Editor's Choice - Nationwide Analysis of Patients Undergoing Iliac Artery Aneurysm Repair in the Netherlands.

OBJECTIVE: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR). METHODS: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests. RESULTS: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively). CONCLUSION: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair.

Improving small-diameter vascular grafts: from the application of an endothelial cell lining to the construction of a tissue-engineered blood vessel.

One of the main reasons why vascular reconstruction with synthetic small-diameter grafts has limited success is the absence of endothelial cells. To improve the outcome of nonvenous vascular bypass surgery, cell seeding of vascular grafts and other tissue-engineering techniques were developed. In this article, an overview is given of the artificial blood vessel as an alternative for venous vascular bypass surgery.

In vivo transluminal microvascular endothelial cell seeding on balloon injured rabbit arteries.

AIM: Seeding venous endothelial cells (EC) onto damaged vascular surfaces attenuates the development of intimal hyperplasia. Unlike venous EC, fat derived microvascular endothelial cells (MVEC) do not require a culture step to increase the yield. The authors investigated whether fat derived MVEC are suitable to reduce intimal hyperplasia after PTA. METHODS: Five rabbits were subjected to percutaneous transluminal angioplasty (PTA) of both iliac arteries. One side was seeded transluminally with autologous perirenal fat derived MVEC, using a double balloon catheter. The contralateral side was sham seeded, and served as a control. Follow-up was 4 weeks. Another rabbit was used for a feasibility experiment. This rabbit was subjected to a 1-sided seeding procedure and was sacrificed after 1 week. In a 7th rabbit, a 1-sided PTA was transformed, and autologous labelled cells were injected in the distal aorta instead of seeded, follow-up was 1 week. Histological investigation was per-formed. RESULTS: The MVEC seeded artery of the pilot experiment was patent. All sham seeded arteries (5) except for 1 were patent. The patent ones showed moderate intimal hyperplasia. MVEC seeding (5) resulted in occlusion twice. In the patent MVEC seeded arteries intimal hyperplasia was present in more extended form than in the sham seeded arteries. Both the patent MVEC- and sham-seeded arteries were covered with an EC layer. Injected labelled MVEC were not found again on the de-endothelialized artery. CONCLUSION: In this study seeding of fat derived MVEC on damaged native arteries results in an increased development of intimal hyperplasia and a decreased patency. One of the reasons may be the presence of non-EC in the seeded cell population.

Application of a clinical grade CD34-mediated method for the enrichment of microvascular endothelial cells from fat tissue.

BACKGROUND: Microvascular endothelial cells (MVEC) derived from s.c. fat are seeded on vascular grafts to prevent early occlusion. We have demonstrated the presence of contaminating cells contributing to MVEC seeding-related intimal hyperplasia in MVEC isolates from fat tissue. We found that cell isolates additionally purified after the isolation process, were associated with a reduced thrombogenicity and development of intimal hyperplasia in vitro. A combination of 11Fibrau (F11)- and CD14-coated Dynabeads was used to deplete the contaminating cells, fibroblasts, and monocytes/macrophages. Unfortunately, clinical-grade F11 is not available, and thus cannot be used for clinical practice. CD34 selection with clinical-grade products is widely used for the isolation of hematopoietic progenitors, and endothelial cells (EC) express CD34 on their surfaces. The aims of this study were to test the effectiveness of two different CD34-selection techniques for purification of MVEC, and to compare the results with those of the F11/CD14-method. METHODS: Liposuction fat was enzymatically digested and centrifuged twice to remove adipocytes and collagenase. CD34 selection was performed using the commercially available methods from Nexell or Miltenyi. Both techniques were modified for our use. The purity after isolation and culture, and recovery were determined by flow-cytometry (CD31-expression) and compared with that of cells purified with the F11/CD14-method. RESULTS: Besides MVEC, the contaminating fibroblasts and macrophages/monocytes weakly expressed the CD34 Ag. Enrichment of MVEC was not successful with the Miltenyi method. Variations in neither the dose of Ab nor the use of direct selection and different separation programs improved the results. With the Nexell method, MVEC were enriched to 86%, a comparable purity to that obtained with the F11/CD14-method. However, a lower recovery was achieved with the Nexell method. CONCLUSION: Enrichment of MVEC could be achieved with a modified protocol of the clinical grade CD34(+) selection method from Nexell, but not with the CD34 method from Miltenyi.

Reduction of non-endothelial cell contamination of microvascular endothelial cell seeded grafts decreases thrombogenicity and intimal hyperplasia.

INTRODUCTION: fat derived microvascular endothelial cells (MVEC) seeded on prosthetic vascular grafts, improve patency in animals. Results in humans were disappointing, due to thrombogenicity and progressive intimal hyperplasia. Also in animals intimal hyperplasia was found. We postulate that contaminating cells present in the transplant are involved in the intimal hyperplasia. We developed a method to further purify human MVEC from 40-90%. Here we tested the effects of enrichment upon thrombogenicity and seeding-related intimal hyperplasia. METHODS: liposuction fat was enzymatically digested and centrifuged. To enrich MVEC, contaminating macrophages and fibroblasts were removed with dynabeads coated with macrophage- and fibroblast-specific antibodies. Thrombogenicity was assessed by measuring tissue factor and thrombomodulin activity, presence of endothelial nitric oxide synthase and via perfusion of the cells with whole blood. To investigate seeding-related intimal hyperplasia, PTFE grafts were seeded with the cells and cultured for 3 weeks. RESULTS: tissue factor activity of purified cells was reduced compared to nonpurified cells. Purified cells showed thrombomodulin activity and eNOS expression. Fragment 1+2 and Fibrinopeptide A generation after perfusion of purified cells were significantly lower than after perfusion of nonpurified cells, and only nonpurified cells were covered with platelets and fibrin. Prostheses seeded with nonpurified cells showed an EC monolayer above a multilayer of myofibroblasts, prostheses seeded with purified cells only showed a single EC monolayer. Mixing experiments with human umbilical cord EC (HUVEC) and fibroblasts showed that when more than 25% HUVEC were present a confluent EC layer was formed. When the amount of fibroblasts was 25% or less, no development of a subendothelial multilayer of myofibroblasts was found within 3 weeks. CONCLUSION: reduction of non-endothelial cell contamination of microvascular endothelial cell seeded grafts decreases thrombogenicity and might prevent seeding-related intimal hyperplasia.

Contaminants from the transplant contribute to intimal hyperplasia associated with microvascular endothelial cell seeding.

OBJECTIVES: seeding prosthetic grafts with fat-derived microvascular endothelial cells (MVEC) results not only in a non-thrombogenic EC layer, but also in intimal hyperplasia. Here we investigated incidence, composition, progression, and cause of this intimal hyperplasia. DESIGN: EPTFE grafts with MVEC were implanted as carotid interpositions in six dogs with 1 month, and in three dogs with 4, 8 and 12 months follow-up. Grafts seeded without cells, implanted in the contralateral carotid, served as a control. In another three dogs labelled cells were seeded to investigate the contribution of the seeded cells (2-3 weeks). MATERIALS AND METHODS: MVEC were isolated from the falciform ligament. Cells were pressure seeded on ePTFE grafts. Labelling was performed using retroviral gene transduction. The grafts were analysed with immunohistochemical techniques. RESULTS: after 1 month, all patent non-seeded grafts (5/6) showed fibrin and platelet deposition, and all patent seeded grafts (5/6) were covered with a confluent endothelial monolayer on top of a multilayer of myofibroblasts, elastin and collagen. After long term follow-up, all non-seeded grafts were occluded, all patent seeded grafts (4 and 12 months) were covered with an EC-layer with intimal hyperplasia underneath. The thickness of the intima did not progress after 1 month. Transduced cells were found in the endothelial monolayer, hyperplastic intima and luminal part of the prosthesis. CONCLUSIONS: MVEC seeding in dogs results in intimal hyperplasia in all patent grafts, which contains myofibroblasts. Contaminants from the transplant contribute to this intimal hyperplasia.

[Prophylactic total thyroidectomy in childhood for multiple endocrine neoplasia type 2A: preliminary results]. / Profylactische totale thyreoïdectomie voor multipele endocriene neoplasie type 2A op de kinderleeftijd: eerste ervaringen.

OBJECTIVE: Evaluation of prophylactic total thyroidectomy in childhood in case of MEN2A gene carriership. DESIGN: Retrospective. METHOD: Prophylactic thyroidectomy was performed in 14 MEN2A gene carriers (7 boys, 7 girls; median age 9.1 year (range: 4.8-14.7)), in June 1993-July 1997 at the department Pediatric Surgery of the Wilhelmina Children's Hospital in Utrecht, the Netherlands. Median time between genetic investigation and operation was 5.5 months (range: 2-35). Lymph node dissection was not performed. The parathyroids were identified and left untouched as far as possible, autotransplantation was performed twice because of doubt about viability. Outpatient follow-up took place every 3-6 months. RESULTS: One patient (13.4 year) showed macroscopic, the other 13 microscopic multifocal medullary thyroid carcinoma, 11 bilateral and 3 unilateral. In 1 child (6.2 year) neuroinvasive growth existed already. Surgical sections were free of tumour. After the operation temporary hoarseness occurred once, temporary hypocalcaemia three times and permanent hypoparathyroidism twice; after autotransplantation no hypocalcaemia occurred. Median follow-up was 3.2 year (range: 1 month-4.0 year). Mild psychological problems were observed in 4 patients, psychiatric problems in 1. CONCLUSION: Prophylactic total thyroidectomy during the first decade is recommended. Additional lymph node dissection and total parathyroidectomy are unnecessary than. In order to prevent postoperative hypoparathyroidism, autotransplantation of at least one parathyroid is advisable.