Dermatofibrosarcoma protuberans: a population-based cancer registry descriptive study of 66 consecutive cases diagnosed between 1982 and 2002

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare malignant tumour of the skin, with an estimated incidence of 0.8 to five cases per 1 million people per year. OBJECTIVE: To study epidemiological, immunohistochemical and clinical features, delay in diagnosis, type of treatment and outcome of DFSP from 1982 to 2002. METHODS: Using data from the population-based cancer registry, 66 patients with pathologically proved DFSP were included (fibrosarcomatous DFSP were excluded). Each patient lived in one of the four departments of Franche-Comté (overall population of 1 million people) at the time of diagnosis. The main data sources came from public and private pathology laboratories and medical records. The rules of the International Agency for Research on Cancer were applied. RESULTS: The estimated incidence of DFSP in Franche-Comté was about three new cases per 1 million people per year. Male patients were affected 1.2 times as often as female patients were. The trunk (45%) followed by the proximal extremities (38%) were the most frequent locations. DFSP occurred mainly in young adults between 20 and 39 years of age. Mean age at diagnosis was 43 years, and the mean delay in diagnosis was 10.08 years. Our 66 patients initially underwent a radical local excision. Among them, 27% experienced one or more local recurrences during 9.6 years of follow-up. There was one regional lymph node recurrence without visceral metastases. These recurrences were significantly related to the initial peripheral resection margins. We observed a local recurrence rate of 47% for margins less than 3 cm, vs. only 7% for margins ranging from 3 to 5 cm [P=0.004; OR=0.229 (95%, CI=0.103-0.510)]. The mean time to a first local recurrence was 2.65 years. Nevertheless, there was no death due to the DFSP course at the end of the follow-up, and the final outcome was favourable. CONCLUSION: Our study emphasizes the importance of wide local excision with margins of at least 3 cm in order to prevent local recurrence. However, the recent development of inhibitors of signal transduction by the PDGFB pathway should soon modify the surgical strategy, which is often too mutilating.     

Mapping the active-site tyrosine of vaccinia virus DNA topoisomerase I.

Site-directed mutagenesis of the vaccinia virus gene encoding a type I DNA topoisomerase implicates Tyr-274 as the active-site residue that forms a covalent adduct with DNA during cycles of DNA-strand breakage and reunion. Replacement of Tyr-274 by phenylalanine results in loss of the ability of the enzyme to relax negatively supercoiled DNA as well as to form the covalent DNA-protein intermediate. Substitution of phenylalanine for tyrosine at nine other sites in the protein has no apparent effect on enzyme activity. Amino acid sequence alignment reveals Tyr-274 to be homologous to Tyr-727 and Tyr-771, respectively, of the type I topoisomerases from Saccharomyces cerevisiae and Saccharomyces pombe; Tyr-727 and Tyr-771 have been shown to represent the active-site tyrosines of those enzymes. Sequence comparison of the active-site regions defines a motif Ser-Lys-Xaa-Xaa-Tyr common to the viral and cellular type I topoisomerases, including the human enzyme.     

Primary hyperparathyroidism and monoclonal gammopathy

Coexistent primary hyperparathyroidism and monoclonal gammopathy, although rare, has been reported previously by a number of investigators. We report four patients with such an occurrence who were seen between 1976 and 1988. Another patient with primary hyperparathyroidism also had multiple myeloma and was in remission for 12 years. These patients represent approximately 1% of the 386 patients with primary hyperparathyroidism seen during the same 12-year period. Although several mechanisms have been proposed to explain this concurrence, we believe it is the result of a chance occurrence. A review of the literature, an estimate of the chance occurrence of coincidental monoclonal gammopathy, benign or malignant, in patients with primary hyperparathyroidism, and some practical implications of this interesting coexistence are presented.     

The impact of poverty on educational outcomes for children

Over the past decade, the unfortunate reality is that the income gap has widened between Canadian families. Educational outcomes are one of the key areas influenced by family incomes. Children from low-income families often start school already behind their peers who come from more affluent families, as shown in measures of school readiness. The incidence, depth, duration and timing of poverty all influence a child’s educational attainment, along with community characteristics and social networks. However, both Canadian and international interventions have shown that the effects of poverty can be reduced using sustainable interventions. Paediatricians and family doctors have many opportunities to influence readiness for school and educational success in primary care settings.