Frontal waves and transmissions for temporal laminates and imperfect chiral interfaces.

The analysis of wave patterns in a structure which possesses periodicity in the spatial and temporal dimensions is presented. The topic of imperfect chiral interfaces is also considered. Although causality is fundamental for physical processes, natural wave phenomena can be observed when a wave is split at a temporal interface. A wave split at a spatial interface is a more common occurrence; however, when the coefficients of the governing equations are time-dependent, the temporal interface becomes important. Here, the associated frontal waves are studied, and regimes are analysed where the growth of the solution in time is found. Imperfect interfaces, across which the displacements are discontinuous, are also considered in the vector case of chiral elastic systems. Analytical study and asymptotic approximations are supplied with illustrative numerical examples. This article is part of the theme issue 'Wave generation and transmission in multi-scale complex media and structured metamaterials (part 1)'.

Quasistatic cloaking of two-dimensional polarizable discrete systems by anomalous resonance.

Discrete systems of infinitely long polarizable line dipoles are considered in the quasistatic limit, interacting with a two-dimensional cloaking system consisting of a hollow plasmonic cylindrical shell. A numerical procedure is described for accurately calculating electromagnetic fields arising in the quasistatic limit, for the case when the relative permittivity of the cloaking shell has a very small imaginary part. Animations are given which illustrate cloaking of discrete systems, both for the case of induced dipoles and induced quadrupoles on the interacting particles. The simulations clarify the physical mechanism for the cloaking.

Prognostic significance of leukocyte-dependent antibody activity in melanoma patients.

Sera from patients with melanoma and control subjects were examined for leukocyte-dependent antibody (LDA) activity against cultured melanoma and control nonmelanoma target cells in 51Cr release cytotoxicity assays. In over a third of 344 melanoma patients, LDA activity against melanoma cells was related to tumor growth, shown by disappearance of the LDA after surgical removal of melanoma. Tumor-related LDA activity was not detected in 143 controls with various nonmelanoma malignant conditions and benign skin lesions. Approximately 5% of the patients had high-titer melanoma LDA that was unchanged by surgical removal of the tumor, and 15% had melanoma LDA revealed in their sera only after the sera had been treated to dissociate immune complexes. In patients with stage I melanoma, the disease-free interval was significantly longer in those with tumor-related LDA compared to those with no LDA. Analysis of the data in relation to known prognostic variables suggested that the main influence of LDA on prolongation of the disease-free interval was in males. An association between tumor-related LDA and a longer disease-free interval was also apparent in patients with stage II melanoma at first presentation but not in those with recurrence after prior treatment of primary melanoma. The results suggest that LDA activity against melanoma cells in the sera of patients after surgical removal of stage I or stage II melanoma is a favorable prognostic factor. Further studies are needed to determine whether induction of melanoma LDA by immunotherapy may improve the outcome in patients without naturally occurring LDA.

Demographic study of clinically atypical (dysplastic) nevi in patients with melanoma and comparison subjects.

We examined 296 patients with a history of melanoma and 145 controls for the presence of atypical (dysplastic) nevi. We found that 34% of patients with melanoma and 7% of controls had clinically atypical (dysplastic) nevi. Patients and controls with atypical (dysplastic) nevi had more nevi than the subjects without. The number of nevi varies negatively and significantly with age (r = 0.37, P less than 0.001). Ten % of patients and controls had hypopigmented halos around one or more nevi. Both patients and comparison subjects with atypical (dysplastic) nevi tended to have this subtle variant of halo nevi more often than those without (r = 0.17, P less than 0.01). The number of nevi on the irides of melanoma patients was greater than that in the comparison group. The results of this study suggest that patients with a melanoma exhibit more commonly cutaneous and ocular pigmentary lesions than comparison subjects without a melanoma.

Determinants of outcome in melanoma patients with cerebral metastases.

PURPOSE: To analyze prognostic factors, effects of treatment, and survival for patients with cerebral metastases from melanoma. PATIENTS AND METHODS: All melanoma patients with cerebral metastases treated at the Sydney Melanoma Unit between 1952 and 2000 were identified. From 1985 to 2000, patients were diagnosed and treated using consistent modern techniques and this cohort was analyzed in detail. Multivariate analysis of prognostic factors for survival was performed. RESULTS: A total of 1137 patients with cerebral metastases were identified; 686 were treated between 1985 and 2000. For these 686 patients, the median time from primary diagnosis to cerebral metastasis was 3.1 years (range, 0 to 41 years). A total of 646 patients (94%) have died as a result of melanoma. The median survival from the time of diagnosis of cerebral metastasis was 4.1 months (range, 0 to 17.2 years). Treatment was as follows: surgery and postoperative radiotherapy, 158 patients; surgery alone, 47 patients; radiotherapy alone, 236 patients; and supportive care alone, 210 patients. Median survival according to treatment received for these four groups was 8.9, 8.7, 3.4, and 2.1 months, respectively; the differences between surgery and nonsurgery groups were statistically significant. On multivariate analysis, significant factors associated with improved survival were surgical treatment (P <.0001), no concurrent extracerebral metastases (P <.0001), younger age (P =.0007), and longer disease-free interval (P =.036). Prognostic factors analysis confirmed the important influence of patient selection on treatment received. CONCLUSION: This large series documents the characteristics of patients who developed cerebral metastases from melanoma. Median survival was dependent on treatment, which in turn was dependent on patient selection.

Thin malignant melanomas and recurrence potential.

Of 846 patients with stage I malignant melanoma that was less than 0.76-mm thick who were followed up for two to 31 years, 61 (7.2%) developed a recurrence. For those patients who did not initially undergo an elective lymph node dissection, the majority of first recurrences were at regional lymph nodes. Attempts have been made to identify those patients at risk of relapsing. Axial lesions, particularly those on the scalp, had the highest recurrence rate, with 15% of all thin scalp lesions recurring compared with only 4% of all thin extremity lesions. Three histological features proved to be useful prognostic indicators when analyzed by single-factor analysis. Evidence of ulceration in the primary lesion increased the recurrence rate from 6.7% to 26.1%. While only 4.3% of lesions displaying low mitotic activity recurred, this rate rose to 23.8% for those lesions of a high mitotic grade. Only 5% of Clark's level II lesions recurred, compared with about 12% of lesions at either level III or IV. Evidence of regression in thin lesions had no deleterious effect on prognosis. This study defines a small subset of patients who may benefit from elective lymph node dissection.

Late relapse from cutaneous stage I malignant melanoma.

In 1,283 patients with cutaneous stage I malignant melanoma who had ten or more years of follow-up, the incidence of late recurrence (first evidence of metastases occurring ten or more years after melanoma diagnosis) was 2.7%. None of the factors of prognostic importance (anatomic site, tumor thickness, ulcerative state of primary lesion, or initial surgical treatment) proved useful in predicting those patients with late recurrence. There was no sex or age difference in either incidence of late recurrence or prognosis subsequent to recurrence. Prognosis subsequent to late recurrence depended on the site of the recurrence. Survival after distant metastases became evident was extremely short. However, in the majority (53%) of patients, late recurrence was local and survival subsequent to treatment of these metastases was often protracted, emphasizing the importance of long-term follow-up in all patients with cutaneous melanoma.

Elective lymph node dissection in patients with primary melanoma of the trunk and limbs treated at the Sydney Melanoma unit from 1960 to 1991.

BACKGROUND: The value of elective lymph node dissection (ELND) in melanoma remains controversial. Published prospective and retrospective studies can be criticized, and results from two ongoing randomized trials are not yet available. A previous retrospective review from the Sydney Melanoma Unit (SMU) showed apparent survival benefit from ELND, especially in tumors of intermediate thickness. STUDY DESIGN: We undertook a retrospective analysis of all patients treated at the SMU since 1960 for melanoma of the trunk or limbs measuring 1.5 mm or more in thickness, without clinical lymph node metastases, whose definitive wide excision (WE) with or without ELND was performed at the SMU within 60 days of initial diagnosis. RESULTS: There were 1,278 patients who fulfilled these criteria. Of these, 845 (66 percent) were treated with ELND and the remaining 34 percent were treated with WE alone. The median follow-up period was 58 months. Patients with thicker tumors and younger age more commonly underwent ELND. Among patients with thinner tumors, males underwent ELND more commonly than females. A multivariate proportional hazard model of melanoma-specific survival stratified by tumor thickness was chosen to allow for the imbalances between the two groups. With or without allowance for covariates, no benefit from ELND was found in the whole group or any subset. In contrast to previous studies from the SMU, we deliberately excluded from the present study patients referred only after WE with or without ELND elsewhere, because these might have been a selectively biased poor prognostic group. CONCLUSIONS: This study does not indicate a benefit from ELND for melanomas of the trunk or limbs measuring over 1.5 mm in thickness.

Experience with 998 cutaneous melanomas of the head and neck over 30 years.

Between 1960 and 1990, a total of 998 patients were treated at the Sydney Melanoma Unit for cutaneous melanoma of the head and neck. There were 595 male and 403 female patients, with a median age of 53 years. The most common primary lesion site was the face (47%), followed by the neck (29%), scalp (14%), and ear (10%). Histologic types were as follows: superficial spreading 30%, nodular melanoma 28%, lentigo maligna melanoma 16%, and other 26%. All patients underwent surgical treatment. Primary closure of wounds was achieved in 52% of patients, and excision margins were 2 cm or less in 45%. A total of 152 patients had therapeutic neck dissections, and 234 had elective neck dissections. The overall local recurrence rate was 13%, and this was significantly influenced by increasing tumor thickness and Clark level. The recurrence rate in the neck after neck dissection was 24%, and the rate of parotid recurrences was 14%. Melanoma-specific survival was 77% at 5 years and 66% at 10 years for the entire group. By univariate analysis, survival varied significantly with age, tumor thickness, ulceration, anatomic sub-site, histologically positive nodes, and the presence of distant metastases. A diagnosis of lentigo maligna melanoma and elective lymph node dissection both appeared to improve survival. With multivariate analysis, all of these factors remained significant prognostic factors except elective node dissection, which lost its beneficial influence.

Histogenesis of malignant melanoma with an adjacent component of the superficial spreading type.

There has been a world-wide exponential increase in the incidence of thin malignant melanoma. At the Sydney Melanoma Unit, the proportion of patients diagnosed as having superficial spreading melanoma has more than doubled from 33% prior to 1960 to 78% during 1980-83. A study was made of the non-invasive component of malignant melanoma with an adjacent non-invasive component of the superficial spreading type in an attempt to elucidate the pathogenetic mechanisms involved in these changing trends. In this study on 723 cases of melanoma with a superficial spreading component, there was evidence that 39% originated in a precursor lesion. In the remaining 61%, the adjacent superficial spreading component consisted of melanoma in situ, suggesting that these were melanomas from the beginning. The latter lesions were thinner and had a lower degree of mitotic activity than melanomas commencing in a precursor lesion. Despite the large increase in incidence of superficial spreading melanomas and the shift to thinner lesions over time, there appeared to be no difference in the proportion of lesions commencing de novo to those commencing in a precursor lesion. This suggests that the precursor lesion may be of genetic origin.

Prognostic histopathological factors in malignant melanoma.

An analysis of prognostic factors in 4000 patients with cutaneous malignant melanoma at the Sydney Melanoma Unit and the University of Alabama in Birmingham has demonstrated that the histological features of the primary melanoma become less predictive of survival the more advanced the disease becomes. Thus, whilst 4 features of primary lesions were independent predictors in localized disease (tumour thickness, ulceration, level of invasion and regression), only one of the stronger ones (ulceration) remained predictive in patients with regional lymph node metastases. Once distant spread was evident, there were no parameters of the primary lesion that predicted survival. Thus, in patients with advanced disease prognosis was dictated by the extent of metastatic involvement: the number of positive lymph nodes in stage II patients and the number and location of metastatic sites in stage III patients.

Semi-solid cultures of primary melanomas and their correlation with histopathological features.

The results of semi-solid cultures of fresh biopsy material from 86 primary human melanomas are reported. Detailed histological assessments by Professor McGovern were available for 80 of the 86 melanomas, and these were compared with the growth characteristics of each specimen. Significant correlations were found between growth in hypoxic semi-solid culture and tumour thickness and numbers of mitoses, and there was a suggestive association between growth and the shape of the lesion. Seventy-seven patients had Stage I disease, and follow-up data were available for 68 of these. Twenty-one patients had relapsed and 9 had died. Time to relapse was significantly shorter in patients whose primary tumour grew in culture and in patients with tumours thicker than 1.5 mm. These results show correlations between the biological behaviour of human melanoma, as assessed in vitro by culture, and the histological assessments previously reported. Growth in culture, tumour thickness and number of mitoses were interdependent variables, with growth and thickness predicting for time to relapse. Further studies will be needed to determine the relative risks attached to each of these.

Immunofluorescent localization of dopamine-like and leucine-enkephalin-like neurons in the supraoesophageal ganglia of the American cockroach, Periplaneta americana.

Leucine-enkephalin- and dopamine-like nerve cells and fibers were localized in the supraoesophageal ganglia (brain) of the American cockroach, Periplaneta americana, using immunofluorescence. The presence of leucine-enkephalin-like material was confirmed using immunoperoxidase staining. Several cells containing leucine-enkephalin-like material were found in the pars lateralis, and nerve fibers belonging to these cells were traced through the brain. Dopamine-like material was detected in deutocerebral neurons as well as the nerve processes arising from these cells which lead into the area of the deutocerebral glomeruli. Specific immunofluorescence was also obtained in the alpha and beta lobes of the corpora pedunculata with both the leucine-enkephalin and dopamine antibodies. However, the fluorescent banding pattern observed in both lobes was distinctly different with the two antibodies. No specific fluorescence was observed in the stalk or peduncle of the corpora pedunculata with either the leucine-enkephalin or the dopamine antibody. The findings suggest a possible interaction of leucine-enkephalinergic and dopaminergic nerve fibers in the alpha and beta lobes of the cockroach corpora pedunculata.

Malignant melanoma: an evolutionary theory to explain its behaviour.

The behaviour of malignant melanoma is discussed in relation to the host/tumour relationships and the factors affecting them, and natural selection of tumour cells is suggested as a possible explanation of its variability. These considerations are taken into account in determining treatment, the results of which are briefly outlined.