Choroidal melanoma: A review of the experience of the Sydney Eye Hospital Professorial Unit 1979–1995

Purpose: This study examines 90 patients presenting with choroidal or ciliochoroidal melanoma to the Professorial Unit at the Sydney Eye Hospital. The indications for treatment, and the outcome for the eye and vision are presented together with an account of mortality and the incidence of metastases. Methods: A retrospective analysis of 90 choroidal melanoma patients managed by one surgeon over a 16-year period was undertaken. Initial findings, investigations performed, incidence of metastatic disease, treatment received and complication rates and mortality, where applicable, were recorded. Results: The group was followed for an average of 64 months (range, 5–172 months). Primary treatment was with either Iodine¹²⁵ (¹²⁵1) brachytherapy, local excision or enucleation. Radiation retinopathy was prominent in ¹²⁵1 cases resulting in poor visual acuity when the tumour resided in the posterior pole. Local excision even of large tumours was effective particularly if peripheral. Overall metastatic disease was seen in 11% with 5-year survival rates for the metastatic group being 10%. Prognosis after diagnosis of metastases was poor. Conclusions: Specific therapy for choroidal melanoma must relate to the size and location of the tumour at the time of diagnosis. Visual outcome relates directly to the proximity of the tumour to the optic nerve and fovea. Metastatic disease latency can be prolonged; therefore caution about prognosis is required long after therapy is given. The 5-year survival is encouraging with all forms of therapy. However, as the natural history of ocular melanoma is variable and not fully delineated it is important to monitor the effects of conservative therapy. Further long-term survival data is required to distinguish whether one form of treatment is advantageous over the others, although case-control studies are difficult for ethical and practical reasons. In this regard the Collaborative Ocular Melanoma Study (COMS) will provide further evidence for the safety and efficacy of conservative therapy with brachytherapy compared to enucleation.     

Prevalence of dermatophytosis in junior secondary schoolchildren in Ogun State, Nigeria

A total of 2772 randomly selected junior secondary school pupils (aged 8-14) from 60 schools were examined for dermatophytic infections by direct microscopy and culture-based laboratory diagnostic methods. Of these, 641 (23.21%) had dermatophytosis. Out of these, 376 (13.56%) were male while 265 (9.56%) were female. Aetiological agents identified with infection were Microsporum canis (30.19%), Microsporum audouinii (32.92%), Trichophyton interdigitale (14.37%), Trichophyton soudanense (9.73%) and Trichophyton tonsurans (12.05%). Most of the dermatophytes encountered were anthropophilic species. Microsporum canis was the only zoophilic dermatophyte. Differences were not observed in infection pattern for all the different geo-political zones that make up the state. The head and the skin of the students were more frequently infected than the nails and toes. Infection frequency increased steadily up to age 11 after which it drastically decreased.     

Predicting a local recurrence after breast-conserving therapy by gene expression profiling

Introduction

To tailor local treatment in breast cancer patients there is a need for predicting ipsilateral recurrences after breast-conserving therapy. After adequate treatment (excision with free margins and radiotherapy), young age and incompletely excised extensive intraductal component are predictors for local recurrence, but many local recurrences can still not be predicted. Here we have used gene expression profiling by microarray analysis to identify gene expression profiles that can help to predict local recurrence in individual patients.

Methods

By using previously established gene expression profiles with proven value in predicting metastasis-free and overall survival (wound-response signature, 70-gene prognosis profile and hypoxia-induced profile) and training towards an optimal prediction of local recurrences in a training series, we establish a classifier for local recurrence after breast-conserving therapy.

Results

Validation of the different gene lists shows that the wound-response signature is able to separate patients with a high (29%) or low (5%) risk of a local recurrence at 10 years (sensitivity 87.5%, specificity 75%). In multivariable analysis the classifier is an independent predictor for local recurrence.

Conclusion

Our findings indicate that gene expression profiling can identify subgroups of patients at increased risk of developing a local recurrence after breast-conserving therapy.     

TRAIL-receptor expression is an independent prognostic factor for survival in patients with a primary glioblastoma multiforme

SummaryPurpose In order to improve the survival of patients with a glioblastoma multiforme tumor (GBM), new therapeutic strategies must be developed. The use of a death inducing ligand such as TRAIL (TNF Related Apoptosis Inducing Ligand) seems a promising innovative therapy. The aim of this study was to quantify the expression of the death regulating receptors TRAIL-R1, TRAIL-R2 and TRAIL on primary GBM specimens and to correlate this expression with survival.Experimental design Expression of TRAIL and TRAIL-receptors was assessed by immunohistochemistry, both quantitatively (% of positive tumor cells) and semi-quantitatively (staining intensity) within both the perinecrotic and intermediate tumor zones of primary GBM specimens. RT-PCR of GBM tissue was performed to show expression of TRAIL receptor mRNA.Results Immunohistochemistry showed a slight diffuse intracytoplasmic and a stronger membranous staining for TRAIL and TRAIL receptors in tumor cells. Semi-quantitative expression of TRAIL showed a significantly higher expression of TRAIL in the perinecrotic zone than in the intermediate zone of the tumor (P=0.0001). TRAIL-R2 expression was significantly higher expressed than TRAIL-R1 (P=0.005). The antigenic load of TRAIL-R2 was positively correlated with survival (P=0.02). Multivariate analysis of TRAIL-R1 within the study group (n=62) showed that age, gender, staining intensity, antigenic load, % of TRAIL-R1 expression, were not statistically correlated with survival however radiotherapy was significantly correlated (multivariate analysis: age: P=0.15; gender: P=0.64; staining intensity: P=0.17; antigenic load: P=0.056; % of TRAIL-R1 expression: P=0.058; radiotherapy: P=0.0001). Subgroup analysis of patients who had received radiotherapy (n=47) showed a significant association of % of TRAIL-R1 expression and the antigenic load of TRAIL-R1 with survival (multivariate analysis: P=0.036, respectively, P=0.023).Multivariate analysis of TRAIL-R2 staining intensity and antigenic load, within the study group (P=0.004, respectively, P=0.03) and the subgroup (P=0.002, respectively, P=0.004), showed a significant association with survival. RT-PCR analysis detected a negative relation between the amount of TRAIL-R1 mRNA and the WHO grade of astrocytic tumors (P=0.03).Conclusions TRAIL-R1 and TRAIL-R2 expression on tumor cells are independent prognostic factors for survival in patients with a glioblastoma multiforme. Both receptors could be targets for TRAIL therapy. As TRAIL-R2 is more expressed, in comparison with TRAIL-R1, on GBM tumor cells, TRAIL-R2 seems to be of more importance as a target for future TRAIL therapy than TRAIL-R1.