Targeted proteomics and metabolomics for biomarker discovery in abdominal aortic aneurysm and post-EVAR sac volume.

BACKGROUND AND AIMS: Abdominal aortic aneurysm (AAA) patients undergo uniform surveillance programs both leading up to, and following surgery. Circulating biomarkers could play a pivotal role in individualizing surveillance. We applied a multi-omics approach to identify relevant biomarkers and gain pathophysiological insights. MATERIALS AND METHODS: In this cross-sectional study, 108 AAA patients and 200 post-endovascular aneurysm repair (post-EVAR) patients were separately investigated. We performed partial least squares regression and ingenuity pathway analysis on circulating concentrations of 96 proteins (92 Olink Cardiovascular-III panel, 4 ELISA-assays) and 199 metabolites (measured by LC-TQMS), and their associations with CT-based AAA/sac volume. RESULTS: The median (25th-75th percentile) maximal diameter was 50.0 mm (46.0, 53.0) in the AAA group, and 55.4 mm (45.0, 64.2) in the post-EVAR group. Correcting for clinical characteristics in AAA patients, the aneurysm volume Z-score differed 0.068 (95 %CI: (0.042, 0.093)), 0.066 (0.047, 0.085) and -0.051 (-0.064, -0.038) per Z-score valine, leucine and uPA, respectively. After correcting for clinical characteristics and orthogonalization in the post-EVAR group, the sac volume Z-score differed 0.049 (0.034, 0.063) per Z-score TIMP-4, -0.050 (-0.064, -0.037) per Z-score LDL-receptor, -0.051 (-0.062, -0.040) per Z-score 1-OG/2-OG and -0.056 (-0.066, -0.045) per Z-score 1-LG/2-LG. CONCLUSIONS: The branched-chain amino acids and uPA were related to AAA volume. For post-EVAR patients, LDL-receptor, monoacylglycerols and TIMP-4 are potential biomarkers for sac volume. Additionally, distinct markers for sac change were identified.

Aneurysm Sac Dynamics and its Prognostic Significance Following Fenestrated and Branched Endovascular Aortic Aneurysm Repair.

OBJECTIVE: This study aimed to assess aneurysm sac dynamics and its prognostic significance following fenestrated and branched endovascular aneurysm repair (F/BEVAR). METHODS: Patients undergoing F/BEVAR for degenerative complex aortic aneurysm from 2008 to 2020 at two large vascular centres with two imaging examinations (30 day and one year) were included. Patients were categorised as regression and non-regression, determined by the proportional volume change (> 5%) at one year compared with 30 days. All cause mortality and freedom from graft related events were assessed using Kaplan-Meier methods. Factors associated with non-regression at one year and aneurysm sac volume over time were examined for FEVAR and BEVAR independently using multivariable logistic regression and linear mixed effects modelling. RESULTS: One hundred and sixty-five patients were included: 122 FEVAR, of whom 34% did not regress at one year imaging (20% stable, 14% expansion); and 43 BEVAR, of whom 53% failed to regress (26% stable, 28% expansion). Following F/BEVAR, after risk adjusted analysis, non-regression was associated with higher risk of all cause mortality within five years (hazard ratio [HR] 2.56, 95% confidence interval [CI] 1.09 - 5.37; p = .032) and higher risk of graft related events within five years (HR 2.44, 95% CI 1.10 - 5.26; p = .029). Following multivariable logistic regression, previous aortic repair (odds ratio [OR] 2.56, 95% CI 1.11 - 5.96; p = .029) and larger baseline aneurysm diameter (OR/mm 1.04, 95% CI 1.00 - 1.09; p = .037) were associated with non-regression at one year, whereas smoking history was inversely associated with non-regression (OR 0.21, 95% CI 0.04 - 0.96; p = .045). Overall following FEVAR, aneurysm sac volume decreased significantly up to two years (baseline vs. two year, 267 [95% CI 250 - 285] cm3vs. 223 [95% CI 197 - 248] cm3), remaining unchanged thereafter. Overall following BEVAR, aneurysm sac volume remained stable over time. CONCLUSION: Like infrarenal EVAR, non-regression at one year imaging is associated with higher five year all cause mortality and graft related events risks after F/BEVAR. Following FEVAR for juxtarenal aortic aneurysm, aneurysm sacs generally displayed regression (66% at one year), whereas after BEVAR for thoraco-abdominal aortic aneurysm, aneurysm sacs displayed a concerning proportion of growth at one year (28%), potentially suggesting a persistent risk of rupture and consequently requiring intensified surveillance following BEVAR. Future studies will have to elucidate how to improve sac regression following complex EVAR, and whether the high expansion risk after BEVAR is due to advanced disease extent.

Circulating biomarkers of cardiovascular disease are related to aneurysm volume in abdominal aortic aneurysm.

BACKGROUND: Surveillance programs in abdominal aortic aneurysms (AAA) are mainly based on imaging and leave room for improvement to timely identify patients at risk for AAA growth. Many biomarkers are dysregulated in patients with AAA, which fuels interest in biomarkers as indicators of disease progression. We examined associations of 92 cardiovascular disease (CVD)-related circulating biomarkers with AAA and sac volume. METHODS: In a cross-sectional analysis, we separately investigated (1) 110 watchful waiting (WW) patients (undergoing periodic surveillance imaging without planned intervention) and (2) 203 patients after endovascular aneurysm repair (EVAR). The Cardiovascular Panel III (Olink Proteomics AB, Sweden) was used to measure 92 CVD-related circulating biomarkers. We used cluster analyses to investigate protein-based subphenotypes, and linear regression to examine associations of biomarkers with AAA and sac volume on CT scans. RESULTS: Cluster analyses revealed two biomarker-based subgroups in both WW and EVAR patients, with higher levels of 76 and 74 proteins, respectively, in one subgroup versus the other. In WW patients, uPA showed a borderline significant association with AAA volume. Adjusting for clinical characteristics, there was a difference of -0.092 (-0.148, -0.036) loge mL in AAA volume per SD uPA. In EVAR patients, after multivariable adjustment, four biomarkers remained significantly associated with sac volume. The mean effects on sac volume per SD difference were: LDLR: -0.128 (-0.212, -0.044), TFPI: 0.139 (0.049, 0.229), TIMP4: 0.110 (0.023, 0.197), IGFBP-2: 0.103 (0.012, 0.194). CONCLUSION: LDLR, TFPI, TIMP4, and IGFBP-2 were independently associated with sac volume after EVAR. Subgroups of patients with high levels of the majority of CVD-related biomarkers emphasize the intertwined relationship between AAA and CVD.ClinicalTrials.gov Identifier: NCT03703947.

Incidence, Prognostic Significance, and Risk Factors of Acute Kidney Injury Following Elective Infrarenal and Complex Endovascular Aneurysm Repair.

OBJECTIVE: Acute kidney injury (AKI) is a well known complication following cardiovascular procedures. The objective was to assess the incidence, risk factors, and prognostic significance of AKI after infrarenal endovascular aneurysm repair (EVAR) and complex EVAR (cEVAR; fenestrated or branched EVAR). METHODS: Consecutive patients undergoing elective infrarenal EVAR or cEVAR between 2000 and 2018 in two large teaching hospitals in the Netherlands were included. AKI was determined by serum creatinine levels increasing > 1.5 times or by an absolute increase of 26.5 mmol/L from baseline value (KDIGO criteria). The primary outcome was incidence of peri-operative AKI development. Secondary outcomes included mid-term renal function (RIFLE criteria), overall survival, and risk factors for AKI development. To determine survival and risk factors for AKI, multivariable Cox regression and logistic regression analyses were performed, accounting for pre-operative renal function and other confounders. RESULTS: In total, 540 patients who underwent infrarenal EVAR with 147 patients who underwent cEVAR also included. The incidence of AKI was 8.7% (n = 47) in infrarenal EVAR patients and 23% (n = 34) in cEVAR patients (fenestrated EVAR 18%; branched EVAR 38%). In contrast to patients without AKI, the renal function of surviving patients with AKI remained significantly reduced at six weeks and did not return to pre-operative values following infrarenal EVAR (three year estimated glomerular filtration rate [eGFR] 59.3 ± 23.1 mL/min/1.73m2vs. pre-operative eGFR 74.0 ± 21.7 mL/min/1.73m2; p = .006) or following cEVAR (three year eGFR 52.0 ± 23.7 mL/min/1.73m2vs. pre-operative eGFR 65.4 ± 18.6 mL/min/1.73m2; p = .082). After risk adjusted analysis, compared with non-AKI, post-operative AKI development was associated with a higher three year mortality rate following both infrarenal and cEVAR (infrarenal EVAR mortality hazard ratio [HR 1.6, 95% confidence interval [CI] 1.01 - 2.7 [p = .046]; cEVAR mortality HR 2.4, 95% CI 1.1 - 5.2 [p = .033]). Following multivariable logistic regression, pre-operative chronic kidney disease (eGFR < 60 mL/min/1.73m2; odds ratio [OR] 2.2, 95% CI 1.03 - 4.8) and neck diameter (OR 1.1, 95% CI 1.01 - 1.2) were significantly associated with AKI following infrarenal EVAR, whereas for cEVAR only contrast volume (OR 1.1, 95% CI 1.0 - 1.2]) was found to be statistically significantly associated with AKI. CONCLUSION: AKI is a well described complication following infrarenal EVAR and is common after cEVAR. As AKI seems to be associated with permanent renal deterioration and lower survival, efforts to prevent AKI are essential. Future studies are required to assess what factors are associated with a higher risk of developing AKI following cEVAR.

Proximal seal dilatation following fenestrated endovascular repair for complex abdominal aortic aneurysms.

OBJECTIVE: Although proximal neck dilatation following infrarenal endovascular aneurysm repair (EVAR) is common and is associated with proximal graft failure, little is known about sealing zone dilatation and its clinical relevance following fenestrated EVAR (FEVAR). We studied proximal seal dilatation (PSD) dynamics following FEVAR and assessed its clinical significance. METHODS: We included all consecutive patients treated for a juxta-/supra-renal aneurysm with fenestrated EVAR using the Zenith Fenestrated Endovascular Graft (Cook Medical, Bloomington, Ind) from 2008 to 2018 in two large teaching hospitals in the Netherlands. The primary outcome was PSD over time and was determined using a linear mixed-effects model. Secondary outcomes included associations for early PSD and difference in aortic dilatation at the level of the covered stent compared with the bare stent. Proximal seal-related adverse events were also obtained. RESULTS: Our cohort included 84 patients with a median computed tomography angiography follow-up time of 24.5 months (interquartile range [IQR], 17-42 months). Maximum aneurysm diameter was 60.1 mm (IQR, 56.9-67.2 mm). Mean proximal seal diameter at baseline was 26.2 mm (standard deviation [SD], ±2.8 mm), mean stent oversizing was 20.1% (SD, ±9.1%), and mean proximal seal length was 29.5 mm (SD, ±11.7 mm). Proximal seal dilatation of 1.7 mm (95% confidence interval [CI], 1.4-2.1 mm) was found in the first year, decelerating thereafter (second year, 0.9 mm/year; 95% CI, 0.7-1.1 mm/y). Over 10% PSD at 1 year occurred in 22 patients (27%) and was associated with stent graft oversizing (odds ratio, 1.1; 95% CI, 1.03-1.2; P = .008) and a lower number of target vessels (four fenestrations/ref two fenestrations: odds ratio, 0.13; 95% CI, 0.02-0.74; P = .029). At last available imaging, dilatation difference was higher at the level of the covered stent compared with the bare stent (3.0 mm [IQR, 1.3-5.1 mm] vs 1.6 mm [IQR, 0.8-2.5 mm]; P < .001). During the study period, only one patient (1.2%) developed a proximal seal-related adverse event (type IA endoleak). CONCLUSIONS: PSD is present following FEVAR, occurring at a faster rate in the first year and subsequently decelerating thereafter, similarly to neck dilatation after standard infrarenal EVAR. Although its clinical implication seems to remain limited in the first years following implantation, further research is required to assess the effect of PSD on long-term FEVAR outcomes.

Unsuccessful Stent Graft Repair of a Hepatic Artery Aneurysm Presenting with Haemobilia: Case Report and Comprehensive Literature Review.

AIMS: To discuss treatment strategies for non-traumatic, non-iatrogenic hepatic artery aneurysms (HAAs) in the presence of an arteriobiliary fistula, illustrated by a case and followed by a comprehensive review of the literature. METHODS: Following the PRISMA guidelines, 24 eligible HAA cases presenting with haemobilia were identified. Characteristics of patients, aneurysms, treatment strategies and their outcomes were collected. RESULTS: A 69 year old patient with no previous hepatobiliary intervention or trauma, presented with jaundice and haemobilia caused by a HAA. Initial treatment by endovascular stenting was chosen to prevent ischaemic liver complications. Unfortunately, this strategy failed because of stent migration due to ongoing infection leading to a type 1A endoleak. The patient had to be converted to open surgery with ligation of the HAA. The patient recovered uneventfully and no complications occurred during the following 12 months. COMPREHENSIVE LITERATURE REVIEW: Of the 24 cases, nine had a true HAA and 15 were pseudo/mycotic aneurysms, mainly caused by endocarditis or cholecystitis. The majority were located in the right hepatic artery. In 20 cases, an endovascular first approach was chosen with embolisation, none with covered stents. Three of these cases had to be converted to open surgery because of rebleeding. In all open (primary or secondary) cases, ligation of the HAA was performed. One patient in these series died. No liver ischaemia or abscesses were reported, although one patient developed an ischaemic gallbladder. CONCLUSIONS: Patients who present with a HAA and haemobilia may be treated safely by embolisation or open ligation. Using a covered stent graft in these patients can cause problems due to ongoing infection and should be monitored closely by imaging. Publication bias and lack of long term follow up imply cautious interpretation of these findings.

Aneurysm Volumes After Endovascular Repair of Ruptured vs Intact Aortic Aneurysms: A Retrospective Observational Study.

PURPOSE: To compare changes in abdominal aortic aneurysm (AAA) sac volume between endovascular aneurysm repairs (EVAR) performed for ruptured (rEVAR) vs intact (iEVAR) AAAs and to determine the impact of early volume shrinkage on future complications. MATERIALS AND METHODS: A retrospective analysis was performed of all patients undergoing standard infrarenal EVAR from 2002 to 2016 at a tertiary referral institution. Only patients with degenerative AAAs and with 30-day and 1-year computed tomography angiography (CTA) imaging were included. Early sac shrinkage was defined as a volume sac reduction >10% between the first (<30-day) and the 1-year CTA. The primary endpoint was to compare AAA sac volume changes between patients undergoing rEVAR (n=51; mean age 71.0±8.5 years; 46 men) vs iEVAR (n=393; mean age 72.3±7.5 years; 350 men). Results are reported as the mean difference with the interquartile range (IQR Q1, Q3). The secondary endpoint was freedom from aneurysm-related complications after 1 year as determined by regression analysis; the results are presented as the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: At baseline, the rEVAR group had larger aneurysms (p<0.001) and shorter (p<0.001) and more angulated (p=0.028) necks. Aneurysm sac volume decreased more in the rEVAR group during the first year [-26.3% (IQR -38.8%, -12.5%)] vs the iEVAR group [-11.9% (IQR -27.5%, 0); p<0.001]. However, after the first year, the change in sac volume was similar between the groups [-3.8% (IQR -32.9%, 31.9%) for rEVAR and -1.5% (IQR -20.9%, 13.6%) for iEVAR, p=0.74]. Endoleak occurrence during follow-up was similar between the groups. In the overall population, patients with early sac shrinkage had a lower incidence of complications after the 1-year examination (adjusted HR 0.59, 95% CI 0.39 to 0.89, p=0.01). CONCLUSION: EVAR patients treated for rupture have more pronounced aneurysm sac shrinkage compared with iEVAR patients during the first year after EVAR. Patients presenting with early shrinkage are less likely to encounter late complications. These parameters may be considered when tailoring surveillance protocols.

Survival After Uncomplicated EVAR in Octogenarians is Similar to the General Population of Octogenarians Without an Abdominal Aortic Aneurysm.

OBJECTIVE: Long term survival after endovascular aortic aneurysm repair (EVAR) in octogenarians remains unclear. This was evaluated by comparing octogenarians after EVAR with a matched group of octogenarians without an abdominal aortic aneurysm (AAA) from the Rotterdam Study (RS). The influence of complications after EVAR on survival was also studied with the aim of identifying risk factors for the development of complications in octogenarians. METHODS: Using propensity score matching (PSM), 83 EVAR octogenarians were matched for comorbidities with 83 octogenarians from the RS, and survival was compared between these two groups using Cox proportional hazard analysis. Then, complications were studied, defined as cardiac or pulmonary, renal deterioration, access site bleeding, acute limb ischaemia or bowel ischaemia, within 30 days of surgery between 83 EVAR octogenarians and 475 EVAR non-octogenarians. Also, the difference in baseline characteristics between the octogenarians with and without complications after EVAR were studied, and survival was compared between the RS controls and the complicated and uncomplicated EVAR octogenarians separately. RESULTS: The total EVAR octogenarian population did not show an increased mortality risk compared with RS octogenarian controls (hazard ratio [HR] 1.28, 95% confidence interval [CI] 0.84-1.97). Post-operative complications occurred in 22 octogenarians (27%) and 59 non-octogenarians (12.4%, p < .001), mainly cardiac, pulmonary, and bleeding complications. All baseline characteristics were similar in the complicated EVAR octogenarians compared with the uncomplicated EVAR octogenarians. After uncomplicated EVAR, octogenarians had a similar survival compared with the RS controls (HR 1.09, 95% CI 0.68-1.77), but after complicated EVAR their mortality risk increased significantly (HR 1.93, 95% CI 1.06-3.54). CONCLUSION: After standard EVAR, the life expectancy of octogenarians is the same as that of a matched group from the general population without an AAA, provided they do not develop early post-operative complications. Patient selection and meticulous peri-operative care are key.

Impact of Aortoiliac Stenosis on Graft and Patient Survival in Kidney Transplant Recipients Using the TASC II Classification.

BACKGROUND: Patients with end-stage renal disease and aortoiliac stenosis are often considered ineligible for kidney transplantation, although kidney transplantation has been acknowledged as the best therapy for end-stage renal disease. The clinical outcomes of kidney transplantation in patients with aortoiliac stenosis are not well-studied. This study aimed to assess the impact of aortoiliac stenosis on graft and patient survival. METHODS: This retrospective, single-center study included kidney transplant recipients transplanted between January 1, 2000, and December 31, 2016, who received contrast-enhanced imaging. Patients with aortoiliac stenosis were classified using the Trans-Atlantic Inter-Society Consensus (TASC) II classification and categorized as having TASC II A/B lesions or having TASC II C/D lesions. Patients without aortoiliac stenosis were functioning as controls. RESULTS: A total number of 374 patients was included in this study (n = 88 with TASC II lesions, n = 286 as controls). Death-censored graft survival was similar to the controls. Patient and uncensored graft survival was decreased in patients with TASC II C/D lesions (log-rank test P < 0.001). Patients with TASC II C/D lesions had a higher risk of 90-day mortality (hazard ratio, 3.96; 95% confidence interval, 1.12-14.04). In multivariable analysis, having a TASC II C/D lesion was an independent risk factor for mortality (hazard ratio, 3.25; 95% confidence interval, 1.87-5.67; P < 0.001). Having any TASC II lesion was not a risk factor for graft loss (overall P = 0.282). CONCLUSIONS: Kidney transplantation in patients with TASC II A/B is feasible and safe without increased risk of perioperative mortality. TASC II C/D decreases patient survival. Death-censored graft survival is unaffected.

Review on management and outcomes of ruptured abdominal aortic aneurysm in women.

Vascular procedures in general, and specifically abdominal aortic aneurysm (AAA) repair, are associated with worse outcomes in female patients. However, how female gender influences outcomes in the setting of aneurysm-rupture remains unclear and may be even more pronounced when compared to elective operations. In this report, the authors aim to review the literature regarding ruptured AAA repair in women. Using the traditional threshold for AAA of 30 mm of maximum diameter, the prevalence in women is lesser than in men. However, the true prevalence may be underestimated due to gender discrepancies in normal aortic diameter. For females, aneurysmal disease seems to manifest later, have more associated comorbidities, and rupture occurs at smaller aortic diameters. This has obvious implications for management. There is still no consensus over the optimal treatment for ruptured AAA in women. They are less frequently treated by endovascular aneurysm repair, possibly due to anatomical restrains. When feasible, endovascular repair shows better outcomes, at least in the short-term, and there is new evidence suggesting a lasting benefit as well. For open repair the results are consensually worse when compared to male counterparts. Finally, despite benefitting of apparently similar healthcare, women have a lower relative survival after rAAA repair when compared to men. Further investigation to determine the reasons of these discrepancies is warranted.

One-Year Follow-Up After Hybrid Thoracoabdominal Aortic Repair.

BACKGROUND: Compared to open thoracoabdominal aortic aneurysm (TAAA) repair, hybrid repair is thought to be less invasive with better perioperative outcomes. Due to the extent of the operation and long recovery period, studying perioperative results may not be sufficient for evaluation of the true treatment effect. The aim of this study is to evaluate 1-year mortality and morbidity in patients with TAAA undergoing hybrid repair. METHODS: In a retrospective cohort study, all medical records of patients undergoing hybrid repair for TAAA at the Erasmus University Medical Center between January 2007 and January 2015 were studied. Primary outcome measures were 30-day and 1-year mortality. Secondary outcome measures included major in-hospital postoperative complications. RESULTS: A total of 15 patients were included. All-cause mortality was 33% (5 of the 15) at 30 days and 60% (9 of the 15) at 1 year. Aneurysm-related mortality was 33% (5 of the 15) and 53% (8 of the 15) at 30-day and 1-year follow-up, respectively, with colon ischemia being the most common cause of death. Major complication rate was high: myocardial infarction in 2 (13%) cases, acute kidney failure in 5 (33%) cases, bowel ischemia in 3 (20%) cases, and spinal cord ischemia in 1 (7%) case. CONCLUSION: The presumed less invasive nature of hybrid TAAA repair does not seem to result in lower complication rates. The high mortality rate at 30 days continues to rise dramatically thereafter, suggesting that 1-year mortality is a more useful clinical parameter to use in preoperative decision-making for this kind of repair.

Unexplained rupture after endovascular aneurysm repair.

We present a case of a 70-year-old man who was admitted with rupture of an abdominal aneurysm 4 years after endovascular aneurysm repair. He was compliant with yearly follow-up computed tomography angiography. One month earlier, his computed tomography angiogram showed perfect exclusion of the aneurysm and no endoleak. We explanted the stent graft and confirmed effective sealing, and the graft was intact. We found no signs of infection during 2 years of follow-up. This rupture is nonpredictable and unexplained and illustrates that unremarkable imaging does not guarantee prevention of rupture. This case shows that the ultimate failure of endovascular aneurysm repair cannot be prevented despite surveillance protocols.

Long-term results of outside "instructions for use" EVAR.

INTRODUCTION: Endovascular aneurysm repair (EVAR) has progressively expanded to more complex anatomies, frequently outside manufacturer's instructions for use (IFU). However, the long term results of off-label use of EVAR remain largely undocumented. The aim of this paper is to examine the long term results of outside IFU EVAR. EVIDENCE ACQUISITION: English literature was searched to identify publications on long term results for outside IFU EVAR. A follow-up extending for at least 5 years was the minimum required as inclusion criteria. The outcomes measured were: overall mortality, aneurysm-related mortality (ARM), freedom from postimplant aneurysm rupture, aneurysm sac enlargement, type I endoleaks and secondary interventions. Results were compared to randomized clinical trials (RCTs) with long term results published (EVAR-1, DREAM, OVER and ACE Trial). EVIDENCE SYNTHESIS: Thirteen studies were included. 7 studies described outcomes associated to a specific breached IFU, while 6 studies presented general outside IFU results. In patients outside IFU, 3 to 8 years estimates of overall mortality ranged from 21.5% to 40% (RCTs:13.7-46%) and ARM from 0-11% (RCTs: 1.2-7%). Five-year estimates of sac enlargement was approximately 43%. Type I endoleak rates for outside IFU (follow-up 5-12 years) ranged from 3.8-15%, which is higher than found in RCT-derived data (6.6-6.9%). Comparable results are seen for postimplant rupture and secondary interventions. CONCLUSIONS: The long term results of off-label use of EVAR are scarcely published. Although overall mortality and ARM does not seem to differ significantly at long-term, higher rates of type I endoleaks may be expected, mainly in short necks. However, for patients with severe angulation or high thrombus load in the proximal neck, results of outside IFU EVAR seem to match the results of inside IFU.

Clinical outcome and morphologic determinants of mural thrombus in abdominal aortic endografts.

OBJECTIVE: Endograft mural thrombus has been associated with stent graft or limb thrombosis after endovascular aneurysm repair (EVAR). This study aimed to identify clinical and morphologic determinants of endograft mural thrombus accumulation and its influence on thromboembolic events after EVAR. METHODS: A prospectively maintained database of patients treated by EVAR at a tertiary institution from 2000 to 2012 was analyzed. Patients treated for degenerative infrarenal abdominal aortic aneurysms and with available imaging for thrombus analysis were considered. All measurements were performed on three-dimensional center-lumen line computed tomography angiography (CTA) reconstructions. Patients with thrombus accumulation within the endograft's main body with a thickness >2 mm and an extension >25% of the main body's circumference were included in the study group and compared with a control group that included all remaining patients. Clinical and morphologic variables were assessed for association with significant thrombus accumulation within the endograft's main body by multivariate regression analysis. Estimates for freedom from thromboembolic events were obtained by Kaplan-Meier plots. RESULTS: Sixty-eight patients (16.4%) presented with endograft mural thrombus. Median follow-up time was 3.54 years (interquartile range, 1.99-5.47 years). In-graft mural thrombus was identified on 30-day CTA in 22 patients (32.4% of the study group), on 6-month CTA in 8 patients (11.8%), and on 1-year CTA in 17 patients (25%). Intraprosthetic thrombus progressively accumulated during the study period in 40 patients of the study group (55.8%). Overall, 17 patients (4.1%) presented with endograft or limb occlusions, 3 (4.4%) in the thrombus group and 14 (4.1%) in the control group (P = .89). Thirty-one patients (7.5%) received an aortouni-iliac (AUI) endograft. Two endograft occlusions were identified among AUI devices (6.5%; overall, 0.5%). None of these patients showed thrombotic deposits in the main body, nor were any outflow abnormalities identified on the immediately preceding CTA. Estimated freedom from thromboembolic events at 5 years was 95% in both groups (P = .97). Endograft thrombus accumulation was associated with >25% proximal aneurysm neck thrombus coverage at baseline (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.3), neck length ≤ 15 mm (OR, 2.4; 95% CI, 1.3-4.2), proximal neck diameter ≥ 30 mm (OR, 2.4; 95% CI, 1.3-4.6), AUI (OR, 2.2; 95% CI, 1.8-5.5), or polyester-covered stent grafts (OR, 4.0; 95% CI, 2.2-7.3) and with main component "barrel-like" configuration (OR, 6.9; 95% CI, 1.7-28.3). CONCLUSIONS: Mural thrombus formation within the main body of the endograft is related to different endograft configurations, main body geometry, and device fabric but appears to have no association with the occurrence of thromboembolic events over time.

Conservative management of persistent aortocaval fistula after endovascular aortic repair.

Endovascular repair is a valid alternative for patients with abdominal aortic aneurysms. However, in patients with concomitant aortocaval fistulas, type II endoleaks may result in a persistent communication between the aneurysm sac and the inferior vena cava. In these patients, prompt closure of the persistent fistula has been advocated. We present a patient with an abdominal aortic aneurysm, with aortocaval fistula, who was managed endovascularly. Aneurysm sac shrinkage was observed despite persistent aortocaval communication due to type II endoleak. This case demonstrates that conservative management of type II endoleaks associated with persistent aortocaval fistulas is possible and may result in favorable aneurysm sac remodelling.

Adequate seal and no endoleak on the first postoperative computed tomography angiography as criteria for no additional imaging up to 5 years after endovascular aneurysm repair.

OBJECTIVE: Intensive image surveillance after endovascular aneurysm repair is generally recommended due to continued risk of complications. However, patients at lower risk may not benefit from this strategy. We evaluated the predictive value of the first postoperative computed tomography angiography (CTA) characteristics for aneurysm-related adverse events as a means of patient selection for risk-adapted surveillance. METHODS: All patients treated with the Low-Permeability Excluder Endoprosthesis (W. L. Gore & Assoc, Flagstaff, Ariz) at a tertiary institution from 2004 to 2011 were included. First postoperative CTAs were analyzed for the presence of endoleaks, endograft kinking, distance from the lowermost renal artery to the start of the endograft, and for proximal and distal sealing length using center lumen line reconstructions. The primary end point was freedom from aneurysm-related adverse events. Multivariable Cox regression was used to test postoperative CTA characteristics as independent risk factors, which were subsequently used as selection criteria for low-risk and high-risk groups. Estimates for freedom from adverse events were obtained using Kaplan-Meier survival curves. RESULTS: Included were 131 patients. The median follow-up was 4.1 years (interquartile range, 2.1-6.1). During this period, 30 patients (23%) sustained aneurysm-related adverse events. Seal length <10 mm and presence of endoleak were significant risk factors for this end point. Patients were subsequently categorized as low-risk (proximal and distal seal length ≥10 mm and no endoleak, n = 62) or high-risk (seal length <10 mm or presence of endoleak, or both; n = 69). During follow-up, four low-risk patients (3%) and 26 high-risk patients (19%) sustained events (P < .001). Four secondary interventions were required in three low-risk patients, and 31 secondary interventions in 23 high-risk patients. Sac growth was observed in two low-risk patients and in 15 high-risk patients. The 5-year estimates for freedom from aneurysm-related adverse events were 98% for the low-risk group and 52% for the high-risk group. For each diagnosis, 81.7 image examinations were necessary in the low-risk group and 8.2 in the high-risk group. CONCLUSIONS: Our results suggest that the first postoperative CTA provides important information for risk stratification after endovascular aneurysm repair when the Excluder endoprosthesis is used. In patients with adequate seal and no endoleaks, the risk of aneurysm-related adverse events was significantly reduced, resulting in a large number of unnecessary image examinations. Adjusting the imaging protocol beyond 30 days and up to 5 years, based on individual patients' risk, may result in a more efficient and rational postoperative surveillance.

Clinical outcome and morphologic analysis after endovascular aneurysm repair using the Excluder endograft.

OBJECTIVE: Long-term follow-up after endovascular aneurysm repair (EVAR) is very scarce, and doubt remains regarding the durability of these procedures. We designed a retrospective cohort study to assess long-term clinical outcome and morphologic changes in patients with abdominal aortic aneurysms (AAAs) treated by EVAR using the Excluder endoprosthesis (W. L. Gore and Associates, Flagstaff, Ariz). METHODS: From 2000 to 2007, 179 patients underwent EVAR in a tertiary institution. Clinical data were retrieved from a prospective database. All patients treated with the Excluder endoprosthesis were included. Computed tomography angiography (CTA) scans were retrospectively analyzed preoperatively, at 30 days, and at the last follow-up using dedicated tridimensional reconstruction software. For patients with complications, all remaining CTAs were also analyzed. The primary end point was clinical success. Secondary end points were freedom from reintervention, sac growth, types I and III endoleak, migration, conversion to open repair, and AAA-related death or rupture. Neck dilatation, renal function, and overall survival were also analyzed. RESULTS: Included were 144 patients (88.2% men; mean age, 71.6 years). Aneurysms were ruptured in 4.9%. American Society of Anesthesiologists classification was III/IV in 61.8%. No patients were lost during a median follow-up of 5.0 years (interquartile range, 3.1-6.4; maximum, 11.2 years). Two patients died of medical complications ≤ 30 days after EVAR. The estimated primary clinical success rates at 5 and 10 years were 63.5% and 41.1%, and secondary clinical success rates were 78.3% and 58.3%, respectively. Sac growth was observed in 37 of 142 patients (26.1%). Cox regression showed type I endoleak during follow-up (hazard ratio, 3.74; P = .008), original design model (hazard ratio, 3.85; P = .001), and preoperative neck diameter (1.27 per mm increase, P = .006) were determinants of sac growth. Secondary interventions were required in 32 patients (22.5%). The estimated 10-year rate of AAA-related death or rupture was 2.1%. Overall life expectancy after AAA repair was 6.8 years. CONCLUSIONS: EVAR using the Excluder endoprosthesis provides a safe and lasting treatment for AAA, despite the need for maintained surveillance and secondary interventions. At up to 11 years, the risk of AAA-related death or postimplantation rupture is remarkably low. The incidences of postimplantation sac growth and secondary intervention were greatly reduced after the introduction of the low-permeability design in 2004.

Anti-beta1 integrin antibody reduces surgery-induced adhesion of colon carcinoma cells to traumatized peritoneal surfaces.

OBJECTIVE: To study the mechanisms behind surgery-induced augmentation of tumor outgrowth. SUMMARY BACKGROUND DATA: Surgery provides the best chance of cure for most primary intra-abdominal carcinomas. Effective treatment is however relatively frequent complicated by peritoneal recurrences, which often originate from free-floating intraperitoneal tumor cells that implant on peritoneal surfaces. We previously reported that surgical trauma promotes development of peritoneal metastases. METHODS: Evaluation of adhesion of CC531s rat colon carcinoma cell line intraperitoneally after laparotomy using in vivo, ex vivo, and in vitro models. Also, human ex vivo models were used to study peritoneal tumor cell adhesion. RESULTS: Peritoneal imprints of operated rats showed that direct damaging of the peritoneum resulted in enhanced adhesion of rat CC531 colon carcinoma cells to submesothelial extracellular matrix (ECM) proteins in vivo, which was confirmed by electron microscopy. Additionally, the inflammatory reaction of the peritoneal cavity led to retraction of mesothelial cells, hereby also exposing ECM at peritoneal surfaces that had not been traumatized directly. Furthermore, we demonstrated that beta1 integrin subunits represented the primary mediators involved in adherence to either isolated ECM components or excised traumatized rat and human peritoneum. Importantly, incubation of CC531s cells with anti-beta1 integrin antibodies resulted in a significant decrease of tumor cell adhesion in vivo. CONCLUSIONS: Surgical trauma results in exposure of ECM at directly and nondirectly damaged peritoneal surfaces, leading to increased beta1 integrin-dependent tumor cell adhesion. Perioperative therapies, which aim to block beta1 integrin subunits, might therefore serve as new clinical tools for the prevention of peritoneal recurrences.

Surgery-derived reactive oxygen species produced by polymorphonuclear leukocytes promote tumor recurrence: studies in an in vitro model.

Tissue injury induces the acute phase response, aimed at minimizing damage and starting the healing process. Polymorphonuclear leukocytes (PMNs) respond to the presence of specific chemoattractants and begin to appear in large numbers. The aim of this study was to investigate the influence of reactive oxygen species (ROS) produced by PMNs on the interaction between colon carcinoma cells and mesothelial cells. An experimental human in vitro model was designed using Caco-2 colon carcinoma cells and primary cultures of mesothelial cells. Tumor cell adhesion to a mesothelial monolayer was assessed after preincubation of the mesothelium with stimulated PMNs and unstimulated PMNs. Mesothelial cells were also incubated with xanthine/xanthine oxidase (X/XO) complex producing ROS after which adhesion of Caco-2 cells was investigated and the expression of adhesion molecules (ICAM-1, VCAM-1, and CD44) by means of enzyme immunoassay. In the control situation the average adhesion of Caco-2 cells to the mesothelial monolayers was 23%. Mesothelial monolayers incubated with unstimulated PMNs showed a 25% increase of tumor cell adhesion (P < 0.05). The adhesion of tumor to the monolayers incubated with the N-formyl-methionyl-leucyl-phenylalanine-stimulated PMNs increased with 40% (P < 0.01). Incubation of the mesothelium with X/XO resulted in an enhancement of adhesion of Caco-2 cells of 70% and an up-regulation of expression of ICAM-1, VCAM-1, and CD44. This study reveals an increase of tumor cell adhesion to the mesothelium induced by incubating the mesothelial monolayers with PMNs. PMNs are producing a number of products, like proteolytic enzymes, cytokines, and ROS. These factors up-regulate the expression of adhesion molecules and in that way stimulate the adhesion of tumor to the mesothelium.