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Papers by Abbey Schepers

Annals of Vascular Surgery

OBJECTIVES Current diagnostic modalities for patients with peripheral artery disease (PAD) mainly... more OBJECTIVES Current diagnostic modalities for patients with peripheral artery disease (PAD) mainly focus on the macrovascular level. For assessment of tissue perfusion, near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) seems promising. In this prospective cohort study, ICG NIR fluorescence imaging was performed pre- and post-revascularization to assess changes in foot perfusion. METHODS ICG NIR fluorescence imaging was performed in 36 patients with PAD pre- and post-intervention. After intravenous bolus injection of 0.1 mg/kg ICG, the camera registered the NIR fluorescence intensity over time on the dorsum of the feet for 15 min using the Quest Spectrum Platform®. Time-intensity curves were plotted for three regions of interest (ROI): (1) the dorsum of the foot, (2) the forefoot, and (3) the hallux. Time-intensity curves were normalized for maximum fluorescence intensity. Extracted parameters were the maximum slope, area under the curve (AUC) for the ingress, and...

Life

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Langenbeck's Archives of Surgery

The original version of this article unfortunately contained a mistake on the fifth and eleventh ... more The original version of this article unfortunately contained a mistake on the fifth and eleventh author names, from Schelto Kruijf to Schelto Kruijff and from Tessa van Ginhoven to Tessa M. van Ginhoven. The corrected author names are shown below. Schelto Kruijff and Tessa M. van Ginhoven Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Journal of Vascular Surgery Cases and Innovative Techniques

A 44-year-old man presented with symptoms of intermittent ischemia of the right foot. Computed to... more A 44-year-old man presented with symptoms of intermittent ischemia of the right foot. Computed tomography scanning of the right foot revealed a talar beak that had a close anatomic relation with the dorsalis pedis artery. Duplex ultrasound performed during a symptomatic episode confirmed ischemia induced by severe vasospasm of the dorsalis pedis artery that normalized 30 minutes later. The talar beak was removed by open surgery that resulted in complete resolution of the patient's symptoms. A talar beak should be considered in intermittent ischemic complaints of the foot in patients without atherosclerosis.

Human Pathology

Summary Medullary thyroid cancer (MTC) accounts for 4% of all thyroid cancers and originates from... more Summary Medullary thyroid cancer (MTC) accounts for 4% of all thyroid cancers and originates from the parafollicular C-cells. Prostate-specific membrane antigen (PSMA) is known for its expression in the epithelium of prostate cancer and has been demonstrated to be useful both for therapeutic and diagnostic purposes as a so-called theranostic target. As PSMA is also expressed in the neovasculature of other solid tumor types, our aim was to assess PSMA expression and its prognostic role in MTC. Tissues from patients that underwent surgery for MTC between 1988 and 2014 in five tertiary referral centers in The Netherlands were included in a tissue microarray. Using immunohistochemistry, total numbers of PSMA and CD31-positive microvessels were evaluated. Results showed that 92% of MTC expressed PSMA in the neovasculature, whereas the tumor cells were consistently negative. The average number of PSMA-positive microvessels did not differ significantly between the primary tumor and initial lymph node metastases (P = .09), nor between initial and recurrent lymph node metastases (P = 1.00). The PSMA score was found to be correlated with progression-free survival and overall survival. In multivariate analysis, a higher number of PSMA-positive microvessels was associated with favorable prognosis (odds ratio 3.6; 95% confidence interval 1.0–12.8; P = .05). In conclusion, over 90% of MTC appears to express PSMA in the neovasculature. A higher number of PSMA-positive microvessels is prognostically favorable. Since it is highly expressed in MTC, PSMA is an interesting novel target for imaging and potentially also as a target for peptide radioligand therapy in MTC.

Textbook of Endocrine Surgery, 2016

Circulation, Nov 23, 2010

Molecular Immunology, 2011

Surgery, 2015

Identification of diseased and normal parathyroid glands during parathyroid surgery can be challe... more Identification of diseased and normal parathyroid glands during parathyroid surgery can be challenging. The aim of this study was to assess whether near-infrared (NIR) fluorescence imaging using administration of a low-dose Methylene Blue (MB) at the start of the operation could provide optical guidance during parathyroid surgery and assist in the detection of parathyroid adenomas. Patients diagnosed with primary hyperparathyroidism planned for parathyroidectomy were included. Patients received 0.5 mg/kg MB intravenously directly after start of anesthesia. During the operation, NIR fluorescence imaging was performed to identify parathyroid adenomas. Imaging results were compared with a previous published feasibility study in which 12 patients received MB after intraoperative identification of the adenoma. A total of 13 patients were included in the current study. In 10 of 12 patients with a histologically proven adenoma, the adenoma was fluorescent. Mean signal to background ratio was 3.1 ± 2.8. Mean diameter of the resected lesions was 17 ± 9 mm (range 5-28 mm). Adenomas could be identified up to 145 minutes after administration, which was the longest timespan until resection. Interestingly, in 3 patients, a total of 6 normal parathyroid glands (median diameter 2.5 mm) with a signal to background ratio of 1.8 ± 0.4 were identified using NIR fluorescence imaging. Early administration of low-dose MB provided guidance during parathyroidectomy by identifying both parathyroid adenomas and normal parathyroid glands. In patients in whom difficult identification of the parathyroid adenoma is expected or when normal glands have to be identified, the administration of MB may improve surgical outcome.

Vascular Pharmacology, 2012

Vascular Pharmacology, 2006

The FASEB Journal, 2005

Genetic factors appear to be important in the restenotic process after percutaneous coronary inte... more Genetic factors appear to be important in the restenotic process after percutaneous coronary intervention (PCI), as well as in inflammation, a pivotal factor in restenosis. TNF␣, a key regulator of inflammatory responses, may exert critical influence on the development of restenosis after PCI. The GENetic DEterminants of Restenosis (GENDER) project included 3104 patients who underwent a successful PCI. Systematic genotyping for six polymorphisms in the TNF␣ gene was performed. The role of TNF␣ in restenosis was also assessed in ApoE*3-Leiden mice, TNF␣ knockout mice, and by local delivery of a TNF␣ biosynthesis inhibitor, thalidomide. The-238G-1031T haplotype of the TNF␣ gene increased clinical and angiographic risk of restenosis (P‫20.0؍‬ and P‫,200.0؍‬ respectively). In a mouse model of reactive stenosis, arterial TNF␣ mRNA was significantly time-dependently up-regulated. Mice lacking TNF␣ or treated locally with thalidomide showed a reduction in reactive stenosis (P‫10.0؍‬ and P‫,500.0؍‬ respectively). Clinical and preclinical data indicate that TNF␣ plays an important role in restenosis. Therefore, TNF␣ genotype may be used as a risk marker for restenosis and may contribute to individual patient screening prior to PCI in clinical practice. Inhibition of TNF␣ may be an anti-restenotic target strategy.

Journal of Vascular Surgery, 2009

Inflammatory responses to vascular injury are key events in vein graft disease and accelerated at... more Inflammatory responses to vascular injury are key events in vein graft disease and accelerated atherosclerosis, which may result in bypass failure. The monocyte chemoattractant protein-1 (MCP-1)/CC-chemokine receptor (CCR)-2 pathway is hypothesized to play a central role. A murine model for vein graft disease was used to study the effect of local application of lentiviral short hairpin RNA (shRNA) targeted against CCR2. A venous interposition was placed into the carotid artery of hypercholesterolemic apolipoprotein E3-Leiden (APOE*3-Leiden) mice to induce vein graft thickening with features of accelerated atherosclerosis. To demonstrate the efficacy of the lentiviral shRNA targeting murine CCR2 (shCCR2) in blocking vein graft disease in vivo, lentiviral shCCR2 or a control lentivirus was used to infect the vein graft locally (n = 8). Vascular CCR2 and MCP-1 messenger RNA expression levels were significantly upregulated during lesion progression in the vein graft. Infection of smooth muscle cells (SMCs) with a lentiviral shRNA targeting shCCR2 completely abolished MCP-1-induced SMC migration and inhibited SMC proliferation in vitro (n = 3 per group). Morphometric analysis of sections of grafts showed a significant 38% reduction in vein graft thickening in the shCCR2-treated mice 4 weeks after surgery (control, 0.42 +/- 0.05 mm(2); shCCR2, 0.26 +/- 0.03 mm(2); P = .007). Vascular CCR2 contributes to vein graft disease, and local application of shRNA against CCR2 to the vessel wall prevents vein graft thickening in hypercholesterolemic mice, suggesting that local overexpressing of shRNA using organ-targeted lentiviral gene delivery may be a promising therapeutic tool to improve vein graft disease in bypassed patients. Vein graft disease is an important clinical issue that results from an inflammatory response. The monocyte chemoattractant protein (MCP)-1/CC-chemokine receptor (CCR)-2 pathway plays a key role in the initiation and development of vein graft disease. This study demonstrates that perivascular overexpression of short hairpin RNA, targeted against CCR2, inhibits vein graft thickening. These data show that organ-targeted gene therapy against CCR2 in the vessel wall could be a promising therapeutic tool to improve vein graft patency in bypassed patients.

Journal of Surgical Research, 2010

Background. In some patients with colorectal liver metastases it is not clear whether liver resec... more Background. In some patients with colorectal liver metastases it is not clear whether liver resection or isolated liver perfusion is the best treatment option. For instance, the risk of complications after surgery may be so substantial and affect subsequent survival. Aim of the present study is to compare complication occurrence and its effect on survival after liver resection and perfusion. Methods. Patient records of all 225 patients with colorectal liver metastases treated with liver resection (n [ 121) or liver perfusion (n [ 104) in the period 1997-2006 were reviewed for complications during the initial hospitalisation until 30 d after discharge, and to assess patient survival until the last hospital visit. Median duration of follow-up was 38 mo for overall survival and 22 mo for survival after surgery. Results. Complications occurred less often in patients undergoing resection than perfusion (29.8% versus 49.0%, X 2 [ 8.77, P < 0.01). Postoperative mortality rates were similar in both groups (4.1% and 4.8%, respectively). As expected, long term survival after liver surgery was better in the resection group: at 3 y, 60% of patients survived in the resection group, compared with 22% after liver perfusion (log rank X 2 [ 35.29 P < 0.001). However, liver resection patients with postoperative complications, had similar survival as perfusion patients without complications (log rank X 2 [ 2.45, p [ 0.12). This remained after adjustment for differences between the patient groups at time of surgery. Conclusion. Liver resection has superior long-term survival, but survival is significantly reduced by the occurrence of post-surgical complications. When complications occur after liver resection, survival is comparable to patients who underwent uncomplicated liver perfusion.

European Journal of Radiology, 2004

Objective: The objective of this study was to compare three-dimensional phase-contrast angiograph... more Objective: The objective of this study was to compare three-dimensional phase-contrast angiography (3D PCA), 2D time-of-flight (2D TOF), and 3D TOF magnetic resonance (MR) angiography and a proton density weighted technique in terms of their ability to detect head and neck paragangliomas. Materials and methods: 14 patients with 29 paragangliomas were examined at 1.5 T. Three MR angiography sequences (3D PCA, 2D TOF, and multi-slab 3D TOF) and a proton density (PD) weighted sequence were reviewed by four neuroradiologists. The gold standard was digital subtraction angiography. Presence of tumor was assessed in five grades of confidence. Sensitivity and specificity were calculated after dichotomizing the results. Data was analyzed using the logistic regression method. Results: Mean sensitivity and specificity for the four observers were for PD: 72%/97%, for 3D PCA: 75%/90%, for 2D TOF: 66%/93%, and for 3D TOF: 90%/92%. Sensitivity was significantly better for 3D TOF MRA (P < 0.001). No substantial between-observer variation for tumor detection was present. Conclusion: Our results demonstrate that, using 3D TOF MRA, paragangliomas in the head and neck region can be detected with high sensitivity and specificity. Further investigation is necessary to judge the value of 3D TOF MR angiography against fat suppressed contrast enhanced T1 weighted and fat suppressed T2 weighted MR sequences to find the optimal imaging sequence for paragangliomas.

Circulation, 2004

Background— Therapeutic angiogenesis by delivery of vascular endothelial growth factor (VEGF) has... more Background— Therapeutic angiogenesis by delivery of vascular endothelial growth factor (VEGF) has attracted attention. However, the role and function of VEGF in experimental restenosis (neointimal formation) after vascular intraluminal injury have not been addressed. Methods and Results— We report herein that blockade of VEGF by soluble VEGF receptor 1 ( sFlt-1 ) gene transfer attenuated neointimal formation after intraluminal injury in rabbits, rats, and mice. sFlt-1 gene transfer markedly attenuated the early vascular inflammation and proliferation and later neointimal formation. sFlt-1 gene transfer also inhibited increased expression of inflammatory factors such as monocyte chemoattractant protein-1 and VEGF. Intravascular VEGF gene transfer enhanced angiogenesis in the adventitia but did not reduce neointimal formation. Conclusions— Increased expression and activity of VEGF are essential in the development of experimental restenosis after intraluminal injury by recruiting monoc...

Atherosclerosis, 2012

Objectives: Arterial pressure induced vein graft injury can result in endothelial loss, accelerat... more Objectives: Arterial pressure induced vein graft injury can result in endothelial loss, accelerated atherosclerosis and vein graft failure. Inflammation, including complement activation, is assumed to play a pivotal role herein. Here, we analyzed the effects of C1-esterase inhibitor (C1inh) on early vein graft remodeling. Methods: Human saphenous vein graft segments (n = 8) were perfused in vitro with autologous blood either supplemented or not with purified human C1inh at arterial pressure for 6 h. The vein segments and perfusion blood were analyzed for cell damage and complement activation. In addition, the effect of purified C1inh on vein graft remodeling was analyzed in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. Results: Application of C1inh in the in vitro perfusion model resulted in significantly higher blood levels and significantly more depositions of C1inh in the vein wall. This coincided with a significant reduction in endothelial loss and deposition of C3d and C4d in the vein wall, especially in the circular layer, compared to vein segments perfused without supplemented C1inh. Administration of purified C1inh significantly inhibited vein graft intimal thickening in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. Conclusion: C1inh significantly protects against early vein graft remodeling, including loss of endothelium and intimal thickening. These data suggest that it may be worth considering its use in patients undergoing coronary artery bypass grafting.