Beyond Diameter: Enhancing Abdominal Aortic Aneurysm Surveillance with Volumetric Assessments after Endovascular Aneurysm Repair (EVAR).

This study aimed to investigate the relationship between maximum transverse diameter (MTD) and volume measurements in patients who underwent reoperations after endovascular aneurysm repair (EVAR), and their association with the occurrence of endoleaks. The study included 51 patients who underwent EVAR and subsequent re-operations caused by endoleaks type I-III. In some number of events, multiple re-operations were needed. MTD was measured using the Horos software, and segmentations of the AAA were performed using 3D Slicer. This study first evaluated post-operative computed tomography angiography (CTA) to measure MTD and volume. Then, similar measurements were made in the control scan for re-operation qualification. Negative remodeling (increase in MTD and/or volume) was observed in 40 cases using MTD, and 48 cases using volume measurements. The volume measurement showed lower missed negatives than MTD, indicating its effectiveness in screening for negative remodeling (p < 0.001). Combining both methods identified 51 negative remodeling cases and 8 positive changes, with a higher sensitivity compared to MTD alone. The volume of the sac did not predict specific endoleak types. Decreases in MTD were observed in smaller sacs, with smaller volume changes. Volume measurement is a valuable screening tool, and combining MTD and volume enhances sensitivity. However, sac volume does not predict endoleak type.

Efficacy of Liver Chemoembolization after Prior Cetuximab Monotherapy in Patients with Metastatic Colorectal Cancer.

Purpose: Chemoembolization of liver lesions, metastatic from colorectal cancer (CRC), with irinotecan-loaded microspheres shows less efficacy if applied after previous systemic chemotherapy. This is because cancer cells acquire resistance to previously used chemotherapeutic agents, e.g., irinotecan or perhaps via, e.g., modulations of EGFR receptors after use of anti-EGFR antibodies. Objective: To evaluate the effects of prior treatment with anti-EGFR (cetuximab) antibodies on the efficacy of chemoembolization, with irinotecan-loaded microspheres, of liver lesions metastatic from CRC. Patients and methods: The study included 50 patients (27 female, 23 male) with inoperable liver metastases in the course of CRC who underwent a total of 192 chemoembolization procedures with microspheres loaded with 100 mg of irinotecan. Chemoembolization of the right or left liver lobes was performed alternately at three-week intervals. Patients were divided into two groups: group A (n = 26): patients who had previously received anti-EGFR (cetuximab) antibodies; and group B (n = 24): patients who had never received anti-EGFR antibodies. Response to treatment was assessed according to mRECIST criteria. Overall survival time (OS) was calculated using the Kaplan−Meier method. Evaluation of adverse effects was performed according to the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (Version 5.0). Results: Analysis did not show a statistically significant difference in radiological response between the two groups: partial response: 36.2% in group A and 32.9% in group B (p = 0.139); and stable disease: 19.2% in group A and 21.7% in group B (p = 0.224). Post-treatment progression was comparable at 46.2% in group A and 41.6% in group B (p = 0.343). There was a significant difference in OS (p = 0.043 log-rank test), however, prior treatment with cetuximab showed no significant effect on OS in a Cox proportional hazards regression model HR 1.906 (0.977−3.716), p = 0.058. Mean OS was 15.2 months (95% confidence interval (Cl): 6 to 23 months) in group A and 13.1 months (95% Cl: 7 to 22 months) in group B. In both groups, there was a negative correlation between carcinoembryonic antigen (CEA) levels below 10 mg/mL before surgery and OS (hazard ratio (HR) 0.83 (0.47−8.43), p = 0.005 in group A and HR 1.02 (0.56−7.39), p = 0.003 in group B). There was no significant difference in the number of prominent complications between group A (7 complications) and group B (6 complications), p = 0.663. Conclusions: Previous therapy with anti-EGFR antibodies before treatment with irinotecan chemoembolization of liver metastatic lesions did not have a significant effect on radiological response to treatment or post-treatment progression. However, higher baseline levels of CEA (>10 ng/mL) were correlated with worse OS (p = 0.039).

Relationship between aortic wall oxidative stress/proteolytic enzyme expression and intraluminal thrombus thickness indicates a novel pathomechanism in the progression of human abdominal aortic aneurysm.

The possibility that oxidative stress promotes degradation of the extracellular matrix and a relationship between intraluminal thrombus (ILT) thickness and proteolytic activity within the abdominal aortic aneurysm (AAA) wall has been suggested. In the present study, the hypothesis that thin ILT is correlated with an increase in oxidative stress-related enzymes and matrix metalloproteinase-9 (MMP-9) expression within the human AAA wall was investigated. We also studied the antioxidant activity of superoxide dismutases, catalase, glutathione peroxidase, glutathione reductase, and thioredoxin within the full-thickness AAA wall and through fluoroimmunohistochemical staining of catalase and MMP-9 expression within the inner and outer media, in relation to ILT thickness. Reactive oxygen species control the degradation and remodeling of the extracellular matrix by up-regulating proteolytic enzymes, such as MMPs. Results showed that oxidative stress and proteolytic enzyme expression were simultaneously, significantly higher within thin thrombus (≤10 mm)-covered aneurysm wall when compared with the wall covered by thick thrombus (≥25 mm). These findings provide the first demonstration, to our knowledge, of a causative link between oxidative stress instigating proteolytic enzyme expression at the tissue level and human AAA development. Presence of a thin circumferential thrombus should always be considered as a risk factor for the greatest increase in aneurysm growth rate and rupture, giving an indication for surgery timing.-Wiernicki, I., Parafiniuk, M., Kolasa-Wolosiuk, A., Gutowska, I., Kazimierczak, A., Clark, J., Baranowska-Bosiacka, I., Szumilowicz, P., Gutowski, P. Relationship between aortic wall oxidative stress/proteolytic enzyme expression and intraluminal thrombus thickness indicates a novel pathomechanism in the progression of human abdominal aortic aneurysm.

Cosmetic effects of skin-crease camouflage incision versus longitudinal incision following carotid endarterectomy.

INTRODUCTION: Despite the increasing use of carotid angioplasty and stenting (CAS), carotid endarterectomy (CEA) nonetheless remains a more medically beneficial method of treatment for carotid artery stenosis. Therefore, one possibility for progress within this procedure may be to use minimally invasive carotid surgery, especially when the scar is in plain sight: the use of the natural wrinkles (skin crease) as a camouflage of the skin incision provides significant cosmetic improvements. AIM: To compare the cosmetic effects of classic and trans-wrinkle CEA. To assess the distance between the carotid artery bifurcation (CAB) and the skin-crease incision whilst attempting CEA. MATERIAL AND METHODS: It was a randomized prospective study with two groups: patients undergoing classic surgery (control group; n = 100) and skin-crease trans-wrinkle camouflaged CEA (study group; n = 100). Follow-up was at 2 months and 1 year. RESULTS: The medical results of the treatment were similar in both groups. The cumulative count of strokes and myocardial infarctions was 0.5% within 30 days, and after one year 3.5% (and 5.5% including cases of death). The superiority of the transverse crease being hidden compared to the conventional longitudinal technique was proven in the Patient and Observer Scar Assessment Scale (POSAS) score, respectively 11.4 ±1.0 vs. 14.1 ±3.4 (p = 0.0001) after 2 months and 13.5 ±2.8 vs. 14.1 ±3.4 (p = 0.039) after a year. CONCLUSIONS: Trans-wrinkle incision gives better cosmetic results, can be safely performed in most cases, and offers a comfortable approach during CEA.

Significant changes in combined consistent biomarkers and CTAngiography revealed during an interval of 6months before abdominal aortic aneurysm rupture.

The most commonly used predictor of rupture of abdominal aortic aneurysm (AAA) is the diameter, but this does not correlate well with the risk of rupture. Therefore, in order to make further improvements in clinical decisions regarding AAA patients, the development of additional predictive tools other than aneurysm size alone is needed. We herein report a case of a 72-year-old man with AAA that underwent rupture transformation during six months. We review the morphological features changes detected by computed tomography and also observe several alters circulating biomarkers at the same time. In the study presented essentially an association of those combined parameters with the risk of AAA impending rupture.

Lead enhances fluoride influence on apoptotic processes in the HepG2 liver cell line.

Chronic long-term exposure to high levels of fluoride leads to fluorosis, manifested by skeletal fluorosis and damage to internal organs, including kidneys, liver, parathyroid glands, and brain. Excess fluoride can also cause DNA damage, trigger apoptosis, and change cell cycle. The effect of fluoride may be exacerbated by lead (Pb), a potent inhibitor of many enzymes and a factor causing apoptosis, still present in the environment in excessive amounts. Therefore, in this study, we investigated the effects of sodium fluoride (NaF) and/or lead acetate (PbAc) on development of apoptosis, cell vitality, and proliferation in the liver cell line HepG2. We examined hepatocytes from the liver cell line HepG2, incubated for 48 h with NaF, PbAc, and their mixture (NaF + PbAc), and used for measuring apoptosis, index of proliferation, and vitality of cells. Incubation of the hepatocytes with NaF or PbAc increased apoptosis, more when fluoride and Pb were used simultaneously. Vitality of the cells depended on the compound used and its concentration. Proliferation slightly increased and then decreased in a high fluoride environment; it decreased significantly after addition of Pb in a dose-dependent manner. When used together, fluoride inhibited the decreasing effect of Pb on cell proliferation.

The blood flow channel index as novel predictor of abdominal aortic aneurysm impending rupture based on the intraluminal thrombus angio-CT study.

OBJECTIVE: In this study the hypothesis that the thickness of the thinnest part of the thrombus, combined with bleeding into the intraluminal thrombus (ILT), is associated with a possible higher risk of abdominal aortic aneurysm (AAA) rupture was investigated, independently of aneurysm diameter, by using angio-CT. This article describes blood flow channel index based on the CT imaging findings that may help identify impending rupture prior to complete rupture. METHODS: Computed tomographic images of 310 hospitalized patients with infrarenal AAA, were collected over a three-year period. They were divided into two main groups: 125 with bleeding into the ILT and control group 185 without the presence of blood in the thrombus. Patients were also analyzed in subgroups with ruptured, symptomatic and asymptomatic AAAs. A blood flow channel index was formulated as: maximal/minimal thickness ratio of thrombus from the same CT scan. RESULTS: In dissected ILT group blood flow channel index was over a twofold higher than in group with intact ILT (19.0 [1.2-89.3] vs. (9.7 [1.3-38.9]; p<0.001), respectively. Median thickness at the thinnest part of the ILT in dissected thrombus group was lower (1.3mm [0.3-16.0]) than in group with intact ILT (1.7 mm [0.2-23.4]; p<0.003). CONCLUSION: An association between a high blood flow channel index and bleeding into the ILT based on angio-CT study was demonstrated, and can suggest the aneurysm propensity for rupture.

Leucocytosis as a specific risk predictor after abdominal aortic aneurysm open repair.

INTRODUCTION: Prediction of early death in abdominal aortic aneurysm - open repair is widely described. There is no superiority of any risk stratification tool. Some of the risk calculators are quite accurate, but very complicated (e.g. P-POSSUM, V-POSSUM). Some are simpler but never used in vascular surgery (e.g. ECOG). Therefore, only leucocytosis itself appears to be an independent and highly specific factor in prediction of early death prior to surgery. This might be used as an early warning factor raising surgeons' attention, especially in centers not using any risk calculators on a regular basis. The aim of this study was to comparison of commonly used early death prediction calculators for abdominal aortic aneurysm - open repair. We took into account the following scales: Glasgow Aneurysm Score (GAS), V-POSSUM, Eagle score, American Society of Anesthesia Score, ECOG, Goldman/Detsky. However, we also have been looking for independent risk factors of early postoperative death. MATERIAL AND METHODS: Retrospective analysis of 79 patients who underwent elective open repair of abdominal aortic aneurysm over 3 years (2011-2013 Szczecin, Poland). We have excluded patients treated due to ruptured aneurysms and with the use of a stentgraft. Receiver operating curve analysis was used to asses all prediction abilities. RESULTS: We noted 6 deaths (7.59%). Receiver operating curve analysis confirms good prediction force for V-POSSUM (p = 0.0001, criterion over 1.9%) and GAS (p = 0.0109, criterion over 73 pt.). Areas under curve are respectively 0.806 and 0.743. However, leucocytosis itself over 10 T/L was the most specific (over 88%) risk factor in early death prediction (p < 0.0001). CONCLUSION: V-POSSUM and GAS are suitable risk calculators for abdominal aortic aneurysm - open repair. Leucocytosis discovered prior to the surgery is a highly specific early death predictor.

Stent-graft implantation to treat an inferior vena cava aneurysm.

PURPOSE: To present a patient with a primary inferior vena cava aneurysm who was subjected to endovascular treatment. CASE REPORT: A 60-year-old man, suffering from pulmonary embolism, was diagnosed with a vena cava aneurysm located below the renal veins. Through the right common femoral vein, a custom-made stent-graft was implanted. Proximal and distal barbs were incorporated in the frame to assist fixation and avoid caudal or cephalad migration. The procedure was performed without any technical or clinical complications, and the aneurysm was completely excluded from the circulation. During the 6-month follow-up, imaging verified the correct position of the stent-graft and exclusion of the aneurysm without endoleak or any other complication. CONCLUSION: In patients with inferior vena cava aneurysm, stent-graft implantation may be an alternative to open surgery.

MMP-9, homocysteine and CRP circulating levels are associated with intraluminal thrombus thickness of abdominal aortic aneurysms: new implication of the old biomarkers.

BACKGROUND: Abdominal aortic aneurysms (AAAs) are characterized by presence of high proteolytic activity, atherosclerotic lesions, extensive transmural inflammation and the presence of variably sized and shaped intraluminal thrombus (ILT). Therefore, we evaluated a possible association between plasma matrix metalloproteinase-9 (MMP-9), homocysteine (Hcy), high-sensitivity C-reactive protein (hsCRP) levels and ILT thickness in patients with AAA. METHODS: Plasma concentrations of MMP-9, Hcy and hsCRP were determined and ILT thickness was measured in 71 patients with AAA. They were divided into 2 groups according to ILT thickness: 34 patients with ILT mean thickness ⩾ 9 mm and 37 patients with ILT < 9 mm. RESULTS: Plasma MMP-9 and CRP concentrations in patients with thin ILT were significantly higher than in group with thick ILT (medians 610 vs. 485 ng/mL, p=0.00003, and 7.7 vs. 3.3 mg/L, p < 0.00001, respectively). In contrast, plasma Hcy concentrations in patients with thin ILT were significantly lower than in the group with thick ILT (medians 14.3 vs. 19.2 µmol/L, p < 0.00001). Multiple regression models adjusted for age and AAA diameter showed that thin ILT is an independent predictor of high MMP-9 and CRP concentrations, while thick ILT predicts high Hcy concentrations. CONCLUSIONS: Association of higher plasma levels of MMP-9 and CRP with thin ILT may be related to two phenomena: thin thrombi convey more elastolysis-stimulating factors from blood to the AAA wall and thin thrombi convey more factors involved in proteolysis and inflammation from AAA wall to blood. The association of thin ILT with lower plasma Hcy concentrations may be related to the role of Hcy as a prothrombotic marker and needs further research.

The effect of L-ascorbic acid and/or tocopherol supplementation on electrophysiological parameters of the colon of rats chronically exposed to lead.

BACKGROUND: The aim of this study was to assess the effect of diet supplementation with L-ascorbic acid (500 mg/L), tocopherol (3 mg/kg b.w.), and/or a water soluble analog of tocopherol (Trolox) (48 mg/L) on ion transport in the colon of rats subjected to a chronic exposure (9 months) to 0.1% lead acetate in drinking water. MATERIAL/METHODS: The electrophysiological parameters of the colon wall were measured with Ussing methods. Lead content in the whole blood was analyzed by graphite furnace atomic absorption spectrometry (GFAAS) using Zeeman correction. L-ascorbic acid and tocopherol in plasma was measured by high performance liquid chromatography. Immunohistochemical reaction was carried out for visualization of occludin, the intracellular tight junction protein. RESULTS: We showed a strong inhibitory effect of lead on the electrophysiological parameters, changes in intestinal permeability, disappearance of junctional occludin, decreased amount of mucus covering the colon surface, and the accumulation of PAS-positive substance in the apical region of the cytoplasm in the absorptive cells. CONCLUSIONS: Supplementation with tocopherol or Trolox did not exert a beneficial influence on the studied parameters. L-ascorbic acid positively influenced the examined electrophysiological parameters, as it cancelled the inhibitory influence of lead on ion transport in the rat colon. L-ascorbic acid also protected against tight junction disruption of epithelial cells in the colon of the lead-treated rats. A similar effect was observed in the group of rats receiving lead and supplemented with L-ascorbic acid plus Trolox.

Enhanced matrix-degrading proteolytic activity within the thin thrombus-covered wall of human abdominal aortic aneurysms.

OBJECTIVE: The maintenance of an arterial elastin's integrity is essential in the prevention of abdominal aortic aneurysm (AAA) development. So far, the effect of intraluminal thrombus (ILT) thickness on the elastolytic activity within the AAA wall has not been studied. In the present study the hypothesis that thin thrombus is associated with enhanced proteolytic activity within human AAA wall was investigated. METHODS: The specimens for analysis, from both thin (< or = 10 mm) thrombus-covered and thick (> or = 25 mm) thrombus-covered wall, had been taken from 40 patients undergoing elective repair of AAA. We evaluated neutrophil elastase activity with the enzymatic assay. Concentrations of active matrix metalloproteinase-9 (MMP-9), total matrix metalloproteinase-8 (MMP-8), and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) were measured by ELISA. Biochemical parameters were compared with the Wilcoxon signed-rank test. RESULTS: Statistical analysis showed that the activity of elastase (P<0.0001) as well as concentrations of active MMP-9 (P=0.001), total MMP-8 (P<0.0001) and active MMP-9/total TIMP-1 ratio (P=0.002) were significantly higher in the thin thrombus-covered wall. Furthermore the TIMP-1 was found to have a lower concentration in the thin thrombus-covered in comparison with the thick thrombus-covered wall (P=0.003). There was a significant positive correlation between measurements in AAA wall sites with thin and thick thrombus for elastase, TIMP-1, MMP-9/TIMP-1 ratio, and a borderline correlation was observed for MMP-8. Active MMP-9 concentration did not correlate between sites. CONCLUSION: The current study demonstrates the differentiation of protease activity within the same AAA wall and its enhancement within the thin thrombus-covered aneurysm wall.

Haptoglobin 2-1 phenotype predicts rapid growth of abdominal aortic aneurysms.

BACKGROUND: Haptoglobin (Hp) polymorphism is associated with the prevalence and clinical evolution of many inflammatory diseases and atherosclerosis. Circulating neutrophils and neutrophil-associated proteases are an important initial component of experimental abdominal aortic aneurysm (AAA) formation. Elastase and C-reactive protein (CRP) levels are elevated in patients with AAAs. This study assessed the relationship between AAA expansion and Hp phenotypes, neutrophil count, elastase, and CRP levels. METHODS: Eighty-three consecutive AAA patients underwent annual ultrasound scans. Three major Hp phenotypes (1-1, 2-1, and 2-2) were determined, and the neutrophil count, serum elastase, and high-sensitivity (hs) CRP levels were measured at the initial examination. After initial screening, patients were rescanned at 6- to 12-month intervals up to a period of 2 to 7 years. The mean yearly growth of the AAA largest transverse diameter was estimated for each group of Hp patients. The results are presented as median (interquartile range). RESULTS: Hp 2-1 patients had a significantly higher growth rate (3.69 [2.40] mm/y) of AAA compared with patients with Hp 2-2 (1.24 [0.79], P < .00001) and Hp 1-1 (1.45 [0.68], P = .00004). This association remained significant in the multivariate analysis. Elevated elastase serum activity was also evident in AAA patients with Hp 2-1 (0.119 [0.084] arbitrary units) in contrast to Hp 2-2 (0.064 [0.041], P < .00001) and Hp 1-1 (0.071 [0.040], P = .0006) patients. CRP serum levels (mg/L) were significantly higher in patients with Hp 2-1 (7.2 [7.1]) than in Hp 2-2 (3.4 [3.1], P = .0058) and Hp 1-1 (2.8 [4.1], P = .044). The neutrophil count was not significantly different among Hp groups. CONCLUSIONS: The Hp 2-1 phenotype showed a strong association with increased rates of the expansion of AAAs and may be a useful independent predictor of growth rate. Further large follow-up studies will be needed to investigate the pathomechanisms of association and the role of elastase and inflammation in the progression of AAA.