Metastatic deaths in retinoblastoma patients treated with intraarterial chemotherapy (ophthalmic artery chemosurgery) worldwide.

Ophthalmic artery chemosurgery [OAC, intra-arterial chemotherapy (IAC)] was introduced in 2006 as treatment modality for intraocular retinoblastoma. The purpose of this commentary is to retrospectively review the incidence of metastatic deaths in retinoblastoma patients treated with OAC worldwide over a 10 year period. Retrospective data regarding metastatic deaths was collected from six international retinoblastoma centers (New York City USA, Philadelphia USA, Sao Paulo Brazil, Siena Italy, Lausanne Switzerland and Buenos Aires Argentina). All retinoblastoma patients from these centers (naive and recurrent, unilateral and bilateral) treated with OAC/IAC since 2006 have been included in this study. Data regarding number of patients, number of OAC/IAC infusions, number unilateral and bilateral, number treated for naive disease or salvage and number of metastatic deaths have been assessed. Over a 10-year period of time 1139 patients received OAC/IAC for 4396 infusions. At last follow-up there were only three metastatic deaths (all treated in Buenos Aires). The current survey assessed the recorded risk of metastatic deaths in six retinoblastoma centers worldwide in children with retinoblastoma (unilateral or bilateral) treated with OAC/IAC as primary or secondary therapy. Overall, the observed risk for metastatic deaths from retinoblastoma was <1% in OAC/IAC treated children

Maternal vitamin D deficiency delays glomerular maturity in F1 and F2 offspring.

BACKGROUND: There is a high prevalence of vitamin D insufficiency in women of reproductive age. METHODS: This work studied the first two generations of offspring (F1 and F2) of Swiss mice from mothers fed one of two diets: SC (standard chow) or VitD- (vitamin D-deficient). Functional and developmental kidney measurements were taken. RESULTS: The first two generations of the VitD- group had higher blood pressure at 6 months of age than the offspring of the SC group as well as an increase in renin and AT1r expression. However, at all ages, both F1 and F2 VitD- mice had shorter glomerular diameters, and diet played a significant role in the total variation. Both the F1 and F2 generations of the VitD- group had more immature glomeruli than offspring from the SC group. Immature glomeruli begin to disappear at 10 days, but at this age, F1-VitD- mice had more immature and mature glomeruli than F1-SC mice. At 6 months of age, F1-VitD- mice exhibited more glomeruli, while F2-VitD- mice exhibited the same number of glomeruli as F2-SC mice, but fewer glomeruli compared to the F1-VitD group. Both diet and generation account for the total variation in the number of glomeruli. Decreases in urine output and podocin expression and increases in urea and creatinine in the urine were observed in F1 offspring. CONCLUSION: These findings demonstrate that maternal vitamin D deficiency accompanies changes in the renal expression of important factors that may retard the maturation of glomeruli by extending the period of nephrogenesis

Photomicrographs of developing kidneys from offspring at 10 days of age.

<p>Hematoxylin and eosin stain, same magnification in all pictures. (a) SC offspring and (b) VitD- offspring in the F1 generation; (c) SC offspring and (d) VitD- offspring in the F2 generation. We used the same test frame size over the photomicrographs of the two groups to emphasize that the number of glomeruli was greater in the VitD- group than in the SC group. As observed at birth (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041740#pone-0041740-g005" target="_blank">Fig. 5</a>). Differences between the SC group (c) and the VitD- group (d) are less marked in the F2 generation.</p

Body mass evolution in both the F1 and F2 generations at 3 and 6 months of age.

<p>Data are reported as means ± SEM; P<0.05, one-way ANOVA and post-hoc of Tukey's test: † compared to SC counterpart.</p

Number of developing immature and mature glomeruli at birth in both the F1 and F2 generations.

<p>Data are reported as means ± SEM; P<0.05, one-way ANOVA and post-hoc of Tukey's test: † compared to SC counterpart; ‡ compared to F1 generation.</p

Western blotting analysis of renal tissue at weaning and 6 months of age for AT1 receptor expression.

<p>The average values were measured and equal protein loading was confirmed by probing blots with beta-actin antibody and is expressed as a percentage of the SC counterpart. Data are reported as means ± SEM; P<0.05, one-way ANOVA and post-hoc of Tukey's test: † compared to SC counterpart; ‡ compared to F1 generation.</p

Western blotting analysis of renal tissue at weaning and 6 months of age for podocin expression.

<p>The average values were measured and equal protein loading was confirmed by probing blots with beta-actin antibody and is expressed as a percentage of the SC counterpart. Data are reported as means ± SEM; P<0.05, one-way ANOVA and post-hoc of Tukey's test: † compared to SC counterpart; ‡ compared to F1 generation.</p

Number of developing immature and mature glomeruli at 10 days in both the F1 and F2 generations.

<p>Data are reported as means ± SEM; P<0.05, one-way ANOVA and post-hoc of Tukey's test: † compared to SC counterpart; ‡ compared to F1 generation.</p

Photomicrographs of the developing kidneys of offspring at birth.

<p>Hematoxylin and eosin stain, same magnification in all pictures. (a) SC offspring and (b) VitD- offspring in the F1 generation; (c) SC offspring and (d) VitD- offspring in the F2 generation; (arrows) clusters with comma-shaped and S-shaped glomerular structures at the cortex; (open arrows) vascularized glomerular structures in the inner region.</p