Seung Jae Byun

Colloidal gold nanoparticles as a blood-pool contrast agent for X-ray computed tomography in mice.

Objectives:To present the pharmacokinetics and computed tomographic imaging efficacy of colloidal gold nanoparticles (AuNPs) as a blood-pool agent for x-ray computed tomography (CT). Methods and Materials:To prepare the colloidal AuNPs, gold nanocrystals were modified using sulfhydrated polyethylene glycol (PEG). Cytotoxicity and histopathologic tests were carried out for toxicity evaluation. Six adult Balb/c mice underwent microcomputed tomography scans after injection of colloidal AuNPs (2.5 &mgr;mol Au/g body weight). Four mice with HT-1080 tumors were imaged for visualization of the tumor vasculature. Results:The PEG coated colloidal AuNPs appeared as spherical nanoparticles with 38-nm diameters. The AuNPs-PEG showed a biocompatibility without toxicity in the mice. We identified a stable imaging window for visualizing the vasculature system, immediately to 24 hours after injection. Microcomputed tomography imaging using AuNPs-PEG clearly visualized the tumor vascular structures. Conclusion:Colloidal AuNPs show potential as a blood-pool agent for x-ray CT imaging.

Micro-CT Imaging with a Hepatocyte-selective Contrast Agent for Detecting Liver Metastasis in Living Mice

RATIONALE AND OBJECTIVES Micro-computed tomography (CT) is a important tool for longitudinal imaging of tumor development. The detection and monitoring of tumors in the liver in live animals using micro-CT is challenging. We evaluated the feasibility of high-resolution micro-CT enhanced with a hepatocyte-selective contrast agent for detecting liver metastases in a live murine model. MATERIALS AND METHODS Hepatic metastases were induced in 10 BALB/C mice. Two mice each were randomly selected on days 3, 5, 7, 10, and 13 after CT26 colon adenocarcinoma cells were injected into the portal vein; micro-CT imaging was performed at 10 minutes and 4 hours after intravenous administration of a hepatocyte-selective contrast agent at a dose of 0.4 mL/mouse. The attenuation values of the normal liver and the tumors were obtained. The number of metastases was counted and their sizes were measured on the micro-CT images. Gross or histopathologic evaluation was performed for correlating the liver tumors with the micro-CT images. RESULTS A total of 74 separate tumor sites larger than 300 microm in diameter were detected on pathologic examination of the mice that were sacrificed 7 days after cell injection. On micro-CT, 66 of 74 tumors were detected (83.8%). The smallest tumor detected on micro-CT was 300 microm. There were eight false-negative readings on micro-CT. The sizes of the individual liver metastases measured by micro-CT and on the excised specimen were highly correlated (P < .001). The correlation between the CT scan measurement and the actual measurement was r = 0.8354 (P < .0001). CONCLUSIONS High-resolution micro-CT enhanced with a hepatocyte-selective contrast agent can be a promising tool for detecting liver metastases in a live murine model.

β-Lapachone, a substrate of NAD(P)H:quinone oxidoreductase, induces anti-inflammatory heme oxygenase-1 via AMP-activated protein kinase activation in RAW264.7 macrophages

AMP-activated protein kinase (AMPK), a crucial regulator of energy metabolic homeostasis, is suggested to regulate inflammatory responses, but its precise mechanisms are not fully understood. It has been reported that pharmacological activation of AMPK induces heme oxygenase-1 (HO-1) expression. β-Lapachone (BL), a well-known substrate of NAD(P)H:quinone oxidoreductase (NQO1), has been demonstrated to stimulate AMPK activation via NQO1 activation, and to exert anti-inflammatory effects in macrophages. Here we examined whether AMPK activation by BL would be linked to HO-1 expression in RAW264.7 macrophages and whether HO-1 expression could mediate the anti-inflammatory effects of BL. BL treatment induced concentration- and time-dependent AMPK phosphorylation and HO-1 expression. 5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, an AMPK activator, also induced HO-1 expression. In contrast, compound C (CC), an inhibitor of AMPK activation, prevented the increase in BL-induced HO-1 expression. BL pretreatment reduced lipopolysaccharide-induced production of tumor necrosis factor-α, a pro-inflammatory cytokine, and expression of inducible nitric oxide synthase, a pro-inflammatory enzyme. These inhibitory effects BL were almost completely abolished by CC and partly by tin protoporphyrin-IX, a competitive inhibitor of HO-1. Accordingly, the present results indicate that BL induces anti-inflammatory HO-1 expression in macrophages via AMPK activation, providing one of possible mechanisms by which BL can exert anti-inflammatory effects.

Successful aspiration and thrombolytic therapy for acute superior mesenteric artery occlusion

To report a case of acute superior mesenteric artery (SMA) embolism successfully treated with aspiration and pharmacological thrombolysis. A 74-year-old female was admitted to the hospital with acute abdominal pain 5 hours in duration. Computed tomography angiography revealed a complete embolic occlusion distal to the first jejunal branch of the SMA. Aspiration and local continuous thrombolysis with urokinase resulted in near complete revascularization of the mesenteric flow after 4 hours and almost complete restoration after 20 hours. The patient made a complete recovery and continues to do well on warfarin therapy after treatment. Aspiration and thrombolytic therapy can be an alternative treatment modality in surgical high risk patient.

Combined Radiofrequency Ablation and Double Anti-Angiogenic Protein Therapy to Increase Coagulation Efficacy: An Experimental Study in a Murine Renal Carcinoma Model

Objective To evaluate whether suppression of tumor microvasculature by double anti-angiogenic protein (DAAP) treatment could increase the extent of radiofrequency ablation (RFA)-induced coagulation in a murine renal cell carcinoma model. Materials and Methods Renal cell carcinoma cell lines were implanted subcutaneously into 10 nude mice. Four mice received adenoviral DAAP treatment and 6 mice received sterile 0.9% saline solution as DAAP-untreated group. The effect of DAAP was evaluated according to the vascularity by contrast-enhanced ultrasound (CEUS) using microbubbles. Four DAAP-treated mice and 4 DAAP-untreated mice were then treated with RFA, resulting in 3 groups: no-therapy (n = 2), RFA only (n = 4), and RFA combined with DAAP treatment (n = 4). Immediately after RFA, the size of coagulation necrosis and mitochondrial enzyme activity were compared between the groups using analysis of variance (ANOVA) and post hoc test. Results The contrast enhancement ratio for tumor vascularization on CEUS was significantly lower in the DAAP treated group than in DAAP-untreated group (30.2 ± 9.9% vs. 77.4 ± 17.3%; p = 0.021). After RFA, the mean coagulation diameter was 0 mm for no-therapy group, 6.7 ± 0.7 mm for the RFA only group and 8.5 ± 0.4 mm for the RFA with DAAP group (ANOVA, p < 0.001). The area of viable mitochondria within the tumor was 27.9 ± 3.9% in no-therapy group, 10.3 ± 4.5% in the RFA only group, and 2.1 ± 0.7% in the RFA with DAAP group (ANOVA, p < 0.001). Conclusion Our results suggest the potential value of combining RFA with anti-angiogenic therapy.

Anatomical Features and Early Outcomes of Endovascular Repair of Abdominal Aortic Aneurysm from a Korean Multicenter Registry.

Purpose: To introduce a nation-based endovascular aneurysm repair (EVAR) registry in South Korea and to analyze the anatomical features and early clinical outcomes of abdominal aortic aneurysms (AAA) in patients who underwent EVAR. Materials and methods: The Korean EVAR registry (KER) was a template-based online registry developed and established in 2009. The KER recruited 389 patients who underwent EVAR from 13 medical centers in South Korea from January 2010 to June 2010. We retrospectively reviewed the anatomic features and 30-day clinical outcomes. Results: Initial deployment without open conversion was achieved in all cases and procedure-related 30-day mortality rate was 1.9%. Anatomic features showed the following variables: proximal aortic neck angle 48.8±25.7° (mean±standard deviation), vertical neck length 35.0±17.2 mm, aneurysmal sac diameter 57.2±14.2 mm, common iliac artery (CIA) involvement in 218 (56.3%) patients, and median right CIA length 34.9 mm. Two hundred and nineteen (56.3%) patients showed neck calcification, 98 patients (25.2%) had neck thrombus, and the inferior mesenteric arteries of 91 patients (23.4%) were occluded. Conclusion: Anatomical features of AAA in patients from the KER were characterized as having angulated proximal neck, tortuous iliac artery, and a higher rate of CIA involvement. Long-term follow-up and ongoing studies are required.

The Advantage of Common Femoral Endarterectomy Alone or Combined with Endovascular Treatment

Purpose Although common femoral artery endarterectomy (CFAE) is regarded as the standard treatment modality for common femoral artery (CFA) disease, availability of advanced endovascular techniques has resulted in an increased number of CFA disease being treated. We evaluated clinical outcomes in a contemporary series of patients who were treated for CFA disease using endarterectomy alone or combined with endovascular treatment. Materials and Methods We retrospectively reviewed 46 patients from November 2001 through December 2007. The treated lesions were divided into 4 groups based on operative procedure: group I (n=11), CFAE alone; group II (n=15), CFAE and iliac artery (IA) endovascular treatment; group III (n=6), CFAE and superficial femoral artery (SFA) endovascular treatment; group IV (n=14), CFAE and IA and SFA endovascular treatment or bypass surgery. Results The degree of CFA steno-occlusion was not different among the groups. The 3-year primary patency rates of each group were 88.9±10.5%, 60.0±14.5%, 62.5±21.3%, and 83.9±10.4%, respectively. The 3-year primary assisted patency rates were 100%, 70.0±13.0%, 62.5±21.3%, and 89.3±10.4%, while 3-year secondary patency rates were 100%, 80.0±13.0%, 62.5±21.3%, and 92.3±7.4%, respectively. There was no procedure-related mortality. Significant improvement of ankle-brachial index was achieved in all groups. Conclusion CFAE alone is the treatment of choice for excellent patency and clinical improvement in steno-occlusive lesions confined to the CFA. In multiple steno-occlusive diseases, this procedure could be combined with endovascular procedures to reduce the operative risk in conditions with high morbidity.

Hybrid treatment of multilevel revascularization in patients with peripheral arterial disease – a multi-centre study in Korea

BACKGROUND Endovascular treatment is an alternative first-line management for peripheral artery disease (PAD). Hybrid treatment (HT) is defined as a combined treatment for patients with PAD using endovascular and open surgery, simultaneously performed in an operating room. The results of HT are reportedly good for multilevel revascularization (MR) in patients with chronic limb ischaemia, and even in older high-risk patients. The goal of this study was to examine the clinical and haemodynamic outcomes of HT in patients who need MR. PATIENTS AND METHODS Nine university hospitals in Korea participated in this multicentre study. A total of 134 patients with multilevel PAD underwent HT and MR. Patients were enrolled from July 2014 to June 2015 and were followed for 18 months. RESULTS The mean age of the patients was 68.8 ± 9.93 years and 88.1 % were men. Patients with Rutherford category 2 to 3 and 4 to 6 comprised 59.0 % and 42.0 % of the group, respectively. The technical success rate was 100 %. The primary patency rates at 12 and 18 months were 77.6 % and 63.9 %, respectively. The primary-assisted patency rates at 12 and 18 months were both 90.0 %. The pre-operative mean ankle brachial index (0.43 ± 0.23) increased to 0.87 ± 0.23 at six months post-operatively (t-test, p < 0.05). The amputation free survival rate was 97.1 %. CONCLUSIONS Although outcomes of multilevel PAD are reportedly poor when endovascular treatment alone is used, we have shown that HT is a feasible alternative modality for patients with multilevel PAD, with satisfactory amputation-free survival and freedom from re-intervention rates.

Early experience of thoracic endovascular aortic repair: a local single hospital experience

Purpose The purpose of this retrospective study was to evaluate the short- to mid-term results of thoracic endovascular aortic repair (TEVAR) in Wonkwang University School of Medicine & Hospital. Methods Between February 2009 and May 2011, 8 consecutive patients had undergone endovascular stent-grafting for thoracic aortic diseases. Five patients were treated for traumatic thoracic aortic injuries, two patients were treated for thoracic aneurysms and one patient was treated for a pseudoaneurysm due to penetrating aortic ulcers. Attempted stent-graft deployment was performed electively in 6 patients and emergently in 2. Follow-up was performed at 1-month, 6-month, 1-year, and annually thereafter. Results Technical success rates were achieved in 87.5% and the 30-day mortality rate was 0%. Mean hospital length of stay after TEVAR was 30 days in traumatic thoracic aortic injuries and 10 days in thoracic aneurismal diseases. Intra-operative Type I endoleak due to migration at deflation was visualized in 1 patient, which was treated by insertion of another stent-graft. During follow-up, a major complication was encountered in one patient who received carotid-subclavian bypass to relieve left arm ischemia. After 5 months he was treated with arch replacement for aortic arch aneurysm with type I endoleak at proximal site after endovascular treatment. The 30-day mortality rate was 0%. However, 1 case of mortality (12.5%) was observed during the follow-up period. Conclusion The short and mid-term results of endovascular repair of thoracic aortic diseases are promising. TEVAR is an effective procedure in the management of thoracic aortic diseases.