[Investigation of malignant melanoma. The Danish Melanoma Group].
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Denmark↗
Biomedical subjects
K T Drzewiecki
Publications and source records attributed to K T Drzewiecki.
[Risks for the recipients of donated blood or donated organs].
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Blood Donors↗
[Primary breast reconstruction in connection with mastectomy for breast cancer. Indication, procedure and immediate surgical results].
Mastectomy and immediate reconstruction of 122 breasts were performed in 109 patients in close collaboration between plastic surgeons and general surgeons. In 56 patients reconstruction was performed using tissue expanders including 13 bilateral operations, 29 patients had a latissimus dorsi myocutaneous flap and 24 a free transverse rectus abdominis myocutaneous flap. There were 27 postoperative local complications in 122 reconstructions (22%), in five the reconstruction was lost. Only patients clinically in stage I were considered for reconstruction. After histopathological staging 27 patients received systemic treatment and 10 local radiotherapy as well. There was no complication during systemic therapy related to reconstruction. In 10 cases local radiotherapy was performed in full, with a delay of four weeks in one patient and a need for correction of the radiation field during treatment in one patient.
Adult↗
Tumor infiltrating lymphocytes in melanoma comprise high numbers of T-cell clonotypes that are lost during in vitro culture.
Melanoma is generally accepted as being an antigenic tumor capable of eliciting T-cell responses that, however, in most cases are inadequate to control tumor growth. Tumor-infiltrating lymphocytes (TIL) in melanoma lesions comprise clonotypic T cells, indicating the in situ recognition of melanoma-associated peptide epitopes. Cultured TIL have been studied in order to unveil characteristics of TIL and the interactions of TIL and melanoma cells. Whether in vitro cultured TIL mirrors the in situ situation has, however, been questioned. In the present study we have taken advantage of T-cell receptor clonotype mapping methodology to conduct a full and detailed analysis of the T-cell clonotypes in melanoma lesions and in corresponding lines of TIL established in vitro. All melanoma lesions and the corresponding TIL cultures comprised high numbers of T-cell clonotypes, typically in the range of 40 to more than 60. The subsequent comparison of T-cell clonotypes present in the original lesions and in the corresponding T-cell lines established in vitro demonstrated that a very limited number of the T-cell clonotypes established in vitro are identical to the T-cell clonotypes expanded in situ. These results demonstrate that in situ T-cell clonotypes in melanoma are not readily expanded in vitro and that the majority of T-cell clonotypes present in cultured TIL are not present in situ.
Cell Count↗
Use of fluorine-18 fluorodeoxyglucose positron emission tomography in the detection of silent metastases from malignant melanoma.
Correct staging is crucial for the management and prognosis of patients with malignant melanoma. The aim of this prospective study was to compare staging by whole-body positron emission tomography using fluorine-18 fluorodeoxyglucose (18F-FDG) with staging by conventional methods. Thirty-eight patients with malignant melanoma of clinical stage II (local recurrence, in-transit and regional lymph node metastases) or III (metastases to other sites than in stage II) were included in the study. The results of the PET scans were compared with those obtained by clinical examination, computed tomography, ultrasound, radiography, and liver function tests and histology or clinical follow-up. With 18F-FDG PET we found for all foci a sensitivity of 97% and a specificity of 56%, compared with 62% and 22%, respectively, when using routine methods. For intra-abdominal foci, the sensitivity and specificity were 100% for both 18F-FDG PET and routine methods. Corresponding figures for pulmonary/intrathoracic foci were 100% and 33%, respectively. Of the patients included in this study, 34% would not have been staged correctly by conventional methods alone. We conclude from this study that 18F-FDG PET is a sensitive method superior to conventional methods for detecting widespread metastases from malignant melanoma. Mutilating surgery of no benefit can thereby be avoided. 18F-FDG PET is useful as a supplement to clinical examination in melanoma staging.
Female↗
Naevi as a risk factor for basal cell carcinoma in Caucasians: a Danish case-control study.
The number of melanocytic naevi in Caucasians is related to previous exposure to the sun and is a well-documented major risk factor for cutaneous malignant melanoma. Basal cell carcinoma, which is the most common form of skin cancer, has also been shown to be related to exposure to the sun. To investigate whether the number of common naevi is a risk factor for basal cell carcinoma in Caucasians we performed whole-body counting of naevi > or =2 mm in a Danish case-control study with 145 cases of primary basal cell carcinoma and 119 controls matched on age, gender and place of residence. Naevi were recorded according to size and body region and the skin phototype was assessed. There was no correlation between self-reported skin type and the number of naevi. Females with basal cell carcinoma had more naevi than did female controls (median number of naevi: 65 and 32, respectively) while males with basal cell carcinoma did not differ from male controls (median number of naevi: 48 and 43, respectively). Female cases had more small size naevi (2 mm), intermediate size naevi (3-4 mm) and large size naevi (> or =5 mm) than did female controls. Females with basal cell carcinoma had a substantially higher number of naevi on the arms and the legs than did female controls, but also had more naevi on the trunk. For females, the risk for basal cell carcinoma increased with increasing number of naevi. Naevi were not a risk factor for basal cell carcinoma in males.
Adult↗
Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study.
To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell carcinoma and 174 matched controls, and 168 cases with cutaneous malignant melanoma and 176 matched controls. Controls were matched on age, gender and place of residence. Subjects indicated their hair colour before 7 years of age, and at 25 years of age and their skin phototype. Interviewers assessed the present hair colour and eye colour, and the constitutive skin pigmentation was measured objectively by skin reflectance of UV unexposed buttock skin. There were no differences between basal cell carcinoma cases and controls in hair colour or eye colour or constitutive skin pigmentation, but more cases were of skin type II than skin type IV; skin type 11 was a risk factor for basal cell carcinoma with an odds ratio (OR) of 2.3. For cutaneous malignant melanoma, more cases than controls were red-haired or blond and of skin type II, but there was no difference in constitutive skin pigmentation. Hair colour and skin type were found to be independent risk factors for cutaneous malignant melanoma; red hair vs. black/brown: OR >9.7, blond hair vs. brown/black: OR = 2.4, and skin type 11 vs. type IV: OR=2.0. There were no gender-related differences in risk factors for basal cell carcinoma and cutaneous malignant melanoma.
Adult↗
The measurement of constitutive and facultative skin pigmentation and estimation of sun exposure in Caucasians with basal cell carcinoma and cutaneous malignant melanoma.
In two identical and simultaneously performed case-control studies of basal cell carcinoma (BCC) and cutaneous malignant melanoma (CMM) with age-matched, sex-matched and residence-matched controls, skin pigmentation was measured objectively by skin reflectance spectroscopy in 145 BCC patients and 174 matched controls and in 168 CMM patients and 176 matched controls. Measurements were performed at the forehead, the upper chest, the upper back, the lateral and medial aspects of the upper arm, and the buttocks. Self-estimation of sun exposure in childhood, in youth and in adulthood was performed by all subjects. There were no statistically significant differences in constitutive skin pigmentation at the buttocks between BCC patients and controls (P = 0.96) or between CMM patients and controls (P = 0.13). Facultative skin pigmentation in ultraviolet-exposed sites was not significantly different between BCC patients and controls except that women patients had higher pigmentation at the lateral side of the upper arm. For CMM, men patients had higher pigmentation at the lateral side of the upper arm. Self-estimations of sun exposure did not show differences between patients and controls but indicated high exposure levels in childhood and youth and in adult leisure time. Sun exposure estimated by increase in facultative pigmentation above the constitutive level (the Sun Exposure Index) was not significantly different between BCC patients and controls, whereas CMM men patients had higher estimates for the lateral side of the upper arm, the chest and the back.
Adolescent↗
Prognosis of thin cutaneous head and neck melanoma (<1mm).
Thin malignant melanomas, i.e. tumours less than 1 mm, are generally considered to have a good prognosis. The records of 148 patients with thin invasive melanomas located to the head and neck region were reviewed. All patients were followed for the excision of the primary tumour until death, or the closing date of this study (31 December 1989). Follow-up was median 9.6 years, (range: 3 months to 26.5 years). Increasing tumour thickness led to an increasing number of recurrences. However, there was no statistically significant difference in the length of recurrence-free survival or total survival between patients with tumours less than 0.76 mm and patients with tumours measuring between 0.76 mm and 0.99 mm (P>0.08). Tumours located in the scalp, neck and ears did relapse more often than tumours located to the face (P<0.03). No difference in prognosis was found in tumours that were excised with a free margin of <2.0 cm or of > or = 2.0 cm (P>0.29). Sixteen of the patients (11%) developed recurrences, 12 of these 16 patients (75%) died of disseminated melanoma. We conclude that thin head and neck melanomas do not necessarily carry an excellent prognosis. Prognosis is not dependent upon tumour thickness when less than 1.00 mm.
Adult↗
[Primary breast reconstruction after mastectomy for breast cancer].
Primary breast reconstruction in connection with mastectomy is a well-established procedure. The reconstruction may be carried out by the submuscular implantation of a prosthesis, in some cases preceded by tissue expansion. In situations where there is insufficient skin--or muscle-coverage, a musculocutaneous transposition flap may be used. The aim of breast reconstruction is to prevent the psychosocial sequelae of mastectomy. From experiences with secondary reconstruction, it seems that the reconstruction especially helps correct loss of feminine identity and negative body-image. Certain investigations indicate that primary reconstruction results in a clearly reduced postoperative psychological stress, whereas the extent of social and sexual sequelae seems not to vary when compared to results of secondary reconstruction. Conditions for adjuvant treatment as well as for follow-up concerning loco-regional tumour reappearance do not seem to be affected by the reconstruction. In studies published to date, consisting of relatively small patient groups and short observation periods, numbers without relapse and overall survival are found to be equivalent to that following mastectomy without reconstruction.
Breast Implants↗
Analysis of T cell receptor alpha beta variability in lymphocytes infiltrating melanoma primary tumours and metastatic lesions.
The T cell receptor (TCR) alpha beta variable (V) gene family usage of tumour-infiltrating lymphocytes (TIL) in four different primary human malignant melanomas and their corresponding metastatic lesions was characterized using a recently developed method based on the reverse-transcription-coupled polymerase chain reaction (RT-PCR). All patients were typed for HLA-A1 and -A2, either serologically or by a newly developed RT-PCR method. Two of these patients expressed HLA-A2, one the HLA-A1 haplotype and one further patient was heterozygous HLA-A1/-A2. The prognostic parameters for all four patients indicated that rapid progression of the disease was to be expected. However, only two of the patients showed rapid progression, while the remaining two patients are still alive after more than 3 years. In TIL in primary melanomas, a possible correlation was suggested between HLA-A2 and the preferential usage of the TCR V gene families V alpha 4, V alpha 5, V alpha 22 and V beta 8, whereas the V beta 3 gene family appeared to be expressed together with HLA-A1. Other highly expressed V gene families, apparently not restricted to either HLA-A1 or -A2, were V alpha 1 (expressed in three of four primary tumours) and V alpha 21 (expressed in two of four tumours). We found no evidence suggesting any correlations between the haplotypes HLA-A1 and -A2 and preferential V gene family expression in the metastatic lesions, and the only common feature was V alpha 8, which was found to be highly expressed in two out of three subcutaneous metastases. The V gene families, which were highly expressed in the primary tumour were generally not, or only very weakly, expressed in metastases and vice versa, possibly reflecting a change in the phenotype of the metastatic melanoma target cells. With regards to patient 0368, it was possible to obtain and study material from two subcutaneous metastases. The first metastasis was excised more than a year after the primary tumour, showing a completely different V region repertoire. The second metastasis was excised at surgery 2 years after primary surgery and likewise showed a dramatic shift in comparison to the first subcutaneous metastasis. Although the present study only included a small number of patients, it suggests that the estimation of V gene expression, if applied to a larger amount of patient material, might make it possible to substantiate further the suggested correlations between the T cell response against the tumour, HLA and antigen expression.(ABSTRACT TRUNCATED AT 400 WORDS)
Aged↗
[Significant prognostic factors for recurrence-free survival after surgical treatment of head-neck melanoma].
The clinico-pathological and therapeutic data of 512 patients with clinical stage I invasive head and neck melanoma of the skin were re-evaluated. There were 287 females and 225 males. The median age at primary surgery was 65 years, range 18 to 96 years. The median observation period was 5 years, range 1 month to 25 years. Sex, age, ulcerated tumor and tumor thickness were found by Cox multivariate regression analysis to act as independent prognostic factors for recurrence-free survival. In addition, size of the excision margin was found of no significance for survival without relapse when adjusting for the independent risk factors.
Adolescent↗
[Hyperthermic regional perfusion in malignant melanoma of an extremity].
Circulatory isolation of an upper or lower limb and perfusion of this with heated cytostatics is an established method of treating local recurrence and in-transit metastases from malignant melanoma. Not only recurrence-free survival but also total survival are increased compared with the results after surgical excision alone. Even when this method is employed in connection with excision of a primary tumour, there appear to be favourable effects as regards recurrence-free and total survival of patients in high risk groups (tumour thickness > 1.5 mm and/or Clark level IV-V). The actual treatment is well tolerated by the patients and complications in the form of oedema of the limb and wound infection are reversible. The frequency of amputation is low and, similarly, the mortality which is 0.6%. As the frequency of malignant melanoma is increasing and, as a great proportion of the melanomata are localized to the extremities, these patients should be offered hyperthermic regional perfusion on removal of the primary tumour and also if recurrence occurs.
Antineoplastic Agents↗
[Malignant melanoma of the skin in Denmark--epidemiology, diagnosis and treatment].
About 700 new cases of malignant melanoma of the skin are registered annually in Denmark. The incidence is increasing rapidly and the number of new cases increases by more than 5% per annum. The most important phenotypical risk factors are the number of acquired pigmented naevi and exposure to sunlight is the most important risk factor in the external environment so that severe sunburn in children and intermittent intense exposure to sunlight increase the risk of melanoma. The thickness of the tumour at the time of the diagnosis is the most important prognostic factor. The prognosis deteriorates with increasing thickness. Treatment is primarily surgical. In cases of inoperable local melanoma and regional recurrences, irradiation may be administered. Chemotherapy and/or immunotherapy are of experimental character. In the light of the rapidly increasing incidence, it is important that knowledge of risk factors for development of the disease and the clinical characteristics of early melanoma is spread to not only the medical profession but also to the general public.
Denmark↗
Skin melanoma of the head and neck. Prognostic factors and recurrence-free survival in 512 patients.
The clinicopathologic and therapeutic data of 512 patients, with clinical Stage I invasive head and neck melanoma of the skin were retrospectively evaluated. There were 287 females and 225 males. Median age at primary surgery was 65 years (range, 18 to 96 years). Median observation period was 5 years (range, 1 month to 25 years). Site of first recurrence was local in 7% (38 of 512), regional in 13% (67 of 512) and distant in 6% (31 of 512). Sex, age, ulcerated tumor, and tumor thickness were found to act as independent risk factors to recurrence-free survival by Cox multivariate regression analysis. In addition, size of excision margin was found to be of no significance to survival without relapse when adjusting for the independent risk factors.
Adult↗
The presence of dysplastic nevus remnants in malignant melanomas. A population-based study of 551 malignant melanomas.
We examined 512 malignant melanomas, representing all newly diagnosed cutaneous malignant melanomas, excluding lentigo maligna melanomas, from the period October 1, 1982 to March 31, 1985 occurring in the region of eastern Denmark in patients aged 20-79 years for the presence of dysplastic nevus remnants. Criteria for the diagnosis of a dysplastic nevus remnant include all the following changes (a) lentiginous or epithelioid melanocyte hyperplasia, (b) cytologic melanocyte atypia, (c) eosinophilic fibroplasia, (d) lamellar fibroplasia, and (e) lymphocytic infiltration in the dermis. Dysplastic nevus remnants were found in association with 34 (7%) of the evaluable 512 malignant melanomas. Fourteen (41%) of the remnants were of compound nevus type. In nine (27%) of the remnants, atypia was pronounced. Most (62%) dysplastic nevus remnants were contiguous to thin superficial spreading melanomas. We conclude from this population-based study that about 7% of malignant melanomas arise in prior dysplastic nevi.
Adult↗
Expression of intercellular adhesion molecule-1 (ICAM-1) in benign naevi and malignant melanomas.
Intercellular adhesion molecule-1 (ICAM-1) is a membrane-bound glycoprotein that is a ligand for lymphocyte function-associated antigen-1 (LFA-1) and is important for a number of cell adhesions in immune reactions. The molecule is expressed by several cell types (e.g. macrophages, endothelial cells, keratinocytes, melanoma cells and cell lines) and there are some indications that expression of this molecule in melanocytic lesions is confined to malignant tumours and is more pronounced in metastatic and advanced tumours than in earlier lesions. In an attempt to elucidate this issue, we have studied biopsy samples from benign naevi (n = 7) and malignant melanomas (n = 33) regarding reactivity with monoclonal anti-ICAM-1 (CD54). The results indicate that the great majority of malignant melanomas are ICAM-1-positive. The most abundant staining is seen in metastatic melanomas. In primary melanomas, staining is more variable and generally weaker. However, no correlation was found between the degree of ICAM-1 labelling and the degree of tumour invasion. Furthermore, ICAM-1 expression was not confined to malignant lesions, but was also seen in benign naevi. These data contrast with earlier reports and indicate that ICAM-1 expression is unlikely to be of major prognostic or diagnostic value in melanocytic tumours.
Antigens, CD↗
[European organization for research and treatment of cancer. Melanoma Cooperative Group meeting, Copenhagen, 26-28, April 1990].
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Denmark↗