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C Garbe

Publications and source records attributed to C Garbe.

At least 37 records · Page 2Linked to original sources

Is sentinel lymph node biopsy of therapeutic relevance for melanoma?

INTRODUCTION: It is still unclear whether sentinel lymph node biopsy (SLNB) has an effect on the survival or recurrence-free survival of patients. It would be necessary to compare patients with SLNB (or with selective lymph node dissection in the case of positive SLNB) and patients without SLNB who received only a close clinical and sonographic follow-up. To date, no results from prospective, randomized studies of SLNB are available. MATERIAL AND METHODS: Patients with SLNB (n = 283) and patients in clinical stage I and II with close follow-up examinations only (n = 3,514) were studied retrospectively in this investigation with regard to prognostic factors established in the literature: sex, age, tumor thickness, histological tumor type, ulceration and localization. RESULTS: Multivariate analysis did not show an independent significant advantage with regard to survival when SLNB had been performed (p = 0.37). Compared with patients in clinical stage I and II with close follow-up only (n = 2,617),patients in stage I and II with negative SLNB (n = 238) had no significantly lower melanoma-related mortality (p =0.36) but significantly fewer recurrences in the regional lymph node area (p = 0.0015). With regard to survival without distant metastases and disease-specific survival, patients with positive SLNB (n = 33) did not significantly benefit by comparison with patients who developed lymph node metastasis identified clinically or sonographically later during follow-up examinations (n = 246; p =0.89 and p = 0.38, respectively). CONCLUSION: In the relatively short follow-up period after SLNB, patients for whom SLNB had been performed did not have - on the whole - a prognostic advantage over patients who were subject only to close follow-up monitoring. Patients for whom subclinical lymph node metastases had been removed as the result of a positive SLNB did not have a better prognosis than patients without SLNB who had developed lymph node metastases within the follow-up period [corrected]

Adolescent↗

Phase II trial of intralesional therapy with interleukin-2 in soft-tissue melanoma metastases.

The objective of the present study was to validate the use of intralesional injection of interleukin-2 (IL-2) in patients with skin and soft-tissue melanoma metastases. A total of 24 patients with AJCC stage III or IV melanoma and single or multiple skin and soft-tissue metastases were included. Interleukin-2 injections were administered intralesionally into the total number of cutaneous and soft-tissue metastases accessible from the skin, 2-3 times weekly, over 1-57 weeks. Single doses varied from 0.6 to 6 x 10(6) IU, depending on lesion size. The clinical response was monitored by sonography and confirmed by histopathology; response evaluation was confined to the intralesionally treated tumours. Complete response (CR) of the treated metastases was achieved in 15 patients (62.5%), the longest remission lasting 38 months to date. In five patients, partial response (PR) was achieved (21%) and in another three patients, progressive disease was observed (one patient not assessable). A total of 245 metastases were treated with CR in 209 (85%), and PR in 21 (6%). The therapy was generally well tolerated; the observed adverse events were mainly of grade 1-2 severity. Immunohistochemical studies showed the tumour cells undergoing apoptosis and revealed a mixed character of the inflammatory infiltrate. The unusual high CR rate in metastatic melanoma of 62.5% and the limited toxicity suggest that treatment of skin and soft-tissue melanoma metastases with intralesional injection of IL-2 may be a safe and effective alternative to conventional therapies. The optimal dosage and duration of this therapy still remain to be defined in larger prospective multicentre trials.

Adult↗

[Correlation between dermoscopy and histopathology in pigmented and non-pigmented skin tumours].

Dermoscopy (dermatoscopy, epiluminescence microscopy, surface microscopy) is a non-invasive method in dermatology. With this method pigmented and non-pigmented skin tumours can be diagnosed with a clear higher sensitivity and specificity compared to clinical examination. Malignant skin tumours are detected earlier and unnecessary excisions of benign skin tumours can be avoided. The knowledge about the correlation between dermoscopy and histopathology is hereby an essential condition. In this continuing medical education article the correlation of both examination techniques is presented for the dermoscopic differential diagnoses.

Basal Cell Carcinoma↗

[Prognostic parameters and surgical strategies for facial melanomas].

BACKGROUND: In treated facial melanomas, the safety margins generally applied in other body sites cannot be achieved for functional and esthetical reasons. To date there are no controlled studies on safety margins for facial melanomas. Clinical parameters and surgical strategies influencing the prognosis of patients with a facial melanoma were evaluated in a retrospective study of melanoma patients in the Department of Dermatology of the University of Tuebingen (1980-1999). PATIENTS AND METHODS: The 368 melanomas of the face comprised 9.3% of 3960 primary stage I and II melanomas and 63% of the melanomas in the head and neck area. RESULTS: Multistep procedures, excisional biopsy for histological diagnosis followed by a subsequent resection of a clinical safety margin or re-excision when the tumor extended to the margin, were associated with a higher probability for recurrence-free survival (p = 0.0007), but had no statistical influence on overall survival. In a multivariate analysis, level of invasion (p = 0.0049), ulceration (p = 0.011), 3D-histology (p = 0.027) and defined safety margins (tumor thickness < or = 1.00 mm: 10 mm; > 1.00 mm 20 mm; lentigo maligna melanoma 5 mm with 3D-histology) (p = 0,033) were independent significant risk factors for recurrence-free survival. Level of invasion (p = 0.032), ulceration (p = 0.029), 3D-histology (p = 0.0047) were identified as independent significant risk factors for overall survival. Multivariate analysis did not show that the histological type of melanoma was of prognostic significance. CONCLUSION: Reduced safety margins can be employed in melanomas of the face. 3D-histology allows further reduction of safety margins, detects subclinical tumor strands and is correlated with an improved prognosis in patients with facial melanomas.

Aged↗

The dermoscopic classification of atypical melanocytic naevi (Clark naevi) is useful to discriminate benign from malignant melanocytic lesions.

BACKGROUND: The dermoscopic classification is a useful tool for handling patients with atypical naevi (Clark naevi). OBJECTIVES: To investigate if the dermoscopic classification of atypical naevi is of any value to discriminate benign from malignant melanocytic lesions. METHODS: Consecutive patients (n = 205) were included with 254 suspicious melanocytic lesions, confirmed by histopathology at the Pigmented Lesions Clinic of the Department of Dermatology, University Medical Center, University of Tuebingen, Germany. In this retrospective study, dermoscopic images of benign and malignant melanocytic lesions were classified according to the dermoscopic classification of atypical naevi (reticular, globular, homogeneous or combinations of two of these) and pigmentation (uniform, central hyper- or hypopigmentation, eccentric peripheral hyper- or hypopigmentation, or multifocal hyper- or hypopigmentation). The three-structure type (reticular, globular and homogeneous) was additionally defined. RESULTS: Reticular, homogeneous and reticular-homogeneous types were significantly more frequent in naevi than in melanomas, whereas the three-structure type was significantly more frequent in melanomas (P < 0.001). A sensitivity of 86.7%, specificity of 87.7% and diagnostic accuracy of 87.4% was obtained. Uniformly pigmented and centrally hyperpigmented types were significantly more frequent in naevi than in melanomas, whereas eccentric peripheral hyperpigmented and multifocal hyper- or hypopigmented types were significantly more frequent in melanomas (P < 0.001). CONCLUSIONS: The dermoscopic classification of atypical naevi (Clark naevi) is useful to discriminate benign from malignant melanocytic lesions. The three-structure type and eccentric peripheral hyperpigmentation were significantly more frequently found in malignant than in benign melanocytic lesions. The knowledge of these two dermoscopic types should be helpful for the management of patients presenting with multiple melanocytic lesions.

Adolescent↗

Surveillance and follow-up examinations in cutaneous melanoma.

The main goal of follow-up examinations of patients with cutaneous melanomas is early diagnosis of developing recurrent or second tumors. Timely recognition of recurrence has a relevant effect on the prognosis. In 80% of the cases recurrences are diagnosed for the first time in the course of follow-up when follow-up procedures are carried out systematically. Most recurrences are discovered during a physical examination. Sonographic examination of the lymph nodes is also a very sensitive method which can lead to the diagnosis of locoregional recurrences before they are palpable. Further image-producing techniques are not necessary for surveillance of primary tumors. In contrast to former recommendations, new research indicates that less extensive diagnostic procedures are sufficient in primary tumor stages, especially when the tumor thickness of the melanoma is less than 1 mm. Consequently, costs can be reduced considerably without additional risk to the patient.

Aftercare↗

Metastatic pathways and time courses in the orderly progression of cutaneous melanoma.

BACKGROUND: It is known that two-thirds of patients who develop clinical metastases following treatment of a primary cutaneous melanoma initially present with locoregional metastases and one-third initially present with distant metastases. However, few reports in the literature give detailed figures on different metastatic pathways in cutaneous melanoma. OBJECTIVES: The aim of the present study was to perform a detailed analysis of the different metastatic pathways, the time course of the development of metastases and the factors influencing them. METHODS: In a series of 3001 patients with primary cutaneous melanoma at first presentation, 466 subsequently developed metastasis and were followed-up over the long term at the University of Tuebingen, Germany between 1976 and 1996. Different pathways of metastatic spread were traced. Associated risk factors for the different pathways were assessed. Differences in survival probabilities were calculated by the Kaplan-Meier method and evaluated by the log-rank test. RESULTS: In 50.2% of the patients the first metastasis after treatment of the primary tumour developed in the regional lymph nodes. In the remaining half of the patient sample the first metastasis developed in the lymphatic drainage area in front of the regional lymph nodes, as satellite or in-transit metastases (21.7%) or as direct distant metastases (28.1%). Anatomical location, sex and tumour thickness were significant risk factors for the development of metastasis by different pathways. The most important risk factor appeared to be the location of the primary tumour. The median intervals elapsing before the first metastasis differed significantly between the different metastatic pathways. The direct distant metastases became manifest after a median period of 25 months, thus later than the direct regional lymph node metastases (median latency period, 16 months) and the direct satellite and in-transit metastases (median latency period, 17 months). In patients who developed distant metastases the period of development was independent of the metastatic route. The time at which the distant metastases developed was roughly the same (between 24 and 30 months after the detection of the primary tumour), irrespective of whether satellite or in-transit metastases, lymph node metastases or distant metastases were the first to occur. CONCLUSIONS: The time course of the development of distant metastasis was more or less the same irrespective of the metastatic pathway; this suggests that in patients with in-transit or satellite metastasis or regional lymph node metastasis, haematogenic metastatic spread had already taken place. Thus, the diagnostic value of sentinel lymph node biopsy and the therapeutic benefit of elective lymph node dissection may be limited, as satellite and in-transit metastases or direct distant metastases will not be detected and haematogenous spread may already have taken place when the intervention is performed.

Adolescent↗

[Manifestations of the "pretherapeutic phase" of malignant melanoma of the skin in Switzerland 1996-1998].

62 patients with a histologically confirmed diagnosis of cutaneous malignant melanoma were interviewed from 1996 to 1998. Lesions were found mostly on patients backs (30.6%) and they were noted most frequently because of a change in colour (darker) (50%) and increase in size (43.5%). The median time between first noticing the melanoma and visiting a physician was one month, but for 28% of the patients it was more than three months. The median time between a medical examination and surgical removal was shorter than one month, but for 22% of the patients it was more than three months. Patients with bleeding lesions sought medical help later (14 months). Misdiagnosis led to a six months delay in treatment and if no action was taken there was a 13 months delay.

Adult↗

Dacarbazine and interferon alpha with or without interleukin 2 in metastatic melanoma: a randomized phase III multicentre trial of the Dermatologic Cooperative Oncology Group (DeCOG).

In several phase II-trials encouraging tumour responses rates in advanced metastatic melanoma (stage IV; AJCC-classification) have been reported for the application of biochemotherapy containing interleukin 2. This study was designed to compare the efficacy of therapy with dacarbazine (DTIC) and interferon alpha (IFN-alpha) only to that of therapy with DTIC and IFN-alpha with the addition of interleukin 2 (IL-2) in terms of the overall survival time and rate of objective remissions and to provide an elaborated toxicity profile for both types of therapy. 290 patients were randomized to receive either DTIC (850 mg/m(2)every 28 days) plus IFN-alpha2a/b (3 MIU/m(2), twice on day 1, once daily from days 2 to 5; 5 MIU/m(2)3 times a week from week 2 to 4) with or without IL-2 (4.5 MIU/m(2)for 3 hours i.v. on day 3; 9.0 MIU/m(2) i.v. day 3/4; 4.5 MIU/m(2) s.c. days 4 to 7). The treatment plan required at least 2 treatment cycles (8 weeks of therapy) for every patient. Of 290 randomized patients 281 were eligible for an intention-to-treat analysis. There was no difference in terms of survival time from treatment onset between the two arms (median 11.0 months each). In 273 patients treated according to protocol tumour response was assessable. The response rates did not differ between both arms (P = 0.87) with 18.0% objective responses (9.7% PR; 8.3% CR) for DTIC plus IFN-alpha as compared to 16.1% (8.8% PR; 7.3% CR) for DTIC, IFN-alpha and IL-2. Treatment cessation due to adverse reactions was significantly more common in patients receiving IL-2 (13.9%) than in patients receiving DTIC/IFN-alpha only (5.6%). In conclusion, there was neither a difference in survival time nor in tumour response rates when IL-2, applied according to the combined intravenous and subcutaneous schedule used for this study, was added to DTIC and IFN-alpha. However, toxicity was increased in melanoma patients treated with IL-2. Further phase III trials with continuous infusion and higher dosages must be performed before any final conclusions can be drawn on the potential usefulness of IL-2 in biochemotherapy of advanced melanoma.

Adolescent↗

Interlaboratory evaluation of a new reverse transcriptase polymerase chain reaction-based enzyme-linked immunosorbent assay for the detection of circulating melanoma cells: a multicenter study of the Dermatologic Cooperative Oncology Group.

PURPOSE: Reverse transcription-polymerase chain reaction (RT-PCR)-based detection of tyrosinase mRNA is the most frequently used laboratory method for the detection of circulating tumor cells in melanoma patients. However, previously published results showed considerable variability in the PCR positivity rates. MATERIALS AND METHODS: We designed a collaborative study to assess the sensitivity, specificity, and clinical relevance of a new standardized RT-PCR-based enzyme-linked immunosorbent assay (ELISA) for the detection of circulating melanoma cells. Blood samples of healthy donors mixed with cells of a melanoma cell line were prepared in a blinded fashion, and aliquots were sent to seven participating laboratories experienced in RT-PCR. RESULTS: The results demonstrate a high sensitivity (1 melanoma cell/mL blood) and specificity (no false-negatives and 7.4% [2 of 28] false-positives) of the assay and a satisfactory rate of interlaboratory reproducibility. The analysis of aliquots of blinded samples derived from 60 melanoma patients identified tyrosinase mRNA in 17 of 60 (28.3%): three (20%) of 15 stage I patients, two (13.3%) of 15 stage II patients, five (35.7%) of 14 stage III patients, and seven (43.8%) of 16 stage IV patients. The interlaboratory reproducibility of positive samples, however, was extremely low and indicates the presence of low amounts of target mRNA. CONCLUSION: Reverse transcriptase-PCR ELISA has a high sensitivity and specificity for the detection of tyrosinase mRNA in peripheral blood cells. The low interlaboratory reproducibility for the detection of tumor cells in blood samples of melanoma patients, however, raises the question of relevance of this assay for clinical use.

Adult↗

Dermatoscopy turns histopathologist's attention to the suspicious area in melanocytic lesions.

BACKGROUND: Histopathologically, the diagnosis of nevus-associated melanoma or melanoma close to a common nevus can be missed if the specimen is cut in a nonrepresentative area or if the section shows only the associated common nevus. OBJECTIVE: To find out whether dermatoscopy of suspicious areas within a nevus can improve the histological diagnosis of malignant melanocytic lesions of the skin. MATERIALS: The study was based on dermatoscopic images of more than 2000 benign and 115 malignant pigmented lesions and a collection of corresponding histopathologic slides. METHODS: The dermatoscopic images and the corresponding histopathologic diagnoses were compared. In case of differences, the histopathologic findings were reevaluated and compared with the dermatoscopic findings. RESULTS: Three cases were identified in which melanoma could have been histopathologically missed as a result of improper sectioning. After the dermatoscopic findings were evaluated, the specimens were reembedded and further sections were obtained. Finally, nevus-associated melanoma or melanoma close to a common nevus was diagnosed. CONCLUSIONS: Specific dermatoscopic patterns of malignancy can be found in highly suspicious areas, eg, broadened networks, radial streaming, pseudopods, or dots located at the periphery. The dermatoscopic-histopathologic correlation can improve the diagnosis of melanoma. Therefore, the clinician should point to the most suspicious area with a drawing or image, and the suspected diagnosis of melanoma and the history of the lesion should be also mentioned.

Abdomen↗

Dermoscopic classification of atypical melanocytic nevi (Clark nevi).

OBJECTIVES: To create a dermoscopic classification of atypical melanocytic nevi (Clark nevi) and to investigate whether individuals bear a predominant type. DESIGN: Digital dermoscopic images of Clark nevi were classified according to structural features, ie, reticular, globular, or homogeneous patterns or combinations of these types. The nevi were also characterized as central hypopigmented or hyperpigmented, eccentric peripheral hypopigmented or hyperpigmented, or multifocal hypopigmented or hyperpigmented. SETTING: Two pigmented skin lesion clinics. PATIENTS: We examined 829 Clark nevi on 23 individuals. MAIN OUTCOME MEASURE: A reliable dermoscopic classification of Clark nevi and frequency of different dermoscopic types. RESULTS: Using the dermoscopic classification, the 829 Clark nevi were classified as follows: 221 (26.7%) as reticular, 167 (20.1%) as reticular-homogeneous, 148 (17.9%) as globular-homogeneous, 112 (13.5%) as reticular-globular, 89 (10.7%) as homogeneous, 84 (10.1%) as globular, and 8 (1.0%) as unclassified. Most individuals were prone to a predominant type of Clark nevus. Seven individuals (30%) showed a single type of Clark nevus in more than 50% of their nevi and 5 (22%) in more than 40% of their nevi. CONCLUSIONS: The proposed dermoscopic classification of Clark nevi is easily applicable and allows a detailed characterization of the different dermoscopic types of Clark nevi. Knowledge of these dermoscopic types should reduce unnecessary surgery for benign melanocytic lesions. Exact classification of the different types of Clark nevi is a necessary prerequisite for further clinical, dermoscopic, and histopathologic studies, which will give new insights in the biology of acquired melanocytic nevi.

Adolescent↗

Detection of micrometastasis in sentinel lymph nodes of patients with primary cutaneous melanoma.

The technique of sentinel lymph node (SLN) biopsy has been demonstrated to be highly predictive for the detection of melanoma micrometastases in the regional lymph node basin. Therefore, the SLN was proposed to accurately reflect the lymph node status of patients with primary cutaneous melanoma. As the regional lymph node status is one of the most powerful predictors of survival in patients with primary melanoma, the histopathologic assessment is critically important for accurate staging. In approximately 20% (ranging from 9% to 42%) of patients with primary melanoma, the SLN was found to be tumor-positive by histopathology or immunohistochemistry. However, the true incidence of metastatic melanoma cells in (sentinel) lymph nodes is underestimated by histopathologic examination. Recently, the method of reverse transcription-polymerase chain reaction (RT-PCR) for tyrosinase mRNA has been used as a molecular marker for the presence of melanoma cells. Tyrosinase RT-PCR was demonstrated to significantly increase the detection of melanoma cells in SLNs as compared to histopathology. All lymph nodes positive by histopathology were shown to express tyrosinase by RT-PCR. Furthermore, tyrosinase transcripts were also detected in 36-52% of stage I and II melanoma patients with SLNs negative by histopathology. Importantly, the recurrence rate was significantly higher in patients with histologically negative SLNs who were found to be positive by RT-PCR than in patients with negative results by both techniques. These findings indicate that RT-PCR status of the SLN is more sensitive for detection of minimal melanoma disease than histopathology. Therefore, the RT-PCR status of the SLN may be suitable to improve melanoma staging and may serve as a prognostic factor in patients with primary cutaneous melanoma.

Biomarkers, Tumor↗

Polymerase chain reaction in the detection of circulating tumour cells in peripheral blood of melanoma patients.

Conflicting results were obtained by various research groups using the tyrosinase reverse transcription polymerase chain reaction (RT-PCR) for detecting melanoma cells circulating in peripheral blood. Whereas 100% positivity was initially reported for stage IV patients, more recent investigations reported positive detection rates between 30% and 50% in patients with disseminated melanoma. While the high detection rate initially reported in metastatic melanoma may be explained by contamination problems, methodological differences in different steps of the technical procedure of RT-PCR may account for the differences reported in more recent examinations. Major differences may result from the kind of blood preparation, the RNA isolation method, the kind of RT enzyme used, and the gene targeted by PCR primers. In our experience, blood purification by a Ficoll gradient increased melanoma cell detection rates compared to RNA extraction from total blood or after erythrocyte lysis. Amplification of MelanA in addition to tyrosinase resulted in a 30% enhanced sensitivity of melanoma cell detection compared to amplification to tyrosinase alone, whereas gp100/pMel17 and MUC18 gene products were already detected in blood from nonmelanoma patients. These findings are in agreement with those of other groups. Currently, an increase in the sensitivity for detection of circulating tumour cells to more than 50% of patients with disseminated melanoma seems to be unlikely. It is interesting that between 15% and 30% positive results and sometimes more have already been obtained from patients with primary melanoma. So far, there is no data for judging the prognostic significance of the detection of circulating tumour cells in patients without clinically recognisable metastases. Our limited experience shows that staging examinations in these patients reveal no proof of macrometastasis. Therefore, it is presently unclear whether these positive findings are associated with long-term prognosis or if they merely reflect false positive findings in this highly sensitive RT-PCR technique.

Biomarkers, Tumor↗

Dermcidin: a novel human antibiotic peptide secreted by sweat glands.

Antimicrobial peptides are an important component of the innate response in many species. Here we describe the isolation of the gene Dermcidin, which encodes an antimicrobial peptide that has a broad spectrum of activity and no homology to other known antimicrobial peptides. This protein was specifically and constitutively expressed in the sweat glands, secreted into the sweat and transported to the epidermal surface. In sweat, a proteolytically processed 47-amino acid peptide was generated that showed antimicrobial activity in response to a variety of pathogenic microorganisms. The activity of the peptide was maintained over a broad pH range and in high salt concentrations that resembled the conditions in human sweat. This indicated that sweat plays a role in the regulation of human skin flora through the presence of an antimicrobial peptide. This peptide may help limit infection by potential pathogens in the first few hours following bacterial colonization.

Amino Acid Sequence↗

Should adjuvant radiotherapy be recommended following resection of regional lymph node metastases of malignant melanomas?

BACKGROUND: Several authors have recommended adjuvant radiotherapy following resection of regional lymph node metastases in cutaneous malignant melanoma. There is, however, little evidence from controlled trials that patients benefit from this treatment. OBJECTIVES: To evaluate the usefulness of adjuvant radiotherapy following resection of lymph node metastases in cutaneous malignant melanoma. METHODS: We performed a retrospective study comparing 58 patients who underwent radiotherapy following resection of regional lymph node metastases with 58 controls from another centre who exclusively underwent regional lymphadenectomy. Patients and their controls were matched with respect to the number of tumour-bearing lymph nodes (1 vs. > 1) and to gender, although the proportion of thick tumours was greater in the irradiation group. RESULTS: The overall survival curves were almost identical in the two groups. There were nine disease recurrences in the study group and 12 in the control group (not significant). Regional recurrences in the irradiated patients were usually accompanied by metastases at other sites. CONCLUSIONS: The present study does not support the recommendation of adjuvant radiotherapy following resection of regional lymph node metastases in patients with malignant melanoma.

Disease-Free Survival↗

Intralesional rituximab for cutaneous B-cell lymphoma.

Rituximab, a chimeric anti-CD20 monoclonal antibody, has been approved for systemic treatment of relapsed or refractory CD20-positive B-cell non-Hodgkin's lymphoma. As cutaneous B-cell lymphoma (CBCL) also expresses the CD20 molecule, three patients with histologically and immunohistochemically confirmed CBCL without systemic involvement were treated with low-dose intralesional rituximab in a pilot study. Single doses applied ranged from 10 to 30 mg per lesion, according to lesion extent, with a cumulative dose of up to 350 mg. Injections were given two or three times weekly for 3-5 weeks, with a second cycle after 6 weeks in one patient with incomplete remission. Complete and lasting remission was achieved in each patient; this has persisted for up to more than 1 year. The observed adverse events were of grade 1 severity. Results suggest that intralesional rituximab may be a safe and effective new therapy modality for CBCL.

Adult↗