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C Garbe

Publications and source records attributed to C Garbe.

At least 109 records · Page 6Linked to original sources
PubMed1997

Problems in defining cutoff points of continuous prognostic factors: example of tumor thickness in primary cutaneous melanoma.

Continuous prognostic factors are often categorized by defining optimized cutoff points. One component of criticism of this approach is the problem of multiple testing that leads to an overestimation of the true prognostic impact of the variable. The present study focuses on another crucial point by investigating the dependence of optimized cutoff points on the observed distribution of the continuous variable. The continuous variable investigated was the vertical tumor thickness according to Breslow, which is known to be the most important prognostic factor in primary melanoma. Based on the data of 5093 patients, stratified random samples were drawn out of six artificially created distributions of tumor thickness. For each of these samples, Cox models were calculated to explore optimized cutoff points for tumor thickness together with other prognostic variables. The optimized cutoff points for tumour thickness varied considerably with the underlying distribution. Even in samples from the same distribution, the range of cutoff points was amazingly broad and, for some of the distributions, covered the whole region of possible values. The results of the present study demonstrate that optimized cutoff points are extremely data dependent and vary notably even if prerequisites are constant. Therefore, if the classification of a continuous prognostic factor is necessary, it should not be based on the results of one single study, but on consensus discussions including the findings of several investigations.

Female↗
PubMed1997

Investigation of oestrogen receptors, sex steroids and soluble adhesion molecules in the progression of malignant melanoma.

The question of whether melanoma tumours have classical oestrogen receptors (ERs) is unresolved, but epidemiological data clearly show a survival benefit for female patients with metastatic melanoma. The aims of this study were to examine to what extent the presence of ER in melanoma tumours might relate to disease progression and whether disease progression relates to patients' sex steroid status. Additionally, levels of two soluble adhesion molecules [circulating intercellular adhesion molecule-1 (sICAM-1) and circulating vascular cell adhesion molecule-1 (sVCAM-1)] were examined as independent, possibly prognostic indicators of disease progression. ER immunocytochemical assay identified only two lesions (out of 69 investigated) which had any evidence of the receptors, and staining in these lesions was very modest. No significant changes in oestrone or androstenedione levels were noted for male or female patients with disease progression. As expected, oestradiol levels reflected the menopausal status of the female patients but, for all post-menopausal female patients and male patients, there was no significant relationship to tumour stage. However, a significant decrease in sex hormone-binding globulin occurred with disease progression in male but not female patients, and sex differences in the levels of soluble adhesion molecules were also seen in advanced metastatic disease.

Adolescent↗
PubMed1997

Inactivation of ribonucleotide reductase in tumour cells and inhibition of tumour cell growth by p-alkoxyphenols.

A significant correlation between the inactivation of the growth-regulating enzyme ribonucleotide reductase (RR) with the growth inhibition of four different tumour cell lines has been found for seven different p-alkoxyphenol derivatives with varying lengths of alkyl side chain. In Novikoff hepatoma and human leukaemia cells, inactivation of RR by p-alkoxyphenols was monitored by electron paramagnetic resonance (EPR) spectroscopy of the catalytically essential tyrosyl radical in the subunit R2 of RR. A significant inhibition of cellular growth of Novikoff hepatoma cells, human leukaemia cells and two human melanoma cell lines (MeWo and M5) by p-alkoxyphenols was also observed by growth inhibition assays. Inactivation of RR in whole tumour cells as well as inhibition of cellular growth of tumour cell lines by p-alkoxyphenols both show an increase in inhibition with increasing length of the alkyl side chain; the most effective inhibitors are p-isobutoxyphenol, p-butoxyphenol and p-propoxyphenol. The enzyme RR, and in particular the catalytically essential tyrosyl radical in the active site, is recognized as an important cellular target for growth inhibition of Novikoff hepatoma cells, human leukaemia cells and melanoma cells by p-alkoxyphenols. Thus, the most potent RR inhibitors-p-isobutoxyphenol, p-butoxyphenol and p-propoxyphenol-may be considered as future antiproliferative drugs for the systemic treatment of melanoma as well as leukaemia and possibly other malignancies.

Animals↗
PubMed1997

Ultraviolet light exposure, pigmentary traits and the development of melanocytic naevi and cutaneous melanoma. A case-control study of the German Central Malignant Melanoma Registry.

The present study firstly aimed at understanding the relationship between sun exposure, pigmentary traits and the history of sunburns. Secondly, the significance of UV-exposure for cutaneous melanoma and for melanocytic naevi was investigated. The case-controlled study comprised 513 patients with primary cutaneous melanoma and 498 controls matched by age and gender. Multivariate logistic regression analysis was used to study melanoma risk factors. The number of common melanocytic naevi was associated with age, gender, the history of sunburns and UV-exposure during holidays (odds-ratio = 1.9; 95% confidence interval = [1.1, 3.4]) for 3 weeks or more. The number of atypical melanocytic naevi was significantly related to age, gender, pigmentary traits, the history of sunburns and UV-exposure during holidays (odds-ratio = 3.5; 95% confidence interval = [1.4, 9.0]) for 2 months or more. The results of the present study showed that both the history of sunburn and intensive sun exposure during holidays were important for the development of melanocytic naevi and, therefore, indirectly for cutaneous melanoma. In addition, a particular type of pigmentation was found to be related to atypical melanocytic naevi.

Adolescent↗
PubMed1996

[Elective lymph node dissection in primary malignant melanoma].

The role of elective lymph node dissection (ELND) in primary malignant melanoma is controversial. Our purpose was to evaluate the benefit of ELND regarding survival and disease-free survival in malignant melanoma of the trunk and extremities. By matched-pair analysis, 375 patients treated by wide local excision (WLE) plus ELND were compared to 375 patients treated by WLE only. There was no difference in survival between the two treatment groups; however, the disease-free interval was significantly higher in the collective treated by WLE plus ELND (P < 0.05). Increased survival rates were noted for intermediate tumor thickness of 1.51-4.0 mm for the WLE+ELND group although the difference was not significant (P = 0.14), and disease-free survival was significantly improved in this group (P < 0.001). ELND elicited a higher benefit in male patients with intermediate thickness melanoma. Our results confirm the findings of several studies that ELND improves the outcome after primary treatment of malignant melanoma of intermediate tumor thickness.

Adult↗
PubMed1996

[Increased survival in distant melanoma metastasis and the effect of treatments. Analysis of the disease course of patients with a survival of 2 years or more].

The median survival time for patients with disseminated malignant melanoma is 5-7 months; it is still not really known whether therapeutic measures prolong survival. The aim of the present investigation was to identify patients with prolonged survival in stage IV disease and to analyse the possible impact of therapy on the course of the disease. In the Department of Dermatology, Benjamin Franklin University Medical Centre at the Free University of Berlin, 263 patients with were diagnosed as having stage IV melanoma and enrolled in a computer-based registry between 1970 and 1993. In 89 cases systemic medical mentous treatment was given and 111 patients underwent surgery and/or radiation therapy. There were 48 patients who received both systemic and local therapy. On the other hand, 111 patients received no treatment. Twenty two patients were identified survived longer than 24 months (median survival time 33 months). None of the patients who had received no treatment survived for 2 years or longer. The 22 patients with prolonged survival were treated by multimodality included 16 who had received both systemic treatment and surgery and/or radiation, while 3 had had only systemic drug therapy and another 3, only local treatment. Twelve of the 22 patients became tumour free after their initial surgery or radiation. Active therapy in disseminated melanoma with reduction of tumour mass by surgery and radiation and with systemic medical treatment may lead to prolonged survival in a considerable percentage of patients.

Adult↗
PubMed1996

[Therapeutic experiences with extracorporeal photopheresis. Technical procedure, follow-up and clinical outcome in 31 skin diseases].

Extracorporeal photophoresis (ECP), a therapeutic modality that has been under investigation for some years, is based on separation of a leucocyte/lymphocyte-enriched cell fraction from the peripheral blood, extracorporeal treatment of the cells with 8-MOP/UVA and subsequent reinfusion of the cells in the patient. Its main effects seem to consist in changes to the immunologic behaviour of the photoinactivated/modulated cells. The immune response of the host is obviously stimulated by this treatment. ECP is normally performed for 4 h per day on 2 consecutive days every 4 weeks. The treatment is well tolerated and causes few side effects. In our department, 1210 ECP treatments were administered to 41 patients between 1990 and 1994 and a preliminary evaluation was performed. These patients included 21 with cutaneous T-cell lymphoma (CTCL), 10 with progressive systemic scleroderma, 4 with chronic graft-versus-host disease and 1 each with pemphigus vulgaris, epidermolysis bullosa acquisita, lupus erythematosus and cutaneous mucinosis. Patients with erythroderma and preserved immunocompetence achieved the best responses of all patients with CTCL. A treatment combining ECP with rIFN-alpha, PUVA and/or radiation was also successful in patients with tumour-stage CTCL and lymph node involvement. Progressive systemic scleroderma responded in more than 50% of our cases. Treatment results were impressive in 4 patients with chronic graft-versus-host disease presenting with sclerodermatous and lichenoid changes of the skin and mucous membranes. A clear improvement was also observed in the patient with pemphigus vulgaris refractory to standard therapies and in another patient with scleromyxoedema (Arndt-Gottron syndrome). The effectiveness of ECP seems to be quite well established in CTCL, but remains to be examined in autoimmune dermatoses. ECP is an attractive addition to the dermatological therapies available but our experience is still preliminary.

Adult↗
PubMed1996

K+ channels and the intracellular calcium signal in human melanoma cell proliferation.

K+ channels, membrane voltage, and intracellular free Ca2+ are involved in regulating proliferation in a human melanoma cell line (SK MEL 28). Using patch-clamp techniques, we found an inwardly rectifying K+ channel and a calcium-activated K+ channel. The inwardly rectifying K+ channel was calcium independent, insensitive to charybdotoxin, and carried the major part of the whole-cell current. The K+ channel blockers quinidine, tetraethylammonium chloride and Ba2+ and elevated extracellular K+ caused a dose-dependent membrane depolarization. This depolarization was correlated to an inhibition of cell proliferation. Charybdotoxin affected neither membrane voltage nor proliferation. Basic fibroblast growth factor and fetal calf serum induced a transient peak in intracellular Ca2+ followed by a long-lasting Ca2+ influx. Depolarization by voltage clamp decreased and hyperpolarization increased intracellular Ca2+, illustrating a transmembrane flux of Ca2+ following its electrochemical gradient. We conclude that K+ channel blockers inhibit cell-cycle progression by membrane depolarization. This in turn reduces the driving force for the influx of Ca2+, a messenger in the mitogenic signal cascade of human melanoma cells.

Animals↗
PubMed1996

Oral hairy leukoplakia in 71 HIV-seropositive patients: clinical symptoms, relation to immunologic status, and prognostic significance.

BACKGROUND: Oral hairy leukoplakia (OHL) is a benign hyperplasia of the oral mucosa that is induced by Epstein-Barr virus. It occurs nearly exclusively in men infected with HIV. OHL is a marker of moderate to advanced immunodeficiency and disease progression in patients with HIV infection. OBJECTIVE: We attempted to determine the clinical characteristics of OHL in a large group of patients infected with HIV and to analyze its relation to immune status and prognosis. METHODS: A total of 456 patients with HIV-associated skin disorders were evaluated during the years 1982 through 1992. All patients had an oral examination. CD4+ cell counts were obtained within 3 months of the examination. RESULTS: OHL was diagnosed in 15.6% of 456 patients. The median age of the patients was 35 years. OHL was found most often on the lateral aspect of the tongue; in one patient the lesion covered the entire dorsal surface of the tongue. Significant immunosuppression was present in the majority of patients at the time of OHL diagnosis (median CD4+ T-lymphocyte count, 235/microliter; median CD4+/CD8+ ratio, 0.3). The median survival time was 20 months in patients with OHL. In patients with a higher CD4 cell count (CD4+ T lymphocyte count, > or = 300/microliter) the diagnosis of OHL was associated with shorter survival times (median survival time, 25 months) compared with other patients with HIV (median survival time, 52 months). CONCLUSION: OHL is a frequent finding in patients with HIV and indicates advanced immunosuppression. Even in patients with more than 300/microliter CD4+ T lymphocytes, OHL is associated with a poor prognosis.

AIDS-Related Opportunistic Infections↗
PubMed1996

Failure of gadopentetate dimeglumine-enhanced, high-resolution magnetic resonance imaging to differentiate among melanin-containing skin tumors.

RATIONALE AND OBJECTIVES: We evaluated the diagnostic potential of gadopentetate dimeglumine-enhanced, high-resolution magnetic resonance (MR) imaging to differentiate benign from malignant melanin-containing skin tumors. METHODS: Forty-five patients were prospectively examined using high-resolution MR imaging at 1.5 T using a 2.5-cm surface coil. For tumor assessment, T1-weighted and T2-weighted transverse spin-echo sequences were acquired. After intravenous administration of gadopentetate dimeglumine (0.1 mmol/kg), the T1-weighted transverse sequence was repeated. Contrast enhancement was quantitatively determined as the percentage increase of signal intensity. Histologic findings were correlated using the Wilcoxon signed-ranks test. The quality of contrast enhancement was assessed by three independent investigators who were unaware of the patients' history and histologic data. The signal-to-noise ratio (SNR) was calculated in the T2-weighted sequence. Significance was tested using the Wilcoxon signed-ranks test. RESULTS: In all tumors, contrast enhancement was visually discernible. Half of the cases were enhanced inhomogeneously. The percentage of contrast enhancement did not correlate with histologic findings. Malignant melanomas could not be differentiated from benign melanocytic nevi with the use of gadopentetate dimeglumine. Determination of the SNR in T2-weighted sequences revealed no significant difference for histologic subgroups or tumor type. CONCLUSION: Gadopentetate dimeglumine-enhanced MR imaging does not differentiate malignant melanomas from benign melanocytic nevi. Determination of the SNR in the T2-weighted sequences revealed no significant difference for histologic subgroups.

Adolescent↗
PubMed1996

Increase of melanocytic nevus counts in children during 5 years of follow-up and analysis of associated factors.

OBJECTIVES: To investigate nevus development in childhood and to examine causative related factors such as pigment phenotype and the role of sun exposure in the development of melanocytic nevi. DESIGN AND PARTICIPANTS: Nevus counts were performed in kindergarteners (n = 866) before the age of 7 years and again 5 years later (n = 377). Eligible for analysis were 357 children who were examined twice. Possible related factors were searched for by standardized interviews with parents. RESULTS: The mean number of nevi measuring 1 mm or more was 9 in the first examination and the number measuring 2 mm or more, 4. Five years later, the mean number of nevi measuring 1 mm or more was 40 and the number measuring 2 mm or more was 16. Children with poor sun tolerance had statistically significant more nevi (relative risk, 3.7;95% confidence interval, 1.9-7.2). The presence of freckles was a strong predictor for a high increase of melanocytic nevi (relative risk, 2.1; 95% confidence interval, 1.3-3.3). The number of days per year with intensive solar exposure was an independent prognostic factor. The relative risk for the development of melanocytic nevi was increased by a factor of 1.6 in children who had more than 21 days of intensive sun exposure per year (95% confidence interval, 1.0-2.5). CONCLUSION: The development of melanocytic nevi in childhood is strongly related to characteristics of pigmentation associated with poor sun tolerance. In addition, we found evidence for the influence of UV radiation on the number of acquired melanocytic nevi in childhood.

Child↗
PubMed1995

Overall and site-specific risk of malignant melanoma associated with nevus counts at different body sites: a multicenter case-control study of the German Central Malignant-Melanoma Registry.

A large number of benign melanocytic nevi is the major risk factor for malignant melanoma (MM). In a multicenter case-control study, the number of common (CN) and clinically atypical (AN) nevi were counted separately at individual sites in 278 melanoma patients and 278 age- and gender-matched non-melanoma controls. Relative risk (RR) adjusted for age and sex was calculated. In men as well as women, the number of CN on the legs was the best predictor of overall melanoma risk. In men, RR for developing MM when > or = 1 AN were present on the trunk was 4-fold (vs. none). In women, presence of AN on the arms increased RR 9.5-fold. For men and women combined, after adjusting for age and gender, the RR for developing MM on the trunk and on the legs was best predicted by counts of CN at the respective body region. However, high counts of CN on the arms were associated with high melanoma risk on the legs (somewhat lower on the trunk). For AN, no site-specificity of melanoma risk was found. Our data suggest that nevus counts of the legs are the best predictor of overall melanoma risk if total body nevus counts are not feasible. Although high counts of CN on the trunk and legs are associated with a higher risk of developing MM at the respective site than at another site, our data do not unequivocally support a direct site-specific melanoma risk.

Arm↗
PubMed1995

Primary cutaneous melanoma. Identification of prognostic groups and estimation of individual prognosis for 5093 patients.

BACKGROUND: Numerous investigations have examined prognostic factors for patients with primary cutaneous melanoma. However, only a few studies have been published on the definition of prognostic groups. The first aim of the present study was to determine the relative importance of different prognostic factors in a large collective study. The second aim was to define prognostic groups of patients based on combinations of prognostic factors and to define a model that allows the estimation of individual survival probability. METHODS: Long term follow-up of 5264 patients with invasive primary cutaneous melanoma was performed from 1970 to 1988 at four German University Departments of Dermatology (Berlin-Steglitz, Münster-Hornheide, Tübingen, and Würzburg). The multivariate Cox model was used to analyze 5093 patients, and 4371 patients with complete information were included in a classification and regression tree analysis (CART). RESULTS: Tumor thickness, sex, anatomic location, and level of invasion were highly significant prognostic factors according to the multivariate analysis (P < 0.0001). However, histologic subtype and age influenced prognosis less significantly (P < 0.05). The CART analysis resulted in 12 groups defined mainly by tumor thickness, sex, and anatomic location, which were combined into five prognostic groups. The prognostic stratification defined by the five groups was superior compared with the standard TNM model. Ten-year survival rates of the five groups ranged from 97% to 14% (P < 0.0001), and an equation was used to calculate individual survival probabilities based on the significant factors of the Cox model. CONCLUSIONS: Consideration of all significant prognostic factors of patients with primary cutaneous melanoma investigated in the present study allows for the definition of prognostic groups with a more reliable estimation of prognosis than by previous staging systems and also enables calculation of individual survival probabilities.

Age Factors↗
PubMed1995

Primary cutaneous melanoma. Prognostic classification of anatomic location.

BACKGROUND: Anatomic location has been identified by several investigators as a significant prognostic factor for patients with primary cutaneous melanoma (CM). However, the best determination of higher and lower risk sites is still controversial, and the biologic significance of tumor site in the course of primary CM is unknown. The aim of the present study was to identify higher and lower risk sites based on multivariate analysis. METHODS: A series of 5093 patients with invasive primary cutaneous melanoma followed from 1970 to 1988 at four university centers in Germany was investigated using the multivariate Cox proportional hazard model to analyze the importance of anatomic location for survival probability. RESULTS: The anatomic location was found to be a highly significant prognostic factor for patients with primary melanoma by multivariate analysis (P < 0.0001). An optimized classification into sites of higher and lower risk with respect to survival was evaluated by multivariate analysis controlling for the possible confounding effects of the other significant prognostic factors. Relative to the lower leg as the prognostically favorable baseline, the following locations were associated with a significantly higher risk of death caused by primary cutaneous melanoma: back and breast (thorax), upper arm, neck, and scalp (TANS regions). The lower trunk, thigh, lower leg, foot, lower arms, hands, and face were identified as lower risk sites. CONCLUSIONS: Anatomic location was confirmed as an independent prognostic factor for patients with primary cutaneous melanoma. The TANS regions were identified as high risk sites, and the lower trunk, thigh, lower leg, foot, lower arms, hands, and face were identified as intermediate sites.

Arm↗