Vascular photodynamic therapy : a multifactorial approach to inhibit intimal hyperplasia

The Wellman Laboratories of Photomedicine at the Massachusetts General Hospital in Boston is an internationally known institute for the development and application of laser in medicinco Besides fundamental research which investigates the interaction of light with cells and molecules, a great deal of studies arc performed towards clinical application to treat human diseases. For this reason, all known medical specialties are involved in research programmes examining the use of laser for their purposes: from ophtalmologists, using photodynamic therapy to treat choroidal neovascularization, oncologists to photochemically target and remove breast cancer cells from bone marrow, urologist to detect bladder cancer with fluorescence, gastroenterologists to treat Barret's oesophagus to dermatologists removing latloes and treating multiple skin diseases with the laser. The application of laser to treat vascular diseases was started decades ago, but more recently the concept of photodynamic therapy was introduced by the research group of Dr. LaMuraglia to prevent restenosis. As a research fellow in surgery I joined this group in 1994 and our research goal was to better understand how photodynamic therapy affects the vascular wall. The results from these investigations are presented in tllis thesis. The first part gives an outline of the problem of restenosis, the concept of photodynamic therapy and aims of the study. The following chapters describe how photodynamic therapy interacts with biological factors that regulate the vascular healing process. Finally, considerations for possible clinical use are discussed

A comparison of balloon injury models of endovascular lesions in rat arteries

BACKGROUND: Balloon injury (BI) of the rat carotid artery (CCA) is widely used to study intimal hyperplasia (IH) and decrease in lumen diameter (LD), but CCA's small diameter impedes the evaluation of endovascular therapies. Therefore, we validated BI in the aorta (AA) and iliac artery (CIA) to compare it with CCA. METHODS: Rats underwent BI or a sham procedure (control). Light microscopic evaluation was performed either directly or at 1, 2, 3, 4 and 16 weeks follow-up. The area of IH and the change in LD (LD at 16 weeks minus LD post BI) were compared. RESULTS: In the BI-groups the area of IH increased to 0.14 +/- 0.08 mm2 (CCA), 0.14 +/- 0.03 mm2 (CIA) and 0.12 +/- 0.04 mm2 (AA) at 16 weeks (NS). The LD decreased with 0.49 +/- 0.07 mm (CCA), compared to 0.22 +/- 0.07 mm (CIA) and 0.07 +/- 0.10 mm (AA) at 16 weeks (p < 0.05). The constrictive vascular remodelling (CVR = wall circumference loss combined with a decrease in LD) was -0.17 +/- 0.05 mm in CIA but absent in CCA and AA. No IH, no decrease in LD and no CVR was seen in the control groups. CONCLUSIONS: BI resulted in: (1.) a decrease in LD in CCA due to IH, (2.) a decrease in LD in CIA due to IH and CVR, (3.) no change in LD in AA, (4.) Comparable IH development in all arteries, (5.) CCA has no vasa vasorum compared to CIA and AA, (6.) The CIA model combines good access for 2 F endovascular catheters with a decrease in LD due to IH and CVR after BI

Nationwide study of the treatment of mycotic abdominal aortic aneurysms comparing open and endovascular repair in The Netherlands

Contains fulltext : 226470.pdf (Publisher’s version ) (Closed access)OBJECTIVE: Mycotic aneurysms of the abdominal aorta (MAAA) can be treated by open repair (OR) or endovascular aneurysm repair (EVAR). This nationwide study provides an overview of the situation of MAAA treatment in The Netherlands in 2016. METHODS: A retrospective cohort study was conducted with all centers that registered aortic abdominal aneurysms in the Dutch Surgical Aneurysm Audit in 2016. Questionnaires on 1-year outcomes were sent to all centers that treated patients with MAAA. The primary aim was to determine 30-day and 1-year mortality and morbidity of OR- and EVAR-treated patients. Morbidity was determined by the need for reoperations and the number of readmissions to the hospital. RESULTS: Twenty-six MAAA were detected in the Dutch Surgical Aneurysm Audit database of 2016, resulting in an incidence of 0.7% of all registered abdominal aortic aneurysms. The 30-day mortality for OR and EVAR treated patients was 1 in 13 and 0 in 13, respectively. Major and minor reinterventions within 30 days were needed for two (one OR and one EVAR) and two (one OR and one EVAR) patients, respectively. Two patients (15.4%) in the OR group and one patient (7.7%) in the EVAR group were readmitted to hospital within 30 days. In total, 1-year outcomes of 23 patients were available. In the OR group, one patient (9.1%) died in the first postoperative year. There was one major reintervention (removal of endoprosthesis and spiralvein reconstruction) in the EVAR group. Two patients (18.2%) treated with OR and two (16.7%) treated with EVAR required a minor reintervention. In both groups, four patients (OR, 36.4%; EVAR, 33.3%) were readmitted to hospital within 1 year postoperatively. CONCLUSIONS: Both OR- and EVAR-treated patients show acceptable clinical outcomes after 30 days and at the 1-year follow-up. Depending on the clinical course of the patient, EVAR may be considered in the management of this disease

Percutaneous transluminal angioplasty and drug-eluting stents for infrapopliteal lesions in critical limb ischemia (PADI) trial

Background - Endovascular infrapopliteal treatment of patients with critical limb ischemia using percutaneous transluminal angioplasty (PTA) and bail-out bare metal stenting (BMS) is hampered by restenosis. In interventional cardiology, drug-eluting stents (DES) have shown better patency rates and are standard practice nowadays. An investigator-initiated, multicenter, randomized trial was conducted to assess whether DES also improve patency and clinical outcome of infrapopliteal lesions. Methods and Results - Adults with critical limb ischemia (Rutherford category ≥4) and infrapopliteal lesions were randomized to receive PTA±BMS or DES with paclitaxel. Primary end point was 6-month primary binary patency of treated lesions, defined as ≤50% stenosis on computed tomographic angiography. Stenosis >50%, retreatment, major amputation, and critical limb ischemia-related death were regarded as treatment failure. Severity of failure was assessed with an ordinal score, ranging from vessel stenosis through occlusion to the clinical failures. Seventy-four limbs (73 patients) were treated with DES and 66 limbs (64 patients) received PTA±BMS. Six-month patency rates were 48.0% for DES and 35.1% for PTA±BMS (P=0.096) in the modified-intention-to-treat and 51.9% and 35.1% (P=0.037) in the per-protocol analysis. The ordinal score showed significantly worse treatment failure for PTA±BMS versus DES (P=0.041). The observed major amputation rate remained lower in the DES group until 2 years post-treatment, with a trend toward significance (P=0.066). Less minor amputations occurred after DES until 6 months post-treatment (P=0.03). Conclusions - In patients with critical limb ischemia caused by infrapopliteal lesions, DES provide better 6-month patency rates and less amputations after 6 and 12 months compared with PTA±BMS

Saccular Abdominal Aortic Aneurysms Patient Characteristics, Clinical Presentation, Treatment, and Outcomes in the Netherlands

Objective: The aim of this was to analyze differences between saccularshaped abdominal aortic aneurysms (SaAAAs) and fusiform abdominal aortic aneurysms (FuAAAs) regarding patient characteristics, treatment, and outcome, to advise a threshold for intervention for SaAAAs.Background: Based on the assumption that SaAAAs are more prone to rupture, guidelines suggest early elective treatment. However, little is known about the natural history of SaAAAs and the threshold for intervention is not substantiated.Methods: Observational study including primary repairs of degenerative AAAs in the Netherlands between 2016 and 2018 in which the shape was registered, registered in the Dutch Surgical Aneurysm Audit (DSAA). Patients were stratified by urgency of surgery; elective versus acute (symptomatic/ruptured). Patient characteristics, treatment, and outcome were compared between SaAAAs and FuAAAs.Results: A total of 7659 primary AAA-patients were included, 6.1% (n = 471) SaAAAs and 93.9% (n = 7188) FuAAAs. There were 5945 elective patients (6.5% SaAAA) and 1714 acute (4.8% SaAAA). Acute SaAAApatients were more often female (28.9% vs 17.2%, P = 0.007) compared with acute FuAAA-patients. SaAAAs had smaller diameters than FuAAAs, in elective (53.0mm vs 61 mm, P = 0.000) and acute (68mm vs 75 mm, P = 0.002) patients, even after adjusting for sex. In addition, 25.2% of acute SaAAA-patients presented with diameters <55mm and 8.4% <45 mm, versus 8.1% and 0.6% of acute FuAAA-patients (P = 0.000). Postoperative outcomes did not significantly differ between shapes in both elective and acute patients.Conclusions: SaAAAs become acute at smaller diameters than FuAAAs in DSAA patients. This study therefore supports the current idea that SaAAAs should be electively treated at smaller diameters than FuAAAs. The exact diameter threshold for elective treatment of SaAAAs is difficult to determine, but a diameter of 45mm seems to be an acceptable threshold.Vascular Surger