Coronary artery disease surveillance among childhood, adolescent and young adult cancer survivors: A systematic review and recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

BACKGROUND: Coronary artery disease (CAD) is a concerning late outcome for cancer survivors. However, uniform surveillance guidelines are lacking. AIM: To harmonise international recommendations for CAD surveillance for survivors of childhood, adolescent and young adult (CAYA) cancers. METHODS: A systematic literature review was performed and evidence graded using the Grading of Recommendations, Assessment, Development and Evaluation criteria. Eligibility included English language studies, a minimum of 20 off-therapy cancer survivors assessed for CAD, and 75% diagnosed prior to age 35 years. All study designs were included, and a multidisciplinary guideline panel formulated and graded recommendations. RESULTS: 32 of 522 identified articles met eligibility criteria. The prevalence of CAD ranged from 0 to 72% and was significantly increased compared to control populations. The risk of CAD was increased among survivors who received radiotherapy exposing the heart, especially at doses ≥15 Gy (moderate-quality evidence). The guideline panel agreed that healthcare providers and CAYA cancer survivors treated with radiotherapy exposing the heart should be counselled about the increased risk for premature CAD. While the evidence is insufficient to support primary screening, monitoring and early management of modifiable cardiovascular risk factors are recommended. Initiation and frequency of surveillance should be based on the intensity of treatment exposures, family history, and presence of co-morbidities but at least by age 40 years and at a minimum of every 5 years. All were strong recommendations. CONCLUSION: These systematically assessed and harmonised recommendations for CAD surveillance will inform care and guide research concerning this critical outcome for CAYA cancer survivors.

Magnetic resonance imaging of mouse islet grafts labeled with novel chitosan-coated superparamagnetic iron oxide nanoparticles.

OBJECT: To better understand the fate of islet isografts and allografts, we utilized a magnetic resonance (MR) imaging technique to monitor mouse islets labeled with a novel MR contrast agent, chitosan-coated superparamagnetic iron oxide (CSPIO) nanoparticles. MATERIALS AND METHODS: After being incubated with and without CSPIO (10 µg/ml), C57BL/6 mouse islets were examined under transmission electron microscope (TEM) and their insulin secretion was measured. Cytotoxicity was examined in α (αTC1) and ß (NIT-1 and ßTC) cell lines as well as islets. C57BL/6 mice were used as donors and inbred C57BL/6 and Balb/c mice were used as recipients of islet transplantation. Three hundred islets were transplanted under the left kidney capsule of each mouse and then MR was performed in the recipients periodically. At the end of study, the islet graft was removed for histology and TEM studies. RESULTS: After incubation of mouse islets with CSPIO (10 µg/mL), TEM showed CSPIO in endocytotic vesicles of α- and ß-cells at 8 h. Incubation with CSPIO did not affect insulin secretion from islets and death rates of αTC1, NIT-1 and ßTC cell lines as well as islets. After syngeneic and allogeneic transplantation, grafts of CSPIO-labeled islets were visualized on MR scans as persistent hypointense areas. At 8 weeks after syngeneic transplantation and 31 days after allogeneic transplantation, histology of CSPIO-labeled islet grafts showed colocalized insulin and iron staining in the same areas but the size of allografts decreased with time. TEM with elementary iron mapping demonstrated CSPIO distributed in the cytoplasm of islet cells, which maintained intact ultrastructure. CONCLUSION: Our results indicate that after syngeneic and allogeneic transplantation, islets labeled with CSPIO nanoparticles can be effectively and safely imaged by MR.

Coronary revascularization and mortality in men with congestive heart failure or prior myocardial infarction who receive androgen deprivation.

BACKGROUND: A study was undertaken to determine the impact of prior coronary revascularization (angioplasty, stent, or coronary artery bypass graft) on the risk of all-cause mortality after neoadjuvant hormonal therapy (HT) for prostate cancer (PC) in men with a history of coronary artery disease (CAD)-induced congestive heart failure (CHF) or myocardial infarction (MI). METHODS: Among 7839 men who received radiation with or without a median of 4 months of HT for PC from 1991 to 2006, 495 (6.3%) had CAD-induced CHF or MI and formed the study cohort. Of these men, 250 (50.5%) had been revascularized before treatment for PC. Cox regression was used to determine whether HT increased the risk of all-cause mortality, and whether revascularization altered this risk, after adjusting for known PC prognostic factors and a propensity score for revascularization. RESULTS: Median follow-up was 4.1 years. Neoadjuvant HT was associated with an increased risk of all-cause mortality (28.9% vs 15.7% at 5 years; adjusted hazard ratio [HR], 1.73; 95% confidence interval [CI], 1.13-2.64; P = .01). Men who received HT without revascularization had the highest risk of all-cause mortality (33.3%; adjusted HR, 1.48; 95% CI, 1.01-2.18; P = .047), whereas men who were revascularized and did not receive HT had the lowest risk of all-cause mortality (9.4%; adjusted HR, 0.51; 95% CI, 0.28-0.93; P = .028). The reference group had an intermediate risk of all-cause mortality (23.4%) and was comprised of men in whom HT use and revascularization were either both given or both withheld. CONCLUSIONS: In men with a history of CAD-induced CHF or MI, neoadjuvant HT is associated with an excess risk of mortality, which appears to be reduced but not eliminated by prior revascularization.

Risk of all-cause and prostate cancer-specific mortality after brachytherapy in men with small prostate size.

BACKGROUND: Brachytherapy for prostate cancer can be technically challenging in men with small prostates (≤20 cc), but it is unknown whether their outcomes are different than those of men with larger prostates. METHODS AND MATERIALS: We studied 6,416 men treated with brachytherapy in one of 21 community-based practices. Cox regression and Fine and Gray's regression were used to determine whether volume ≤20 cc was associated with a higher risk of all-cause mortality (ACM) or prostate cancer-specific mortality (PCSM), respectively, after adjustment for other known prognostic factors. RESULTS: 443 patients (6.9%) had a prostate volume ≤20 cc. After a median follow-up of 2.91 years (interquartile range, 1.06-4.79), volume ≤20 cc was associated with a significantly higher risk of ACM (adjusted hazard ratio = 1.33 [95% CI 1.08-1.65], p = 0.0085) with 3-year estimates of ACM for ≤20 cc vs. >20 cc of 13.0% vs. 6.9% (p = 0.028). Only 23 men (0.36%) have died of prostate cancer, and no difference was seen in PCSM by volume (p = 0.4). CONCLUSION: Men with small prostates at the time of implant had a 33% higher risk of ACM, and the underlying cause of this remains uncertain. No increase in PCSM was observed in men with volume ≤20cc, suggesting that a small prostate should not in itself be a contraindication for brachytherapy, but inasmuch as absolute rates of PCSM were small, further follow-up will be needed to confirm this finding.

Optimizing the concentration of hydroxyethylstarch in a novel intestinal-specific preservation solution.

INTRODUCTION: Our lab has developed an effective nutrient-rich solution that facilitates energy production and control of oxidative stress during static cold storage of the intestine; however, the requirement for oncotic agents, such as hydroxyethylstarch (HES), has not been evaluated. This study investigated the effectiveness and requirement for HES in an intraluminal preservation solution during a clinically relevant period of cold storage. METHODS: Rat intestines were procured, including an intravascular flush with University of Wisconsin solution followed by a 'back table' intraluminal flush with a nutrient-rich preservation solution containing varying amounts of HES (n=6 per group): Group 1, 0%; Group 2, 2.5%; Group 3, 5%; Group 4, 10%. Energetics, oxidative stress, and morphology were assessed over a 24h time-course of cold storage. RESULTS: Overall, the 5% HES solution, Group 3, demonstrated superior energetic status (ATP and total adenylates) compared to all groups, P<0.05. Malondialdehyde levels indicated a reduction in oxidative stress in Groups 3 and 4 (P<0.05). After 12h, median modified Parks' grades for Groups 2 and 3 were significantly lower than Groups 1 and 4, P<0.05. CONCLUSION: Our data suggests that when employing an intraluminal preservation solution for static organ storage, oncotic support is a fundamental requirement; 5% HES is optimal.

Using the magnitude of PSA bounce after MRI-guided prostate brachytherapy to distinguish recurrence, benign precipitating factors, and idiopathic bounce.

PURPOSE: To identify events that precipitated a prostate-specific antigen (PSA) bounce and characterize the magnitude, duration, and time to PSA bounce after MRI-guided prostate brachytherapy. METHODS AND MATERIALS: Between 1997 and 2001, 186 patients with low-risk prostate cancer underwent MRI-guided permanent 125I source implantation, with or without external beam radiotherapy. A PSA bounce was defined as a >or=15% elevation in PSA compared with the most recent value, followed by a decline to a level at or less than the prebounce value. At the time of PSA measurement, data were prospectively collected on whether the patient had recent ejaculation, ongoing radiation proctitis, or recent instrumentation. RESULTS: A total of 115 patients (61.8%) had a total of 156 PSA bounces. Of these, 36 patients had PSA bounces associated with ejaculation, proctitis, or instrumentation, and 79 experienced idiopathic PSA bounces (not associated with a precipitating event). The magnitude of the PSA bounce was significantly lower for the idiopathic PSA bounce (0.6 ng/mL) compared with that associated with ejaculation (p = 0.003), proctitis (p <0.0001), or instrumentation (p = 0.007). Patients with biopsy-proven local recurrence had a median PSA elevation of 1.2 ng/mL, significantly higher (p = 0.006) than the magnitude of the idiopathic PSA bounce, but not significantly different from the magnitude of the PSA bounce due to ejaculation, proctitis, or instrumentation. CONCLUSION: In patients treated with MRI-guided prostate brachytherapy, recent ejaculation, instrumentation, or ongoing radiation proctitis can cause a transient increase in PSA, the magnitude of which is significantly higher than that for idiopathic PSA bounce, but is similar to that in patients with recurrent disease.