin tumors, as well as in perilesional skin, of immunocompetent patients using two polymerase chain reaction primer sets; (ii) the prevalence of infections in normal skin; and (iii) the prevalence of HPV 38 or HPV 38 related viruses in melanoma. The HPV types detected in lesions from renal allograft recipient were present not only in the perilesional skin and tumors of immunocompetent patients, but also in 35% of normal skin biopsies. HPV DNA was present in 13% of the melanoma samples, but none harbored HPV 38 DNA. We identified four putatively new HPV types. Infections with different types of human papillomavirus are widespread and often occur in clinically normal skin. In vitro studies are required to determine the specific molecular mechanisms by which these HPV types may be involved in the etiology of nonmelanoma skin cancer.

Adult↗

Application of argon plasma coagulation in skin surgery.

BACKGROUND: Argon plasma coagulation (APC) is a noncontact electrosurgical technique which has been used in open surgery for about 20 years and in endoscopy for about 5 years. OBJECTIVE: The aim of the present study was to provide preliminary results on the effect of this method in skin surgery. METHODS: The effects of variations in gas flow, output power and coagulation times on the extent of the resulting skin coagulation zone were tested in a pig skin model. Furthermore, preliminary results were obtained from 48 patients. RESULTS: The depth of the coagulation zone, which depends on the output power of the high-frequency (HF) generator and the application time, was examined clinically and histologically in 150 different pig skin coagulations. The maximum depth of the coagulation zone was 4 mm. Coagulation zones below 4 mm can be maintained by controlling the output power of the HF generator and/or the duration of application. Variations of argon flow did not influence the depth of the coagulation zone significantly. In preliminary clinical tests, 48 patients with common warts, senile hemangiomas and actinic keratoses were treated with APC. In all cases, APC was highly effective and easy to perform. No severe problems or complications were observed. The skin lesions were destroyed with minimal or no scarring and without damaging the surrounding tissue. CONCLUSION: In the present preliminary study, APC proved to be an effective treatment with well-controlled tissue destruction. Further clinical studies are required to evaluate the suitability and the indications of this method in the treatment of cutaneous lesions.

Animals↗

Metastatic melanoma of unknown primary origin shows prognostic similarities to regional metastatic melanoma: recommendations for initial staging examinations.

BACKGROUND: Metastatic melanoma of unknown primary origin accounts for approximately 2-6% of all melanoma cases. The prognostic significance of this diagnosis is still controversial. METHODS: Of 3258 patients with malignant melanoma recorded during the period 1976-1996, 2.3% had metastases of unknown primary origin. Anatomic distribution, clinical stage, and survival probabilities were evaluated. RESULTS: Thirty patients were classified as having cutaneous or subcutaneous in-transit metastases, and they showed a 5-year survival rate of 83%. Thirty-seven patients were classified as having lymph node metastasis, and their 5-year survival rate was 50%. Disseminated disease was diagnosed in only 8 patients, who had a median survival of 6 months. Comparison of survival probabilities for patients with in-transit metastases and unknown primary tumors with the probabilities for those with cutaneous primary tumors revealed a significant advantage for the former group. No significant differences were found for patients with lymph node metastasis when those with unknown primary tumors were compared with those who had cutaneous melanomas with regional lymph node metastasis. CONCLUSIONS: The clinical disease course of patients with metastatic melanoma of unknown primary origin is similar to that of patients with primary cutaneous melanoma when the same clinical stages of the disease are compared. Based on the assumption that the majority of regional metastases develop from completely regressed primary cutaneous melanoma, recommendations for initial staging examinations in patients with unknown primary tumors are given in this article.

Adolescent↗

Prolonged survival of 2 years or longer for patients with disseminated melanoma. An analysis of related prognostic factors.

BACKGROUND: Once melanoma has metastasized to distant sites, the prognosis is usually poor, showing an overall median survival of 6-8 months. Long term survival is extremely rare, and there is still controversy concerning the prognostic significance of therapeutic modalities. The aim of the current study was to identify important prognostic factors associated with Stage IV melanoma. METHODS: The current study was based on data for 3258 melanoma patients, for whom clinical, pathologic, and long term follow-up information was recorded during the period 1976-1996 at the Eberhard-Karls-University in Tuebingen. Germany. The attainment of 2 years' or longer survival time by patients with disseminated melanoma was addressed, and a multivariate analysis of related prognostic factors was performed by logistic regression. RESULTS: Four hundred forty-two patients (13.6%) developed distant metastasis. The median survival time was 7 months, and the 2-year, 5-year, and 10-year survival rates were 11.9%, 6.7%, and 4.7%, respectively. Forty-five patients had prolonged survival of 2 years or longer. Significantly more females belonged to the group of long term survivors (P = 0.0186). Of the modalities of therapy given, only surgery was associated with prolonged survival (P < 0.0001). Primary metastasis to the skin (P = 0.006), the brain (P = 0.015), more than a single metastatic site (P = 0.002), and Karnofsky performance status of less than 80 (P = 0.0035) were significantly related to short term survival. In addition, subsequent development of two or more new metastatic sites was also associated with short term survival (P = 0.0025). CONCLUSIONS: In the current analysis, prolonged survival of 2 years or longer for patients with disseminated melanoma was shown to depend on gender, site of primary metastasis, number of metastatic sites, and Karnofsky performance status. Of the modalities of therapy given, only surgery significantly influenced survival. However, in a small percentage of patients, long term complete remission was achieved with chemotherapy alone or in combination with surgery, suggesting that such regimens might be curative in selected cases.

Adult↗

[Mollusca contagiosa in HIV infection. Clinical manifestation, relation to immune status and prognostic value in 39 patients].

Mollusca contagiosa predominantly affect children; their occurrence in adults is rare. In recent years many descriptions of mollusca contagiosa in immunosuppressed patients, mostly in HIV-infected individuals, have appeared. We analysed the occurrence of mollusca contagiosa in a large group of HIV-patients and examined their relation to the immune status and their prognostic significance. 456 patients with HIV-associated skin disorders were documented in the HIV follow-up clinics at the Department of Dermatology, University Medical Center Benjamin Franklin, Berlin, during the years 1982-1992. Molluscum contagiosum was diagnosed in 39 patients (8.6%). 38 of the 39 patients were homosexual and/or bisexual men. The median age of the patients was 34 years. Large, papular and nodular lesions up to 1 cm in diameter were observed in some, individuals. Frequently, multiple lesions in atypical localizations such as the face were found. Significant immunosuppression was present in the majority of patients with mollusca contagiosa at the time of their first diagnosis; median CD(4+)-T-lymphocyte count was 122/microliter and the median CD4+/CD(8+)-ratio was 0.2. The median survival time was 12 months in patients with mollusca contagiosa. There was no significant difference between the prognosis of patients with mollusca contagiosa and other HIV-infected patients showing similar reduction of their immune status. Our study showed that mollusca contagiosa are a rather frequent infection in HIV-patients. Mainly localized to the face, they are easily diagnosed and may serve as an excellent clinical marker for recognizing advanced immunosuppression in HIV-infection. Survival prognosis of patients with molluscum contagiosum is unfavourable, corresponding to their reduced immune status. The presence of mollusca, however, is not an independent prognostic marker, if the immune status is considered.

AIDS-Related Opportunistic Infections↗

[The difficulty of ultrasound diagnosis of lymph node metastases of malignant melanoma in protracted tumor growth].

Lymph node ultrasound examinations are performed during the follow-up of cutaneous melanoma in order to early recognise regional metastases. The excision of regional metastases is the only way to inhibit disseminated metastasis in a certain percentage of cases. Lymph node ultrasound has a sensitivity of 95% in the diagnosis of pathological lymph node changes. Sonographic findings normally show typical features of malignancy; only in some doubtful cases are further control examinations warranted over a period of 4-6 weeks. In violation of this rule, two cases are presented with a delayed onset of metastases causing difficulties in the diagnosis of malignant transformation. Four years after the excision of a nodular melanoma with 0.8 mm tumor thickness at the right lower leg, a suspicious lymph node change in the right groin was sonographically detected which did not fulfill all criteria of malignancy. Control examinations over a period of 1 year found only a further growth of 3 mm. Excision after 1 1/2 years showed a lymph node metastasis. The second case presented 9 years after the excision of a superficial spreading melanoma with 0.76 mm tumor thickness with a suspicious lymph node in the right axilla which similarly grew very slowly. The subsequent excision showed likewise a melanoma metastasis. A protracted growth may occur in thin malignant melanomas with late development of ultrasound features of malignancy. In doubtful cases an early biopsy is recommended.

Aged↗

[Standards in histopathologic diagnosis of malignant melanomas. Recommendations of the Working Group of the Central Malignant Melanoma Registry of the German Dermatologic Society].

The evaluation of melanocytic tumors represents one of the most intriguing and challenging aspects of the daily practice in dermatohistopathology. For the diagnosis of malignant melanoma and melanocytic nevi, standardized and reproducible criteria are required. In case of the diagnosis of melanoma, the histopathological report must include all important data relevant for the prognosis which may also influence the therapeutic procedure. The following paper summarizes the recommendations of the study group on malignant melanoma formed by the Deutsche Dermatologische Gesellschaft.

Biomarkers, Tumor↗