Stable Abdominal Aortic Aneurysm Research Articles

Evaluation of associations between outflow morphology and rupture risk of abdominal aortic aneurysms

PurposeThis study aimed to evaluate the association between the outflow morphology and abdominal aortic aneurysm (AAA) rupture risk, to find risk factors for future prediction models. Materials and methodsWe retrospectively analyzed 46 patients with ruptured AAAs and 46 patients with stable AAAs using a 1:1 match for sex, age, and maximum aneurysm diameter. The chi-square test, paired t-test, and Wilcoxon signed-rank test were used to compare variables. Logistic regression was performed to evaluate variables potentially associated with AAA rupture. Receiver operating characteristic curve analysis and the area under the curve (AUC) were used to assess the regression models. ResultsRuptured AAAs had a shorter proximal aortic neck (median (interquartile range, IQR): 24.0 (9.4–34.2) mm vs. 33.3 (20.0–52.8) mm, p = 0.004), higher tortuosity (median(IQR): 1.35 (1.23–1.49) vs. 1.29 (1.23–1.39), p = 0.036), and smaller minimum luminal area of the right common iliac artery (CIA) (median (IQR): 86.7 (69.9–126.4) mm2 vs. 118.9 (86.3–164.1)mm2, p = 0.001) and left CIA (median(IQR): 92.2 (67.3,125.1) mm2 vs. 110.7 (80.12, 161.1) mm2, p = 0.010) than stable AAA did. Multiple regression analysis demonstrated significant associations of the minimum luminal area of the bilateral CIAs (odds ratio [OR] = 0.996, 95 % confidence interval [CI] 0.991–0.999, p = 0.037), neck length (OR = 0.969, 95 % CI 0.941–0.993, p = 0.017), and aneurysm tortuosity (OR = 1.031, 95 % CI 1.003–1.063, p = 0.038) with ruptured AAAs. The AUC of this regression model was 0.762 (95 % CI 0.664–0.860, p < 0.001). ConclusionsThe smaller minimum luminal area of the CIA is associated with an increased risk of rupture. This study highlights the potential of utilizing outflow parameters as novel and additional tools in risk assessment. It also provides a compelling rationale to further intensify research in this area.

Construction of the miRNA/Pyroptosis-Related Molecular Regulatory Axis in Abdominal Aortic Aneurysm: Evidence From Transcriptome Data Combined With Multiple Machine Learning Approaches Followed by Experiment Validation.

Background: Abdominal aortic aneurysm (AAA) represents a permanent and localized widening of the abdominal aorta, posing a potentially lethal risk of aortic rupture. Several recent studies have highlighted the role of pyroptosis, a pro-inflammatory programed cell death, as critical molecular regulators in AAA occurrence, progression, and rupture. However, the potential effects of pyroptosis in AAA and its upstream microRNA (miRNA) have not been comprehensively clarified. Methods: Through a search of the gene expression omnibus (GEO) database, the expression profiles of mRNAs (GSE7084, GSE57691, and GSE98278) and miRNAs (GSE62179) and corresponding clinical features were downloaded, respectively. Expression profiles of 15 AAA and 10 normal vascular samples were consecutively collected for in vitro experimentation and subsequent analysis. Various machine learning techniques were employed to identify hub pyroptosis-related genes (PRGs), leading to the development of a predictive model termed the PRG classifier. Quantitative real-time-polymerase chain reaction (qRT-PCR), western blot (WB), and enzyme-linked immunosorbent assay (ELISA) were used to confirm the expression of the hub PRGs. The diagnostic and predictive capabilities of the model were comprehensively evaluated in GEO and hospital cohorts. Then, the crucial immune cell infiltration and molecular pathways implicated in the initiation and rupture of AAA and their association with pyroptosis were explored. Lastly, a miRNA/hub pyroptosis-related molecular regulatory axis was constructed using the TargetScan dataset, which was further explored through loss-of-function assays. Results: Differential analysis, enrichment score analysis, and principal component analysis (PCA) revealed that pyroptosis-related molecules were significantly involved in the occurrence of AAA. Utilizing multiple machine learning algorithms, eight key PRGs (cysteinyl aspartate specific proteinase [CASP]1, infiltrating lymphocyte [IL]1B, IL18, IL6, NOD-, LRR- and pyrin domain-containing protein [NLRP]1, NLRP2, NLRP3, and tumor necrosis factor [TNF]) were integrated to establish a PRG classifier. Demonstrating robust diagnostic capabilities (area under curve [AUC] > 0.90), the PRG classifier provided clinical insights across two GEO datasets and effectively differentiated small AAA from large AAA, elective stable AAA (eAAA), and ruptured AAA (rAAA), respectively. qRT-PCR, WB, and ELISA verified the mRNA and protein expression of the hub PRGs. Notably, in hospital cohorts, a substantial positive link was unveiled between the PRG classifier and AAA risk factors (hypertension history, diastolic pressure, triglyceride levels, and aneurysm diameter). Furthermore, immune cell infiltration and functional enrichment analysis revealed significant associations of the PRG classifier/PRGs with M2 macrophage infiltration, activated dendritic cells, and enrichment scores of the cytosolic deoxyribonucleic acid (DNA) sensing pathway and tryptophan metabolism, potentially mediating AAA onset and rupture. Finally, based on 90 differentially expressed miRNAs (DEmiRNAs) and eight hub PRGs through TargetScan dataset, a hsa-miR-331-3p/TNF regulatory axis was constructed, wherein upregulation of hsa-miR-331-3p expression significantly reduced TNF and CASP1 protein levels. Conclusion: A predictive model (PRG classifier) incorporating eight PRGs through multiple machine learning algorithms was developed and validated. This model may stand as a potent tool for diagnosing AAA and assessing disease severity. The identification of the cytosolic DNA sensing pathway and the hsa-miR-331-3p/TNF interaction axis may represent crucial targets for AAA treatment, offering deeper insights into its potential pathogenesis.

Early Results of Elective Endovascular Repair of Infrarenal Abdominal Aortic Aneurysms With the MinosTM Stent-Graft System.

A variety of last-generation endografts are currently available for standard endovascular repair (EVAR) of infrarenal abdominal aortic aneurysms (AAAs). The purpose of this study is to report the preliminary clinical outcomes of the Minos trimodular stent-graft system, which was recently introduced to the European market. Between February 2020 and 2022, we treated 41 consecutive AAA patients (mean age 72.2±8.5, 37 males) with elective standard EVAR using the Minos. The mean maximum diameter of AAAs was 54.7±6.6 mm, the mean proximal neck's (PN) diameter was 24.8±2.7 mm, while the relevant length and angulation were 16.0 mm and 21.7°, respectively. Overall, 22 (53.6%) patients presented with shorter and angulated PN, according to the stent-graft's instructions of use, and in 6 (14.6%) patients the PN angulation >60° was combined with concomitant iliac angulation >60°. Eleven (26.8%) EVARs were performed with concomitant enormous iliac artery narrowing and tortuosity. Finally, in 19 (46.3%) AAAs, the distal iliac landing zone was aneurysmatic and they were treated with the bell-bottom technique in 17 patients and with limb extension to the external iliac artery in two cases. We evaluated technical and clinical success of the index procedures, which was based on the combination of five factors: freedom from EVAR-related mortality, from graft-related endoleak of any type, from migration at any part of graft as well the absence of notable increase AAA's sac maximum diameter and the patency of bifurcated stent-graft and of access vessels. Primary technical and clinical success of index procedures was 100%. During a median 12-month radiological follow-up the clinical success remained 100%. No type I or III endoleak, stent-graft migration, EVAR-related death, AAA rupture, or graft-related adverse events or reinterventions were documented. Four (9.8%) type II endoleaks were detected with stable AAA sac diameter. The overall incidence of sac regression was 34.1% (n=14). The preliminary results of our series showed that Minos provided excellent feasibility and safety features even through angulated and tortuous iliac vessels and in short and angulated PNs. The overall clinical success at 1 year suggests that performance of Minos follows very high standards. Further validation of these promising results with long-term data is acquired to complete the evaluation of this recently introduced stent-graft system. The current study explored the clinical performance of a new in market ultra-low profile bifurcated abdominal aortic stent-graft, the MINOS. The early and 12-month results of study suggest that implantation of this stent-graft in standard EVAR, even in hostile proximal aortic neck and iliac vessels conditions, follows very high clinical standards and encourage the further clinical use of MINOS.

Predictors of Abdominal Aortic Aneurysm Shrinkage after Endovascular Repair.

Recent studies demonstrate that patients with a shrinking abdominal aortic aneurysm (AAA), one-year after endovascular repair (EVAR), have better long-term outcomes than patients with a stable AAA. It is not known what factors determine whether an AAA will shrink or not. In this study, a range of parameters was investigated to identify their use in differentiating patients that will develop a shrinking AAA from those with a stable AAA one-year after EVAR. Hundred-seventy-four patients (67 shrinking AAA, 107 stable AAA) who underwent elective, infrarenal EVAR were enrolled between 2011–2018. Long-term survival was significantly better in patients with a shrinking AAA, compared to those with a stable AAA (p = 0.038). Larger preoperative maximum AAA diameter was associated with an increased likelihood of developing AAA shrinkage one-year after EVAR—whereas older age and larger preoperative infrarenal β angle were associated with a reduced likelihood of AAA shrinkage. However, this multivariate logistic regression model was only able to correctly identify 66.7% of patients with AAA shrinkage from the total cohort. This is not sufficient for implementation in clinical care, and therefore future research is recommended to dive deeper into AAA anatomy, and explore potential predictors using artificial intelligence and radiomics.

Mouse Abdominal Aortic Aneurysm Model Induced by Perivascular Application of Elastase.

Abdominal aortic aneurysm (AAA), although primarily asymptomatic, is potentially life-threatening as the rupture of AAA usually has a devastating outcome. Currently, there are several distinct experimental models of AAA, each emphasizing a different aspect in the pathogenesis of AAA. The elastase-induced AAA model is the second most used rodent AAA model. This model involves direct infusion or application of porcine pancreatic elastase (PPE) to the infrarenal segment of the aorta. Due to technical challenges, most elastase-induced AAA model nowadays is performed with the external application rather than an intraluminal infusion of PPE. The infiltration of elastase will cause degradation of elastic lamellae in the medial layers, resulting in the loss of aortic wall integrity and subsequent dilation of the abdominal aorta. However, one disadvantage of the elastase-induced AAA model is the inevitable variation of how the surgery is performed. Specifically, the surgical technique of isolating the infrarenal segment of the aorta, the material used for aorta wrapping and PPE incubation, the enzymatic activity of PPE, and the time duration of PPE application can all be important determinants that affect the eventual AAA formation rate and aneurysm diameter. Notably, the difference in these factors from different studies on AAA can lead to reproducibility issues. This article describes a detailed surgical process of the elastase-induced AAA model through direct application of PPE to the adventitia of the infrarenal abdominal aorta in the mouse. Following this procedure, a stable AAA formation rate of around 80% in male and female mice is achievable. The consistency and reproducibility of AAA studies using an elastase-induced AAA model can be significantly enhanced by establishing a standard surgical procedure.

Blood Biomarkers and Serologic Immunological Profiles Related to Periodontitis in Abdominal Aortic Aneurysm Patients.

BackgroundPeriodontitis is a chronic inflammatory gum disease associated with systemic diseases such as cardiovascular diseases.AimTo investigate the association of systemic blood biomarkers, C-reactive protein (CRP), levels of lipopolysaccharide (LPS), and IgG levels against periodontal pathogens Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) with the stability, based on the aortic diameter, the growth rate and the eligibility for surgical intervention, of patients with abdominal aortic aneurysm (AAA).MethodsPatients with stable AAA (n = 30) and unstable AAA (n = 31) were recruited. The anti-A. actinomycetemcomitans and anti-P. gingivalis IgG levels were analyzed by ELISA, the LPS analysis was performed by using the limulus amebocyte lysate (LAL) test, and plasma levels of CRP were determined using an immune turbidimetric method. The association between these blood systemic biomarkers, AAA features, periodontal clinical parameters and oral microbial profiles were explored. Regression models were used to test the relationship between variables.ResultsThe presence of antibodies against Pg and Aa, LPS and high CRP concentrations were found in all AAA patients. The IgG levels were similar in patients with stable and unstable AAA (both for Aa and Pg). Among investigated blood biomarkers, only CRP was associated with AAA stability. The amount of LPS in saliva, supra, and subgingival plaque were significantly associated with the systemic LPS (p <0.05).ConclusionsThis post-hoc study emphasizes the presence of antibodies against Pg and Aa, LPS and high CRP concentrations in all AAA patients. The presence of Pg in saliva and subgingival plaque was significantly associated with the blood LPS levels. For further studies investigating periodontitis and systemic diseases, specific predictive blood biomarkers should be considered instead of the use of antibodies alone.

Patterns of immune infiltration in stable and raptured abdominal aortic aneurysms: A gene-expression-based retrospective study.

Abdominal aortic aneurysm (AAA) is a disease characterized by weakening arterial wall and permanent expansion with high mortality once rupture, which was involved with immune system activation. However, owing to technical difficulties, previous research has limited the impact of one or limited immune cells on AAA. We analyzed the composition of immune cells using the CIBERSORT algorithm through transcriptome sequencing data from patients with stable (eAAA) and ruptured aneurysms (rAAA). The whole transcriptome sequencing data, including 17 patients with ruptured AAA and 31 patients with stable AAA were downloaded from Gene Expression Omnibus (GEO, GSE98278). After normalizing and data processing, five rAAA and seventeen eAAA patients entered the follow-up analysis. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to identify several pathways that were significantly enriched in rAAA compared to eAAA tissues. We demonstrated that the compositions of infiltrative immune cell in eAAA and rAAA were different. Naïve B cells, both resting and activated CD4+ memory T cells were found significantly higher in ruptured AAA, while memory B cells and activated mast cells were much less in ruptured AAA than that in stable AAA. Besides, PTX3 was significantly highly expressed in rAAA, which might be associated with the complement system and polarization of macrophages. Finally, differentially expressed genes and the related immune cells were mapped in a network to reveal the relationship between gene expression and infiltrative immune cells. We identified the infiltrated immune cell profile of eAAA and rAAA patients, which might be the potential target of AAA treatment.

Further evidence on the relationship between abdominal aortic aneurysm and periodontitis: A cross-sectional study.

Periodontitis is a chronic inflammatory disease characterized by Gram-negative bacteria responsible for the degradation of tissues surrounding tooth. Moreover, periopathogens can invade the bloodstream, disseminate and promote cardiovascular disease, such as the link between Porphyromonas gingivalis and atherosclerosis. The aim of this study was to explore the relationship between the severity of periodontitis and of abdominal aortic aneurysm (AAA). This cross-sectional study compared patients with stable AAA (n = 30) and patients with unstable AAA (n = 31) based on aortic diameter, growth rate, and eligibility for surgical intervention. Periodontal clinical parameters were recorded as well as the Periodontal Inflamed Surface Area and the Periodontal Index for Risk of Infectiousness (PIRI). Microbiological analyses were performed on saliva and supragingival and subgingival plaque. Quantification of Tannerella forsythia (Tf), Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans (Aa), Fusobacterium nucleatum (Fn), and Prevotella intermedia (Pi) was done by quantitative polymerase chain reaction. The two AAA groups were homogeneous for age, sex, and most risk factors except hypertension and chronic obstructive pulmonary disease. Periodontal parameters were comparable but the proportion of patients with high PIRI scores was greater in those with unstable AAA (51.6% versus 23.3%). The probing depth (PD) and the proportion of PD >6 mm were positively correlated with AAA size and thrombus volume. Several associations were found between periopathogens such as Pg and AAA diameters and volumes, but no difference could be evidenced between stable and unstable AAA groups. Periodontitis was highly prevalent in both stable and unstable AAA patients. Severe and progressive periodontitis (stage IV and grade C) tended to be more frequent in the group of patients with unstable AAA. Moreover, Pg was observed in all the samples (saliva, supragingival, and subgingival plaque) and was correlated with AAA diameters and volumes. The study evidenced potential relationships between periodontitis severity and size of AAA.

High-frequency murine ultrasound provides enhanced metrics of BAPN-induced AAA growth.

An abdominal aortic aneurysm (AAA), defined as a pathological expansion of the largest artery in the abdomen, is a common vascular disease that frequently leads to death if rupture occurs. Once diagnosed, clinicians typically evaluate the rupture risk based on maximum diameter of the aneurysm, a limited metric that is not accurate for all patients. In this study, we worked to evaluate additional distinguishing factors between growing and stable murine aneurysms toward the aim of eventually improving clinical rupture risk assessment. With the use of a relatively new mouse model that combines surgical application of topical elastase to cause initial aortic expansion and a lysyl oxidase inhibitor, β-aminopropionitrile (BAPN), in the drinking water, we were able to create large AAAs that expanded over 28 days. We further sought to develop and demonstrate applications of advanced imaging approaches, including four-dimensional ultrasound (4DUS), to evaluate alternative geometric and biomechanical parameters between 1) growing AAAs, 2) stable AAAs, and 3) nonaneurysmal control mice. Our study confirmed the reproducibility of this murine model and found reduced circumferential strain values, greater tortuosity, and increased elastin degradation in mice with aneurysms. We also found that expanding murine AAAs had increased peak wall stress and surface area per length compared with stable aneurysms. The results from this work provide clear growth patterns associated with BAPN-elastase murine aneurysms and demonstrate the capabilities of high-frequency ultrasound. These data could help lay the groundwork for improving insight into clinical prediction of AAA expansion.NEW & NOTEWORTHY This work characterizes a relatively new murine model of abdominal aortic aneurysms (AAAs) by quantifying vascular strain, stress, and geometry. Furthermore, Green-Lagrange strain was calculated with a novel mapping approach using four-dimensional ultrasound. We also compared growing and stable AAAs, finding peak wall stress and surface area per length to be most indicative of growth. In all AAAs, strain and elastin health declined, whereas tortuosity increased.

Abstract 321: The Aortic Luminal Area is a Potential Marker of Increased Rupture Risk in AbdominalAorticAneurysms

Introduction: Diameter is currently the only factor used to estimate rupture risk of abdominal aortic aneurysms (AAAs). Many large AAAs, however, do not rupture, and a significant portion of small AAAs do. Our aim was to investigate if simple two-dimensional geometric measurements can improve rupture risk prediction in AAAs, and relate these measurements to biomechanical determinants of AAAs. Methods: Thirty patients with ruptured AAAs (mean age was 77 ± 5 years and 23 were male) and 60 patients (mean age 60 ± 8 years, and 46 were male) with asymptomatic AAAs were included. At the location of the maximal diameter, the diameter, the luminal area and the vessel area were measured. Finite element analysis was used to compute 3D-geometric and biomechanical parameters of the asymptomatic AAAs, using A4 Clinics Software (VASCOPS, Austria). An automatic matching function was used to construct diameter-matched groups. Results: Analysis of all stable AAAs (n=60) and ruptured AAAs (n=30) showed that ruptured AAAs had a significantly larger diameter, 77 ± 15 mm vs. 62 ± 13 mm (p&lt;0.01) and significantly larger luminal area 2281 ± 1964 mm 2 vs. 1059 ± 674 mm 2 (p&lt;0.01). In order to control for diameter as a confounder, two diameter-matched groups, one with ruptured AAAs (n=28) and one with stable AAAs (n=15) were formed (74 ± 12 mm vs 73 ± 11, p = .67). Diameter-matched ruptured AAAs had a larger luminal area (1954 ± 1254 mm 2 vs. 1120 ± 623 mm 2 , p = .02) and a lower relative ILT area (55 ± 24 % vs 68 ± 24%, p= .03). In multivariate regression of 60 asymptomatic AAAs, including the maximal diameter, the luminal area explained the largest amount of variance in the biomechanical rupture risk parameters, followed by the ILT-area. Conclusions: We demonstrate that the luminal area is increased in ruptured AAAs compared to stable AAAs. Further, we show that this finding may in part be explained by a correlation between luminal area and biomechanical rupture risk parameters.

Midterm Outcomes of the Nellix Endovascular Aneurysm Sealing System

Purpose: To report midterm outcomes of the Nellix Endovascular Aneurysm Sealing (EVAS) System in the treatment of abdominal aortic aneurysm (AAA). Methods: Between September 2013 and July 2014, 64 AAA patients (mean age 76.6±6.8 years; 61 men) were treated with the EVAS system at 2 centers (only procedures performed at least 12 months prior to the analysis were included). Most patients were treated for a stable AAA, while 1 patient was treated for a ruptured aneurysm. Mean aneurysm diameter was 57.3±9.3 mm. The proximal neck measured a mean 21.5±3.3 mm in diameter and 27.0±12.1 mm long; the neck angle was 16.9°±19.3°. Eleven (17.2%) patients were treated outside the instructions for use (IFU). Results: Technical success was achieved in 63 (98.4%) of 64 patients; 1 type Ia endoleak was treated intraoperatively. One (1.6%) aneurysm-related death occurred at 4 months due to a secondary aortoenteric fistula. Overall, endoleaks occurred in 3 (4.7%) patients (2 type Ia, 1 type II). The estimated rates for 18-month overall survival, freedom from aneurysm-related death, and freedom from secondary interventions were 92.7%, 98.4%, and 95.0%, respectively. Patients treated outside the IFU had a significantly higher incidence of device-related complications (p=0.03). Conclusion: The use of the Nellix device in everyday clinical practice is safe and offers promising midterm results. The risk of secondary aortoenteric fistula requires further analysis. Longer follow-up is needed to assess the actual efficacy of the device, although the risk of migration with late endoleak seems low.

Biomarkers for AAA: Encouraging steps but clinical relevance still to be delivered.

Potential biomarkers have been investigated using proteomic studies in a variety of diseases. Some biomarkers have central roles in both diagnosis and monitoring of various disorders in clinical medicine, such as troponins, brain natriuretic peptide, and C-reactive protein. Although several biomarkers have been suggested in human abdominal aortic aneurysm (AAA), reliable markers have been lacking. In this issue, Moxon et al. [Proteomics Clin Appl. 2014, 8, 762-772] undertook a broad and systematic proteomic approach toward identification of biomarkers in a commonly used AAA mouse model (AAA created by angiotensin-II infusion). In this mouse model, apolipoprotein C1 and matrix metalloproteinase-9 were identified as novel biomarkers of stable AAA. This finding represents an important step forward, toward a clinically relevant role of biomarkers in AAA. This also encourages for further studies toward the identification of biomarkers (or their combinations) that can predict AAA progression and rupture, which would represent a major progress in AAA management and would establish an AAA biomarker as a much anticipated clinical tool.

In Vivo Characterization of a New Abdominal Aortic Aneurysm Mouse Model With Conventional and Molecular Magnetic Resonance Imaging

The goal of this study was to use noninvasive conventional and molecular magnetic resonance imaging (MRI) to detect and characterize abdominal aortic aneurysms (AAAs) in vivo. Collagen is an essential constituent of aneurysms. Noninvasive MRI of collagen may represent an opportunity to help detect and better characterize AAAs and initiate intervention. We used an AAA C57BL/6 mouse model in which a combination of angiotensin II infusion and transforming growth factor-β neutralization results in AAA formation with incidence of aortic rupture. High-resolution, multisequence MRI was performed to characterize the temporal progression of an AAA. To allow molecular MRI of collagen, paramagnetic/fluorescent micellar nanoparticles functionalized with a collagen-binding protein (CNA-35) were intravenously administered. In vivo imaging results were corroborated with immunohistochemistry and confocal fluorescence microscopy. High-resolution, multisequence MRI allowed the visualization of the primary fibrotic response in the aortic wall. As the aneurysm progressed, the formation of a secondary channel or dissection was detected. Further analysis revealed a dramatic increase of the aortic diameter. Injection of CNA-35 micelles resulted in a significantly higher magnetic resonance signal enhancement in the aneurysmal wall compared with nonspecific micelles. Histological studies revealed the presence of collagen in regions of magnetic resonance signal enhancement, and confocal microscopy proved the precise co-localization of CNA-35 micelles with type I collagen. In addition, in a proof-of-concept experiment, we reported the potential of CNA-35 micelles to discriminate between stable AAA lesions and aneurysms that were likely to rapidly progress or rupture. High-resolution, multisequence MRI allowed longitudinal monitoring of AAA progression while the presence of collagen was visualized by nanoparticle-enhanced MRI.

Concomitant abdominal aortic aneurysm and rectal cancer: a treatment dilemma

While the coincident presentation of abdominal aortic aneurysm (AAA) and rectal cancer is relatively rare, it is being encountered with increasing frequency as our population ages. Despite this, a recent survey of 46 general and vascular surgeons revealed a glaring lack of consensus in dealing with this problem [1]. This commentary aims to elucidate the principles of management, address conflicting issues and recommend context-specific treatment guidelines [2]. There is a consensus that with concomitant AAA and rectal cancers, the symptomatic lesion should be treated first [3, 4], and the cancer should be treated first if the AAA is less than 5 cm [1, 5]. Our commentary accepts these two premises and scrutinizes the dilemma posed when both lesions are asymptomatic, and the AAA exceeds 5 cm. While there are ample, anecdotal reports of synchronous and staged treatments of AAA and rectal cancer, there is no evidence of the uniform superiority of one approach. Treating the AAA and cancer simultaneously raises the concern of either bacterial seeding of the graft or the risks associated with prolonged operative time. The arguments against this are that with appropriate bowel preparation, perioperative antibiotics and meticulous operative and anesthetic technique, these complications are avoidable. Those supporting a synchronous approach cite (1) avoiding the risks of a second, major operation and (2) obviating the risk of aneurysm rupture during recovery from colon surgery. Treating the cancer first with associated chemotherapy further raises the possibility of chemotherapyrelated AAA growth and rupture [6]. Fixing the AAA first poses a risk of graft infection during subsequent colon surgery and increases the time to eventual cancer treatment, with any delay in recovery potentially increasing the complications and risks associated with cancer growth. In the absence of evidence supporting a uniform approach to patients with coexistent AAA and rectal cancer, we acknowledge that decisions tend to be made based on surgeon experience and what seems most intuitive. Furthermore, we believe that the recommendations should be strictly individualized. Aneurysm size (an independent predictor of aneurysm rupture), cancer stage, patient co-morbidities and life expectancy based on either co-morbidities or cancer prognosis are all relevant in informing the management priorities The AAA should be treated first in a patient with a large AAA and a small, early-stage cancer. If, however, co-morbidities are prohibitive for the repair of a large juxtarenal AAA, we would suggest that the small cancer be treated first, and the AAA reassessed based on how the patient tolerates the colon surgery. Alternatively, in a healthy patient with few co-morbidities, the coexistence of a pre-obstructing cancer and a large AAA might merit concomitant treatment of both. With a large, non-metastatic cancer and a stable AAA less than 5.5 cm, we would recommend that the cancer be treated first. Both patients presented in this series had retroperitoneal aneurysm repairs first. We do not believe that there is a substantial advantage of the retroperitoneal over a transperitoneal approach in these cases. While the retroperitoneal approach might have a slight early morbidity advantage, this is not sufficient to justify fixing the AAA first in all cases. Finally, with advancing technology and the ever-widening applications of minimally invasive This comment refers to the article doi: 10.1007/s10151-009-0542-y.

Up-Regulation and Coexpression of MIF and Matrix Metalloproteinases in Human Abdominal Aortic Aneurysms

Abdominal aortic aneurysm (AAA) is a localized dilatation of the arterial wall as a result of extensive breakdown of its structural proteins by matrix metalloproteinases (MMPs). AAA continuously expand and may eventually rupture, causing high mortality rates. The molecular processes underlying expansion and rupture of AAA are only poorly understood. In this study, evidence was sought for a direct involvement of macrophage migration inhibitory factor (MIF) in the pathogenesis of AAA through up-regulating MMPs, with particular reference to macrophages. To this end, expression and cellular localization of MIF were analyzed in human aortic wall samples of stable AAA and ruptured AAA, and compared with control aorta and atherosclerotic aorta (AS). MIF expression was up-regulated in stable AAA and further intensified in ruptured AAA. The increased aneurysmal MIF expression was paralleled by an enhanced expression of specific MMPs, viz. MMP-1, MMP-9, and MMP-12, and by a decrease of their inhibitors. Immunohistochemical analysis of AAA and AS showed MIF protein in endothelial cells, smooth muscle cells (SMCs), macrophages, and T cells. MMP-1 (in SMCs and macrophages) and MMP-9 (in macrophages) were colocalized with MIF at the cellular level in ruptured AAA. The up-regulation of aneurysmal MIF/MMP expression was associated with an increased content of cytotoxic T cells.

The utility of commercially available endografts in the treatment of contained ruptured abdominal aortic aneurysm with hemodynamic stability

Purpose Food and Drug Administration–approved endografts are suitable for the elective repair of abdominal aortic aneurysms (AAAs) with favorable aneurysm anatomy. Our aim is to illustrate the feasibility and versatility of commercially available endografts for emergency AAA repair in hemodynamically stable AAA rupture. Methods From June 2001 to July 2002, five patients presented with severe abdominal pain and were diagnosed with contained rupture of an infrarenal AAA. In all cases, patients were deemed unfit to withstand conventional open repair by both the referring outside medical center as well as our center's team. All patients were hemodynamically stable on arrival at our medical center. Measurement and selection of endovascular devices were based on computed tomography (CT) scans performed emergently at the outside referring center. The required emergently procured endografts were obtained within 2 to 4.5 hours (mean, 3.1 hours) of presentation. Complex anatomy at the proximal and distal fixation zones or difficult access was present in every case. Results All patients survived endograft repair and had successful exclusion of their aneurysm sac on the basis of intraoperative arteriography and postoperative CT surveillance. All were discharged to home at baseline function within a mean of 6.8 days (range, 2-13 days). There were no deaths. There was one postoperative pulmonary embolism, one myocardial infarct, and one type 2 endoleak. Mean operative time and blood loss were 4.67 hours and 217 mL, respectively. At a mean follow-up of 18 months, CT scans showed stable or shrinking aneurysm sacs. Conclusions In patients with contained ruptured AAAs who present with hemodynamic stability and comorbidities that preclude open surgery, commercially available endografts are a versatile treatment option even in the face of complicated aneurysm anatomy.

The utility of commercially available endografts in the treatment of contained ruptured abdominal aortic aneurysm with hemodynamic stability*1

PurposeFood and Drug Administration–approved endografts are suitable for the elective repair of abdominal aortic aneurysms (AAAs) with favorable aneurysm anatomy. Our aim is to illustrate the feasibility and versatility of commercially available endografts for emergency AAA repair in hemodynamically stable AAA rupture.MethodsFrom June 2001 to July 2002, five patients presented with severe abdominal pain and were diagnosed with contained rupture of an infrarenal AAA. In all cases, patients were deemed unfit to withstand conventional open repair by both the referring outside medical center as well as our center's team. All patients were hemodynamically stable on arrival at our medical center. Measurement and selection of endovascular devices were based on computed tomography (CT) scans performed emergently at the outside referring center. The required emergently procured endografts were obtained within 2 to 4.5 hours (mean, 3.1 hours) of presentation. Complex anatomy at the proximal and distal fixation zones or difficult access was present in every case.ResultsAll patients survived endograft repair and had successful exclusion of their aneurysm sac on the basis of intraoperative arteriography and postoperative CT surveillance. All were discharged to home at baseline function within a mean of 6.8 days (range, 2-13 days). There were no deaths. There was one postoperative pulmonary embolism, one myocardial infarct, and one type 2 endoleak. Mean operative time and blood loss were 4.67 hours and 217 mL, respectively. At a mean follow-up of 18 months, CT scans showed stable or shrinking aneurysm sacs.ConclusionsIn patients with contained ruptured AAAs who present with hemodynamic stability and comorbidities that preclude open surgery, commercially available endografts are a versatile treatment option even in the face of complicated aneurysm anatomy.

The Association Between Connective Tissue Laxity and the Risk of an Abdominal Aortic Aneurysm

Aims: to investigate whether connective tissue laxity is associated with abdominal aortic aneurysms (AAA). Methods: a nested case control study in a population-based screening programme. The presence of pes planus, scoliosis, pectus deformities, flexible auricular cartilages and Gorling's sign were combined with the Beighton joint mobility score to form a connective tissue laxity score. The association between connective tissue laxity and the risk of AAA was investigated through a logistic regression model. Type III collagen turnover was assessed using a serum radio-immunoassay for type III procollagen (PIIINP). Results: data from 231 controls (aortic diameter <2.5 cm) and 190 cases (AAA >2.9 cm) were analysed. Odds ratios (OR), adjusted for known confounders were 3.1 (95% CI: 1.1–8.6) for the highest group of connective tissue scores and 2.4 (95% CI: 1.0–5.4) for the middle group, compared with those with no signs of abnormal connective tissue function. There was no difference in mean collagen turnover between cases and controls, nor between those with a stable AAA >4 cm and those with an expanding AAA. Conclusion: connective tissue laxity is associated with a higher risk of having an AAA. The collagen turnover is similar in subjects with an AAA and controls. Aneurysms may be associated with abnormal connective tissue rather than an increased breakdown of normal collagen.

Aortic Aneurysm-Induced Disseminated Intravascular Coagulation

Disseminated intravascular coagulation (DIC) may result in hemorrhagic and thrombotic complications and is rarely associated with stable abdominal aortic aneurysms. In a retrospective review of our experience over the past 5 years, we identified only two instances of DIC-associated abdominal aortic aneurysms among a total of 67 patients who were operated on for asymptomatic aneurysms. In the first patient with DIC induced by abdominal aortic aneurysm, consumptive coagulopathy and a bleeding diathesis developed. The second patient's course was complicated by consumptive coagulopathy and migrating thrombophlebitis. In both instances coagulopathy resolved after surgical intervention. In this report we briefly discuss the pathogenesis and laboratory diagnosis of aneurysm-associated DIC and review current management strategies.

Morphology Predicts Rapid Growth of Small Abdominal Aortic Aneurysms

This study evaluated CT scans of small abdominal aortic aneurysms (AAAs) (< 5 cm) to assess anatomic features associated with rapid expansion. Serial CT scans obtained at least 10 months apart (mean 15 months) from patients with small AAAs were reviewed. Each cross-sectional image of the AAAs was analyzed using a computer-assisted design program. The circumference of the AAA in each CT image was divided into eight equal arcs, from which the apparent radius of curvature (Rc) for each segment was calculated. Flattening of the wall curvature results in an increased segmental Rc. The CT scans of nine patients with expanding AAAs (expansion > or = 0.5 cm/yr) were compared to those of 10 patients with stable AAAs (expansion < or = 0.2 cm/yr). To adjust for differences in AAA size, the Rc for each segment was normalized by dividing each individual Rc by the average of the eight Rcs (RcAvg) calculated for that cross-sectional CT image. Analysis of variance showed that the left posterolateral segments in expanding AAAs had larger Rc/RcAvg ratios than those segments in stable AAAs (1.14 +/- 0.19 vs. 0.80 +/- 0.09, p < 0.02). Laplace's law indicates that the left posterolateral segment in AAAs that grow more rapidly is subjected to greater wall tension. Flattening in the curvature of the left posterolateral wall segment was significantly associated with an increased rate of expansion in small AAAs. This finding, readily derived from standard CT scan images, may predict which small AAAs are more prone to rapid expansion.