Radiotherapy-related arterial intima thickening and plaque formation in childhood cancer survivors detected with very-high resolution ultrasound during young adulthood.

BACKGROUND: The aim of the study was to evaluate arterial morphology and function in a national cohort of long-term survivors of high-risk neuroblastoma (NBL) treated with high-dose chemotherapy and autologous hematopoietic stem cell transplantation with or without total body irradiation (TBI). METHODS AND RESULTS: Common carotid, femoral, brachial, and radial artery morphology were assessed with very-high-resolution vascular ultrasound (25-55 MHz), and carotid artery stiffness and brachial artery flow-mediated dilatation measured with conventional vascular ultrasound in 19 adult or pubertal (age 22.7 ± 4.9 years, range 16-30) NBL survivors transplanted during 1984-1999 at the mean age of 2.5 ± 1.0 years. Results were compared with 20 age- and sex-matched healthy controls. The cardiovascular risk assessment included history, body mass index, fasting plasma lipids, glucose, and 24-h ambulatory blood pressure (BP). The survivors had consistently smaller arterial lumens, increased carotid intima-media thickness (IMT), plaque formation (N = 3), and stiffness, as well as increased radial artery intima thickness (N = 5) compared with the control group. Survivors displayed higher plasma triglyceride and cholesterol levels, and increased heart rate, as well as increased systolic and diastolic BPs. TBI (N = 10) and a low body surface area were independent predictors for decreased arterial lumen size and increased IMT. Three out of five survivors with subclinical intima thickening had arterial plaques. Plaques occurred only among TBI-treated survivors. CONCLUSIONS: Long-term childhood cancer survivors treated with TBI during early childhood display significant signs of premature arterial aging during young adulthood.

Repeatability and agreement of real time three-dimensional echocardiography measurements of left ventricular mass and synchrony in young patients.

BACKGROUND: Left ventricular mass (LVM) and synchrony have prognostic value for many cardiovascular disease states. We report the agreement and repeatability of LVM estimation by three-dimensional (3D) versus M-mode and repeatability of 3D estimation of systolic dyssynchrony. METHODS: 3DLVM was computed by subtraction of endocardial from epicardial volume X1.05 both at end-diastole and end-systole. M-mode measurements were made at end-diastole. This prospective study comprised 40 subjects, 20 patients with chronic kidney disease or treated neuroblastoma and 20 healthy individuals. The median age was 17 (range 6-29 years). RESULTS: Intra- and inter-observer intraclass correlation was excellent for 3D systolic LVM (0.99, 0.87), 3D diastolic LVM (0.99, 0.93), M-mode LVM (0.88, 0.93), moderate for 16-segment SDI (0.77, 062), moderate to low for 12-segment SDI (0.48, 0.73), and 6-segment SDI (0.37, 0.69). The median (range) LVM measurement for 3D diastolic LVM was 125 g (50-253), 3D systolic LVM 109 g (40-195), and M-mode LVM 115 g (range 40-207). There was a significant bias for diastolic 3DLVM to be higher than systolic 3D or M-mode. Limits of agreement between methods were wide. The median (range) systolic dyssynchrony measurements were 2.0 (0.4-7.0), 1.5 (0.3-4.3), and 1.4 (0.3-4.5) for 16-segment, 12-segment, and 6-segment models, respectively. CONCLUSION: 3D and M-mode measurement of LVM are highly repeatable. Measurement bias and wide limits of agreement mean that the same echocardiographic technique should be used during follow-up. Measurement of 3D systolic dyssynchrony is most repeatable using a 16-segment model.

Adult testicular volume predicts spermatogenetic recovery after allogeneic HSCT in childhood and adolescence.

BACKGROUND: Testicular dysfunction and infertility are of major concern in long-term survivors after allogeneic hematopoietic stem cell transplantation (HSCT). This study assesses predictive factors for very long-term testicular recovery after allogeneic HSCT in childhood and adolescence. PROCEDURE: Testicular volume, sperm production and long-term need of testosterone substitution were evaluated among 106 male survivors transplanted at Huddinge and Helsinki University Hospitals from 1978 through 2000, at a mean age of 8 ± 4.6 years (range 1-17). A mean ± SD of 13 ± 4.8 years (range 4-28) had elapsed since their HSCT and the mean age of the participants was 22 ± 6.0 years (range 12-42). An adult testicular volume was recorded in 74 patients at a mean age of 19 ± 3.3 years (range 14-36). RESULTS: Recipients conditioned with busulfan-based regimens or regimens containing only cyclophosphamide had significantly larger adult testicular volumes (mean volume 18 ml and 16 ml vs. 9 ml, P < 0.00001, respectively) and lower serum levels of FSH (mean 9 IU and 5 IU vs. 19 IU, P < 0.01 and 0.001, respectively) compared to those conditioned with total body irradiation (TBI). Multivariate analysis demonstrated that a non-leukemia diagnosis (P < 0.01) and adult testicular volume ≥ 15 ml (P < 0.03) positively impacted spermatogenetic recovery. CONCLUSIONS: A larger adult testicular volume, normal serum levels of FSH and spermatozoa detected in a majority of seminal fluids after busulfan-based or cyclophosphamide conditionings suggest very long-term recovery of spermatogenesis after chemotherapy-based regimens. A simple measurement of adult testicular volume may help predict spermatogenetic potential among pediatric HSCT survivors.