Publications by authors named "Willem Wisselink"

99 Publications

Editor's Choice - Post-operative Surveillance and Long Term Outcome after Endovascular Aortic Aneurysm Repair in Patients with an Initial Post-operative Computed Tomography Angiogram Without Abnormalities: the Multicentre Retrospective ODYSSEUS Study.

Eur J Vasc Endovasc Surg 2022 03 16;63(3):390-399. Epub 2022 Feb 16.

Amsterdam University Medical Centres, Amsterdam Cardiovascular Sciences, Department of Surgery, Amsterdam, The Netherlands. Electronic address:

Objective: Lifelong imaging surveillance is recommended following endovascular aneurysm repair (EVAR). This study aimed to examine the association between adherence to post-operative surveillance and survival and secondary interventions in patients with an initial post-operative computed tomography angiogram (CTA) without abnormalities.

Methods: All consecutive patients undergoing EVAR for intact abdominal aortic aneurysm (AAA) in 16 hospitals between 2007 and 2012 were identified retrospectively, with follow up until December 2018. Patients were included if the initial post-operative CTA showed no types I - III endoleak, kinking, infection, or limb occlusion. Discontinued follow up was defined as at least one 16 month period in which no imaging surveillance was performed. Primary outcomes were aneurysm related mortality and secondary interventions, and secondary outcome all cause mortality. Kaplan-Meier analysis was used to estimate survival, and Cox regression analyses to identify the association between independent variables and outcome. Sensitivity analyses were performed by varying the definition of continued yearly follow up. The study protocol was published (bmjopen-2019-033584).

Results: 1 596 patients (552 continued, 1 044 discontinued follow up) were included with a median (interquartile range) follow up of 89.1 months (52.6). Cumulative aneurysm related, overall, and intervention free survival was 99.4/94.8/96.1%, 98.5/72.9/85.9%, and 96.3/45.4/71.1% at 1, 5, and 10 years, respectively. American Society of Anesthesiologists (ASA) classification (ASA IV hazard ratio [HR] 3.810, 95% confidence interval [CI] 1.296 - 11.198), increase in AAA diameter (HR 3.299, 95% CI 1.408 - 7.729), and continued follow up (HR 3.611, 95% CI 1.780 - 7.323) were independently associated with aneurysm related mortality. The same variables and age (HR 1.063 per year, 95% CI 1.052 - 1.074) were significantly associated with all cause mortality. No difference in secondary interventions was observed between patients with continued vs. discontinued follow up (89/552; 16% vs. 136/1044; 13%; p = .091). Sensitivity analyses showed worse aneurysm related and overall survival in patients with continued follow up.

Conclusion: Discontinued follow up is not associated with poor outcomes. Future prospective studies are indicated to determine in which patients imaging follow up can be safely reduced.
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http://dx.doi.org/10.1016/j.ejvs.2021.11.018DOI Listing
March 2022

A systematic review and meta-analysis of treatment modalities for anterior accessory saphenous vein insufficiency.

Phlebology 2022 Apr 30;37(3):165-179. Epub 2021 Dec 30.

Department of Surgery, 1140Northwest Clinics, Alkmaar, The Netherlands.

Objective: To investigate and compare the outcomes of the available treatment modalities for anterior accessory saphenous vein (AASV) incompetence.

Methods: A systematic literature search was performed in MEDLINE, Embase, and the Cochrane Library. Studies reporting the outcomes of patients who were treated for primary AASV incompetence were included. The methodologic quality of the articles was assessed using the Methodological Index for Non-Randomized Studies (MINORS). A random-effects model was used to estimate anatomic success, defined as AASV occlusion. The secondary outcomes were pain during and after treatment, venous clinical severity score, quality of life, esthetic result, time to return to daily activities, and complications.

Results: The search identified 860 articles, of which 16 met the inclusion criteria. A total of 609 AASVs were reported. The included studies were of poor or moderate quality according to MINORS score. The pooled anatomic success rates were 91.8% after endovenous laser ablation and radiofrequency ablation (EVLA, RFA, 11 studies), 93.6% after cyanoacrylate closure (3 studies), and 79.8% after sclerotherapy (2 studies). The non-pooled anatomic success rate was 97.9% after phlebectomy and 82% after CHIVA. Paresthesia was seen after EVLA in 0.7% of patients (6 studies). Phlebitis was seen in 2.6% of patients after RFA (2 studies), 27% after sclerotherapy (1 study), and 12% after the phlebectomy (1 study). Deep venous thrombosis and skin burn did not occur.

Conclusion: Treatment of AASV incompetence is safe and effective. Despite limited evidence, occlusion of the AASV can be achieved with endovenous thermal ablation and cyanoacrylate. There does not appear to be a benefit of EVLA compared to RFA regarding treatment efficacy. Phlebectomy shows promising results if the saphenofemoral junction is competent. Lower results are seen after sclerotherapy and CHIVA. However, studies with sufficient sample sizes of solely treatment of AASV incompetence are needed to draw firm conclusions.
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http://dx.doi.org/10.1177/02683555211060998DOI Listing
April 2022

Therapeutic Use of Microbubbles and Ultrasound in Acute Peripheral Arterial Thrombosis: A Systematic Review.

Ultrasound Med Biol 2021 10 13;47(10):2821-2838. Epub 2021 Jul 13.

Department of Surgery, Amsterdam University Medical Centers (VUmc), Amsterdam, The Netherlands; Department of Physiology, Amsterdam University Medical Centers (VUmc), Amsterdam, The Netherlands.

Catheter-directed thrombolysis (CDT) for acute peripheral arterial occlusion is time consuming and carries a risk of major hemorrhage. Contrast-enhanced sonothrombolysis (CEST) might enhance outcomes compared with standard CDT. In the study described here, we systematically reviewed all in vivo studies on contrast-enhanced sonothrombolysis in a setting of arterial thrombosis. A systematic search of the PubMed, Embase, Cochrane Library and Web of Science databases was conducted. Two reviewers independently performed the study selection, quality assessment and data extraction. Primary outcomes were recanalization rate and thrombus weight. Secondary outcome was any possible adverse event. The 35 studies included in this review were conducted in four different (pre)clinical settings: ischemic stroke, myocardial infarction, (peripheral) arterial thrombosis and arteriovenous graft occlusion. Because of the high heterogeneity among the studies, it was not possible to conduct a meta-analysis. In almost all studies, recanalization rates were higher in the group that underwent a form of CEST. One study was terminated early because of a higher incidence of intracranial hemorrhage. Studies on CEST suggest that adding microbubbles and ultrasound to standard intra-arterial CDT is safe and might improve outcomes in acute peripheral arterial thrombosis. Further research is needed before CEST can be implemented in daily practice.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2021.06.001DOI Listing
October 2021

A systematic review and meta-analysis of mechanochemical endovenous ablation using Flebogrif for varicose veins.

J Vasc Surg Venous Lymphat Disord 2022 01 6;10(1):248-257.e2. Epub 2021 Jun 6.

Department of Surgery, Northwest Clinics, Alkmaar, The Netherlands.

Objective: In the present study, we reviewed and analyzed the currently available data on the Flebogrif device (Balton, Warsaw, Poland) to define its role in the global varicose vein treatment devices market.

Methods: A systematic literature search was performed in MEDLINE, Embase, and the Cochrane Library. Studies were eligible if they had included patients treated using the Flebogrif for saphenous vein incompetence, had been reported in English, and had the full text available. The methodologic quality of the studies was assessed using the methodologic index for nonrandomized studies (MINORS) score. A random effects model was used to estimate the primary outcome of anatomic success, defined as the occlusion rate of the treated vein. The estimates are reported with the 95% confidence intervals (CIs). The secondary outcomes were clinical success, complication rate, pain during and after the procedure, and time to return to work.

Results: Five articles met the inclusion criteria, reporting 348 procedures in 392 patients. Four studies reported the 3-month anatomic success, and three studies reported the 12-month anatomic success. The pooled 3-month anatomic success rate was 95.6% (95% CI, 93.2%-98.0%). The 12-month anatomic success rate was 93.2% (95% CI, 90.3%-96.1%). The only major complication reported within 3 months was deep vein thrombosis, which developed in 0.3% of the patients. The minor complications of thrombophlebitis and hyperpigmentation had occurred in 13.3% to 14.5% and 3.3% to 10.0% of patients, respectively, within 3 months. The methodologic quality of the included studies was moderate.

Conclusions: Mechanochemical ablation using the Flebogrif device is a safe and well-tolerated procedure for the treatment of saphenous vein insufficiency. However, well-designed studies of sufficient sample size and follow-up are required to compare the effectiveness with other endovenous treatment modalities and define the definitive role of the Flebogrif device.
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http://dx.doi.org/10.1016/j.jvsv.2021.05.010DOI Listing
January 2022

Robot-assisted transthoracic first rib resection for venous thoracic outlet syndrome.

Vascular 2022 Apr 9;30(2):217-224. Epub 2021 Apr 9.

Cardiovascular Sciences, Department of Vascular Surgery, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, Netherlands.

Background: Venous thoracic outlet syndrome (vTOS) is caused by external compression of the subclavian vein at the costoclavicular junction. It can be subdivided in McCleery Syndrome and Paget-Schroetter Syndrome (PSS). To improve the venous outflow of the arm and to prevent recurrent thrombosis, first rib resection with venolysis of the subclavian vein can be performed. Open transaxillary, supraclavicular, infraclavicular or combined paraclavicular approaches are well known, but more recent robot-assisted techniques are introduced. We report our short- and long-term results of a minimal invasive transthoracic approach for resection of the anteromedial part of the first rib using the DaVinci surgical robot, performed through three trocars.

Methods: We analyzed all patients with vTOS who were scheduled to undergo robot-assisted transthoracic first rib resection in the period July 2012 to May 2016. Outcomes were: technical success, operation time, blood loss, hospital stay, 30-day complications and patency. Functional outcomes were assessed using the "Disability of the Arm, Shoulder and Hand" (DASH) questionnaire.

Results: Fifteen patients (8 male, 7 female; mean age 32.9 years, range 20-54 years) underwent robot-assisted transthoracic first rib resection. Conversion to transaxillary resection was necessary in three patients. Average operation time was 147.9 min (range 88-320 min) with a mean blood loss of 79.5 cc (range 10-550 cc). Mean hospital stay was 3.5 days (range 2-9). In three patients, complications were reported (Clavien-Dindo grade 2-3a). Patency was 91% at 15.5 months' follow-up. DASH scores at one and three years showed excellent functional outcomes (7.1 (SD= 6.9, range 0-20.8) and 6.0 (SD= 6.4, range 0-25)) and are comparable to the scores of the normative general population.

Conclusion: Robot-assisted transthoracic first rib resection with only three trocars is a feasible minimal invasive approach for first rib resection in the management of vTOS. This technique enables the surgeon to perform venolysis under direct 3D vision with good patency and long-term functional outcome. Studies with larger cohort size are needed to compare the outcomes of this robot-assisted technique with other more established approaches.
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http://dx.doi.org/10.1177/1708538121997332DOI Listing
April 2022

Survival and Living Situation After Ruptured Abdominal Aneurysm Repair in Octogenarians.

Eur J Vasc Endovasc Surg 2021 03 6;61(3):375-381. Epub 2021 Jan 6.

Department of Vascular Surgery, Dijklander Ziekenhuis, Hoorn, The Netherlands; Department of Vascular Surgery, Amsterdam UMC, Amsterdam, The Netherlands.

Objective: To determine the 30 day and one year mortality and post-operative living situation in octogenarians treated for ruptured abdominal aortic aneurysm (rAAA).

Methods: A retrospective study was performed at four centres in the Netherlands. All consecutive patients aged ≥80 years, presenting with a rAAA between January 2013 and October 2018, were included. The primary outcomes were post-operative living situation and one year mortality.

Results: In total, 157 patients were included. Forty-seven received palliative care and 110 patients had surgery. After endovascular or open repair, the one year mortality rate was 50.0%. The 30 day mortality rate was 40.8% (95% confidence interval [CI] 27-55) and 31.7% (95% CI 20-44), for endovascular and open repair, respectively (p = .32). Sixty-five per cent of survivors were discharged home, while 34.8% went to a nursing home for rehabilitation. Of the surviving patients, 82.6% went back to living in their pre-rupture home situation. Of the investigated variables, only a high body mass index proved a significant predictor of death at 30 days and one year. Compared with operated patients, patients turned down for surgery were older (mean age 87.5 ± 3.8 vs. 84.0 ± 3.5; p < .001), lived significantly more often in a nursing home (odds ratio 1.02, 95% CI 1.00-1.03; p < .001), were more often dependent (odds ratio 3.69, 95% CI 2.31-5.88; p < .001) and had a lower Glasgow Coma Scale score on arrival (odds ratio 0.42, 95% CI 0.25-0.69; p = .002). All palliative patients died within three days.

Conclusion: Overall treatment outcomes showed that octogenarians should not be denied surgery based on age alone, as half of the octogenarians that undergo surgical treatment are still alive one year after rAAA repair. In addition, > 80% returned to their own home after rehabilitation.
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http://dx.doi.org/10.1016/j.ejvs.2020.11.023DOI Listing
March 2021

Anatomic Suitability for Branched Thoracic Endovascular Repair in Patients with Aortic Arch Pathological Features.

J Am Heart Assoc 2020 10 3;9(20):e016695. Epub 2020 Oct 3.

Department of Surgery Amsterdam Cardiovascular Sciences Amsterdam University Medical Centres, Vrije Universiteit Amsterdam Amsterdam the Netherlands.

Background Endovascular repair has become a viable alternative for aortic pathological features, including those located within the aortic arch. We investigated the anatomic suitability for branched thoracic endovascular repair in patients previously treated with conventional open surgery for aortic arch pathological features. Methods and Results Patients who underwent open surgery for aortic arch pathological features at our institution between 2000 and 2018 were included. Anatomic suitability was determined by strict compliance with the anatomic criteria within manufacturers' instructions for use for each of the following branched thoracic stent grafts: Relay Plus Double-Branched (Terumo-Aortic), TAG Thoracic Branch Endoprosthesis (W.L. Gore & Associates), Zenith Arch Branched Device (Cook-Medical), and Nexus Stent Graft System (Endospan Ltd/Jotec GmbH). Computed tomography angiography images were analyzed with outer luminal line measurements. A total of 377 patients (mean age, 64±14 years; 64% men) were identified, 153 of whom had suitable computed tomography angiography images for measurements. In total, 59 patients (15.6% of the total cohort and 38.6% of the measured cohort) were eligible for endovascular repair using at least one of the devices. Device suitability was 30.9% for thoracic aneurysms, 4.6% for type A dissections, 62.5% for type B dissections, and 28.6% for other pathological features. Conclusions The anatomic suitability for endovascular repair of all aortic arch pathological features was modest. The highest suitability rates were observed for thoracic aneurysms and for type B dissections, of which repair included part of the aortic arch. We suggest endovascular repair of arch pathological features should be reserved for high-volume centers with experience in endovascular arch repair.
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http://dx.doi.org/10.1161/JAHA.120.016695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763389PMC
October 2020

Image Fusion During Standard and Complex Endovascular Aortic Repair, to Fuse or Not to Fuse? A Meta-analysis and Additional Data From a Single-Center Retrospective Cohort.

J Endovasc Ther 2021 Feb 23;28(1):78-92. Epub 2020 Sep 23.

Department of Surgery, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands.

Purpose: To determine if image fusion will reduce contrast volume, radiation dose, and fluoroscopy and procedure times in standard and complex (fenestrated/branched) endovascular aneurysm repair (EVAR).

Materials And Methods: A search of the PubMed, Embase, and Cochrane databases was performed in December 2019 to identify articles describing results of standard and complex EVAR procedures using image fusion compared with a control group. Study selection, data extraction, and assessment of the methodological quality of the included publications were performed by 2 reviewers working independently. Primary outcomes of the pooled analysis were contrast volume, fluoroscopy time, radiation dose, and procedure time. Eleven articles were identified comprising 1547 patients. Data on 140 patients satisfying the study inclusion criteria were added from the authors' center. Mean differences (MDs) are presented with the 95% confidence interval (CI).

Results: For standard EVAR, contrast volume and procedure time showed a significant reduction with an MD of -29 mL (95% CI -40.5 to -18.5, p<0.001) and -11 minutes (95% CI -21.0 to -1.8, p<0.01), respectively. For complex EVAR, significant reductions in favor of image fusion were found for contrast volume (MD -79 mL, 95% CI -105.7 to -52.4, p<0.001), fluoroscopy time (MD -14 minutes, 95% CI -24.2 to -3.5, p<0.001), and procedure time (MD -52 minutes, 95% CI -75.7 to -27.9, p<0.001).

Conclusion: The results of this meta-analysis confirm that image fusion significantly reduces contrast volume, fluoroscopy time, and procedure time in complex EVAR but only contrast volume and procedure time for standard EVAR. Though a reduction was suggested, the radiation dose was not significantly affected by the use of fusion imaging in either standard or complex EVAR.
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http://dx.doi.org/10.1177/1526602820960444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816548PMC
February 2021

Secondary Interventions and Long-term Follow-up after Endovascular Abdominal Aortic Aneurysm Repair.

Ann Vasc Surg 2021 Feb 5;71:381-391. Epub 2020 Aug 5.

Department of Surgery, Amsterdam University Medical Centres, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands. Electronic address:

Background: Early morbidity and mortality are low after endovascular abdominal aneurysm repair (EVAR), but secondary interventions and late complications are common. The aim of the present multicenter cohort study is to detail the frequency and indication for interventions after EVAR and the impact on long-term survival.

Methods: A retrospective multicenter cohort study of secondary interventions after elective EVAR for an infrarenal abdominal aortic aneurysm was conducted. Consecutive patients (n = 349) undergoing EVAR between January 2007 and January 2012 were analyzed, with long-term follow-up until December 2018. Those requiring intervention were classified in accordance with the indications and specific nature of the intervention and treatment. The primary study end point was overall survival classified for patients with and without intervention. Kaplan-Meier analysis was used to estimate overall survival for those who did and who did not undergo secondary interventions. Univariable and multivariable Cox regression were performed to identify independent variables associated with mortality.

Results: Some 56 patients (16%) underwent 72 secondary interventions after EVAR during a median (interquartile range) follow-up period of 53.2 months (60.1). Some 45 patients (80.4%) underwent one intervention. Indications for intervention included mainly endograft kinking/outflow obstruction and type II endoleak. An endovascular technique was used in 40.3% of interventions. Median time to secondary intervention was 24.1 months. In 93 patients with abnormalities on imaging, no intervention was performed mainly because the abnormality had disappeared on follow-up imaging (43%). Kaplan-Meier curves showed no difference in survival for patients with and without secondary interventions (P = 0.153). Age (hazard ratio [HR]: 1.089, 95% confidence interval [CI]: 1.063-1.116), ASA classification (ASA III, IV HR: 1.517, 95% CI: 1.056-2.178) were significantly related to mortality.

Conclusions: Secondary intervention rates are still considerable after EVAR. Endograft kinking/outflow obstruction and endoleak type II are the most common indications for a secondary intervention. Secondary interventions did not adversely affect long-term overall survival after EVAR.
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http://dx.doi.org/10.1016/j.avsg.2020.07.042DOI Listing
February 2021

Gutter Characteristics and Stent Compression of Self-Expanding vs Balloon-Expandable Chimney Grafts in Juxtarenal Aneurysm Models.

J Endovasc Ther 2020 Jun 21;27(3):452-461. Epub 2020 Apr 21.

Department of Vascular Surgery, Amsterdam University Medical Centers, VU Medical Center, Amsterdam, the Netherlands.

To assess in silicone juxtarenal aneurysm models the gutter characteristics and compression of different types of chimney graft (CG) configurations. Fifty-seven combinations of Excluder C3 or Conformable Excluder stent-grafts (23, 26, and 28.5 mm) were deployed in 2 silicone juxtarenal aneurysm models with 3 types of CGs: Viabahn self-expanding (VSE; 6 and 13 mm) or Viabahn balloon-expandable (VBX; 6, 10, and 12 mm) stent-grafts and Advanta V12 balloon-expandable stent-grafts (ABX; 6 and 12 mm). Setups were divided into 4 groups on the basis of increasing CG and main graft (MG) diameters. Two independent observers assessed gutter size and type as well as CG compression on computed tomography scans using postprocessing software. In the smaller diameter combinations (6-mm CG and 23-, 26-, and 28.5-mm MGs), both VSE (p=0.006 to 0.050) and ABX (p=0.045 to 0.050) showed lower gutter areas and volumes compared with VBX. In turn, the VBX showed a nonsignificant tendency to decreased compression, especially compared to ABX. Use of the Excluder C3 showed a 6-fold increase in type A1 gutters (related to type Ia endoleak) as compared to the Conformable Excluder (p=0.018). Balloon-expandable stent-grafts (both ABX and VBX) showed a 3-fold increase in type A1 gutters in comparison with self-expanding stent-grafts (p=0.008). The current study suggests that use of the Conformable Excluder in combination with VSE chimney grafts is superior to the other tested CG/MG combinations in terms of gutter size, gutter type, and CG compression.
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http://dx.doi.org/10.1177/1526602820915262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288858PMC
June 2020

Outcome of Ruptured Abdominal Aortic Aneurysm Repair in Octogenarians: A Systematic Review and Meta-Analysis.

Eur J Vasc Endovasc Surg 2020 Jan 4;59(1):16-22. Epub 2019 Dec 4.

Department of Vascular Surgery, Dijklander Ziekenhuis, Hoorn, the Netherlands; Department of Vascular Surgery, Amsterdam UMC, Amsterdam, the Netherlands. Electronic address:

Objective: This meta-analysis sought to identify the mortality and ambulatory state 30 days and one year post-operatively in octogenarians treated for ruptured abdominal aortic aneurysm (rAAA) by endovascular aneurysm repair (EVAR) or open repair (OR). rAAA is a life threatening emergency occurring increasingly in octogenarians. Surgical treatment, open or endovascular, offers the only chance of survival albeit with significant mortality and morbidity rates and a high burden to society. In order to make an informed decision on management, contemporary treatment outcomes should be known. The aim of this study was to perform a systematic review and meta-analysis on rAAA repair in octogenarians.

Methods: The Pubmed, Embase and Cochrane databases were searched for articles published between 2013 and October 2018 on octogenarians treated for a rAAA. Meta-analysis was performed using the random effects model to calculate the 30 day and one year mortality.

Results: The search resulted in a total of 1569 articles, of which eight retrospective studies could be included, reporting on 7526 patients. All studies reported 30 day mortality in octogenarians, and the one year mortality was addressed in four studies. Ambulatory state was not reported. Meta-analysis showed a 30 day mortality of 43% (95% confidence interval (CI) 33-53) and a one year mortality of 47% (95% CI 32-62). Patients after EVAR had a significant lower mortality at 30 days (risk ratio (RR) 0.50, 95% CI 0.38-0.67) and at one year (RR 0.65, 95% CI 0.44-0.96).

Conclusion: The 30 day and one year mortality rates for rAAA repair in octogenarians are similar to the outcome at all ages, with a significant survival advantage of EVAR over OR. Patients should therefore not be denied treatment of a rAAA based on age alone.
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http://dx.doi.org/10.1016/j.ejvs.2019.07.014DOI Listing
January 2020

Cold Renal Perfusion During Simulation of Juxtarenal Aortic Aneurysm Repair Reduces Systemic Oxidative Stress and Sigmoid Damage in Rats.

Eur J Vasc Endovasc Surg 2019 Dec;58(6):891-901

Amsterdam University Medical Centres, Location VUmc, Department of Surgery, Amsterdam, the Netherlands; Amsterdam University Medical Centres, Location VUmc, Department of Physiology, Amsterdam, the Netherlands. Electronic address:

Objectives: Juxtarenal aortic surgery induces renal ischaemia reperfusion, which contributes to systemic inflammatory tissue injury and remote organ damage. Renal cooling during suprarenal cross clamping has been shown to reduce renal damage. It is hypothesised that renal cooling during suprarenal cross clamping also has systemic effects and could decrease damage to other organs, like the sigmoid colon.

Methods: Open juxtarenal aortic aneurysm repair was simulated in 28 male Wistar rats with suprarenal cross clamping for 45 min, followed by 20 min of infrarenal aortic clamping. Four groups were created: sham, no, warm (37 °C saline), and cold (4 °C saline) renal perfusion during suprarenal cross clamping. Primary outcomes were renal damage and sigmoid damage. To assess renal damage, procedure completion serum creatinine rises were measured. Peri-operative microcirculatory flow ratios were determined in the sigmoid using laser Doppler flux. Semi-quantitative immunofluorescence microscopy was used to measure alterations in systemic inflammation parameters, including reactive oxygen species (ROS) production in circulating leukocytes and leukocyte infiltration in the sigmoid. Sigmoid damage was assessed using digestive enzyme (intestinal fatty acid binding protein - I-FABP) leakage, a marker of intestinal integrity.

Results: Suprarenal cross clamping caused deterioration of all systemic parameters. Only cold renal perfusion protected against serum creatinine rise: 0.45 mg/dL without renal perfusion, 0.33 mg/dL, and 0.14 mg/dL (p = .009) with warm and cold perfusion, respectively. Microcirculation in the sigmoid was attenuated with warm (p = .002) and cold renal perfusion (p = .002). A smaller increase of ROS production (p = .034) was seen only after cold perfusion, while leukocyte infiltration in the sigmoid colon decreased after warm (p = .006) and cold perfusion (p = .018). Finally, digestive enzyme leakage increased more without (1.5AU) than with warm (1.3AU; p = .007) and cold renal perfusion (1.2AU; p = .002).

Conclusions: Renal ischaemia/reperfusion injury after suprarenal cross clamping decreased microcirculatory flow, increased systemic ROS production, leukocyte infiltration, and I-FABP leakage in the sigmoid colon. Cold renal perfusion was superior to warm perfusion and reduced renal damage and had beneficial systemic effects, reducing sigmoid damage in this experimental study.
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http://dx.doi.org/10.1016/j.ejvs.2019.05.021DOI Listing
December 2019

Design and protocol of a comprehensive multicentre biobank for abdominal aortic aneurysms.

BMJ Open 2019 08 1;9(8):e028858. Epub 2019 Aug 1.

Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Introduction: The pathophysiology and natural course of abdominal aortic aneurysms (AAAs) are insufficiently understood. In order to improve our understanding, it is imperative to carry out longitudinal research that combines biomarkers with clinical and imaging data measured over multiple time points. Therefore, a multicentre biobank, databank and imagebank has been established in the Netherlands: the '' (AAA bank).

Methods And Analysis: The AAA bank is a prospective multicentre observational biobank, databank and imagebank of patients with an AAA. It is embedded within the framework of the Parelsnoer Institute, which facilitates uniform biobanking in all university medical centres (UMCs) in the Netherlands. The AAA bank has been initiated by the two UMCs of Amsterdam UMC and by Leiden University Medical Center. Participants will be followed during AAA follow-up. Clinical data are collected every patient contact. Three types of biomaterials are collected at baseline and during follow-up: blood (including DNA and RNA), urine and AAA tissue if open surgical repair is performed. Imaging data that are obtained as part of clinical care are stored in the imagebank. All data and biomaterials are processed and stored in a standardised manner. AAA growth will be based on multiple measurements and will be analysed with a repeated measures analysis. Potential associations between AAA growth and risk factors that are also measured on multiple time points can be assessed with multivariable mixed-effects models, while potential associations between AAA rupture and risk factors can be tested with a conditional dynamic prediction model with landmarking or with joint models in which linear mixed-effects models are combined with Cox regression.

Ethics And Dissemination: The AAA bank is approved by the Medical Ethics Board of the Amsterdam UMC (University of Amsterdam).

Trial Registration Number: NCT03320408.
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http://dx.doi.org/10.1136/bmjopen-2018-028858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688677PMC
August 2019

Catheter Directed Thrombolysis Protocols for Peripheral Arterial Occlusions: a Systematic Review.

Eur J Vasc Endovasc Surg 2019 05 17;57(5):667-675. Epub 2019 Apr 17.

Department of Vascular Surgery, Amsterdam UMC, Amsterdam, the Netherlands. Electronic address:

Objective: Catheter directed thrombolysis (CDT) for peripheral arterial occlusions is a well established alternative to thrombo-embolectomy in patients with (sub)acute limb ischaemia. However, protocols are heterogeneous and need optimisation to improve results and lower bleeding risks. The objective was to review the results and outcomes of different CDT protocols for patients with peripheral arterial occlusions.

Data Sources: Electronic information sources (MEDLINE, Embase, Cochrane) and reference lists were searched to identify studies reporting results of CDT of peripheral arterial occlusions.

Methods: Two independent observers performed study selection, quality assessment and data extraction. Primary outcomes were treatment duration, success rates, and bleeding complications. Secondary outcomes were mortality and amputation rates.

Results: One hundred and six studies were included: 19 randomised controlled trials (RCTs), 38 prospective studies, 48 retrospective studies, and one mixed cohort study. The studies comprised a total number of 10,643 cases of which 9877 received CDT for lower extremity arterial occlusion, with a mean treatment duration of 21.4 h (95% confidence interval [CI] 21.0-21.8), an angiographic patency of 75% (95% CI 74.6-75.1), and freedom from amputation rate of 91% (95% CI 90.3-90.7). Pooled results showed a thrombolysis duration with high dose protocols of 21.9 h (95% CI 21.4-22.5) and 32.7 h with low dose protocols, with bleeding rates of 16.7% (95% CI 16.3-17.1) and 13.4% (95% CI 12.8-14.0), respectively. Weighted mean results for all RCTs and prospective cohorts of >100 cases analysed separately, showed comparable results to all observational cohorts pooled. Bleeding complications occurred in 18% (95% CI 17.8-18.3) of patients and remain an important risk of CDT.

Conclusion: CDT is an effective treatment for peripheral arterial occlusions, the main concern is bleeding complications. Although no formal meta-analysis could be performed, the pooled results suggest that lower doses of fibrinolytics lead to similar success rates at a cost of longer treatment duration but with less bleeding. There is large variation in treatment protocols and the available literature suffers from absence of reporting standards and high heterogeneity.
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http://dx.doi.org/10.1016/j.ejvs.2018.11.018DOI Listing
May 2019

Giant, 20 cm Diameter, Ruptured Abdominal Aortic Aneurysm: A Case Report.

EJVES Short Rep 2019 29;42:18-20. Epub 2018 Dec 29.

Division of Vascular Surgery, Amsterdam UMC, The Netherlands.

Introduction: The rupture risk of abdominal aortic aneurysms (AAAs) depends primarily on their diameter and increases exponentially with aneurysm growth. Therefore, giant AAAs, defined as > 13.0 cm in diameter, are rare clinical entities.

Report: A giant ruptured AAA that measured >20 cm in diameter was successfully treated by open repair.

Conclusion: It remains unclear why giant AAAs continue to grow to extreme size without rupturing. Open repair seems to be the treatment of choice for most giant aneurysms, both ruptured and unruptured.
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http://dx.doi.org/10.1016/j.ejvssr.2018.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357693PMC
December 2018

The Potential Role of Neutrophil Gelatinase-Associated Lipocalin in the Development of Abdominal Aortic Aneurysms.

Ann Vasc Surg 2019 May 24;57:210-219. Epub 2019 Jan 24.

Department of Vascular Surgery, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, Amsterdam, The Netherlands; Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, Amsterdam, The Netherlands. Electronic address:

Background: In abdominal aortic aneurysm (AAA), pathophysiology deterioration of the medial aortic layer plays a critical role. Key players in vessel wall degeneration are reactive oxygen species (ROS), smooth muscle cell apoptosis, and extracellular matrix degeneration by matrix metalloproteinase-9 (MMP-9). Lipocalin-2, also neutrophil gelatinase-associated lipocalin (NGAL), is suggested to be involved in these degenerative processes in other cardiovascular diseases. We aimed to further investigate the role of NGAL in AAA development and rupture.

Methods: In this observational study, aneurysm tissue and blood of ruptured (n = 13) AAA patients were investigated versus nonruptured (n = 26) patients. Nondilated aortas (n = 5) from deceased patients and venous blood from healthy volunteers (n = 10) served as controls. NGAL concentrations in tissue and blood were measured by enzyme-linked immunosorbent assay and immunofluorescence microscopy. Nitrotyrosine (marker of ROS), MMP-9, and caspase-3 (marker of apoptosis) in aneurysm tissue were measured by immunofluorescence microscopy. AAA expansion rates were calculated retrospectively.

Results: NGAL (in μg/mL) blood concentration in ruptured AAA was 46 (range 22-122) vs. 26 (range 6-55) in nonruptured AAA (P < 0.01) and 14 (range 12-22) in controls (P < 0.01). In the aneurysm wall of ruptured AAA, NGAL concentration was 4.7 (range 1.4-25) vs. 4.4 (range 0.2-14) in nonruptured AAA (not significant) and 1.8 (range 1.2-2.7) in nondilated aortas (P = 0.04). In the medial layer, NGAL correlated positively with nitrotyrosine (Rs = 0.80, P < 0.01), MMP-9 (Rs = 0.56, P = 0.02), and caspase-3 (Rs = 0.75, P = 0.01). NGAL did not correlate to AAA expansion rate in blood or tissue (P = 0.34 and P = 0.95, respectively).

Conclusions: This study demonstrates that NGAL blood concentration is higher in ruptured AAA patients than in nonruptured AAA. NGAL expression in the AAA wall is also higher than in nondilated aorta. Furthermore, its expression is associated with factors of vessel wall deterioration. Based on our study results, we could not determine NGAL as a biomarker for AAA growth or rupture. However, our findings do support a potential role of NGAL in the development of AAA.
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http://dx.doi.org/10.1016/j.avsg.2018.11.006DOI Listing
May 2019

Secondary Fill Minimizes Gutter Size in Chimney EVAS Configurations In Vitro.

J Endovasc Ther 2019 02 21;26(1):62-71. Epub 2018 Dec 21.

1 Department of Vascular Surgery, VU University Medical Center, Amsterdam, the Netherlands.

Purpose: To investigate in an in vitro model if secondary endobag filling can reduce gutter size during chimney endovascular aneurysm sealing (chEVAS).

Materials And Methods: Nellix EVAS systems were deployed in 2 silicone juxtarenal aneurysm models with suprarenal aortic diameters of 19 and 24 mm. Four configurations were tested: EVAS with 6-mm balloon-expandable (BE) or self-expanding (SE) chimney grafts (CGs) in the renal branches of both models. Balloons were inflated simultaneously in the CGs and main endografts during primary and secondary endobag filling and polymer curing. Computed tomography (CT) was performed immediately after the primary and secondary fills. Cross-sectional lumen areas were measured on the CT images to calculate gutter volumes and percent change. CG compression was calculated as the reduction in lumen surface area measured perpendicular to the central lumen line. The largest gutter volume and highest compression were presented per CG configuration per model.

Results: Secondary endobag filling reduced the largest gutter volumes from 99.4 to 73.1 mm (13.2% change) and 84.2 to 72.0 mm (27.6% change) in the BECG configurations and from 67.2 to 44.0 mm (34.5% change) and 92.7 to 82.3 mm (11.2% change) in the SECG configurations in the 19- and 24-mm models, respectively. Secondary endobag filling increased CG compression in 6 of 8 configurations. BECG compression changed by -0.2% and 5.4% and by -1.0% and 0.4% in the 19- and 24-mm models, respectively. SECG compression changed by 10.2% and 16.0% and by 7.2% and 7.3% in the 19- and 24-mm models, respectively.

Conclusion: Secondary endobag filling reduced paragraft gutters; however, this technique did not obliterate them. Increased CG compression and prolonged renal ischemia time should be considered if secondary endobag filling is used.
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http://dx.doi.org/10.1177/1526602818819494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330694PMC
February 2019

The Value of Sigmoidoscopy to Detect Colonic Ischaemia After Ruptured Abdominal Aortic Aneurysm Repair.

Eur J Vasc Endovasc Surg 2019 02 11;57(2):229-237. Epub 2018 Oct 11.

Amsterdam UMC, University of Amsterdam, Department of Surgery, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands.

Objectives: Diagnosing colonic ischaemia (CI) after ruptured abdominal aortic aneurysm (RAAA) repair is challenging. This study determined the diagnostic value of sigmoidoscopy in patients suspected of CI after RAAA repair.

Methods: This was a retrospective multicentre cohort study. Patients who underwent RAAA repair in three hospitals in Amsterdam, the Netherlands, between 2004 and 2011 (AJAX cohort) were included. Sigmoidoscopies were carried out based on clinical judgment. Endoscopy results were classified as "no ischaemia," "mild CI," or "moderate to severe CI." The surgical diagnosis was classified as "transmural" or "no transmural" CI. The value of sigmoidoscopy was assessed with calculation of positive and negative predictive values (PPV, NPV) with 95% CI for transmural CI. Logistic regression analysis was used to express the association of risk factors with CI as adjusted OR.

Results: Transmural CI was diagnosed in 23 of 351 patients (6.6%). Thirteen of sixteen patients (81%) who underwent direct laparotomy for high suspicion of CI indeed had transmural CI. Forty-six patients (13%) underwent sigmoidoscopy. The prevalence of transmural CI was 22% (10/46; 95% CI 12-36%) in these patients. The PPV for transmural CI of "moderate to severe CI" on sigmoidoscopy was 73% (8/11; 95% CI 43-90%). The PPV of "mild CI" on sigmoidoscopy was 11% (2/19; 95% CI 2.9-31%). The NPV of "no ischaemia" on sigmoidoscopy was 100% (95% CI 78-100%). Cardiac comorbidity (OR 3.1, 95% CI 1.19-7.97), low first haemoglobin (OR 0.6, 95% CI 0.47-0.87), and high vasopressor administration (OR 9.4, 95% CI 1.99-44.46) were independently associated with CI.

Conclusions: Sigmoidoscopy increases the likelihood of correctly identifying the presence or absence of transmural CI, especially in patients with a moderate clinical suspicion for CI after RAAA repair.
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http://dx.doi.org/10.1016/j.ejvs.2018.08.041DOI Listing
February 2019

High Density of Periaortic Adipose Tissue in Abdominal Aortic Aneurysm.

Eur J Vasc Endovasc Surg 2018 Nov 14;56(5):663-671. Epub 2018 Aug 14.

Department of Vascular Surgery, VU University Medical Centre, Amsterdam, The Netherlands; Department of Physiology (Amsterdam Cardiovascular Sciences) VU University Medical Centre, Amsterdam, The Netherlands. Electronic address:

Objectives: Perivascular adipose tissue (PVAT) is currently seen as a paracrine organ that produces vasoactive substances, including inflammatory agents, which may have an impact on the vasculature. In this study PVAT density was quantified in patients with an aortic aneurysm and compared with those with a non-dilated aorta. Since chronic inflammation, as the pathway to medial thinning, is a hallmark of abdominal aortic aneurysms (AAAs), it was hypothesised that PVAT density is higher in AAA patients.

Methods: In this multicentre retrospective case control study, three groups of patients were included: non-treated asymptomatic AAA (n = 140), aortoiliac occlusive disease (AIOD) (n = 104), and individuals without aortic pathology (n = 97). A Hounsfield units based analysis was performed by computed tomography (CT). As a proxy for PVAT, the density of adipose tissue 10 mm circumferential to the infrarenal aorta was analysed in each consecutive CT slice. Intra-individual PVAT differences were reported as the difference in PVAT density between the region of the maximum AAA diameter (or the mid-aortic region in patients with AIOD or controls) and the two uppermost slices of infrarenal non-dilated aorta just below the renal arteries. Furthermore, subcutaneous (SAT) and visceral (VAT) adipose tissue measurements were performed. Linear models were fitted to assess the association between the study groups, different adipose tissue compartments, and between adipose tissue compartments and aortic dimensions.

Results: AAA patients presented higher intra-individual PVAT differences, with higher PVAT density around the aneurysm sac than the healthy neck. This association persisted after adjustment for cardiovascular risk factors and diseases and other fat compartments (β = 13.175, SE 4.732, p = .006). Furthermore, intra-individual PVAT differences presented the highest correlation with aortic volume that persisted after adjustment for other fat compartments, body mass index, sex, and age (β = 0.566, 0.200, p = .005).

Conclusion: The results suggest a relation between the deposition of PVAT and AAA pathophysiology. Further research should explore the exact underlying processes.
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http://dx.doi.org/10.1016/j.ejvs.2018.07.008DOI Listing
November 2018

Systematic Review of Circulating, Biomechanical, and Genetic Markers for the Prediction of Abdominal Aortic Aneurysm Growth and Rupture.

J Am Heart Assoc 2018 06 30;7(13). Epub 2018 Jun 30.

Department of Vascular Surgery, Amsterdam Cardiovascular Sciences (ACS), VU University Medical Center (VUmc), Amsterdam, The Netherlands

Background: The natural course of abdominal aortic aneurysms (AAA) is growth and rupture if left untreated. Numerous markers have been investigated; however, none are broadly acknowledged. Our aim was to identify potential prognostic markers for AAA growth and rupture.

Methods And Results: Potential circulating, biomechanical, and genetic markers were studied. A comprehensive search was conducted in PubMed, Embase, and Cochrane Library in February 2017, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Study selection, data extraction, and methodological quality assessment were conducted by 2 independent researchers. Plausibility of markers was based on the amount of publications regarding the marker (more than 3), pooled sample size (more than 100), bias risk and statistical significance of the studies. Eighty-two studies were included, which examined circulating (n=40), biomechanical (n=27), and genetic markers (n=7) and combinations of markers (n=8). Factors with an increased expansion risk included: AAA diameter (9 studies; n=1938; low bias risk), chlamydophila pneumonia (4 studies; n=311; medium bias risk), S-elastin peptides (3 studies; n=205; medium bias risk), fluorodeoxyglucose uptake (3 studies; n=104; medium bias risk), and intraluminal thrombus size (5 studies; n=758; medium bias risk). Factors with an increased rupture risk rupture included: peak wall stress (9 studies; n=579; medium bias risk) and AAA diameter (8 studies; n=354; medium bias risk). No meta-analysis was conducted because of clinical and methodological heterogeneity.

Conclusions: We identified 5 potential markers with a prognostic value for AAA growth and 2 for rupture. While interpreting these data, one must realize that conclusions are based on small sample sizes and clinical and methodological heterogeneity. Prospective and methodological consonant studies are strongly urged to further study these potential markers.
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http://dx.doi.org/10.1161/JAHA.117.007791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6064909PMC
June 2018

An in vitro method to keep human aortic tissue sections functionally and structurally intact.

Sci Rep 2018 05 25;8(1):8094. Epub 2018 May 25.

VU University Medical Center, Department of Vascular Surgery, Amsterdam, The Netherlands.

The pathophysiology of aortic aneurysms (AA) is far from being understood. One reason for this lack of understanding is basic research being constrained to fixated cells or isolated cell cultures, by which cell-to-cell and cell-to-matrix communications are missed. We present a new, in vitro method for extended preservation of aortic wall sections to study pathophysiological processes. Intraoperatively harvested, live aortic specimens were cut into 150 μm sections and cultured. Viability was quantified up to 92 days using immunofluorescence. Cell types were characterized using immunostaining. After 14 days, individual cells of enzymatically digested tissues were examined for cell type and viability. Analysis of AA sections (N = 8) showed a viability of 40% at 7 days and smooth muscle cells, leukocytes, and macrophages were observed. Protocol optimization (N = 4) showed higher stable viability at day 62 and proliferation of new cells at day 92. Digested tissues showed different cell types and a viability up to 75% at day 14. Aortic tissue viability can be preserved until at least 62 days after harvesting. Cultured tissues can be digested into viable single cells for additional techniques. Present protocol provides an appropriate ex vivo setting to discover and study pathways and mechanisms in cultured human aneurysmal aortic tissue.
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http://dx.doi.org/10.1038/s41598-018-26549-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5970251PMC
May 2018

Efficacy versus Complications in Arterial Thrombolysis.

Ann Vasc Surg 2018 Apr 6;48:111-118. Epub 2017 Dec 6.

Department of Surgery, Westfriesgasthuis, Hoorn, The Netherlands; Department of Vascular Surgery, VU University Medical Center, Amsterdam, The Netherlands. Electronic address:

Background: Acute peripheral arterial occlusions threaten life and limb. Thrombolysis is an established, minimally invasive alternative treatment for surgical thromboembolectomy. Yet, there is no consensus regarding an optimal thrombolysis protocol, and current knowledge is largely based on studies from the 1990s. This study reviews a contemporary cohort of patients treated with thrombolysis and aims to evaluate the treatment results and to identify possible predictors for outcome and (bleeding) complications.

Methods: The electronic health record data of all consecutive patients who underwent thrombolysis for acute limb ischemia due to thromboembolic lower extremity arterial occlusions between April 2006 and June 2012 were analyzed. End points were change in clinical stage of ischemia, incidence of bleeding complications, duration of thrombolysis, predictors of outcome and complications, and mortality and amputation-free rates after 30-day and 6-months follow-up.

Results: In total, 109 cases were included. Clinical improvement was observed in 79%. Amputation-free rates at 30 days and 6 months were 94% and 90%, respectively. The incidence of major bleeding complications was 13%. Median duration of thrombolysis was 27 (4-68) hr. Mortality rates at 30 days and 6 months were 7% and 16%, respectively; none bleeding related. In addition to age, popliteal artery occlusions and a progressed chronic vascular stage are predictive for a worse outcome. Age, female sex, and cardiac history were risk factors for bleeding.

Conclusions: Treatment of peripheral arterial occlusions with high-dose thrombolysis on an intensive-care unit yields high clinical success rates, but major bleeding complications are often observed. Strict clinical observation remains essential since intensive monitoring of hemostatic parameters during thrombolysis does not predict bleeding complications.
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http://dx.doi.org/10.1016/j.avsg.2017.10.012DOI Listing
April 2018

Betaglycan (TGFBR3) up-regulation correlates with increased TGF-β signaling in Marfan patient fibroblasts in vitro.

Cardiovasc Pathol 2018 Jan - Feb;32:44-49. Epub 2017 Nov 4.

Department of Vascular Surgery, Amsterdam Cardiovascular Sciences, VU University Medical Center, Amsterdam, The Netherlands; Department of Physiology, Amsterdam Cardiovascular Sciences, VU University Medical Center, Amsterdam, The Netherlands. Electronic address:

Background: Marfan syndrome (MFS), a congenital connective tissue disorder leading to aortic aneurysm development, is caused by fibrillin-1 (FBN1) gene mutations. Transforming growth factor beta (TGF-β) might play a role in the pathogenesis. It is still a matter of discussion if and how TGF-β up-regulates the intracellular downstream pathway, although TGF-β receptor 3 (TGFBR3 or Betaglycan) is thought to be involved. We aimed to elucidate the role of TGFBR3 protein in TGF-β signaling in Marfan patients.

Methods: Dermal fibroblasts of MFS patients with haploinsufficient (HI; n=9) or dominant negative (DN; n=4) FBN1 gene mutations, leading to insufficient or malfunctioning fibrillin-1, respectively, were used. Control cells (n=10) were from healthy volunteers. We quantified TGFBR3 protein expression by immunofluorescence microscopy and gene expression of FBN1, TGFB1, its receptors, and downstream transcriptional target genes by quantitative polymerase chain reaction.

Results: Betaglycan protein expression in FBN1 mutants pooled was higher than in controls (P=.004) and in DN higher than in HI (P=.015). In DN, significantly higher mRNA expression of FBN1 (P=.014), SMAD7 (P=.019), HSP47 (P=.023), and SERPINE1 (P=.008), but a lower HSPA5 expression (P=.029), was observed than in HI. A pattern of higher expression was noted for TGFB1 (P=.059), FN1 (P=.089), and COL1A1 (P=.089) in DN as compared to HI. TGFBR3 protein expression in cells, both presence in the endoplasmic reticulum and amount of vesicles per cell, correlated positively with TGFB1 mRNA expression (Rs=0.60, P=.017; Rs=0.55, P=.029; respectively). TGFBR3 gene expression did not differ between groups.

Conclusion: We demonstrated that activation of TGF-β signaling is higher in patients with a DN than an HI FBN1 gene mutation. Also, TGFBR3 protein expression is increased in the DN group and correlates positively with TGFB1 expression in groups pooled. We suggest that TGFBR3 protein expression is involved in up-regulated TGF-β signaling in MFS patients with a DN FBN1 gene mutation.
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http://dx.doi.org/10.1016/j.carpath.2017.10.003DOI Listing
August 2018

Long-term survival after acute kidney injury following ruptured abdominal aortic aneurysm repair.

J Vasc Surg 2017 12 9;66(6):1712-1718.e2. Epub 2017 Sep 9.

Department of Vascular Surgery, Academic Medical Center, Amsterdam, The Netherlands. Electronic address:

Objective: Acute kidney injury (AKI) is a major complication of ruptured abdominal aortic aneurysm (RAAA). Severe AKI is associated with high morbidity and mortality in the short term. The objective of this study was to determine the association between AKI after RAAA repair and long-term survival.

Methods: We conducted a retrospective cohort study of all patients undergoing RAAA repair in three hospitals between 2004 and 2011. Outcomes were long-term survival after RAAA repair, incidence of postoperative AKI, and chronic dialysis rates. Survival rates were compared between different AKI groups (no AKI, Risk, Injury, Failure) with Kaplan-Meier survival analyses and log-rank tests. Univariable and multivariable Cox regression analyses were carried out to assess the association of survival with AKI, preoperative shock, postoperative shock, and sex. The main analysis focused on the group of patients surviving initial hospital stay.

Results: Our study encompassed 362 patients with RAAA. AKI occurred in 267 of 362 patients (74%). At discharge, 267 patients were alive (74%). Median survival in this group was 7.2 years. Survival was not significantly different between the four AKI groups (P = .07). However, the univariable Cox regression analysis demonstrated a significant association between Failure and reduced long-term survival compared with having no AKI (hazard ratio, 1.85; 95% confidence interval, 1.15-2.97). This association did not remain significant after multivariable adjustment. Four patients were discharged with chronic dialysis, and four other patients needed chronic dialysis later after discharge.

Conclusions: This study demonstrates no significant independent association between AKI after RAAA repair and long-term survival. Only a small proportion of patients developed end-stage renal disease at a later stage in life.
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http://dx.doi.org/10.1016/j.jvs.2017.04.049DOI Listing
December 2017

Microbubbles and UltraSound-accelerated Thrombolysis (MUST) for peripheral arterial occlusions: protocol for a phase II single-arm trial.

BMJ Open 2017 08 11;7(8):e014365. Epub 2017 Aug 11.

Departments of Surgery, VU University Medical Center, Amsterdam, the Netherlands.

Introduction: Acute peripheral arterial occlusions can be treated with intra-arterial catheter-directed thrombolysis as an alternative to surgical thromboembolectomy. Although less invasive, this treatment is time-consuming and carries a significant risk of haemorrhagic complications. Contrast-enhanced ultrasound using microbubbles could accelerate dissolution of thrombi by thrombolytic medications due to mechanical effects caused by oscillation; this could allow for lower dosages of thrombolytics and faster thrombolysis, thereby reducing the risk of haemorrhagic complications. In this study, the safety and practical applicability of this treatment will be investigated.

Methods And Analysis: A single-arm phase II trial will be performed in 20 patients with acute peripheral arterial occlusions eligible for thrombolytic treatment. Low-dose catheter-directed thrombolysis with urokinase will be used. The investigated treatment will be performed during the first hour of thrombolysis, consisting of intravenous infusion of 4 Luminity phials (6 mL in total, diluted with saline 0.9% to 40 mL total) of microbubbles with the use of local ultrasound at the site of occlusion. Primary end points are the incidence of complications and technical feasibility. Secondary end points are angiographic and clinical success, duration of thrombolytic infusion, treatment-related mortality, amputations, additional interventions and quality of life.

Ethics And Dissemination: Ethical approval for this study was obtained in 2015 from the Medical Ethics Committee of the VU University Medical Center, Amsterdam, the Netherlands. A statement of consent for this study was given by the Dutch national competent authority. Data will be presented at national and international conferences and published in a peer-reviewed journal.

Trial Registration Numbers: Dutch National Trial Registry: NTR4731; European Clinical Trials Database of the European Medicines Agency: 2014-003469-10; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2016-014365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5724158PMC
August 2017

Case Presentation: Mycotic Aortic Aneurysm and Psoas Abscess as a Complication of Bacillus Calmette-Guérin Instillations.

Eur Urol Focus 2016 Oct 26;2(4):351-353. Epub 2016 Apr 26.

Department of Vascular Surgery, VU University Medical Center, Amsterdam, The Netherlands.

To prevent life-threatening aortic ruptures, it is important that primary care physicians and urologists are aware of the symptoms of a mycotic abdominal aortic aneurysm, even several months or years after bacillus Calmette-Guérin therapy.
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http://dx.doi.org/10.1016/j.euf.2016.04.006DOI Listing
October 2016

Intravenous Targeted Microbubbles Carrying Urokinase versus Urokinase Alone in Acute Peripheral Arterial Thrombosis in a Porcine Model.

Ann Vasc Surg 2017 Oct 22;44:400-407. Epub 2017 May 22.

Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands; Department of Physiology, VU University Medical Center, Amsterdam, The Netherlands.

Background: Standard therapy in acute peripheral arterial occlusion consists of intra-arterial catheter-guided thrombolysis. As microbubbles may be used as a carrier for fibrinolytic agents and targeted to adhere to the thrombus, we can theoretically deliver the thrombolytic medication locally following simple intravenous injection. In this intervention-controlled feasibility study, we compared intravenously administered targeted microbubbles incorporating urokinase and locally applied ultrasound, with intravenous urokinase and ultrasound alone.

Methods: In 9 pigs, a thrombus was created in the left external iliac artery, after which animals were assigned to either receive targeted microbubbles and urokinase (UK + tMB group) or urokinase alone (UK group). In both groups, ultrasound was applied at the site of the occlusion. Blood flow through the iliac artery and microcirculation of the affected limb were monitored and the animals were euthanized 1 hr after treatment. Autopsy was performed to determine the weight of the thrombus and to check for adverse effects.

Results: In the UK + tMB group (n = 5), median improvement in arterial blood flow was 5 mL/min (range 0-216). Improvement was seen in 3 of these 5 pigs at conclusion of the experiment. In the UK group (n = 4), median improvement in arterial blood flow was 0 mL/min (-10 to 18), with slight improvement in 1 of 4 pigs. Thrombus weight was significantly lower in the UK + tMB group (median 0.9383 g, range 0.885-1.2809) versus 1.5399 g (1.337-1.7628; P = 0.017). No adverse effects were seen.

Conclusions: Based on this experiment, minimally invasive thrombolysis using intravenously administered targeted microbubbles carrying urokinase combined with local application of ultrasound is feasible and might accelerate thrombolysis compared with treatment with urokinase and ultrasound alone.
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http://dx.doi.org/10.1016/j.avsg.2017.05.011DOI Listing
October 2017

Minimally Invasive, Laparoscopic, and Robotic-assisted Techniques Versus Open Techniques for Kidney Transplant Recipients: A Systematic Review.

Eur Urol 2017 08 3;72(2):205-217. Epub 2017 Mar 3.

Department of Surgery, VU Medical Center, Amsterdam, The Netherlands; Department of Surgery, Dutch Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Context: Literature on conventional and minimally invasive operative techniques has not been systematically reviewed for kidney transplant recipients.

Objective: To systematically evaluate, summarize, and review evidence supporting operating technique and postoperative outcome for kidney transplant recipients.

Evidence Acquisition: A systematic review was conducted in PubMed-Medline, Embase, and Cochrane Library between 1966 up to September 1, 2016, according to Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Articles were included and scored by two independent reviewers using Group Reading Assessment and Diagnostic Evaluation (GRADE), Newcastle-Ottawa Quality Assessment Scale (NOS), and Oxford guidelines for level of evidence. Main outcomes were graft survival, surgical site infection, incisional hernia, and cosmetic result. In total, 18 out of 1954 identified publications were included in this analysis.

Evidence Synthesis: Included reports described conventional open, minimally invasive open, laparoscopic, and robotic-assisted techniques. General level of evidence of included studies was low (GRADE: 1-3; NOS: 0-4; and Oxford level of evidence: 4-2). No differences in graft or patient survival were found. For open techniques, Gibson incision showed better results than the hockey-stick incision for incisional hernia (4% vs 16%), abdominal wall relaxation (8% vs 24%), and cosmesis. Minimally invasive operative recipient techniques showed lowest surgical site infection (range 0-8%) and incisional hernia rates (range 0-6%) with improved cosmetic result and postoperative recovery. Disadvantages included prolonged cold ischemia time, warm ischemia time, and total operation time.

Conclusions: Although the level of evidence was generally low, minimally invasive techniques showed promising results with regard to complications and recovery, and could be considered for use. For open surgery, the smallest possible Gibson incision appeared to yield favorable results.

Patient Summary: In this paper, the available evidence for minimally invasive operation techniques for kidney transplantation was reviewed. The quality of the reviewed research was generally low but suggested possible advantages for minimally invasive, laparoscopic, and robot-assisted techniques.
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http://dx.doi.org/10.1016/j.eururo.2017.02.020DOI Listing
August 2017

Transdifferentiation of Human Dermal Fibroblasts to Smooth Muscle-Like Cells to Study the Effect of MYH11 and ACTA2 Mutations in Aortic Aneurysms.

Hum Mutat 2017 04 27;38(4):439-450. Epub 2017 Jan 27.

Department of Oral Cell Biology, ACTA University of Amsterdam and VU University Amsterdam, MOVE Research Institute, Amsterdam, The Netherlands.

Mutations in genes encoding proteins of the smooth muscle cell (SMC) contractile apparatus contribute to familial aortic aneurysms. To investigate the pathogenicity of these mutations, SMC are required. We demonstrate a novel method to generate SMC-like cells from human dermal fibroblasts by transdifferentiation to study the effect of variants in genes encoding proteins of the SMC contractile apparatus (ACTA2 and MYH11) in patients with aortic aneurysms. Dermal fibroblasts from seven healthy donors and cells from seven patients with MYH11 or ACTA2 variants were transdifferentiated into SMC-like cells within a 2-week duration using 5 ng/ml TGFβ1 on a scaffold containing collagen and elastin. The induced SMC were comparable to primary human aortic SMC in mRNA expression of SMC markers which was confirmed on the protein level by immunofluorescence quantification analysis and Western blotting. In patients with MYH11 or ACTA2 variants, the effect of intronic variants on splicing was demonstrated on the mRNA level in the induced SMC, allowing classification into pathogenic or nonpathogenic variants. In conclusion, direct conversion of human dermal fibroblasts into SMC-like cells is a highly efficient method to investigate the pathogenicity of variants in proteins of the SMC contractile apparatus.
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http://dx.doi.org/10.1002/humu.23174DOI Listing
April 2017

Organ protection during aortic cross-clamping.

Best Pract Res Clin Anaesthesiol 2016 Sep 20;30(3):305-15. Epub 2016 Aug 20.

Department of Vascular Surgery, VU University Medical Center, Amsterdam, The Netherlands. Electronic address:

Open surgical repair of an aortic aneurysm requires aortic cross-clamping, resulting in temporary ischemia of all organs and tissues supplied by the aorta distal to the clamp. Major complications of open aneurysm repair due to aortic cross-clamping include renal ischemia-reperfusion injury and postoperative colonic ischemia in case of supra- and infrarenal aortic aneurysm repair. Ischemia-reperfusion injury results in excessive production of reactive oxygen species and in oxidative stress, which can lead to multiple organ failure. Several perioperative protective strategies have been suggested to preserve renal function during aortic cross-clamping, such as pharmacotherapy and therapeutic hypothermia of the kidneys. In this chapter, we will briefly discuss the pathophysiology of ischemia-reperfusion injury and the preventative measures that can be taken to avoid abdominal organ injury. Finally, techniques to minimize the risk of complications during and after open aneurysm repair will be presented.
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http://dx.doi.org/10.1016/j.bpa.2016.07.005DOI Listing
September 2016
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