Efficacy of superficial and deep regional hyperthermia combined with systemic chemotherapy and radiotherapy in metastatic melanoma

Background and Objective: Response rates of cutaneous‐subcutaneous or lymph node metastases of melanoma to systemic chemotherapy are rather low. We report our clinical experience with superficial and deep regional hyperthermia in combination with radiotherapy and/or chemotherapy with carboplatin. Patients/Methods: We treated 15 patients with metastatic melanoma (6 men, 9 women; age 39 – 84 years, mean age 60 years) by using superficial or deep regional hyperthermia produced by electromagnetic energy. Superficial hyperthermia was delivered to skin or lymph node metastases in combination with radiochemotherapy in 12 patients, while deep regional hyperthermia was administered with an annular array applicator to lymph node metastases either in combination with radiochemotherapy (1 patient) or with carboplatin alone (2 patients). The clinical response was assessed by clinical evaluation and/or computer tomography and/or ultrasonography at monthly intervals. Results. Both superficial and deep regional hyperthermia was well tolerated. We observed 5 complete local remissions (34 %), 6 partial local remissions (40 %) and 2 patients with stable disease (13 %). The best results were obtained in cutaneous or retroperitoneal metastases. Conclusions. Local response can be achieved in inoperable metastatic melanoma using superficial or deep regional hyperthermia in combination with radiochemotherapy or chemotherapy.     

Melanoma with benign melanocytic naevus components: reappraisal of clinicopathological features and prognosis

The clinicopathological features and prognosis of primary cutaneous malignant melanoma with benign melanocytic naevus (BMN) components are still under debate. The purpose of this study was to characterize further the clinical and histopathological features of naevus-associated melanomas, with emphasis on the BMN components, and to examine their prognosis based on a large series. Following a histopathological review of 667 consecutive cases of primary cutaneous melanoma, 148 melanomas with BMN components (22.1%) were identified for further study. A control group of 519 melanomas without BMN components seen in a similar period were also studied. Clinically, patients with melanomas containing BMN components (n = 148; age range 25-86 years, mean age 54 +/- 16 years; male to female ratio 1:1.02) presented with tumours located mainly on the trunk (34.5%), followed by the upper extremities (24.3%), lower extremities (20.3%), and head and neck (14.2%). Compared with tumours without BMN components (n = 519; age range 19-89 years, mean age 57 +/- 15 years; male to female ratio 1:1.3), melanomas with BMN components occurred in slightly younger individuals (P = 0.027). Histopathologically, BMN components mainly showed features of acquired naevi (total 87 cases; dysplastic, 80 cases; banal, seven cases) or congenital naevi (total 57 cases; superficial, 56 cases; deep, one case), but a minority of these lesions (four cases) could not be further subcategorized. Generally, melanomas containing BMN components were relatively thinner than melanomas without BMN components (mean Breslow index 0.95 +/- 0.83 mm and 1.3 +/- 1.6 mm, respectively) (P = 0.015). The follow-up data available in 69 patients with naevus-associated melanomas consistently revealed a relatively good outcome (5 year metastasis-free survival rate 93.75%), although no statistical difference in prognosis was observed between this group and a subset of 283 melanomas patients without BMN components stratified by tumour thickness. We conclude that BMN components in naevus-associated melanomas constitute a heterogeneous group morphologically, consisting mainly of dysplastic and superficial congenital naevi. This finding indicates a more important role for superficial congenital naevus as a precursor lesion of naevus-associated melanomas than presently recognized. Patients with naevus-associated melanomas generally show a good clinical outcome, reflecting their small Breslow index.     

The use of confocal laser-scanning microscopy in microsurgery for invasive squamous cell carcinoma

BACKGROUND: Ex-vivo confocal laser-scanning microscopy offers rapid imaging of excised tissue specimens without conventional histotechnical procedures. As vertical sections are prepared, morphological features can be assessed according to standard criteria used in conventional histopathology. OBJECTIVES: To validate the diagnostic confocal examination of squamous cell carcinoma (SCC) in microscopy-guided surgery. METHODS: Four independent observers received standardized instructions about diagnostic confocal microscopy features of SCC. Subsequently, 120 confocal images of fresh excisions from SCC or normal skin, imaged using a commercially available, near-infrared, reflectance confocal laser-scanning microscope, were evaluated by each observer. RESULTS: General morphology, such as location, size and shape of the cancer area could be visualized by the imaging system. Furthermore, densely packed and irregularly organized nuclei and nuclear atypia could be delineated. Overall, a sensitivity of 95% and a specificity of 96.25% were achieved by the four observers (positive predictive value 96.25%, negative predictive value 95.23%). CONCLUSIONS: This study provides a set of well-described morphological criteria with obvious diagnostic impact which should be used in further investigations. In the future, confocal laser-scanning microscopy may guide microsurgery of any skin cancer.     

Focal epithelial hyperplasia (Heck disease) in a black child

Abstract:  We describe a 3-year-old African male child with focal epithelial hyperplasia (Heck disease). The clinical diagnosis was confirmed histologically and by the finding of human papillomavirus type 32.     

Topical treatment with liposomes containing T4 endonuclease V protects human skin in vivo from ultraviolet-induced upregulation of interleukin-10 and tumor necrosis factor-alpha

Exposing human skin to ultraviolet radiation causes DNA damage, sunburn, immune alterations, and eventually, skin cancer. We wished to determine whether liposomes containing a DNA repair enzyme could prevent any of the acute effects of irradiation when applied after ultraviolet exposure. Fifteen human patients with a prior history of skin cancer were exposed to two minimal erythema doses of ultraviolet radiation on their buttock skin. Liposomes containing T4 endonuclease V or heat-inactivated enzyme were applied immediately and at 2, 4, and 5 h after ultraviolet irradiation. Transmission electron microscopy after anti-T4 endonuclease V-staining and immunogold labeling on biopsies taken at 6 h after ultraviolet exposure revealed that the enzyme was present within cells in the skin. Immunohistochemical DNA damage studies suggested a trend toward improved DNA repair at the active T4 endonuclease V liposome-treated test sites. Although the active T4 endonuclease V liposomes did not significantly affect the ultraviolet-induced erythema response and microscopic sunburn cell formation, they nearly completely prevented ultraviolet-induced upregulation of interleukin-10 and tumor necrosis factor-alpha RNA message and of interleukin-10 protein. These studies demonstrate that liposomes can be used for topical intracellular delivery of small proteins to human skin and suggest that liposomes containing DNA repair enzymes may provide a new avenue for photoprotection against some forms of ultraviolet-induced skin damage.     

Intraoperative radiation with external irradiation: an alternative for nonresectable non-small-cell lung cancer?

In 15 patients with nonresectable non-small-cell lung carcinoma (NSCLC) (10 squamous, 1 large cell, 4 adenocarcinomas; T1-T3, N0-N2, all M0), lymph node dissection and intraoperative irradiation of the tumour (IORT) with doses between 10 and 20 Gy (11-20 MeV electron beam) was performed. Four weeks postoperatively 46-56 Gy external irradiation (8 or 23 MeV photons) was delivered to the mediastinum and 46 Gy to the tumour-bearing area. Four weeks postoperatively, 8 minor responses (MR, tumour regression between 4% and 45%) and 6 partial responses (PR, 50%-84%) were found. In 1 case, CT was inconclusive. Eighteen weeks after IORT, volumetry showed 3 CR, 9 PR (62% to 94%) and 1 28% MR. One patient died from intrabronchial hemorrhage 7 weeks after IORT (50% PR). Two others (both CR) died from unrelated causes, 6 and 12 months, respectively, after IORT. One patient (62% PR) died after 14 months from an unknown cause. Another patient died at 15 months from local relapse after CR. The latest CT volume assessment between 7.5 and 21.5 months, respectively, yielded 8 CR, and 1 63% PR. One further case of local CR has developed contralateral pulmonary metastasis after 10 months. All these patients are alive and well. The median time elapsed since IORT is 12.5 months, 10 patients have survived more than 12 months.     

Computer‐based Training in der Dermatoonkologie – erste Ergebnisse zum Vergleich elektronischer Lernprogramme mit Präsenzlehre

Background: Electronic media are increasingly used in medical education. The question arises whether tutorial programs are as effective as innovative face‐to‐face didactic formats. Methods: 26 students underwent a special dermatooncology course in an integrated undergraduate medical curriculum. One part of the content was acquired face‐to‐face with emphasis on team learning and mini‐lectures; the other part was presented as web‐based electronic computer‐based training objects. The performance of the students in a subsequent multiple choice test was evaluated. Results: In total, questions referring to computer‐based training contents were answered correctly in 90.4 ± 12.5 %, which was significantly superior to the questions referring to team learning in the face‐to‐face teaching format (80.6 ± 13.1 %; p < 0.001). There was, however, a significant correlation between both results for each individual student (r = 0.52; p < 0.01), but there was no correlation between the results obtained for computer‐based training or team learning on the one hand, and the overall performance of the individual student on the other. Conclusions: Though different contents were concerned, our study provides evidence that computer‐based training may be more efficient than face‐to‐face teaching using team learning to communicate dermatooncology contents in an undergraduate medical curriculum.     

Importance of immunohistochemistry of skin tumors

Immunohistological demonstration of cell- and tissue-specific antigens in microscopic slides has remarkably influenced the classification of certain cutaneous neoplasms. The following markers are of particular interest in dermatopathology: cell surface antigens of lymphocyte subpopulations, intracytoplasmic immunoglobulins, intermediate filaments, neural markers, epithelial cell membrane antigens, and endothelial products. During the last years, these methods have contributed to our understanding of histogenesis and classification especially of cutaneous lymphomas, epithelial neoplasms, neurogenic tumors, and angiosarcomas.     

Can ASA grade or Goldman's cardiac risk index predict peri-operative mortality? A study of 16 227 patients

This trial was designed to study the correlation between peri-operative mortality in patients undergoing elective surgery and the physical status classification of the American Society of Anesthesiologists, the Goldman multifactorial cardiac risk index or the two indices combined. All patients scheduled for elective surgery over a 5-year period were evaluated pre-operatively and were scored according to both indices. Of 16 227 patients studied, 215 died within 4 weeks of operation. Both indices correlated significantly with peri-operative mortality, the ASA grade showing a closer correlation. A regression tree analysis divided the combination groups into five subgroups where the mortality was lowest (0.4%) in ASA grade ≤2 and cardiac risk index group I (score 0–5 points) and increased up to 7.3% in ASA grade = 4 and cardiac risk index group ≥3 (score >13 points). We conclude that for this large number of patients peri-operative mortality can be predicted with the ASA grade and, to a lesser degree, with the cardiac risk index. Applied in the correct way, the combination of the two scores can increase the accuracy of prediction of peri-operative mortality.