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Biomedical subjects

A Hauschild

Publications and source records attributed to A Hauschild.

At least 19 recordsLinked to original sources

[Amelanotic malignant melanoma of the scalp clinically resembling a proliferating trichilemmal cyst].

HISTORY AND FINDINGS: A 37-year-old woman was admitted with an ulcerated tumor of the scalp together with an enlarged cervical lymph node. The clinical features resembled proliferative trichilemmal cyst. INVESTIGATIONS: Fine needle aspiration of the lymph node revealed an amelanotic metastasis of a malignant melanoma. TREATMENT AND COURSE: The entire tumor was removed and a radical neck-dissection performed. Histopathological examination confirmed the diagnosis of metastatic malignant melanoma. CONCLUSION: Proliferative trichilemmal cysts and malignant melanoma of the scalp are rare, but should be considered as differential diagnoses of neoplasm in this part of the body.

Adult↗

[Randomised phase III trial of fotemustine versus fotemustine plus whole brain irradiation in cerebral metastases of melanoma].

PURPOSE: The main objective of this prospective multicenter randomised phase III study was to compare a combined regimen of fotemustine plus whole brain irradiation versus fotemustine alone in terms of cerebral response and time to cerebral progression in patients with melanoma brain metastases. PATIENTS AND METHODS: Seventy-six patients (instead of the 106 planned patients; study was stopped after the interim analysis) were randomised receiving either fotemustine (arm A, n = 39) or fotemustine and whole brain irradiation (arm B, n = 37). Fotemustine was administered intravenously at 100 mg m(-2) on day 1, 8 and 15, followed by a 5-week rest period, then every 3 weeks in non-progressive patients. In arm B, a concomitant whole brain irradiation was performed at the total dose of 37.5 Gy (2.5 Gy/d(-1), days 1-5, 3 consecutive weeks). RESULTS: Although patients who received fotemustine alone had worse prognostic factors, there was no significant difference in brain response (arm A: 7.4%, B: 10.0%) or control rates (objective response plus stable disease) after seven weeks (arm A: 30%, B: 47%) and overall survival (arm A: 86d, B: 105d). However, there was a significant difference in favour of arm B for the time to brain progression (p = 0.028, Wilcoxon test). CONCLUSION: Fotemustine plus whole brain irradiation delayed the time to brain progression of melanoma cerebral metastases compared to fotemustine alone but without a significant improvement in terms of objective control or overall survival.

Adult↗

The sebaceous nevus as part of the Schimmelpenning-Feuerstein-Mims Syndrome--an obvious phacomatosis first documented in 1927.

The sebaceous nevus is a common nevus and can be easily diagnosed because of its typical rough fatty surface due to its amount of sebaceous glands. In some rare cases, the sebaceous nevus is part of a genetic disorder, the Schimmelpenning-Feuerstein-Mims (SFM) syndrome. If the SFM syndrome is suspected, further investigation is necessary, because multiple organ involvement is highly likely. We suggest that diagnosis of the SFM syndrome is simple, considering the special linear arrangement of sebaceous nevi in cases of SFM syndrome.

Child↗

Remarkable remission of a follicular lymphoma treated with rituximab and polychemotherapy (CHOP).

We describe a 50-year-old female patient who developed extensive lymphomatous infiltrates on her forehead, scalp and face within a few months. Histology and immunohistochemistry of skin tumours revealed a CD20 positive follicular B-cell lymphoma. Subsequently, extracutaneous manifestations were detected by computed tomography scans and bone marrow biopsy. The patient suffered from a primary nodular malignant lymphoma with extraordinary cutaneous infiltration of the head. Therefore, combination treatment with a monoclonal antibody against the CD20 antigen, rituximab, and polychemotherapy (CHOP scheme) was administered every 3 weeks. After the second course of treatment a complete regression of cutaneous infiltrates was noticed. Follow-up biopsies on the forehead showed no evidence of CD20 positive lymphoma cells, now. Despite mild leucocytopaenia therapy was well tolerated.

Antibodies, Monoclonal↗

A prospective randomized multicentre phase III trial of fotemustine plus whole brain irradiation versus fotemustine alone in cerebral metastases of malignant melanoma.

The main objective of this prospective multicentre randomized phase III study was to compare a combined regimen of fotemustine plus whole brain irradiation with fotemustine alone in terms of cerebral response and time to cerebral progression in patients with melanoma cerebral metastases. Seventy-six patients were randomized to receive either fotemustine (arm A, n = 39) or fotemustine plus whole brain irradiation (arm B, n = 37). Fotemustine was administered intravenously at 100 mg/m(2) on days 1, 8 and 15, followed by a 5 week rest period, then every 3 weeks in non-progressive patients. In arm B, concomitant whole brain irradiation was performed at a total dose of 37.5 Gy (2.5 Gy/day on days 1-5 for three consecutive weeks). Although patients who received fotemustine alone had worse prognostic factors, there was no significant difference in cerebral response (arm A, 7.4%, arm B, 10.0%) or control rates (objective responses plus stable disease) after 7 weeks (arm A, 30%; arm B, 47%) or in overall survival (arm A, 86 days; arm B, 105 days). However, there was a significant difference in favour of arm B for the time to cerebral progression (P = 0.028, Wilcoxon test). In conclusion, fotemustine plus whole brain irradiation delayed the time to cerebral progression of melanoma cerebral metastases compared with fotemustine alone but without a significant improvement in terms of objective control or overall survival.

Adult↗

Surgical standards in the primary care of melanoma patients.

Excisional biopsy is recommended as the procedure of choice whenever there is suspicion of malignant melanoma. There are only few indications for incisional biopsies, which--in contrast to former opinions--do not worsen the prognosis. For nearly 70 years the debate about the optimal resection safety margin around the primary tumor was influenced by historical case reports and paradigms. Recently, controlled clinical studies provided new insights. Accumulating evidence over the past two decades showed that narrower surgical margins do not have any influence on the rate of advanced metastatic disease. Local recurrence is rare (approximately 0.1%) when primary tumors are thin and is seen more often (approximately 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 primary tumors with a tumor thickness up to 2 mm and a resection margin of 2 cm for primary tumors greater than 2 mm appears sufficient. By this procedure primary closure of wounds will be possible in nearly all cases, morbidity and costs of surgical approaches will be reduced. For a long time it has been discussed whether 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 superior to measurement of tumor thickness in primary melanoma. However, it is unclear whether sentinel node biopsy is of benefit for a better survival in affected patients.

Biopsy↗

Adjuvant therapy in melanoma.

Despite intensive research and numerous clinical trials on the adjuvant treatment of patients with high-risk cutaneous melanoma, the issue is still controversial. Early positive results from studies on adjuvant chemo- and immunotherapy were based on historical controls and could not be confirmed by prospective randomized trials. The effect of interleukin-2 in the adjuvant treatment of malignant melanoma is not yet clearly defined. Combined treatment modalities like bio-chemotherapy are still to be analyzed in controlled clinical trials, and results of new studies with active specific immunization (vaccination) will only be available within the next years. Only interferon alpha (IFN alpha) has shown reproducible superiority over observation for high-risk melanoma patients in large prospective randomized trials with respect to disease-free survival (DFS) and partially for overall survival (OS). These studies resulted in the approval of IFN alpha for the adjuvant treatment of malignant melanoma in many countries. Low-dose IFN has shown significant prolongation of DFS, but so far failed to improve OS. The question whether high-dose IFN has shown enough superiority over observation with respect to OS based on one negative and two positive trials to make it the standard therapy in stage IIb,c and stage III melanoma patients still remains unanswered. Results from intermediate-dose IFN alpha, pegylated IFN alpha, and modified high-dose interferon schedules are pending. In conclusion, interferon is the cornerstone of adjuvant therapy in high-risk melanoma today, but the optimal dosage and duration of treatment are still to be defined. Patients with high-risk malignant melanoma should preferentially be treated in prospective randomized multicenter trials to give more detailed data for treatment recommendations.

Antineoplastic Agents↗

[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↗

[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↗

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↗

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↗

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↗

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↗

[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↗

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↗