Anatomic-Clinical Presentation. Testicular Teratocarcinoma with Thoracic-Abdominal Adenopathy

peer reviewedThis case report of a young man with a testicular germ cell-teratoma tumor illustrates the necessity of a multidisciplinary sequential approach to ensure chance of cure. The outcome of patients with advanced germ cell tumor depends on the optimal clinical management. Residual masses are frequent, and their histology can be different than the initial one (i.e., only residual mature teratoma cells or necrosis-fibrosis). Therefore a second surgery on residual masses with curative intent, may be important to optimalize the treatment and follow up

Analysis of positional candidate genes in the AAA1 susceptibility locus for abdominal aortic aneurysms on chromosome 19

ABSTRACT: BACKGROUND: Abdominal aortic aneurysm (AAA) is a complex disorder with multiple genetic risk factors. Using affected relative pair linkage analysis, we previously identified an AAA susceptibility locus on chromosome 19q13. This locus has been designated as the AAA1 susceptibility locus in the Online Mendelian Inheritance in Man (OMIM) database. METHODS: Nine candidate genes were selected from the AAA1 locus based on their function, as well as mRNA expression levels in the aorta. A sample of 394 cases and 419 controls was genotyped for 41 SNPs located in or around the selected nine candidate genes using the Illumina GoldenGate platform. Single marker and haplotype analyses were performed. Three genes (CEBPG, PEPD and CD22) were selected for DNA sequencing based on the association study results, and exonic regions were analyzed. Immunohistochemical staining of aortic tissue sections from AAA and control individuals was carried out for the CD22 and PEPD proteins with specific antibodies. RESULTS: Several SNPs were nominally associated with AAA (p < 0.05). The SNPs with most significant p-values were located near the CCAAT enhancer binding protein (CEBPG), peptidase D (PEPD), and CD22. Haplotype analysis found a nominally associated 5-SNP haplotype in the CEBPG/PEPD locus, as well as a nominally associated 2-SNP haplotype in the CD22 locus. DNA sequencing of the coding regions revealed no variation in CEBPG. Seven sequence variants were identified in PEPD, including three not present in the NCBI SNP (dbSNP) database. Sequencing of all 14 exons of CD22 identified 20 sequence variants, five of which were in the coding region and six were in the 3'-untranslated region. Five variants were not present in dbSNP. Immunohistochemical staining for CD22 revealed protein expression in lymphocytes present in the aneurysmal aortic wall only and no detectable expression in control aorta. PEPD protein was expressed in fibroblasts and myofibroblasts in the media-adventitia border in both aneurysmal and non-aneurysmal tissue samples. CONCLUSIONS: Association testing of the functional positional candidate genes on the AAA1 locus on chromosome 19q13 demonstrated nominal association in three genes. PEPD and CD22 were considered the most promising candidate genes for altering AAA risk, based on gene function, association evidence, gene expression, and protein expression

Evidence for association between the HLA-DQA locus and abdominal aortic aneurysms in the Belgian population: a case control study

BACKGROUND: Chronic inflammation and autoimmunity likely contribute to the pathogenesis of abdominal aortic aneurysms (AAAs). The aim of this study was to investigate the role of autoimmunity in the etiology of AAAs using a genetic association study approach with HLA polymorphisms. METHODS: HLA-DQA1, -DQB1, -DRB1 and -DRB3-5 alleles were determined in 387 AAA cases (180 Belgian and 207 Canadian) and 426 controls (269 Belgian and 157 Canadian) by a PCR and single-strand oligonucleotide probe hybridization assay. RESULTS: We observed a potential association with the HLA-DQA1 locus among Belgian males (empirical p = 0.027, asymptotic p = 0.071). Specifically, there was a significant difference in the HLA-DQA1*0102 allele frequencies between AAA cases (67/322 alleles, 20.8%) and controls (44/356 alleles, 12.4%) in Belgian males (empirical p = 0.019, asymptotic p = 0.003). In haplotype analyses, marginally significant association was found between AAA and haplotype HLA-DQA1-DRB1 (p = 0.049 with global score statistics and p = 0.002 with haplotype-specific score statistics). CONCLUSION: This study showed potential evidence that the HLA-DQA1 locus harbors a genetic risk factor for AAAs suggesting that autoimmunity plays a role in the pathogenesis of AAAs

Analysis of coding sequences for tissue inhibitor of metalloproteinases 1 (TIMP1) and 2 (TIMP2) in patients with aneurysms.

Aneurysms are characterized by dilation, i.e. expansion and thinning of all the arterial wall layers, which is accompanied by remodeling of the connective tissue. Genes involved in the regulation of tissue remodeling are therefore candidate genes. We analyzed TIMP1 and TIMP2 coding sequences in 12 individuals with abdominal aortic aneurysms (AAA), one individual with AAA and intracranial aneurysms (IA), four individuals with IA and two clinically unaffected individuals. We identified two nucleotide variants in both the TIMP1 and the TIMP2 coding sequences. All differences occurred in the third base positions of codons and were neutral polymorphisms. A significant difference was observed in the frequency of TIMP2 nt 573 polymorphism between 168 alleles from AAA patients and 102 control alleles

Marfan syndrome in childhood and adolescence

peer reviewe

Preliminary data from the Liège Screening programme suggests the reported decline in AAA prevalence is not global

peer reviewedBackground: Population based studies have shown evident benefit in terms of mortality from screening for Abdominal Aortic Aneurysm (AAA) among men aged over 65. However, recent studies from USA, UK and Sweden suggest a decrease in the prevalence of AAA in the general population. Whether these findings are generalizable for the rest of Europe is unknown. Thus we decided to set up a screening program in order to detect AAA in Liege, Belgium. Material and Methods: During our ongoing study, over a first 3-month period, abdominal aortic ultrasound was performed on 541 participants, (198 women 343 men) to measure the maximal suprarenal and infrarenal aortic outer-outer diameter as well as the maximal diameter of the common iliac arteries. Moreover, we have measured arm and ankle blood pressure in each subject and the clinical characteristics of the patients, were collected. Results: The overall AAA prevalence was 4.62% (n = 25). In female participants aged ≥ 74 years the AAA prevalence amounted 1.01 %. While in male patients aged ≥ 65 years, it rose to 6.71%. Statistical analysis showed that male gender, aging, history of ischemic heart diseases, hyperlipidemia and varicose veins were significantly associated with AAA. Conclusion: Despite a reported declining prevalence of AAA in some recent population-based studies, we found that the prevalence of AAA in Liège population remains high in men aged 65 years or more. The prevalence of AAA seems to vary in different geographical regions. However, we need a larger sample to confirm our preliminary findings

Extending abdominal aortic aneurysm detection to older age groups: preliminary results from the Liege screening programme.

BACKGROUND: There is evident benefit in terms of reduced aneurysm related mortality from screening programmes of abdominal aortic aneurysm (AAA) in men aged 65 and more. Recent studies in UK and Sweden have shown a decline of the prevalence of AAA in the general population. Current screening policies (e.g. men aged 65-74 years) however do not account for ageing and increased life expectancy of western populations. This study investigated AAA detection by extending the target population to older age groups (75-85 years). METHODS: AAA screening was conducted in the County of Chaudfontaine (Liege, Belgium) on the population of elderly (N=3,054). The participation rate was 36%. The 1,101 participants (722 men aged 65-85 and 379 women aged 74-85 years) were examined by ultrasound (US) scan. AAA was defined as an infrarenal aortic outer-outer diameter of at least 3 cm. Demographics, clinical parameters and risk factors were also recorded. AAA prevalence was estimated and patients with and without AAA were compared by logistic regression. RESULTS: The overall AAA prevalence was 3.6% (n=40). In female participants, AAA prevalence was low (1.3%). In men, it amounted 2.7% in the 65-74 age group but rose to 7.3% in the age-extended group (75-85 years). Further in addition to age, height, current smoking, history of coronary artery disease, hypercholesterolemia, peripheral artery disease of the lower limbs and varicose veins were significantly associated with the presence of AAA. CONCLUSION: These preliminary findings, based on a representative sample of the elderly population of the Liege region, support the idea that current AAA screening policies should be updated to cover an increasingly ageing population. The presence of varicose veins as a potential risk factor for AAA should also be considered during screening