Allelic loss of chromosome 1p as a predictor of unfavorable outcome in patients with neuroblastoma

Background. Neuroblastoma is a childhood tumor derived from cells of the neural crest, with a widely variable outcome. Differences in the behavior and prognosis of the tumor suggest that neuroblastoma can be divided into several biologic subgroups. We evaluated the most frequent genetic abnormalities in neuroblastoma to determine their prognostic value. Methods. We used Southern blot analysis to study the allelic loss of chromosomes 1p, 4p, 11q, and 14q, the duplication of chromosome 17q, and the amplification of the N-myc oncogene in 89 neuroblastomas. We also determined the nuclear DNA content of the tumor cells. Results. Allelic loss of chromosome 1p, N-myc amplification, and extra copies of chromosome 17q were significantly associated with unfavorable outcomes. In a multivariate analysis, loss of chromosome 1p was the most powerful prognostic factor. It provided strong prognostic information when it was included in multivariate models containing the prognostic factors of age and stage or serum ferritin level and stage. Among the patients with stage I, II, or IVS disease, the mean (±SD) three-year event-free survival was 100 percent in those without allelic loss of chromosome 1p and 34±15 percent in those with such loss; the rates of three- year event-free survival among the patients with stage III and stage IV disease were 53±10 percent and 0 percent, respectively. Conclusions. The loss of chromosome 1p is a strong prognostic factor in patients with neuroblastoma, independently of age and stage. It reliably identifies patients at high risk in stages I, II, and IVS, which are otherwise clinically favorable. More intensive therapy may be considered in these patients. Patients in stages III and IV with allelic loss of chromosome 1p have a very poor outlook, whereas those without such loss are at moderate risk

Medical and Technical Considerations in Vascular Surgery

__Abstract__ It is estimated that in the year 2020 more than a million non-cardiac, vascular surgery procedures will be performed annually in Europe. The same applies for the US. With this growing application of high-risk procedures, it is important to continuously strive for improved patient safety and surgical outcome. Regarding patient safety, it is key to recognize a change in patient populations and patient selections. Due to anesthetic and medical improvements as well as surgical innovation, the vascular surgery population is increasing in age, tends to have more co-morbidity and more often uses multiple prescription drugs. In other words, it is a fragile population, undergoing high-risk surgery. Cardiovascular adverse events are responsible for a major proportion of morbidity and mortality in patients undergoing vascular surgery, with an estimated incidence of more than 5% of ischemic complications, and up to 10% new-onset arrhythmias in major vascular surgery. In the first part of this thesis, certain patient safety issues, secondary prevention and future perspectives are discussed, regarding these cardiovascular complications

Calcification of the abdominal aorta as an independent predictor of cardiovascular events: A meta-analysis

Context: Abdominal aortic calcification (AAC) is a common finding in patients with atherosclerosis. Objective: The aim of this study was to demonstrate the incremental value of AAC in predicting long term cardiovascular (CV) outcome by conducting a meta-analysis of observational studies. Data sources: MEDLINE and Cochrane databases. Study selection Longitudinal studies with at least 2 years of follow-up, reporting the influence of AAC on CV outcome of general population patients. Data extraction: Four separate end points - coronary events, cerebrovascular events, all CV events and CV related death - were tested for their relationship with AAC at baseline, using weighted random effects meta-analysis. Heterogeneity was calculated using Q and I 2statistic tests. Publication bias was assessed by funnel plot symmetry and trim and fill methods. The importance of calcium quantification was also explored (sensitivity analysis). Results: 10 studies were included. An increased relative risk (RR) was found for all end points: for coronary events (five studies, n=11250) 1.81 (95% CI 1.54 to 2.14); for cerebrovascular events (four studies, n=9736) 1.37 (1.22 to 3.54); for all CV events (four studies, n=4960) 1.64 (1.24 to 2.17); and for CV death (three studies, n=4986) 1.72 (1.03 to 2.86). Analysis of studies presenting results in categories (no/minimal, moderate and severe calcification) revealed a stepwise increase in the RR for all end points. Significant heterogeneity was found in the included studies. Sources of heterogeneity were identified in the publication date, duration of follow-up, and mean age and gender differences in the included patient cohorts. Conclusion: Existing data suggest that AAC is a strong predictor of CV related events or death in the general population. The predictive impact is greater in more calcified aortas. The generalisability of the meta-anal

Treatment of post-implantation aneurysm growth by laparoscopic sac fenestration: Long-term results

Objectives: Sac growth after endovascular aneurysm repair (EVAR) is an important finding, which may influence prognosis. In case of a type II endoleak or endotension, clipping of side branches and subsequent sac fenestration has been presented as a therapeutic alternative. The long-term clinical efficacy of this procedure is unknown. Methods: The study included eight patients who underwent laparoscopic aortic collateral clipping and sac fenestration for enlarging aneurysms following EVAR. Secondary interventions and clinical outcome were retrieved from hospital records. Sac behaviour was evaluated measuring volumes on periodical computed tomography angiography (CTA) imaging using dedicated software. Results: Follow-up had a median length of 6.6 (range 0.6-8.6) years. During this time, only three pati

The influence of neck thrombus on clinical outcome and aneurysm morphology after endovascular aneurysm repair

Objective: This study investigated the influence of significant aneurysm neck thrombus in clinical and morphologic outcomes after endovascular aneurysm repair (EVAR). Methods: The patient population was derived from a prospective EVAR database from two university institutions in The Netherlands from 2004 to 2008. Patients with significant thrombus in the neck (>2 mm in thickness in at least >25% of circumference) were identified as the thrombus group and were compared with the remaining patients without neck thrombus (no-thrombus group), treated within the same period. The primary end point was clinical success. Secondary end points included technical success and rates of decline in renal function. Detailed morphologic analysis of the aortic neck was serially performed for the thrombus group patients to assess changes in thrombus volume. Results: The study included 389 patients: 43 (39 men; mean age of 72.3 years) met the criteria for the thrombus group; of these, 31 (72%) had significant thrombus in >50% of the aortic neck circumference, and 8 (19%) had circumferential thrombus >2-mm thick. Median follow-up was 3.34 years (interquartile range, 2.67-4.72). The estimated 5-year clinical success rate was 74% for the thrombus group and 62% for the no-thrombus group (P =.23). Endograft migration was more frequent in the thrombus group (P =.02). Multivariable Cox regression analysis showed a significant association between migration and use of a device without active fixation (hazard ratio, 4.9; 95% confidence interval, 1.31-18.23; P =.018) but not with the presence of neck thrombus (P =.063). No differences were found in the rates of decline in estimated glomerular filtration rate at 30 days and during follow-up between the thrombus and no-thrombus groups. The thrombus volume in the first 10 mm of aortic neck was progressively reduced over time until it was not measurable in most patients, resulting in complete circular attachment of the endograft to the vessel wall. Conclusions: Our findings suggest that the presence of aneurysm neck thrombus has no significant influence on short-term and midterm EVAR results

Preoperative left ventricular dysfunction predisposes to postoperative acute kidney injury and long-term mortality

Background: Both preoperative left ventricular dysfunction (LVD) and acute kidney injury (AKI) in the postoperative period are independently associated with mortality. We evaluated the prevalence and prognostic implications of AKI in a cohort of vascular surgery patients. Methods: Before vascular surgery, 1,158 patients were screened for LVD. Development of AKI, defined by RIFLE classification, was detected by serial serum creatinine measurements at days 1 to 3 after surgery. Primary end point was cardiovascular mortality during a median follow-up of 2.2 years (interquartile range [IQR] 1.0-4.0). Results: LVD was present in 558 patients (48%), and 120 patients (10%) developed postoperative AKI. Subjects with LVD developed postoperative AKI more often than patients without LVD (8% vs. 13%, p=0.01). Patients were categorized as (i) no LVD, without AKI (n=551, 48%), (ii) LVD without AKI (n=487, 42%), (iii) no LVD, with AKI (n=49, 4%) and (iv) LVD with AKI (n=71/6%). Patients with LVD prior to surgery who developed postoperative AKI had the highest cardiovascular mortality risk (hazard ratio = 4.9; 95% confidence interval, 2.9-8.2). Conclusion: Patients with preoperatively LVD have an increased risk of developing AKI after vascular surgery. The occurrence of AKI in patients with LVD has an incremental predictive value toward cardiovascular mortality risk during long-term follow-up