Christos Klonaris

Renal angioplasty and stenting under protection: The way for the future?

The purpose of this study was to evaluate the feasibility and safety of renal artery angioplasty and stenting utilizing a distal protection device to reduce the risk of intraprocedural artery embolism and avoid deterioration of the renal function. Fifty‐six hypertensive patients (32 men; mean age, 66 ± 11.8 years; range, 22–87) with atherosclerotic renal artery stenosis (8 bilateral) underwent angioplasty and stenting with distal protection in 65 renal arteries (58 ostial lesions). Five patients had a solitary kidney, 18 a renal insufficiency. The lesion was crossed either with a GuardWire temporary occlusion balloon (n = 38), which was inflated to provide parenchyma protection or with a filter (EPI Filter; n = 26), or with Angioguard (n = 1), which allows a continuous flow. Generated debris was aspirated and analyzed. Blood pressure and serum creatinine levels were followed. Immediate technical success was 100%. All lesions except one were stented, either directly (43 ostial lesions) or after predilatation (22 ostial lesions). Visible debris were aspirated with the PercuSurge in all patients or removed with filters in 80% of the patients. Mean particle number and diameter were 98.1 ± 60.0 per procedure (range, 13–208) and 201.0 ± 76.0 μm (range, 38–6,206), respectively. Mean renal artery occlusion time was 6.55 ± 2.46 min (range, 2.29–13.21) with the PercuSurge device. Mean time in situ (filters) was 4.25 ± 1.12 min. Mean follow‐up was 22.6 ± 17.6 months (range, 1–47). Systolic and diastolic blood pressure declined from 169.0 ± 15.2 and 104.0 ± 13.0 mm Hg, respectively, to 149.7 ± 12.4 and 92.7 ± 6.7 mm Hg after the procedure. The mean creatinine level remains constant during the follow‐up. At 6‐month follow‐up (45 patients), renal function did not deteriorate in any patient, whereas 8 patients with baseline renal insufficiency improved after the procedure. At 3 years (19 patients), renal function deteriorated only in 1 patient with renal insufficiency and in 1 patient treated for bilateral renal stenosis, one side without protection. These preliminary results suggest the feasibility and safety of distal protection during renal interventions to protect against atheroembolism and to avoid renal function deterioration. This techniques beneficial effects should be evaluated by randomized studies. Catheter Cardiovasc Interv 2003;60:299–312.

Vascular endothelial growth factor and endoglin (CD-105) in gastric cancer

BackgroundVascular endothelial growth factor (VEGF) overexpression has been associated with advanced stage and poor survival in several cancers. Additionally, CD-105 (endoglin) was proposed as a marker of neovascularization in solid malignancies. The aim of the present study was to (1) evaluate the VEGF and CD-105 expression in gastric carcinoma, (2) determine the role of VEGF gene sequence variations in VEGF expression in gastric carcinoma, and (3) correlate the results of VEGF and CD-105 expression with other standard prognostic parameters, such as size, grade, stage of the disease, metastases, and patient survival.MethodsVEGF and CD-105 expression were evaluated in 100 unrelated gastric cancer patients using immunohistochemistry. For the genotyping, DNA was isolated from the blood of the gastric cancer patients and from 100 healthy individuals. The genotyping was performed by polymerase chain–restriction fragment length polymorphism analysis.ResultsVEGF protein was strongly expressed in the cytoplasm of 36% of the gastric carcinoma samples tested. In all cases, high VEGF expression was accompanied with high endoglin expression. Our results revealed no statistical significant association of any VEGF gene polymorphism with the VEGF and endoglin expression. The correlation of VEGF/CD-105 expression with the clinicopathological parameters of gastric cancer showed that the high expression of VEGF/CD015 was correlated only with lymph node metastasis (P = 0.028). The Kaplan-Meier survival curves have shown a clear association of overall survival after diagnosis of gastric cancer with high VEGF, as well as high CD-105 expression.ConclusionOur results support that VEGF and CD-105 are closely relevant to lymph node metastasis and act as two valuable indicators of prognosis.

First In Vivo Application of Microwave Radiometry in Human Carotids: A New Noninvasive Method for Detection of Local Inflammatory Activation

OBJECTIVES This study investigated whether temperature differences: 1) can be measured in vivo noninvasively by microwave radiometry (MR); and 2) are associated with ultrasound and histological findings. BACKGROUND Studies of human carotid artery samples showed increased heat production. MR allows in vivo noninvasive measurement of internal temperature of tissues. METHODS Thirty-four patients undergoing carotid endarterectomy underwent screening of carotid atherosclerosis by ultrasound and MR. Healthy volunteers were enrolled as a control group. During ultrasound study, plaque texture, plaque surface, and plaque echogenicity were analyzed. Temperature difference (ΔT) was assigned as maximal minus minimum temperature. Association of thermographic with ultrasound and histological findings was performed. RESULTS ΔT was higher in atherosclerotic carotid arteries compared with the carotid arteries of controls (p < 0.01). Fatty plaques had higher ΔT compared with mixed and calcified (p < 0.01) plaques. Plaques with ulcerated surface had higher ΔT compared with plaques with irregular and regular surface (p < 0.01). Heterogeneous plaques had higher ΔT compared with homogenous (p < 0.01). Specimens with thin fibrous cap and intense expression of CD3, CD68, and vascular endothelial growth factor (VEGF) had higher ΔT compared with specimens with thick cap and low expression of CD3, CD68, and VEGF (p < 0.01). CONCLUSIONS MR provides in vivo noninvasive temperature measurements of carotid plaques, reflecting plaque inflammatory activation.

Surgical Treatment of Carotid Body Tumours

OBJECTIVE To evaluate our results of the treatment of patients with carotid body tumours. DESIGN Retrospective study. SETTING University hospital, Greece. SUBJECTS 17 patients operated on for a carotid body tumour during the past 20 years. MAIN OUTCOME MEASURES Hospital mortality and morbidity, long-term outcome. RESULTS 3 patients had temporary cranial nerve lesions postoperatively, all of which resolved within three months. One patient developed a severe stroke and died seven days postoperatively. During follow-up that ranged from 7 months to 20 years, two patients died of unrelated causes. 5 patients were lost to follow up, and the remaining 10 were doing well with no signs of recurrence at the time of writing. CONCLUSION Excision of a carotid body tumour is recommended at the time of initial diagnosis in good-risk patients to avoid the difficulty of subsequent excision of an enlarging and highly vascular tumour with possible encasement of the carotid artery.

Association of haptoglobin genotype and common cardiovascular risk factors with the amount of iron in atherosclerotic carotid plaques.

INTRODUCTION The aim of this study was to evaluate the iron burden of carotid atherosclerotic plaques removed from patients treated for carotid disease and find any relation with haptoglobin genotype and other common cardiovascular risk factors. METHODS Consecutive patients undergoing carotid endarterectomy were included in the study. All patients had high-grade carotid stenosis (>70%). The clinical characteristics and serum parameters of the study population were recorded and the haptoglobin genotype was determined. The presence of hemosiderin deposits in the plaques was identified using Perls stain on adjacent serial sections. RESULTS 70 specimens were processed for histologic examination: 27 plaques from diabetic patients (16 with the Hp 1-1 or 2-1 genotype and 11 with the Hp 2-2 genotype) and 43 plaques from non diabetic patients (20 with the Hp 1-1 or 2-1 genotype and 23 with the Hp 2-2 genotype). In plaques from diabetic patients the density of Perls iron stain was significantly higher in the Hp 2-2 group compared with that in the Hp 1-1 or 2-1 group (p = 0.008). The correlation and regression analysis of all possible clinical and laboratory predictors of intraplaque iron deposition showed that four factors were independently associated with intraplaque iron deposition: male gender, serum homocysteine, Hp 2-2 genotype and diabetes mellitus treatment. CONCLUSIONS Male diabetic patients with increased plasma levels of homocysteine and the Hp 2-2 genotype had higher carotid plaque iron deposition. Current evidence and pathophysiological considerations suggest that the increased intraplaque iron deposition may be associated with increased oxidative stress, affecting the stability of the carotid plaque.

Lower Extremity Bypass Procedures in Diabetic Patients with End-Stage Renal Disease: Is It Worthwhile?

Backgroud/Aims: Limb-threatening ischemia in patients with end-stage renal disease (ESRD) represents a challenging therapeutic problem. Furthermore, diabetes mellitus is frequently associated with ischemic gangrene, persistent infection and impaired wound healing. The present study was undertaken to examine graft patency, limb salvage and survival in patients with ESRD and diabetes following bypass grafting to treat lower limb critical ischemia. Methods: A retrospective analysis of 56 arterial reconstructions performed in 39 patients with diabetes mellitus and ESRD during a period of 8 years. The indications for bypass grafting were: ischemic rest pain (n = 13), non-healing ulcer (n = 18) or foot gangrene (n = 25). Risk factors in association with surgical morbidity and mortality, limb loss and graft patency were evaluated. Results: Thirty-four patients were on hemodialysis and 5 on peritoneal dialysis. Forty-nine infrainguinal reconstructions were performed; the site of distal anastomosis was the below knee popliteal artery (n = 22), the anterior tibial artery (n = 12), the posterior tibial artery (n = 8), and the peroneal artery (n = 7). Seven axillofemoral reconstructions were also performed; the site of distal anastomosis was the common femoral artery (n = 5) and the above knee popliteal artery (n = 2). The 30-day operative mortality rate was 18% (7 patients). The mean follow-up was 11.5 (range 1–93) months. Patient survival rate at 1 and 2 years was 63 and 45%, respectively. Primary patency rate was 64% at 1 year and 58% at 2 years. The limb salvage rate was 65% in the first year. Conclusion: Limb salvage rate in patients with ESRD and diabetes justifies an aggressive policy of revascularization, despite decreased survival of this population.

Correlation of Peroxisome Proliferator-Activated Receptor-gamma (PPAR-gamma) and Retinoid X Receptor-alpha (RXR-alpha) expression with clinical risk factors in patients with advanced carotid atherosclerosis

Summary Background Peroxisome proliferator-activated Receptor-γ (PPAR-γ) and its nuclear partners, the Retinoid X Receptors (RXRs), have been recognized as crucial players in the pathogenesis of atherosclerosis. The present study aimed to assess the clinical significance of PPAR-γ and RXR-α expression in different cellular populations localized within advanced carotid atherosclerosis lesions. Material/Methods PPAR-γ and RXR-α expression was assessed by immunohistochemistry ïn 134 carotid atherosclerotic plaques obtained from an equal number of patients that underwent endarterectomy procedure for vascular repair, and was correlated with patients’ medical history, risk factors and medication intake. Results Increased incidence of low PPAR-γ expression in both macrophages and smooth muscle cells was noted in patients presenting coronary artery disease (p=0.032 and p=0.046, respectively). PPAR-γ expression in smooth muscle cells was borderline down-regulated in symptomatic compared to asymptomatic patients (p=0.061), reaching statistical significance when analyzing groups of patients with specific cerebrovascular events; amaurosis fugax (p=0.008), amaurosis fugax/stroke (p=0.020) or amaurosis fugax/transient ischemic attack patients (p=0.028) compared to asymptomatic patients. Low RXR-α expression in macrophages was more frequently observed in hypertensive (p=0.048) and hyperlipidemic patients (p=0.049). Increased incidence of low RXR-α expression in smooth muscle cells was also noted in patients presenting advanced carotid stenosis grade (p=0.015). Conclusions PPAR-γ and RXR-α expression down-regulation in macrophages and smooth muscle cells was associated with a more pronounced disease progression in patients with advanced carotid atherosclerotic lesions.

Common Carotid Artery Occlusion Treatment: Revealing a Gap in the Current Guidelines

OBJECTIVE To review the literature on the management of common carotid artery occlusion (CCAO). METHODS A review of English-language medical literature from 1965 to 2012 was conducted using the PubMed and EMBASE databases to find all studies involving management of CCAO. The search identified 21 articles encompassing 146 patients/arteries (73.2% men; mean age 65 ± 6.9 years). RESULTS The majority of the patients (93.8%) were symptomatic. Most of the patients (61.5%) had ipsilateral internal carotid artery (ICA) and external carotid artery (ECA) patent, while an occluded ICA and a patent ECA were found in 26.6% of the patients. Eighty per cent of the patients treated underwent a surgical bypass procedure, with the subclavian artery as the most common inflow vessel (64.1%). During the first 30 days of the procedure two strokes (1.5%) were reported. During a follow-up period spanning an average of 25.6 ± 11.2 months nine patients (6.6%) experienced a clinical cerebrovascular event. Seven restenoses (5.1%) and two reocclusions (1.5%) also occurred-eight after open surgical and one after endovascular repair. CONCLUSION The necessity to intervene to a CCAO remains controversial. This review shows that open surgical management of symptomatic CCA occlusive disease is a safe, durable, and effective therapeutic strategy with low perioperative cerebrovascular morbidity.

Correlation of plasma osteoprotegerin (OPG) and receptor activator of the nuclear factor κB ligand (RANKL) levels with clinical risk factors in patients with advanced carotid atherosclerosis

Summary Background Osteoprotegerin (OPG) is considered to be a crucial regulatory mediator of bone metabolism by acting as a decoy receptor of the receptor activator of nuclear factor κB ligand (RANKL). OPG and RANKL have further become the subject of intense interest for their potential role in cardiovascular disease. The present study aimed to assess the clinical implication of plasma OPG and RANKL levels in patients with advanced carotid atherosclerosis Material/Methods Plasma OPG and RANKL concentrations measured by solid-phase enzyme-linked immunosorbent assay (ELISA) were correlated with medical history, risk factors and medication intake in 131 patients who underwent carotid endarterectomy for vascular repair. Results Plasma OPG concentrations were associated with patients’ age (p=0.0258), homocysteine levels (p<0.00001), eGFR (p=0.0254), history of diabetes (p=0.0324), statins therapy (p=0.0044), hyperlipidemia (p=0.0407), smoking (p=0.0226) and CAD (p=0.0377). Plasma RANKL concentrations were associated with patients’ age (p=0.0191), homocysteine levels (p<0.00001), history of smoking (p=0.0185) and statins therapy (p=0.0004). Diabetes, CAD, smoking status, statins therapy and homocysteine were identified as independent predictors of OPG concentrations (p=0.0157, p=0.0030, p=0.0249, p=0.0047 and p=0.0072, respectively), whereas smoking showed an independent effect for RANKL (p=0.0010). Conclusions The present data reinforce the clinical utility of OPG in carotid atherosclerosis, whereas the clinical implication of RANKL seems uncertain.

Predictors affecting in-hospital mortality of ruptured abdominal aortic aneurysms: a Greek multicenter study.

BACKGROUND Endovascular aortic repair (EVAR) is being used with increasing frequency for the treatment of ruptured abdominal aortic aneurysms (rAAAs), although conflicting results have been reported concerning perioperative mortality. The aim of our study was to evaluate potential difference in mortality rates between EVAR and open surgical repair (OSR) and identify independent risk factors for in-hospital mortality in rAAAs. This study also aimed to evaluate the Glasgow Aneurysm Score (GAS) in predicting in-hospital mortality. A time-trend analysis of EVAR for ruptured AAAs was also performed. METHODS Prospectively collected data from 7 public hospitals in Greece concerning rAAA repairs between January 2006 and April 2012 were analyzed. Primary outcome was in-hospital mortality. Multivariate logistic regression analysis was used to identify independent risk factors. The receiver-operator characteristic curve was used to determine the value of the GAS in predicting in-hospital death. Time-trend analysis, depicting annual changes (%), concerning EVAR for ruptured AAAs was also conducted. RESULTS A total of 418 patients (92.3% men, mean age = 74.3 ± 8.8) with rAAAs were recorded during the study period. Among them, 113 patients (27%) underwent EVAR. Overall in-hospital mortality was 45.2%, whereas in-hospital mortality after EVAR and OSR was 20.4% and 54.3%, respectively (P < 0.001). Multivariate analysis evidenced that hemodynamic instability (P < 0.001), OSR (P < 0.001), age ≥80 years (P < 0.001), coronary artery disease (P < 0.001), and renal insufficiency (P = 0.02) independently increased in-hospital mortality. Area under the curve of GAS was 0.80 (95% confidence interval [CI] = 0.75-0.85, P < 0.001) for OSR and 0.64 (95% CI = 0.51-0.77, P = 0.04) for EVAR. Annual increase of proportion (%) of EVAR for rupture was 5% (P = 0.004). CONCLUSIONS EVAR is being used with increasing frequency for the treatment of rAAAs and it appears to be associated with lower in-hospital mortality compared with OSR, after adjustment for hemodynamic instability and known atherosclerotic risk factors. Preoperative predictors of in-hospital mortality such as GAS should be probably modified in these patients.