Objective Type II endoleak (T2EL) with aneurysm expansion is believed to place patients at risk for aneurysm-related mortality (ARM). Treatment with glue and/or coil embolization of the aneurysm sac, ...inferior mesenteric artery (IMA), and lumbar branches via translumbar or transarterial approaches has been utilized to ablate such endoleaks, and thus decrease ARM. We evaluated the midterm results of percutaneous endovascular treatment of T2EL with aneurysm expansion. Methods Single-institution, 5-year (January 2003 to August 2008) retrospective study of all endovascular interventions for T2EL with sac expansion. Blinded, independent review of all available pre- and post-T2EL intervention computed tomography (CT) scans was performed. Aneurysm sac maximal transverse diameters and aneurysm sac growth rates prior to and following T2EL intervention were analyzed. Results Forty-two patients (34 male, eight female; mean age, 75) underwent T2EL intervention at 26 ± 20 months after endovascular aneurysm repair (EVAR) and were subsequently followed for 23 ± 20 months. Seven out of 42 patients (17%) underwent repeat T2EL intervention. Interventions included 44 translumbar sac embolizations, and transcatheter embolizations of nine IMAs and seven lumbar/hypogastric arteries. Aneurysm diameter was 6.1 ± 1.6 cm at EVAR, 6.6 ± 1.5 cm at initial T2EL treatment, and 6.9 ± 1.7 cm at last follow-up. There were no significant differences in the rates of aneurysm sac growth pre- and post-T2EL treatment. At last follow-up imaging, recurrent or persistent T2EL was noted in 72% of patients. Of 42 patients, nine (21%) received operative endoluminal correction of occult type I or type III endoleaks that were diagnosed during the T2EL angiographic intervention. There were no aneurysm ruptures or ARMs during follow-up; overall mortality for the 5-year study period was 24%. Conclusions In this series, percutaneous endovascular intervention for type II endoleak with aneurysm sac growth does not appear to alter the rate of aneurysm sac growth, and the majority of patients display persistent/recurrent endoleak. However, diagnostic angiographic evaluation may reveal unexpected type I and III endoleaks and is therefore recommended for all patients with T2EL and sac growth. While coil and glue embolization of aneurysm sac and selected branch vessels does not appear to yield benefit in our series, the diagnosis and subsequent definitive treatment of previously occult type I and III endoleaks may explain the absence of delayed rupture and ARM in our series.
Background The late durability of endovascular aneurysm repair (EVAR) has been limited by progressive aortic degeneration believed to be mediated by matrix metalloproteases (MMP). The goal of this ...study was to evaluate the effect of a MMP inhibitor, doxycycline, on EVAR. Methods Patients undergoing EVAR were randomized to doxycycline (100 mg twice daily) or placebo for 6 months following the procedure. Clinical data, blood samples, and computed tomography (CT) scans were obtained preoperatively, postoperatively (blood only), and at 1- and 6-month follow-up. Forty-four subjects were analyzed based on intention-to-treat. Results Plasma MMP-9 decreased significantly below baseline in the doxycycline (N = 20) treated patients at 6 months (−16.4% ± 20.7%, P < .05) while there was a nonsignificant increase in the placebo (N = 24) group (128.1% ± 73.5%). This was primarily related to changes between 1 and 6 months. In patients with endoleaks at 6 months, plasma MMP-9 increased in 83% of the placebo treated patients, but in only 14% of the doxycycline treated group ( P < .03). Among endoleak-free patients with AneuRx or Excluder endografts, doxycycline treatment resulted in greater decreases in maximum aortic diameter than placebo treatment (−13.3% ± 3.3% vs −3.8% ± 3.0%, P < .05). Furthermore, doxycycline treatment significantly reduced the aortic neck dilatation at 6 months in Excluder treated patients. Conclusion There is evidence of persistent MMP release representing ongoing aortic degradation after endografting which can be inhibited by doxycycline therapy. In analyses based on the endograft used, treatment with doxycycline also demonstrated evidence of increased aortic dimensional stability, a surrogate marker for long-term success of EVAR. Although encouraging, these results require confirmation in larger patient populations. Doxycycline should undergo more thorough evaluation as a potential adjuvant treatment to improve the results of EVAR, particularly in certain subgroups.
Abstract Background True aneurysms of the gastroduodenal (GDA) and pancreaticoduodenal (PDA) arteries have been attributed to increased collateral flow due to tandem celiac artery stenosis or ...occlusion. While GDA/PDA aneurysm exclusion is recommended because of the high reported risk of rupture, it remains uncertain whether simultaneous celiac artery reconstruction is necessary to preserve end-organ flow. Study Design A retrospective analysis of consecutive patients admitted 1996-2015 with true aneurysms of the GDA or PDA. Results Twenty subjects with true aneurysms of the PDA (n=16) or GDA (n=4) were identified. The mean age was 61.5 years (range 35-85 y) and 11 (55%) were women. Nine (45%) presented with rupture, 8 (40%) presented with pain, and three (15%) were asymptomatic. All 9 subjects who presented with rupture had contained retroperitoneal hematomas, and none experienced rebleeding. 15 (75%) had an associated celiac artery > 60% stenosis or occlusion, and two (10%) had both celiac and SMA stenoses. Thirteen (65%) subjects underwent successful endovascular coiling, only one of whom had a prophylactic celiac artery bypass. Three (15%) subjects underwent open aneurysm exclusion and celiac bypass, while four (20%) others were observed. There were no aneurysm-related deaths in this series, and no subject who underwent coiling without celiac revascularization developed hepatic ischemia or other mesenteric morbidity during a median follow-up of 6 months (maximum 200 months). Conclusions GDA and PDA aneurysms present most commonly with pain or bleeding, and all should be considered for repair, regardless of size. Aneurysm exclusion is safely and effectively achieved with endovascular coiling. Although associated celiac artery stenosis is found in the majority of cases, celiac revascularization may not be necessary.
Objective Medical management of acute aortic dissections limited to the descending thoracic aorta (AD-desc) is associated with acceptable outcomes. Uncertainty remains about whether acute type B ...aortic dissections involving the aortic arch (AD-arch) have an increased risk of retrograde extension into the ascending aorta or other dissection-related complications. This study compared outcomes of AD-arch with AD-desc managed medically. Methods Consecutive patients admitted from 2005 to 2014 with acute aortic dissections not involving the ascending aorta were retrospectively analyzed. Primary end points included dissection-related death and operative intervention. Results The study included 99 patients (63% men; mean age, 60 ± 14 years) with acute aortic dissections. Dissections were limited to the aorta distal to the left subclavian artery (AD-desc) in 79 patients (80%), and 20 (20%) had involvement of the left subclavian (n = 16), left common carotid (n = 1), or innominate (n = 3) arteries (AD-arch). Dissections ended proximal to the celiac artery in 30 patients (30%), between the celiac artery and aortic bifurcation in 36 (36%), and distal to the aortic bifurcation in 33 (33%). During medical management, further proximal extension into the arch occurred in two AD-arch patients and one AD-desc patient ( P < .05), but proximal dissection into the ascending aorta occurred in only one AD-arch patient with Marfan disease. Compared with patients with AD-desc, those with AD-arch were younger (53 ± 12.5 vs 62 ± 16 years; P < .01) and had more frequent early interventions (40% vs 19%; P = .047), cardiac complications (35% vs 11%; P < .01), and neurologic events (25% vs 6%; P < .01). Seven AD-arch patients (35%) and nine AD-desc patients (11%) died of dissection-related causes ( P < .01). Among survivors, late interventions were performed in four of eight AD-arch patients (50%) and in six of 58 AD-desc patients (10%; P = .02). Medical treatment without intervention was successful in four AD-arch patients (20%) and in 52 AD-desc patients (66%; P < .001). Multivariate logistic regression retained arch involvement as the sole predictor of dissection-related death (odds ratio, 4.2; 95% confidence interval, 1.3-13.4) and failure of medical treatment (odds ratio, 7.7; 95% confidence interval, 2.5-29). The distal extent of dissection had no bearing on outcome. Conclusions AD-arch dissections are associated with a higher risk of cardiac and neurologic events, need for early intervention, and dissection-related death than AD-desc dissections. Because further proximal dissections into the ascending aorta were rare in this study, medical management appears to be safe as the initial treatment of AD-arch dissections. However, surgeons should be aware of the increased risk of complications and the potential need for urgent interventions in these patients.
Background The purpose of this study was to further elucidate the role of the vascular smooth muscle cells (SMCs) in abdominal aortic aneurysm (AAA) disease. We hypothesized that that AAA SMCs are ...unique and actively participate in the process of degrading the aortic matrix. Methods Whole-genome expression profiles of SMCs from AAAs, nondilated abdominal aorta (NAA), and carotid endarterectomy (CEA) were compared. We quantified elastolytic activity by culturing SMCs in 3 Helastin-coated plates and measuring solubilized tritium in the media after 7 days. Matrix metalloproteinase (MMP)-2 and MMP-9 production was assessed using real-time polymerase chain reaction, zymography, and Western blotting. Results Each SMC type exhibited a unique gene expression pattern. AAA SMCs had greater elastolytic activity than NAA-SMCs (+68%; P < .001) and CEA-SMCs (+45%; P < .001). Zymography showed an increase of active MMP-2 (62 kD) in media from AAA SMCs. AAA SMCs demonstrated twofold greater expression of MMP-2 messenger (m)RNA ( P < .05) and 7.3-fold greater MMP-9 expression ( P < .01) than NAA-SMCs. Culture with U937 monocytes caused a synergistic increase of elastolysis by AAA SMCs (41%; P < .001) but not NAA-SMCs or CEA-SMCs ( P = .99). Coculture with U937 caused a large increase in MMP-9 mRNA in AAA-SMCs and NAA-SMCs ( P < .001). MMP-2 mRNA expression was not affected. Western blots of culture media showed a fourfold increase of MMP-9 (92 kD) protein only in AAA-SMCs/U937 but not in NAA-SMCs/U937 ( P < .001) and a large increase in active-MMP2 (62 kD), which was less apparent in NAA-SMCs/U937 media ( P < .01). Conclusions AAA-SMCs have a unique gene expression profile and a proelastolytic phenotype that is augmented by macrophages. This may occur by a failure of post-transcriptional control of MMP-9 synthesis.
Background The position of the gastroesophageal junction is maintained by a complex of fibroelastic ligaments. The purpose of this study was to characterize and compare the histology of these ...ligaments in patients with gastroesophageal reflux disease (GERD) and hiatal hernia (HH) versus GERD alone, with emphasis on the elastin morphology. Study Design Thirteen patients were examined at the time of laparoscopic fundoplication for symptomatic GERD; nine had no significant HH and four had large diaphragmatic hernias (GERD/HH). Tissue biopsies were obtained from the gastrohepatic ligament (GHL, n = 5 and n = 3, GERD and GERD/HH, respectively), the phrenoesophageal ligament (n = 7 and n = 4, respectively), and the gastrophrenic ligament (n = 6 and n = 4, respectively). Sections of fixed tissue were stained with hematoxylin and eosin, Masson's trichrome, and resorcin-fuchsin for analysis of elastic fibers by light microscopy, and elastin area was quantified and expressed as a percentage of the imaged tissue. Results Elastin and collagen fibers were prominent in all ligaments in patients with GERD alone. In patients with GERD/HH, there was fragmentation and distortion of elastin in the phrenoesophageal ligament and gastrohepatic ligament, and to a lesser degree, in the gastrophrenic ligament. Compared with patients with GERD alone, the presence of hiatal hernia was associated with a reduction in elastin area by more than 50% in the phrenoesophageal ligament (mean ± SEM 31.0% ± 3.3% versus 15.1% ± 1.3%, p < 0.01) and gastrohepatic ligament (26.9% ± 0.5% versus 12.5% ± 0.1%, p < 0.008). There was no decrease with respect to elastin in the gastrophrenic ligament. Conclusions The periesophageal ligaments in patients with GERD are characterized by prominent elastic fibers. In contrast, GERD/HH is associated with depletion of elastic fibers in two of three ligaments supporting the gastroesophageal junction. Elastic fiber depletion in the periesophageal ligaments thereby provides a structural basis for the development of HH. It remains unclear if this represents a primary (etiologic) alteration or if it is a secondary phenomenon.
Objective The development of abdominal aortic aneurysms (AAA) is presumed to result from multiple genetic and environmental factors, with exposure to tobacco smoke the single largest known factor ...predisposing to aneurysm growth. We have attempted to adapt the elastase-perfused animal model to determine whether tobacco exposure can lower the threshold of aortic injury necessary for AAA development. Methods Adult C57BL/6 mice underwent transient perfusion of the infrarenal aorta with an active solution of elastase: high-dose (HDE, 0.19 U/mL, n = 9), standard-dose (SDE, 0.16 U/mL, n = 21) or low-dose (LDE, 0.07 U/mL, n = 24). Control animals (n = 24) were treated with heat inactivated elastase (HIE). Twenty LDE perfused mice were exposed to cigarette smoke (LDE-S) beginning 2 weeks before perfusion and continuing until aortic harvest. Aortic diameter (AD) was measured preperfusion, postperfusion, and at harvest on day 14. AAA was defined as %ΔAD ≥100% between preperfusion and harvest. Aortas from each group (except HDE) were analyzed for matrix metalloproteinase-9 (MMP-9) and MMP-12 expression by real-time polymerase chain reaction normalized to glyceraldehyde-3-phosphate dehydrogenase. Results All SDE mice developed large AAA by %ΔAD (189.3% ± 16.9%, mean ± standard error of the mean), but control mice had only a small dilatation (69.7% ± 3.7%, P < .01). Higher doses of elastase did not produce larger aneurysms in HDE mice. In contrast, only 63% of LDE mice showed aneurysmal dilatation, and these were significantly smaller (104.3% ± 4.2%, P < .01). When exposed to cigarette smoke, LDE animals developed significantly larger aneurysms (%ΔAD, 134.5% ± 7.9%, P = .0021). There was no difference in normalized aortic MMP-9 and MMP-12 expression between elastase doses or between smoke-exposed and unexposed animals. Histologic analysis revealed that smoking increased the extent of aortic elastin degradation when compared with LDE-S animals. Conclusion Aneurysm development in the elastase model is dependent on the quantity of active elastase infused. Exposure of animals to tobacco smoke after a relatively minor aortic elastase injury produces increases in elastin degradation and aneurysm size without affecting MMP-9 or MMP-12 expression. To our knowledge, this is the first demonstration in an animal model that smoking can act as a synergistic factor in AAA development. Further understanding of the relationship between smoking and AAA in this model may help unveil the pathophysiologic pathways involved between cigarette smoke and AAAs.
Two consensus histopathological classifications for thoracic aortic aneurysms (TAAs) and inflammatory aortic diseases have been issued to facilitate clinical decision-making and inter-study ...comparison. However, these consensus classifications do not specifically encompass abdominal aortic aneurysms (AAAs). Given its high prevalence and the existing profound pathophysiologic knowledge gaps, extension of the consensus classification scheme to AAAs would be highly instrumental. The aim of this study was to test the applicability of, and if necessary to adapt, the issued consensus classification schemes for AAAs.
Seventy-two AAA anterolateral wall samples were collected during elective and emergency open aneurysm repair performed between 2002 and 2013. Histologic analysis (hematoxylin and eosin and Movat Pentachrome) and (semi-quantitative and qualitative) grading were performed in order to map the histological aspects of AAA. Immunohistochemistry was performed for visualization of aspects of the adaptive and innate immune system, and for a more detailed analysis of atherosclerotic lesions in AAA.
Because the existing consensus classification schemes do not adequately capture the aspects of AAA disease, an AAA-specific 11-point histopathological consensus classification was devised. Systematic application of this classification indicated several universal features for AAA (eg, almost complete elastolysis), but considerable variation for other aspects (eg, inflammation and atherosclerotic lesions).
This first multiparameter histopathological AAA consensus classification illustrates the sharp histological contrasts between thoracic and abdominal aneurysms. The value of the proposed scoring system for AAA disease is illustrated by its discriminatory capacity to identify samples from patients with a nonclassical (genetic) variant of AAA disease.
The pathophysiology of abdominal aortic aneurysm (AAA) disease remains an enigma. Histological evaluation is critical for appreciation of the tissue remodeling and spatial aspects of AAA disease. Histopathological classification schemes have been devised for aortic pathology. Unfortunately, these schemes do not specifically address the most common aortic pathology, AAA disease. In order to facilitate interstudy comparisons and pathophysiologic understanding of AAA disease, we here present a multiparameter consensus histopathological AAA classification scheme. The scheme clearly discriminates AAA disease from thoracic aortic aneurysm disease. Systematic implementation of this AAA classification system indicates a substantial biological variation for AAA disease, and stresses the need for adequate group sizes in order to adequately cover the natural variability. Examples illustrating the diagnostic value of the classification system are provided.
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