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Apeldoorn, Netherlands

Baas A.F.,University Utrecht | Medic J.,University Utrecht | Van'T Slot R.,University Utrecht | De Vries J.-P.P.M.,St. Antonius Hospital | And 10 more authors.

Background: A genetic variant on chromosome 9p21 associates with abdominal aortic aneurysm (AAA) and intracranial aneurysm (IA), indicating that despite the differences in pathology there are shared genetic risk factors. We investigated whether the IA susceptibility genes heparan sulfate proteoglycan 2 (HSPG2) and chondroitin sulfate proteoglycan 2 (CSPG2) associate with AAA as well. Methods: Using tag single nucleotide polymorphisms (SNPs), all common variants were analyzed in a Dutch AAA case-control population in a 2-stage genotyping approach. In stage 1, 12 tag SNPs in HSPG2 and 22 tag SNPs in CSPG2 were genotyped in 376 patients and 648 controls. Genotyping of significantly associated SNPs was replicated in a second independent cohort of 360 cases and 376 controls. Results: In stage 1, no HSPG2 SNPs and 1 CSPG2 SNP associated with AAA (rs2652106, P =.019). Association of this SNP was not replicated (P =.342). Conclusions: Our findings demonstrate that, in contrast to IA, HSPG2 and CSPG2 do not associate with AAA. Source

Lesterhuis W.J.,Radboud University Nijmegen | De Vries I.J.M.,Radboud University Nijmegen | Aarntzen E.A.,Radboud University Nijmegen | De Boer A.,Radboud University Nijmegen | And 7 more authors.
British Journal of Cancer

Background: Dendritic cell (DC) vaccination has been shown to induce anti-tumour immune responses in cancer patients, but so far its clinical efficacy is limited. Recent evidence supports an immunogenic effect of cytotoxic chemotherapy. Pre-clinical data indicate that the combination of chemotherapy and immunotherapy may result in an enhanced anti-cancer activity. Most studies have focused on the immunogenic aspect of chemotherapy-induced cell death, but only few studies have investigated the effect of chemotherapeutic agents on the effector lymphocytes of the immune system. Methods: Here we investigated the effect of treatment with oxaliplatin and capecitabine on non-specific and specific DC vaccine-induced adaptive immune responses. Stage III colon cancer patients receiving standard adjuvant oxaliplatin/capecitabine chemotherapy were vaccinated at the same time with keyhole limpet haemocyanin (KLH) and carcinoembryonic antigen (CEA)-peptide pulsed DCs. Results: In 4 out of 7 patients, functional CEA-specific T-cell responses were found at delayed type hypersensitivity (DTH) skin testing. In addition, we observed an enhanced non-specific T-cell reactivity upon oxaliplatin administration. KLH-specific T-cell responses remained unaffected by the chemotherapy, whereas B-cell responses were diminished. Conclusion: The results strongly support further testing of the combined use of specific anti-tumour vaccination with oxaliplatin-based chemotherapy. © 2010 Cancer Research UK. Source

Hoeks C.M.A.,Radboud University Nijmegen | Schouten M.G.,Radboud University Nijmegen | Bomers J.G.R.,Radboud University Nijmegen | Hoogendoorn S.P.,Radboud University Nijmegen | And 6 more authors.
European Urology

Background: Patients with elevated prostate-specific antigen (PSA) and one or more previous negative transrectal ultrasound (TRUS) biopsy sessions are subject to diagnostic uncertainty due to TRUS-biopsy undersampling. Magnetic resonance (MR)-guided biopsy (MRGB) has shown high prostate cancer (PCa)-detection rates in studies with limited patient numbers. Objective: Determine the detection rate of (clinically significant) PCa for MRGB of cancer-suspicious regions (CSRs) on 3-T multiparametric MR imaging (MP-MRI) in patients with elevated PSA and one or more negative TRUS-biopsy sessions. Design, setting, and participants: Of 844 patients who underwent 3-T MP-MRI in our referral centre between March 2008 and February 2011, 438 consecutive patients with a PSA >4.0 ng/ml and one negative TRUS-biopsy session or more were included. MRGB was performed in 265 patients. Exclusion criteria were existent PCa, endorectal coil use, and MP-MRI for indications other than cancer detection. Intervention: Patients underwent MRGB of MP-MRI CSRs. Measurements: (Clinically significant) MRGB cancer-detection rates were determined. Clinically significant cancer was defined by accepted (i.a. Epstein and d'Amico) criteria based on PSA, Gleason score, stage, and tumour volume. Follow-up PSA and histopathology were collected. Sensitivity analysis was performed for patients with MP-MRI CSRs without MRGB. Results and limitations: In a total of 117 patients, cancer was detected with MRGB (n = 108) or after negative MRGB (n = 9). PCa was detected in 108 of 438 patients (25%) and in 41% (108 of 265) of MRGB patients. The majority of detected cancers (87%) were clinically significant. Clinically significant cancers were detected in seven of nine (78%) negative MRGB patients in whom PCa was detected during follow-up. Sensitivity analysis resulted in increased cancer detection (47-56%). Complications occurred in 0.2% of patients (5 of 265). Conclusions: In patients with elevated PSA and one or more negative TRUS-biopsy sessions, MRGB of MP-MRI CSRs had a PCa-detection rate of 41%. The majority of detected cancers were clinically significant (87%). © 2012 European Association of Urology. Source

Spronk S.,Erasmus Medical Center | Van Kempen B.J.H.,Erasmus Medical Center | Boll A.P.M.,Canisius Wilhelmina Hospital Nijmegen | Jorgensen J.J.,University of Oslo | And 2 more authors.
British Journal of Surgery

Background: The aim of this study was to determine the cost-effectiveness of ultrasound screening for abdominal aortic aneurysm (AAA) in men aged 65 years, for both the Netherlands and Norway. Methods: A Markov model was developed to simulate life expectancy, quality-adjusted life-years, net health benefits, lifetime costs and incremental cost-effectiveness ratios for both screening and no screening for AAA. The best available evidence was retrieved from the literature and combined with primary data from the two countries separately, and analysed from a national perspective. A threshold willingness-to-pay (WTP) of €20 000 and €62 500 was used for data from the Netherlands and Norway respectively. Results: The additional costs of the screening strategy compared with no screening were €421 (95 per cent confidence interval 33 to 806) per person in the Netherlands, and the additional life-years were 0·097 (-0·180 to 0·365), representing €4340 per life-year. For Norway, the values were €562 (59 to 1078), 0·057 (-0·135 to 0·253) life-years and €9860 per life-year respectively. In Norway the results were sensitive to a decrease in the prevalence of AAA in 65-year-old men to 1 per cent, or lower. Probabilistic sensitivity analyses indicated that AAA screening has a 70 per cent probability of being cost-effective in the Netherlands with a WTP threshold of €20 000, and 70 per cent in Norway with a threshold of €62 500. Conclusion: Using this model, screening for AAA in 65-year-old men would be highly cost-effective in both the Netherlands and Norway. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. Source

Pijnenburg-Kleizen K.J.,Radboud University Nijmegen | Borm G.F.,Radboud University Nijmegen | Otten B.J.,Radboud University Nijmegen | Schott D.A.,Radboud University Nijmegen | And 5 more authors.
Hormone Research in Paediatrics

Background/Aims: In classical congenital adrenal hyperplasia (CAH), elevation of adrenal androgens leads to accelerated growth and bone maturation with compromised adult height. In untreated children with non-classical CAH (NC-CAH), in which adrenal androgens are generally only slightly increased, growth velocity may not be significantly elevated. Methods: Twenty-four patients were included and divided into a symptomatic and an asymptomatic group. Height was expressed as height standard deviation scores (HSDS) and corrected for target height (HSDS-THSDS). Bone maturation was expressed as bone age acceleration (BA c = bone age - calendar age). Linear mixed models with random factor patient were used for the analysis of growth and bone age. Results: In symptomatic patients (n = 17), HSDS-THSDS only slightly increased by 0.06 SDS per year (95% CI 0.02-0.10). Mean BA c was 2.21 years (SDS 0.66, p < 0.0001). In asymptomatic patients (n = 7), no significant growth acceleration or BA c was found. Conclusions: In untreated NC-CAH children, growth acceleration is small and generally not visible on their growth charts. BA c is more pronounced. Therefore, the absence of an increase in growth velocity does not exclude the diagnosis of NC-CAH. When considering this diagnosis, bone age acceleration should also be taken into account. Copyright © 2012 S. Karger AG, Basel. Source

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