Case presentation - reconstruction of thumb defect with neurovascular cross-finger flap after electrical burns.

The advantages are underlined of the use of the neurovascular flap, as seen in a patient with injuries in all anatomical structures after electrical burns, with defect in the soft tissue together with tendon, vessel, and nerve injuries and necrosis of the distal phalanx of the thumb, with reference to the value of this technique in modern plastic and reconstructive surgery.

On the biological relevance of MHC class II and B7 expression by tumour cells in melanoma metastases.

A large number of studies have indicated that specific immune reactivity plays a crucial role in the control of malignant melanoma. In this context, expression of MHC I, MHC II and B7 molecules by melanoma cells is seen as relevant for the immune response against the tumour. For a better understanding of the biological relevance of MHC II and B7 expression by tumour cells in metastatic melanoma, we studied the expression of these molecules in melanoma metastases in relation to the inflammatory response, regression of the tumour and survival from 27 patients treated with biochemotherapy (30 mg m(-2) Cisplatin and 250 mg m(-2) decarbazine (dimethyl-triazene-imidazole-carboxamide, DTIC) on days 1-3 i.v., and 10(7) IU IFN-alpha 2b 3 days a week s.c., q. 28d). In 19 out of 27 lesions studied, we found expression of MHC II by the tumour cells, while only in one out of 11 tumour biopsies obtained from untreated metastatic melanoma patients, MHC II expression was detected. Expression of B7.1 and B7.2 by tumour cells was found in nine out of 24 and 19 out of 24 lesions, respectively. In all cases where B7.1 expression was found, expression of B7.2 by the tumour cells was also seen. In general, no or only few inflammatory cells positive for B7 were found. Expression of MHC II by tumour cells was positively correlated with the presence of tumour-infiltrating lymphocytes, regression of the lesion, and with time to progression (TTP) and overall survival (OS) of the patient. However, no significant correlation between B7.1 or B7.2 expression and regression of the tumour, TTP or OS was found. In light of other recent findings, these data altogether do support a role as biomarker for MHC II expression by tumour cells; however, its exact immunological pathomechanism(s) remain to be established.

Biochemotherapy of metastatic malignant melanoma. Predictive value of tumour-infiltrating lymphocytes.

The therapeutic efficacy of biochemotherapy in metastatic malignant melanoma still carries a low remission rate, but with some durable responses. It would therefore be of considerable importance if patients with a high probability of responding could be identified using predictive tests. The response to interferon-alpha (IFN-alpha) correlates with the occurrence of CD4(+) lymphocytes identified by fine-needle aspirates from melanoma metastases (Håkansson et al, 1996). The present investigation studies a possible correlation between tumour-infiltrating CD4(+) lymphocytes in malignant melanoma metastases and the therapeutic effect of biochemotherapy. A total of 25 patients with systemic and 16 with regional metastatic melanoma were analysed before initiation of biochemotherapy (cis-platinum 30 mg/m(2) d.1-3, DTIC 250 mg/m(2) d.1-3 i.v. and IFN-alpha 2 b 10 million IU s.c. 3 days a week, q. 28d.). A monoclonal antibody, anti-CD4, was used to identify tumour-infiltrating lymphocytes in fine-needle aspirates before start of treatment. The presence of these lymphocytes was correlated to response, time to progression and overall survival. A statistically significant correlation (P = 0.01) was found between the occurrence of CD4(+) lymphocytes and tumour regression during biochemotherapy in patients with systemic disease. Out of 14 patients with moderate to high numbers of infiltrating CD4(+) lymphocytes, 12 achieved tumour regression. In contrast, among patients with low numbers of these cells in metastatic lesions, 8 out of 11 had progressive disease. We also found a significantly longer time to progression (P < 0.003) and overall survival (P < 0.01) among patients with moderate to high numbers of these cells compared to patients with low numbers of these cells before initiation of biochemotherapy. Furthermore, in patients with regional disease, we found a significantly longer time to progression (P = 0.01) and a trend toward a longer overall survival time (P = 0.09). Based on these results and as previously shown with IFN-alpha therapy alone, there seems to be a need for CD4(+) lymphocytes infiltrating the tumours before the start of biochemotherapy to make the treatment successful. Determination of these cells in fine-needle aspirates seems to be a method to predict responders to biochemotherapy, thus increasing the cost-benefit of this treatment strategy considerably, both in terms of patient adverse reactions and health care costs.

Long term results of a randomized study by the Swedish Melanoma Study Group on 2-cm versus 5-cm resection margins for patients with cutaneous melanoma with a tumor thickness of 0.8-2.0 mm.

BACKGROUND: Large, prospective, randomized trials with long term follow-up are required to obtain an unbiased evaluation of the significance of resection margins in patients with cutaneous melanoma. METHODS: The Swedish Melanoma Study Group performed a prospective, randomized, multicenter study of patients with primary melanoma located on trunk or extremities and with a tumor thickness > 0.8 mm and 0.8 mm thick and

On down-regulation of the immune response to metastatic malignant melanoma.

Treatment of metastatic malignant melanoma with interferon alpha (IFNalpha) results in objective remission in approximately 15% of patients. In a previous investigation, we found that about 50% of the patients achieved at least minor or short-lived remissions. In some tumours extensive areas of regressive tumour change occurred. However, even in these areas remnants of tumour cells were generally found. The short duration of the immune response in some patients and the incomplete eradication of the tumour can be due either to selection of non-immunogenic tumour cells or to down-regulation of the immune reactivity to the tumour. In the present paper, the expression of the zeta chain of the T cell receptor in CD3+ lymphocytes and the expression of CD28 in CD3+, CD4+ and CD8+ lymphocytes was studied in resectable melanoma metastases from 20 treated (IFNalpha or IFNalpha in combination with cisplatinum and dacarbazine) and 16 untreated patients. A double-staining technique was used, and the occurrence and distribution of lymphocytes showing down-regulation of the zeta chain or CD28 were separately registered in different areas of the metastases: close to the tumour cells in areas of unaffected tumour growth, in areas with regressive tumour changes, in areas with marked fibrosis and in stromal areas with densely packed lymphocytes. CD3+ zeta lymphocytes were found in all metastases, but their number and distribution varied considerably. Down-regulation of the zeta chain was most often found in areas of regressive changes. In contrast, T lymphocytes infiltrating close to the tumour cells had a stronger expression of the zeta chain (P = 0.016). Down-regulation was also found in stromal areas of densely packed lymphocytes and in areas of fibrosis. The pattern of down-regulation of CD28 in various subsets of lymphocytes was similar to that of zeta chain. The same pattern of down-regulation of CD28 and the zeta chain was found in both untreated and treated patients, indicating that the down-regulation is not due to treatment but to the release of immunosuppressor factors from areas with high tumour cell density or extensive destruction of tumour cells. These results concur well with the view that IFNalpha treatment can result in immune-mediated tumour cell destruction early in the treatment period and that this immune response to the tumour can be followed by immunosuppression within a few weeks.

Expression of ICAM-1 during IFN-alpha-based treatment of metastatic malignant melanoma: relation to tumor-infiltrating mononuclear cells and regressive tumor changes.

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in cell to cell interactions. In malignant melanoma, ICAM-1 expression correlates with malignant behavior. We used monoclonal antibodies, anti-ICAM-1, anti-CD4+, anti-CD8+, and anti-CD11c+ to study the effect of interferon-alpha (IFN-alpha) on the expression of ICAM-1 by melanoma cells in regional metastases and its correlation to the occurrence of CD4+, CD8+, and CD11c+ cells close to tumor cells and in the tumor stroma. We also estimated the expression of ICAM-1 and regressive changes in malignant melanoma metastases, correlating the duration of treatment to these effects of IFN-alpha. Twenty-three IFN-alpha-treated and 10 untreated patients with regional metastatic malignant melanoma were studied. The duration of IFN-alpha treatment influenced the expression of ICAM-1. In metastases from patients treated for 1 week only, 1 of 5 showed high expression of ICAM-1 compared with 6 of 11 of those treated for 3 weeks (p = 0.01, chi-square test for trend comparing untreated patients and patients with various durations of IFN-alpha treatment). In IFN-alpha-treated patients with low expression of ICAM-1, none of 7 metastases showed CD4+ cells infiltrating close to tumor cells, in contrast to 6 of 10 metastases expressing high amounts of ICAM-1 (p = 0.03). Similarly, the expression of ICAM-1 was found to correlate with the occurrence of CD8+ cells close to the tumor cells (p = 0.04). We also showed a correlation between ICAM-1 expression and histologic evidence of tumor regression (p = 0.02).

Effect of IFN-alpha on tumor-infiltrating mononuclear cells and regressive changes in metastatic malignant melanoma.

Interferon-alpha (INF-alpha) has a documented activity against metastatic melanoma. To what extent an antiproliferative effect or tumor cell modulation or immunomodulation contributes to this antitumor effect is still uncertain. The role of immune mechanisms in the control of malignant melanoma is suggested by several studies. Therefore, this investigation used monoclonal antibodies, anti-CD4, anti-CD8, and anti-CD11c, to study the occurrence and distribution of tumor-infiltrating mononuclear cells in 10 untreated and 26 IFN-alpha-treated patients with regional metastatic malignant melanoma. IFN-alpha was given for 1-3 weeks before resection of the metastases. The infiltration of mononuclear cells in the stroma and close to tumor cells was studied. The duration of IFN-alpha treatment was found to be of importance for the immunomodulatory effect. In patients treated for < or = 1 week, tumor-infiltrating mononuclear cells were still mainly localized in the stroma, similar to the situation in untreated patients. The differences in CD4+ cells close to the tumor cells, comparing untreated patients and patients with various durations of IFN-alpha treatment, were highly significant (p = 0.009). Thus, IFN-alpha treatment resulted in recruitment of CD4+ cells close to the tumor cells. IFN-alpha had only a weak effect on the recruitment of CD8+ and CD11c+ mononuclear cells close to the tumor cells. Regressive changes in metastases were also analyzed and correlated to duration of treatment. Some of the criteria used for histopathologic regression in primary melanoma (distorted histologic architecture, low tumor cell density, and fibrosis) were applied to analyze the effect of IFN-alpha in metastatic melanoma. The tumor cell density was found to be significantly reduced in metastases with marked tumor regression compared with metastases with no, or only minor, regressive changes (p < 0.005). A chi-square analysis for trend, comparing untreated patients and patients with various durations of IFN-alpha treatment, showed that regressive changes of the tumor increased significantly during IFN-alpha treatment (p = 0.02).

Effect of interferon-alpha on the expression of tumour necrosis factor-alpha by metastatic malignant melanoma in vivo.

To our knowledge modulation of the expression of tumour necrosis factor-alpha (TNF-alpha) in malignant melanoma metastases in vivo has not been reported. The expression of TNF-alpha by malignant melanoma cells was studied immunohistochemically using an anti-TNF-alpha antibody. The specificity of the staining reaction was demonstrated by absorption of the TNF-alpha antibody with human recombinant TNF-alpha, which inhibited the staining reaction. The TNF-alpha expression was also verified by in situ hybridization for mRNA. Metastases from 37 patients were studied, 21 of whom were treated with IFN-alpha. All 16 metastases from untreated patients were positive for TNF-alpha. Based on the average staining intensity of the melanoma cells for TNF-alpha, the metastases were classified into two groups. The expression of TNF-alpha varied considerably between metastases from different patients and also within the same metastasis. Melanoma cells in areas with low cellularity and large numbers of infiltrating inflammatory cells were generally weakly stained. This is in good agreement with a low staining score for TNF-alpha in metastases showing marked histopathological regression. Seven out of 13 patients with a low staining score for TNF-alpha showed a marked regression of their tumours. In contrast one out of five patients with a high staining score for TNF-alpha showed a marked tumour regression, suggesting that tumour cells sensitive to immune-mediated regression express less TNF-alpha. Interferon-alpha (IFN-alpha) appears to modulate the expression of TNF-alpha. Significantly more patients treated with IFN-alpha had metastases with a low TNF-alpha staining score compared with untreated patients. Thus, seven out of 21 patients treated with IFN-alpha showed a high expression of TNF-alpha in contrast to 13 out of 16 in the untreated group (P = 0.01).

The mini bottle brush--a new fastening device in cancellous bone.

A new design for bone implants, the bottle brush, was recently presented in a pilot study on marrow cavities in the femur of rabbits. In this study, the concept is further evaluated on a mini bottle brush. The fixture, 5 x 7 mm, with an implant shaft made of CP-titanium and bristles of nylon coated with sputtered titanium, was inserted into the cancellous bone of the medial femoral condyle in 15 adult rabbits. The titanium fixture was compared with a similar brush without the titanium sputtered surface. The animals were sacrificed after 4 months and the quantity and quality of bone integration were evaluated with pull-out tests and histological examination. In both parameters, the values were significantly higher for the titanium-sputtered brushes, with removal forces similar to titanium cylinders of the same size and with a bone-to-metal contact area of about 50%.

Psoralens used for cosmetic sun tanning: an unusual cause of extensive burn injury.

Psoralen combined with long-wave ultraviolt radiation (UV-A) has become a standard method of psoriasis treatment. A well-known and often appreciated 'side-effect' is the hyperpigmentation caused by this treatment. Three patients demonstrating a novel cause of severe skin loss, 'psoralen burn', are presented. No patient was afflicted by psoriasis and all three had used psoralen and ultraviolet exposure with the intent to enhance sun tanning. In the case histories presented, it is notable that two of the patients share an alarmingly extensive skin injury (90-95 per cent body surface area), while the third had an extensive but rather superficial injury. In addition, a very similar time-table for the development of the injury could be observed, with a maximum distribution of skin loss not reached until 7 or 8 days after exposure. Psorelen-UV-A can cause life-threatening skin losses when used in an erratic manner. Early recognition of the nature and knowledge of the time-course in the development of these lesions is necessary for optimal treatment. Some principles of treatment are discussed. Dermatologists prescribing PUVA treatment should further increase their warnings of uncontrolled use of psoralens in non-psoriatrics.

Tumour-infiltrating lymphocytes in metastatic malignant melanoma and response to interferon alpha treatment.

Interferon alpha (IFN-alpha) has a documented activity against malignant melanoma with a response rate of only approximately 20%. It would therefore be of considerable importance if patients likely to respond could be identified. The degree of mononuclear cell infiltration in primary tumours has been reported to correlate with a favourable prognosis. This investigation used monoclonal antibodies, anti-CD4, -CD8 and -CD11c, to identify subsets of tumour-infiltrating mononuclear cells in fine needle aspirates to study whether the presence of such cells correlates with the therapeutic effect of IFN-alpha. Twenty-one patients with systemic and 20 with regional metastatic malignant melanoma were studied before initiation of IFN-alpha treatment. A statistically significant correlation (P < 0.001) was found between the occurrence of CD4+ lymphocytes in fine needle aspirates and the therapeutic benefit of IFN-alpha in patients with systemic disease. Ten out of 11 with moderate to high numbers of infiltrating CD4+ lymphocytes achieved tumour regression. In contrast, among patients with low numbers of these cells in metastatic lesions, nine out of ten had progressive disease. Similar results were found in patients with regional disease.

Resection margins of 2 versus 5 cm for cutaneous malignant melanoma with a tumor thickness of 0.8 to 2.0 mm: randomized study by the Swedish Melanoma Study Group.

BACKGROUND: The traditional surgical treatment for primary malignant melanoma has often been a wide excision with a margin of about 5 cm. Since the risk of local recurrences is dependent on tumor thickness, thin tumors (<1 mm) have routinely been excised with a narrow margin. For thick tumors, the optimal resection margin is controversial, and can be determined only by prospective, randomized trials. METHODS: The Swedish Melanoma Study Group performed a prospective, randomized multicenter study to evaluate an excision margin of 2 versus 5 cm for patients with cutaneous malignant melanoma with tumor thickness > 0.8 and < or = 2.0 mm. The trial includes 769 patients. Patients with melanomas of the skin of the head, neck, hands, feet, or vulva were not included in the trial. In the event of an excision biopsy for diagnosis, radical surgery was completed within 6 weeks. The median follow-up time was 5.8 years for estimation of survival and 4.0 years for diagnosis of recurrent disease. RESULTS: No significant differences have been observed between the treatment groups regarding local or regional recurrences or survival. CONCLUSIONS: We recommend an excision with a margin of 2 cm for cutaneous malignant melanoma with a tumor thickness > 0.8 and < or = 2.0 mm.

Reduction mammoplasty: comparison of results of plastic and general surgeons.

OBJECTIVE: To compare the results in patients who had reduction mammoplasty in a department of plastic surgery with those of patients who had the same operation in a department of general surgery. DESIGN: Retrospective study of casenotes, and questionnaire. SETTING: Department of Plastic Surgery, University Hospital, Linköping, and Department of General Surgery, County Hospital, Motala. SUBJECTS: All 250 patients who had undergone reduction mammoplasty during the five year period 1980-84 (Linköping, n = 173; Motala, n = 77). MAIN OUTCOME MEASURES: Correlation between symptoms and expectations, and the patients' subjective assessment of the results. RESULTS: There was no difference between the rates of response to the questionnaire (149/173, 86%, from those operated on in the department of plastic surgery compared with 68/77, 88%, in the department of general surgery). Median stay in hospital was 6 days in both groups, and the number of days of sick leave was 29 and 33 days, respectively. The most common histological diagnosis was hyperplastic breast tissue with or without fibroadenosis (149/173, 86%, compared with 64/77, 83%) and there was one carcinoma, which was detected before operation. The main reason for the operation in both groups was the weight of the breasts, which caused shoulder or back pain; in nearly half this interfered with activities of daily living. Most patients had high expectations of the operation, and in over 80% these were fulfilled. CONCLUSION: We could find no reason why reduction mammoplasty should not be done by general surgeons, particularly in view of the long waiting lists, but there are some groups (for example, young women and patients either with exceptionally large breasts or who require only small reductions) who should still be treated by specialist plastic surgeons.