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Biomedical subjects

A Hauschild

Publications and source records attributed to A Hauschild.

At least 19 recordsLinked to original sources
PubMed2002

[Temozolomide as therapeutic option for patients with metastatic melanoma and poor prognosis].

BACKGROUND AND OBJECTIVE: Stage IV melanoma patients with a very advanced disease are usually excluded from clinical trials. We treated 25 stage IV patients with temozolomide - a cytostatic drug with 100% oral bioavailability and considerable penetration of CNS tissue. PATIENTS/METHODS: 25 patients (17 female, 8 male) between 24 and 82 years (mean: 55.5 years) were included in this retrospective study. 19 patients had received at least one and up to four previous chemotherapy regimens during the course of stage IV disease. 11 (44%) patients showed cerebral metastases prior to therapy with temozolomide. 200 mg/m2 temozolomide were given orally at home on day 1 to 5 in week 1 and in week 5, respectively. RESULTS: Out of 23 evaluable patients 2 (8.7%) showed a partial remission, 2 (8,7%) a minor response, 6 (26.1%) had stable disease, 1 (4,3%) a mixed response, and 12 (52.1%) patients experienced disease progression. Sites of remission included brain, lung, liver, lymph nodes and muscle. Two patients interrupted therapy due to severe leuko- and thrombocytopenia (WHO grade 3 and 4). All other patients tolerated treatment with temozolomide well and no dose reduction was necessary. The median overall survival was 7 months (2-28+ months) since beginning of therapy and 15 months (4-63+ months) since onset of stage IV disease. CONCLUSION: Temozolomide represents a safe treatment option in patients with metastatic melanoma and poor prognosis.

Administration, Oral↗
PubMed2002

[Lipoma of the lip. A rare differential diagnosis].

We report on a 49 year-old female patient with a cherry-sized tumor of the lower lip, which over several years had steadily increased in size. The patient was psychologically affected by the appearance of the tumor and had difficulties to eat. We excised the tumor in local anaesthesia. Histology confirmed the clinical suspicion of lipoma. A total of four lipomas at this location have been reported world-wide.

Diagnosis, Differential↗
PubMed2002

Complete remission of a radio-resistant cutaneous angiosarcoma of the scalp by systemic treatment with liposomal doxorubicin.

We report an 80-year-old man suffering from an angiosarcoma of the scalp. Because of the wide extent of the lesions, surgery was not performed. Instead, the patient was treated with electron-beam radiation. Later, the patient failed to benefit from radiotherapy demonstrated by a local relapse and new malignant lesions. Additionally, a cervical lymph node metastasis appeared for the first time. Subsequently, we successfully administered liposomal doxorubicin (Caelyx(R)). Shortly after administration of two cycles the scalp angiosarcoma showed a clear regression. Following six cycles, the patient clinically showed a complete remission of all skin lesions and the cervical lymph node; metastasis was confirmed by histology and fine needle aspiration, respectively. Liposomal and pegylated doxorubicin, a cytostatic drug belonging to the anthracyclines, has already shown to be effective and mostly well tolerated in the therapy of acquired immune deficiency syndrome-related Kaposi's sarcoma and very recently in cutaneous T-cell lymphoma, too. Caelyx(R) appears to be a promising alternative to conventional treatment of cutaneous angiosarcoma.

Aged↗
PubMed2002

Clinical evaluation of 5-S-cysteinyldopa testing using a new and optimized detection system as a tumour marker for malignant melanoma.

5-S-cysteinyldopa (5-S-CD) has been described as a tumour marker for the detection of human metastatic melanoma. We investigated the clinical utility of a new and optimized method to detect 5-S-CD by analysing 207 plasma samples derived from 138 patients with clinical stage I/II ( = 60), III ( = 32) or IV ( = 46) melanoma. Control groups consisted of 27 patients with non-melanoma skin diseases and 30 healthy volunteers. 5-S-CD plasma levels were determined using a new analytical technique based on a fully automated solid phase extraction coupled online to a novel high performance liquid chromatography method. In all the samples from the healthy control subjects 5-S-CD plasma concentrations were below 2.0 microg/l. Increased 5-S-CD-levels (>/=2.0 microg/l) were found in 52%, 67% and 81% of the plasma samples from patients with stages I/II, III and IV malignant melanoma, respectively. The mean values of 5-S-CD were found to rise with increasing tumour stage. Among 27 samples from patients with non-melanoma skin disease, slightly elevated 5-S-CD levels between 2.3 and 2.6 microg/l were found in only four samples from patients with multiple dysplastic naevi. In conclusion, our improved analytical technique provides a high sensitivity in all stages of the disease and represents a useful technique for monitoring melanoma patients.

Biomarkers, Tumor↗
PubMed2001

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↗
PubMed2001

Quantification of melanoma-associated molecules in plasma/serum of melanoma patients.

Tumor markers for metastatic melanoma have, so far, been infrequently used. Although there is good evidence from several studies that protein S-100B serum measurement could serve as a valid marker for micro- and/or macrometastasis, the S-100B-LIAmat test has not been established as part of national and international recommendations for the care of melanoma patients. Future studies should focus on early detection of metastatic disease with S-100B compared to routine clinical, laboratory and technical evaluations. Furthermore, preliminary, interesting results on the predictive value of S-100B for the monitoring of metastatic patients during treatment should be verified in multicenter trials. The same considerations are true for melanoma-inhibitory activity (MIA), a new and interesting tool for the detection of metastatic melanoma. However, available data on the clinical use of on the MIA-ELISA are too limited to speculate on an even higher sensitivity and specificity than reported for S-100B. Melanin metabolites are candidates for valid melanoma markers, too. Quantification of 5-S-cysteinyldopa from blood or urine of melanoma patients has not been transferred from the laboratory to daily routine due to several technical problems in the assessment of this particular molecule. Cytokines, adhesion molecules and metalloproteinases are shed from melanoma cells into the serum, but these cells are not the only source of elevated serum levels. Several inflammatory conditions are responsible for high serum concentrations of these molecules. In general, they are not sensitive and specific enough to serve as "melanoma markers."

Biomarkers, Tumor↗
PubMed2001

[Safety margins in the excision of primary malignant melanoma. Proposals based on controlled clinical trials].

Excisional biopsy is recommended as the procedure of choice whenever there is suspicion of malignant melanoma. Incisional biopsies are only rarely indicated. For nearly seventy years the debate about the optimum resection safety margin around the primary tumor was influenced by historical case reports and paradigms. Recently, controlled clinical studies have provided new insights. Accumulating evidence over the last two decades shows that narrower surgical margins influence neither the rate of satellites or in-transit-metastases nor the occurrence of advanced metastatic disease. Local recurrence is rare (approx. 0.1%) when primary tumors are thin and is seen more often (approx. 10%) in primary tumors of greater thickness (> 4 mm). Analysis of the overall survival in randomized trials shows equal prognosis for malignant melanoma for narrow and wide resection margins. Due to these findings in-toto excisional biopsy for in-situ melanoma, a resection margin of 1 cm for thin primary tumors (< 1 cm tumor thickness) and a resection margin of 1 to 2 cm for primary tumors greater than 1 mm appears sufficient. With these recommendations, primary closure of wounds will be possible in nearly all cases, reducing surgical costs and morbidity. This article should serve as a basis of discussion for the proposed revision of the current guidelines of the German Dermatologic Society (DDG) on the primary surgical care of melanoma patients.

Biopsy↗
PubMed2001

Sentinel node biopsy in melanoma.

There has, for a long time, been an ongoing discussion on whether the prophylactic removal of lymph nodes ("elective lymph node dissection") is of benefit for melanoma patients. More recently, "selective" lymphadenectomy ("sentinel node biopsy", SNB) has been proposed to evaluate the status of the first draining lymph node ("sentinel node") of the regional basin. Several studies now demonstrate that the sentinel node evaluation for underlying metastatic disease reflects the status of the entire lymph node region and is therefore a useful prognostic factor. A multi-institutional study highlighted SNB status as the most significant prognostic factor, superior to measurement of tumor thickness in primary melanoma. Different techniques to detect micrometastasis within the lymph node are under current evaluation. Histology and immunohistology using antibodies against melanoma-associated antigens are routinely performed in SNs. The clinical value of reverse-transcriptase polymerase chain reaction (RT-PCR)based search for minimal melanoma disease in lymph nodes remains unclear.

Antigens, Neoplasm↗
PubMed2000

Telomerase activity in melanocytic lesions: A potential marker of tumor biology.

Telomerase activation, being a cardinal requirement for immortalization, is a crucial step in the development of malignancy. With a view toward diagnostic and biological aspects in melanocytic neoplasia, we investigated the relative levels of telomerase activity in 72 nevi and 16 malignant melanomas by means of a modified telomeric repeat amplification protocol (TRAP) assay, including an internal amplification standard. We further compared telomerase activity with the expression of two different proliferation-specific proteins, Ki-67 and repp86, a protein expressed exclusively in the cell cycle phases S, G2, and M. Telomerase activity was associated with the overall growth fraction (Ki-67) but showed a closer correlation with the expression of repp86. Both telomerase activity and proliferation indices discriminated clearly between malignant melanomas and nevi, but not between common and dysplastic nevi. Nonetheless, a portion of nevi exhibited markedly elevated telomerase activity levels without proportionally increased proliferation. This was independent of discernible morphological changes. Clinicopathological correlations showed an association between high telomerase activity and early metastatic spread in melanomas, linking telomerase to tumor biology. Our results provide arguments in favor of an occasional progression from nevi to melanomas and imply that proliferation measurements in combination with telomerase assays may help to elicit early malignant transformation that is undetectable by conventional morphology.

Adolescent↗
PubMed2000

[Surgical and adjuvant drug therapy in head and neck cutaneous melanoma].

The rapid incidence rise of cutaneous melanoma resulted in an increasing interest in this particular tumor. During the last years public prevention campaigns enlarged the awareness of melanoma, subsequently as a direct effect the mean tumor thickness of melanoma, the most predictable prognostic factor, decreased. Moreover, the biology of melanoma initiation and metastasis has been studied extensively with special interest in molecular biology. Controlled clinical studies answered several critical questions in respect to the standard care of surgery in melanoma. Yet, the guidelines for the surgical treatment of head and neck melanoma are in accordance to that of other localisations with reduced safety margins around the primary tumor. Elective (prophylactic) lymph node dissection (ELND) of regional lymph nodes is no more considered as a standard tool. Moreover, ELND has been given up by most melanoma centers, since it is known that prospective-randomized trials were not able to demonstrate an increase of overall survival for patients with ELND compared with untreated patients. Instead of this potentially aggressive treatment modality the examination of the first draining regional lymph node, sentinel node biopsy (SNB), has been introduced some years ago. Recently, a large clinical trial demonstrated that the SNB status reflects the most valuable prognostic factor for primary melanoma known so far. First studies in head and neck melanoma figured out that this technique is more complex in this special localisation, but produced comparable results. Systemic adjuvant (prophylactic) therapy of high-risk melanoma should preferentially be applied within controlled clinical trials. Most attractive candidates for an effective treatment are interferons. Several studies ruled out that interferon alpha-treated melanoma patients demonstrate an extended disease-free survival. Adjuvant chemotherapy has not shown a clinically relevant benefit. Thus, patients should preferentially be treated within controlled clinical trials.

Antineoplastic Agents↗