Shifting abdominal aortic aneurysm mortality trends in The Netherlands.

OBJECTIVE: Mortality from abdominal aortic aneurysm (AAA) in developed countries has decreased since the late 1990s. Our objective was to get an insight of mortality trends in The Netherlands for AAA disease. METHODS: Data of all AAA deaths (1980 to 2010) were collected from the Dutch cause of death register. Cause of death was divided in two groups: with the mention of rupture and without the mention of rupture. Data were standardized and divided into three age groups (55-69, 70-84, and ≥85 years). Mortality rates per 100,000 were analyzed for both sexes and for each age group. Significant points of change were identified using joinpoint regression analysis. RESULTS: Total standardized AAA mortality increased from 1980 (1062 deaths) until 1995 (1728 deaths), followed by a decline until 2010 (930 deaths). This decline was most prominent in men. Deaths without mention of rupture showed an increase from 1980 until 2010. The age of AAA death was higher in women (79.2 in 1980 and 82.1 in 2010) than in men. This difference declined as the age of death from AAA increased from 72.1 in 1980 to 77.9 years in 2010 in men. Decline in AAA mortality was first seen in the young age group (55-69 years) and then seen consecutively older age groups. CONCLUSIONS: Mortality from AAA is declining due to a reduction in deaths from ruptured AAAs. This was first observed in the young age groups. Men died more often and at a lower age.

Histological analysis of extracranial carotid artery aneurysms.

INTRODUCTION: Extracranial carotid artery aneurysms (ECAA) are rare but may be accompanied with significant morbidity. Previous studies mostly focused on diagnostic imaging and treatment. In contrast, the pathophysiological mechanisms and natural course of ECAA are largely unknown. Understanding the pathophysiological background may add to prediction of risk for adverse outcome and need for surgical exclusion. The aim of this study was to investigate the histopathological characteristics of ECAA in patients who underwent complete surgical ECAA resection. MATERIAL AND METHODS: From March 2004 till June 2013, 13 patients were treated with open ECAA repair. During surgery the aneurysm sac was resected and processed for standardized histological analysis. Sections were stained with routine hematoxylin and eosin and special stains to detect elastin, collagen, different types of inflammatory cells, vascular smooth muscle cells and endothelial cells. RESULTS: Histopathological characterization revealed two distinct categories: dissection (abrupt interruption of the media; n = 3) and degeneration (general loss of elastin fibers in the media; n = 10). In the degenerative samples the elastin fibers in the media were fragmented and were partly absent. Inflammatory cells were observed in the vessel wall of the aneurysms. CONCLUSION: Histological analysis in this small sample size revealed dissection and degeneration as the two distinct underlying mechanisms in ECAA formation.

High reproducibility of histological characterization by whole virtual slide quantification; an example using carotid plaque specimens.

OBJECTIVE: Tissue biobanks are an important source for discovery and validation studies aiming for new proteins that are causally related with disease development. There is an increasing demand for accurate and reproducible histological characterization, especially for subsequent analysis and interpretation of data in association studies. We assessed reproducibility of one semiquantative and two quantitative methods for histological tissue characterization. We introduce a new automated method for whole digital slide quantification. Carotid atherosclerotic plaques were used to test reproducibility. METHODS: 50 atherosclerotic plaques that were obtained during carotid endarterectomy were analysed. For the semiquantitative analysis, 6 different plaque characteristics were scored in categories by two independent observers, and Cohen's κ was used to test intra- and interobserver reproducibility. The computer-aided method (assessed by two independent observers) and automated method were tested on CD68 (for macrophages) and α smooth muscle actin (for smooth muscle cells) stainings. Agreement for these two methods (done on a continuous scale) was assessed by intraclass correlation coefficients (ICCs). RESULTS: For the semiquantitative analysis, κ values ranged from 0.55 to 0.69 for interobserver variability, and were slightly higher for intraobserver reproducibility in both observers. The computer-aided method yielded intra- and interobserver ICCs between 0.6 and 0.9. The new automated method performed most optimal regarding reproducibility, with ICCs ranging from 0.92 to 0.97. CONCLUSIONS: The analysis of performance of three methods for histological slide characterization on carotid atherosclerotic plaques showed high precision and agreement in repeated measurements for the automated method for whole digital slide quantification. We suggest that this method can fulfill the need for reproducible histological quantification.

SlideToolkit: an assistive toolset for the histological quantification of whole slide images.

The demand for accurate and reproducible phenotyping of a disease trait increases with the rising number of biobanks and genome wide association studies. Detailed analysis of histology is a powerful way of phenotyping human tissues. Nonetheless, purely visual assessment of histological slides is time-consuming and liable to sampling variation and optical illusions and thereby observer variation, and external validation may be cumbersome. Therefore, within our own biobank, computerized quantification of digitized histological slides is often preferred as a more precise and reproducible, and sometimes more sensitive approach. Relatively few free toolkits are, however, available for fully digitized microscopic slides, usually known as whole slides images. In order to comply with this need, we developed the slideToolkit as a fast method to handle large quantities of low contrast whole slides images using advanced cell detecting algorithms. The slideToolkit has been developed for modern personal computers and high-performance clusters (HPCs) and is available as an open-source project on github.com. We here illustrate the power of slideToolkit by a repeated measurement of 303 digital slides containing CD3 stained (DAB) abdominal aortic aneurysm tissue from a tissue biobank. Our workflow consists of four consecutive steps. In the first step (acquisition), whole slide images are collected and converted to TIFF files. In the second step (preparation), files are organized. The third step (tiles), creates multiple manageable tiles to count. In the fourth step (analysis), tissue is analyzed and results are stored in a data set. Using this method, two consecutive measurements of 303 slides showed an intraclass correlation of 0.99. In conclusion, slideToolkit provides a free, powerful and versatile collection of tools for automated feature analysis of whole slide images to create reproducible and meaningful phenotypic data sets.