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.     

Models,strategies, and tools

This paper presents a case for careful consideration of theory in planning to implement evidence-based practices into clinical care. As described, theory should be tightly linked to strategic planning through careful choice or creation of an implementation framework. Strategies should be linked to specific interventions and/or intervention components to be implemented, and the choice of tools should match the interventions and overall strategy, linking back to the original theory and framework. The thesis advanced is that in most studies where there is an attempt to implement planned change in clinical processes, theory is used loosely. An example of linking theory to intervention design is presented from a Mental Health Quality Enhancement Research Initiative effort to increase appropriate use of antipsychotic medication among patients with schizophrenia in the Veterans Health Administration.     

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.     

Long-term precision of 18F-fluoride PET skeletal kinetic studies in the assessment of bone metabolism.

(18)F-Fluoride PET allows noninvasive evaluation of regional bone metabolism and has the potential to become a useful tool for assessing patients with metabolic bone disease and evaluating novel drugs being developed for these diseases. The main PET parameter of interest, termed K(i), reflects regional bone metabolism. The aim of this study was to compare the long-term precision of (18)F-fluoride PET with that of biochemical markers of bone turnover assessed over 6 mo. METHODS: Sixteen postmenopausal women with osteoporosis or significant osteopenia and a mean age of 64 y underwent (18)F-fluoride PET of the lumbar spine and measurements of biochemical markers of bone formation (bone-specific alkaline phosphatase and osteocalcin) and bone resorption (urinary deoxypyridinoline) at baseline and 6 mo later. Four different methods for analyzing the (18)F-fluoride PET data were compared: a 4k 3-compartmental model using nonlinear regression analysis (K(i-4k)), a 3k 3-compartmental model using nonlinear regression analysis (K(i-3k)), Patlak analysis (K(i-PAT)), and standardized uptake values. RESULTS: With the exception of a small but significant decrease in K(i-3k) at 6 mo, there were no significant differences between the baseline and 6-mo values for the PET parameters or biochemical markers. The long-term precision, expressed as the coefficient of variation (with 95% confidence interval in parentheses), was 12.2% (9%-19%), 13.8% (10%-22%), 14.4% (11%-22%), and 26.6% (19%-40%) for K(i-3k), K(i-PAT), mean standardized uptake value, and K(i-4k), respectively. For comparison, the precision of the biochemical markers was 10% (7%-15%), 18% (13%-27%), and 14% (10%-21%) for bone-specific alkaline phosphatase, osteocalcin, and urinary deoxypyridinoline, respectively. Intraclass correlation between the baseline and 6-mo values ranged from 0.44 for K(i-4k) to 0.85 for K(i-3k). No significant correlation was found between the repeated mean standardized uptake value measurements. CONCLUSION: The precision and intraclass correlation observed for K(i-3k) and K(i-PAT) was equivalent to that observed for biochemical markers. This study provided initial data on the long-term precision of (18)F-fluoride PET measured at the lumbar spine, which will aid in the accurate interpretation of changes in regional bone metabolism in response to treatment.     

Naphthalimido derivatives as antifolate thymidylate synthase inhibitors

A new series of N-(substituted)benzyl-1,8-naphthalimides 4, structurally related to the previously reported thymidylate synthase (TS) inhibitor naphthaleins 3, were synthesized and compounds tested for their inhibition of several species of TS. Moreover, their in vitro cytotoxicity together with antimycotic and antibacterial properties were assayed. While no activity was detected in the antibacterial tests, the m-nitro (4ae) and the p-nitro (4af) derivatives were found able to partially inhibit TS at low micromolar concentrations. Introduction of nitro or (substituted)-amino groups in position 4 of the naphthalic ring always led to less active compounds.