Hormone receptor conversion in metastatic breast cancer.

Background/Objective: Hormone receptor (HR) status is one of the key factors in determining the treatment of breast cancer. Previous studies suggested that HR status may change in metastatic tissue. However, available studies focused mainly on primary biopsies and there are only few trials comparing HR status in the primary tumour and the metastasis using material from complete resection. The aim of the study was to determine the frequency of HR alterations in metastatic breast cancer. Materials and methods: The study retrospectively examines a total of 50 patients who underwent brain, lung, or liver metastasectomy for metastatic breast cancer between January 2000 and January 2019. Results: HR conversion was observed in a total of 30 cases (60.0%), while HER-2/neu (human epidermal growth factor receptor 2) discrepancy surprisingly occurred only in one case (2.0%). A change in immunophenotype occurred in 28% of cases. Triple-negativity was more frequent in brain metastases (p = 0.039). Conclusions: We have confirmed that HR conversion between the primary tumour and its metastases occurs in a significant number of cases, which has important implications for further treatment decisions.

[Pros and cons of dual kidney transplantation]. / Klady a rizika duální transplantace ledvin.

Dual kidney transplantation is one of the options to utilize so called marginal grafts, kidneys that would be insufficient for normal single transplantation. This time consuming and burdensome surgical procedure can be beneficial in precisely selected patients. This method requires correct algorithm of donors and recipients selections, than we can expect the best results.Key words: dual kidney transplantation, marginal donor, chronic renal failure, expanded criteria donor.

Proteomic analysis of the abdominal aortic aneurysm wall.

PURPOSES: A ruptured AAA (rAAA) is a common cause of death in males over 60 years of age, and the global mortality from rAAA exceeds 80 %. The pathological processes occurring in the wall of the developing AAA are still unclear. The potential pathophysiological mechanisms underlying aortic aneurysms have been examined by many studies using immunohistochemistry and were, therefore, targeted at specific, preselected protein antigens. METHODS: We collected samples of tissue from anterior wall of an aneurysm sac from 15 patients indicated for AAA resection (group A) during the period from 2010 to 2011. These samples were subjected to a proteomic analysis. In addition, we collected control samples of identical aortic tissue from 10 heart-beating deceased organ donors (group B). RESULTS: A total of 417 differentially expressed protein fractions were identified, 18 of which were only detected in the healthy controls, while 85 were specific for aneurysm tissue and 314 were detectable in both groups. In 175 protein fractions, the gel-derived spot volumes differed significantly between aneurismal and healthy aortic tissue. CONCLUSIONS: We found a significant difference in the proteome of the AAA tissue and non-dilated aortic tissue. We demonstrated that the AAA proteome is considerably richer and more varied than the healthy and atherosclerotic aorta. We believe that our results clearly demonstrate a completely different etiopathogenesis of atherosclerosis and aneurismal disease.

The Impacts of the Sterilization Method and the Electrospinning Conditions of Nanofibrous Biodegradable Layers on Their Degradation and Hemocompatibility Behavior.

The use of electrospun polymeric biodegradable materials for medical applications is becoming increasingly widespread. One of the most important parameters regarding the functionality of nanofiber scaffolds during implantation and the subsequent regeneration of damaged tissues concerns their stability and degradation behavior, both of which are influenced by a wide range of factors (the properties of the polymer and the polymer solution, the technological processing approach, the sterilization method, etc.). This study monitored the degradation of nanofibrous materials fabricated from degradable polyesters as a result of the sterilization method applied (ethylene oxide and gamma irradiation) and the solvent system used to prepare the spun polymer solution. Aliphatic polyesters PCL and PLCL were chosen for this study and selected with respect to the applicability and handling in the surgical setting of these nanofibrous materials for vascular bandaging. The results revealed that the choice of solvent system exerts a significant impact on degradation during sterilization, especially at higher gamma irradiation values. The subsequent enzyme-catalyzed degradation of the materials following sterilization indicated that the choice of the sterilization method influenced the degradation behavior of the materials. Whereas wave-like degradation was evident concerning ethylene oxide sterilization, no such behavior was observed following gamma-irradiation sterilization. With concern for some of the tested materials, the results also indicated the potential for influencing the development of degradation within the bulk versus degradation from the surface of the material. Both the sterilization method and the choice of the spinning solvent system were found to impact degradation, which was observed to be most accelerated in the case of PLCL (L-lactide-co-caprolactone copolymer) electrospun from organic acids and subsequently sterilized using gamma irradiation. Since we planned to use these materials in cardiovascular applications, it was decided that their hemocompatibility would also be tested. The results of these tests revealed that changes in the structures of the materials initiated by sterilization may exert thrombogenic and anticoagulant impacts. Moreover, the microscopic analysis suggested that the solvent system used in the preparation of the materials potentially affects the behavior of erythrocytes; however, no indication of the occurrence of hemolysis was detected.

Asymptomatic abdominal aortic aneurysms show histological signs of progression: a quantitative histochemical analysis.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a serious disease due to its covert nature, relatively high prevalence and fatal prognosis in the case of rupture. To obtain new insights into AAA pathogenesis, we examined the relationships between histopathology, multiplex in vitro immunoassay data, diameter and symptomatology. METHODS: In a prospective, non-randomised study, we evaluated samples from 6 normal infrarenal aortae and 65 AAA patients (65 walls, 55 thrombi). The AAA patients were either asymptomatic (n = 44), symptomatic (n = 7) or with ruptured AAA (n = 14). The AAA diameter was classified as small (<5 cm, n = 18), medium (5-7 cm, n = 26) and large (>7 cm, n = 21). We quantified the histopathology of the AAA wall and the adjacent thrombus. We assessed the expression of proteins in the same samples. RESULTS: Asymptomatic AAAs had walls with more abundant inflammatory infiltrates, lower amounts of PAI-1, a higher number of tPA-positive elements, a tendency towards decreased collagen content, whereas the adjacent thrombi had a greater concentration of VCAM-1 and MMP-2 when compared with symptomatic AAAs. Compared with the aneurysmatic aorta, the normal aorta contained less collagen and more elastin, actin, desmin and PAI-1-positive elements; in addition, it was more vascular. Medium-sized AAAs were the most actin and vimentin rich, and large AAAs were the most vascular. CONCLUSION: Our results show that asymptomatic AAA walls often have more potentially deleterious histopathological alterations than symptomatic AAA walls. This result indicates that a progression from an asymptomatic AAA to rupture can be expected and screening patients who are at risk of rupture could be beneficial.

Correlation between atmospheric pressure changes and abdominal aortic aneurysm rupture: results of a single-center study.

PURPOSE: There is much interest in all factors that influence the etiopathogenesis of abdominal aortic aneurysm (AAA) rupture. Apart from the well-established factors such as arterial hypertension, smoking, age, and genetic predisposition, less common factors that may play a role in the mechanism of the rupture are the subject of much discussion. These include atmospheric conditions, temperature, and atmospheric pressure. We conducted this study to investigate the effects of the absolute value of atmospheric pressure and its changes on the frequency of AAA rupture. METHODS: We retrospectively examined 54 patients who underwent treatment for a ruptured AAA at the Clinic of Surgery in the University Hospital in Pilsen between 1 January 2005 and 31 December 2009. We collected data on the atmospheric pressure in this period from the Czech Hydrometeorological Institute in Pilsen. RESULTS: We did not find a significant difference in atmospheric pressure values between the days when the rupture occurred versus the other days (p < 0.5888). Moreover, we did not find significant changes in the atmospheric pressure during the 48 h preceding the rupture (Student's test p < 0.4434) versus the day of rupture or in the mean atmospheric pressure in that month. CONCLUSION: These findings suggest that atmospheric pressure and its changes do not affect the pathogenesis of AAA rupture.

Unicentric form of Castleman´s disease, pitfalls of diagnosis and surgical treatment.

Background: Castleman´s disease is an extremely rare heterogenous lymphoproliferative pathology with a mostly benign behavior. It is a localized or generalized lymph node enlargement of an unknown aetiology. Unicentric form is typically a slow-growing solitary mass occurring mostly in the mediastinum, abdominal cavity, retroperitoneum, pelvis and neck. Aetiology and pathogenesis of CD is probably diverse, varying in different types of this heterogeneous disease. Materials and Methods: Authors present a review of this issue based on their extensive experience. The aim is to summarize the crucial factors in the management of diagnostics and a surgical treatment of the unicentric form of Castleman´s disease. One of the key issues in the unicentric form is precise preoperative diagnostics and thus choosing the right surgical treatment strategy. Authors highlight pitfalls of the diagnosis and surgical treatment. Results: All histological types such as a hyaline vascular type, plasmacytic type and a mixed type are presented as well as options of surgical and conservative treatment. Differential diagnosis and malignant potential is discussed. Conclusion: Patients with Castleman´s disease should be treated in the high- volume centers, with a great experience in major surgical procedures as well as with preoperative imaging diagnostic techniques. Specialized pathologists and oncologists focusing on this issue are also absolutely necessary to avoid misdiagnosis. Only this complex approach can lead to excellent outcomes in patients with UCD.

[Morphology and etiopathogenesis of the abdominal aortic aneurysm]. / Morfologie a etiopatogeneze aneuryzmatu brisní aorty.

The paper summarizes the latest research on the abdominal aorta aneurysm etiopathogenesis and compares normal aorta morphology with changes in the aortic aneurysm wall. The role of risk factors, especially hemodynamic and genetic, is discussed in detail. Special attention is paid to inflammatory processes including cytokines and matrix degrading proteases that contribute to the development of aneurysm. The role of thrombus and the current results of research into biomarkers indicating the risks and progression of the disease are analysed. Finally, a review of pharmacomodulation of the aortic aneurysm using statins, antibiotics, antihypertensive and nonsteroidal antiinflammatory drugs is presented.

Use of a Silver-Impregnated Vascular Graft: Single-Center Experience.

INTRODUCTION: Vascular graft infection is a life threatening situation with significant morbidity and mortality. Bacterial graft infection can lead to false aneurysms, bleeding and sepsis. There are a lot of risky situations where grafts can become infected. It is therefore highly desirable to have a vascular graft that is resistant to infection. In this retrospective clinical study, a silver-impregnated vascular graft was evaluated in various indications. METHODS: Our study included a total of 71 patients who received a silver-impregnated vascular graft during the period from 2013 to 2018. Patients had an aortoiliac localization of vascular graft in 61 cases (86%), and a peripheral localization on the lower limbs in 10 cases (14%). Indications for the use of these special vascular grafts were trophic lesions or gangrene in the lower limbs in 24 cases (34%), suspicious mycotic abdominal aortic aneurysm (mAAA) in 4 cases (5.5%), salmonela aortitis or aneurysms in 4 cases (5.5%), infection of the previous vascular graft in 11 cases (15.5%), other infections in 12 cases (17%), AAA rupture in 10 cases (14%) and other reasons (pre-transplant condition, multiple trauma, graft-enteric fistula) in 6 cases (8.5%). Thirty-day mortality, morbidity, the need for reintervention and amputation, primary and secondary graft patency, and finally the presence of a proven vascular graft infection were evaluated. RESULTS: The 30-day mortality was 19.7%, and morbidity was 42.2%. The primary patency of the vascular graft was 91.5%. Reoperation was necessary in 10 cases (14%) and amputation was necessary in 10 cases (14%). The median length of hospital stay was 13 days and the mean follow-up period was 48 ± 9 months. During the follow-up period, six patients (8.5%) died from reasons unrelated to surgery or without any relation to the vascular graft. Secondary patency after one year was 88%. Infection of the silver graft was observed in three patients (4.2%). CONCLUSIONS: Based on our results, the silver graft is a very suitable alternative for solving infectious, or potentially infectious, situations in vascular surgery. In particular, in urgent or acute cases, a silver graft is often the only option.

HDL metabolism and functions impacting on cell cholesterol homeostasis are specifically altered in patients with abdominal aortic aneurysm.

Background: The etiopathogenesis of abdominal aortic aneurysm (AAA) is still unclarified, but vascular inflammation and matrix metalloproteases activation have a recognized role in AAA development and progression. Circulating lipoproteins are involved in tissue inflammation and repair, particularly through the regulation of intracellular cholesterol, whose excess is associated to cell damage and proinflammatory activation. We analyzed lipoprotein metabolism and function in AAA and in control vasculopathic patients, to highlight possible non-atherosclerosis-related, specific abnormalities. Methods: We measured fluorometrically serum esterified/total cholesterol ratio, as an index of lecithin-cholesterol acyltransferase (LCAT) activity, and cholesteryl ester transfer protein (CETP) activity in patients referred to vascular surgery either for AAA (n=30) or stenotic aortic/peripheral atherosclerosis (n=21) having similar burden of cardiovascular risk factors and disease. We measured high-density lipoprotein (HDL)-cholesterol efflux capacity (CEC), through the ATP-binding cassette G1 (ABCG1) and A1 (ABCA1) pathways and serum cell cholesterol loading capacity (CLC), by radioisotopic and fluorimetric methods, respectively. Results: We found higher LCAT (+23%; p < 0.0001) and CETP (+49%; p < 0.0001) activity in AAA sera. HDL ABCG1-CEC was lower (-16%; p < 0.001) and ABCA1-CEC was higher (+31.7%; p < 0.0001) in AAA. Stratification suggests that smoking may partly contribute to these modifications. CEC and CETP activity correlated with CLC only in AAA. Conclusions: We demonstrated that compared to patients with stenotic atherosclerosis, patients with AAA had altered HDL metabolism and functions involved in their anti-inflammatory and tissue repair activity, particularly through the ABCG1-related intracellular signaling. Clarifying the relevance of this mechanism for AAA evolution might help in developing new diagnostic parameters and therapeutic targets for the early management of this condition.

Bevacizumab Does Not Inhibit the Formation of Liver Vessels and Liver Regeneration Following Major Hepatectomy: A Large Animal Model Study.

BACKGROUND/AIM: Patients with unresectable liver colorectal cancer metastases are treated with neoadjuvant chemotherapy often accompanied by biological therapy aimed at reducing the mass of metastases and thus increasing the chances of resectability. Bevacizumab comprises an anti-VEGF (vascular endothelial growth factor) humanized IgG monoclonal antibody that is used for biological therapy purposes. It acts to inhibit angiogenesis, thereby slowing down the growth of metastases. Due to its being administered systematically, bevacizumab also exerts an effect on the surrounding healthy liver parenchyma and potentially limits the process of neovascularization and thus regeneration of the liver. Since the remnant liver volume forms an important factor in postoperative morbidity and mortality following a major hepatectomy, we decided to study the effect of bevacizumab on vascular and biliary microarchitecture in healthy liver parenchyma and its ability to regenerate following major hepatectomy. MATERIALS AND METHODS: We performed an experiment employing a large animal model where a total of 16 piglets were divided into two groups (8 piglets in the control group and 8 piglets in the experimental group with bevacizumab). All the animals were subjected to major hepatectomy and the experimental group was given bevacizumab prior to hepatectomy. All the animals were sacrificed after 4 weeks. We performed biochemical analyses at regular time intervals during the follow-up period. Histological examination of the liver tissue was performed following sacrifice of the animals. RESULTS: No statistical difference was shown between groups in terms of the biochemical and immunohistochemical parameters. The histological examination of the regenerating liver tissue revealed the higher length density of sinusoids in the experimental group. CONCLUSION: Bevacizumab does not act to impair liver regeneration following hepatectomy.

Assessment of abdominal aortic aneurysm wall distensibility with electrocardiography-gated computed tomography.

BACKGROUND: Despite the fact that abdominal aortic aneurysm (AAA) is asymptomatic in the vast majority of cases, sudden rupture with a fatal outcome may still occur. Early planned resection or endovascular aneurysm repair of small AAAs may help prevent a rupture, but both methods are associated with significant mortality. The aim of our study was to determine AAA wall distensibility and to compare it with distensibility of the "healthy" aorta of the same patient. METHODS: We evaluated 12 patients with AAA, mean age of 65 years, 10 men and 2 women. The mean diameter of the aneurysm was 5.95 cm. RESULTS: We did not find any correlation between aneurysm diameter and any of the following parameters: (1) distensibility of AAA wall (p = 0.8119), (2) distensibility of AAA lumen (p = 0.1262), and (3) distensibility of normal aorta (p = 0.9828). We proved by use of the Wilcoxon test that distensibility of the wall of the normal aorta is significantly greater than distensibility of the AAA wall (p = 0.0141). A significant difference between distensibility of the AAA wall and AAA lumen was proved (p = 0.0221) also by use of the Wilcoxon test. Distensibility of the AAA wall is significantly lower. Despite the proved significant differences between distensibility of the AAA wall and normal aorta, values of AAA wall distensibility nearly reached values of distensibility of the normal aorta above the AAA in some particular cases; the value was even higher in one case. We observed this phenomenon in four patients of our small population, two of them suffering from rapidly increasing aneurysm. CONCLUSION: In our opinion, electrocardiography-synchronized computed tomographic angiography may contribute to diagnostics in the future. Lumen distensibility is significantly higher than distensibility of the wall. The thrombus acts in this respect as a buffer, thus inhibiting the effect of pulse waves on the wall. From a mechanical point of view, the thrombus rather acts protectively against the risk of rupture. Distensibility assessment could be another fragment of the diagnostic algorithm and decision making on intervention.

Perfusion of a Kidney Graft from a Donor After Cardiac Death Based on Immediately Started Machine Perfusion: An Experimental Study on a Big Animal.

BACKGROUND: Donation after circulatory death donors are becoming a common source of organs for transplant. Despite good long-term outcomes of grafts from donation after circulatory death, this group is affected by a higher occurrence of delayed graft function and primary nonfunction. Our hypothesis is based on the assumption that washing the kidney grafts in the donor's body using a simple mechanical perfusion pump will result in faster and better perfusion of the parenchyma and more efficient cooling compared with hydrostatic perfusion alone. METHODS: A total of 7 experimental animals (pigs) were used. The animals were divided into 2 groups: group A (n = 3) and group B (n = 4). After a 30-minute ischemic period for the selected kidney (clamped renal vessels), intra-arterial perfusion was performed. In group A perfusion was performed using hydrostatic pressure; in group B mechanical controlled perfusion was performed. After perfusion, declamping of the renal vessels caused restoration of flow. For graft quality evaluation, biopsy specimens were harvested, and the cooling speed was observed. Laboratory markers or renal failure were determined. RESULTS: We found no significant differences between temperature drop and total diuresis between groups A and B. A significant difference was found between the groups in both flow parameters (flow maximum and mean flow) (P = .007, respectively P = .019). No laboratory parameters were found to be statistically significantly different. Histopathological analysis strongly supports the hypothesis of better flushing of kidney grafts using mechanical perfusion. CONCLUSIONS: Based on our results, better kidney graft quality can be expected after immediately started mechanical perfusion in situ.

Management of Concomitant Abdominal Aortic Aneurysm and Intra-abdominal, Retroperitoneal Malignancy.

BACKGROUND/AIM: As the population ages, there are increasing findings of coincidental diseases such as abdominal aortic aneurysm (AAA) and intra-abdominal, retroperitoneal malignancy. The aim of this study was to propose an optimal treatment procedure for these patients. PATIENTS AND METHODS: Over a twenty-year-period, surgery was performed on a total of 1,098 patients with AAA and 32 (2.9%) patients with AAA and intra-abdominal, retroperitoneal malignancy: 18 renal, 6 colorectal carcinomas, 3 carcinomas of the small intestine, 3 primary liver tumours, 1 stomach carcinoma and 1 teratoma. The median age of patients was 72.5 years, there were 20 men (62.5%) and 12 women (37.5%). A one-stage procedure was performed on 19 patients (59.4%), and a two-stage procedure on 13 (40.6%) patients. RESULTS: The average time of hospitalization was 12.4±6.9 days (median=11.0 days) for one-stage procedure, for a two-stage procedure 21.3±9.3 days (median=20.0 days), p=0.0045. Seven patients (21.9%) died within 30 days after the operation. All the deaths were in the group of one-stage procedures (p=0.0252). The 1-, 3- and 5-year overall survival for patients following one-stage and twostage procedures was 61.0/56.3/51.5% and 89.0/79.9/53.0% respectively (p=0.1199). CONCLUSION: Symptomatic disease must be resolved first. Two-stage procedures are the method of choice and offer better short-term results compared to one-stage procedures.

Bilateral post-traumatic carotid dissection as a result of a strangulation injury.

Carotid trauma is always very serious. Post-traumatic carotid dissection is rather rare and can be diagnosed late. Authors present a case report of post-traumatic bilateral carotid dissection and its spontaneous recovery. Symptoms, diagnosis, and treatment are discussed.

Littoral cell angioma of the spleen: A case report.

Spleen tumors are an uncommon disease. Littoral cell angioma belongs to the group of vascular tumors. It is believed that this tumor originates from the tissue of the red pulp sinuses, specifically from the cells that are lining the sinuses. If this rare tumor is diagnosed, it is necessary to search for synchronous or metachronous visceral neoplasia. Littoral cell angioma can also mimic metastatic lesion of the spleen. This case report wants to draw attention on this rare tumor of the spleen which is very often associated with other visceral malignancy.

Optimization of the model of abdominal aortic aneurysm--experiment in an animal model.

BACKGROUND: Many studies have been performed in order to model abdominal aortic aneurysm (AAA) in an experimental animal, most commonly in small laboratory animals. In our study, we tried to find the best AAA model in a pig by using various mechanical and enzymatic mechanisms. METHODS: Twenty-two pigs were operated on. We combined 3 mechanisms of creating an AAA, using an intraluminal infusion of porcine pancreatic elastase into the abdominal aortic segment, application of plastic cuff below the renal arteries causing turbulent blood flow, and inserting a patch into the longitudinal aortotomy. RESULTS: We found different results in different groups according to the mechanisms used. In group A, with a combination of the intraluminal elastase infusion and application of a stenosing cuff, AAA developed in all 7 animals (100%). In this group, we also found the largest histological changes in the abdominal aorta samples. CONCLUSION: The use of intraluminal pancreatic elastase infusion, together with increased turbulent flow caused by the stenosing cuff, seems to be the best model of AAA in pigs. This model is suitable for further research in the etiopathology of AAA. In fact, it is the first successful approach to a large-caliber native aneurysm model.

Abdominal aortic aneurysm in prostate cancer patients: the "road map" from incidental detection to advanced predictive, preventive, and personalized approach utilizing common follow-up for both pathologies.

Abdominal aortic aneurysm (AAA) is often a hidden pathological process showing no clinical symptoms. Genetic burden, smoking, male gender, age > 65 years, and white race have been identified as the main risk factors. A regular screening program has been introduced but is, as yet, unclear and is not performed in most countries. Prostate cancer is the most frequent male malignant disease in Western countries. Prostate cancer is a disease of older age with a median primary diagnosis of over 60 years. In recent years, advanced imaging methods have been established as important diagnostic tools in prostate cancer diagnostics. The incidental detection of AAA during diagnostic imaging performed due to prostate cancer diagnosis could reveal some asymptomatic aneurysms. Using our experience, the incidental detection of AAA during 18F-fluoromethylcholine PET/CT imaging, performed due to the staging, follow-up, and restaging of the prostate cancer, was reworked into a regular tool of secondary prevention within the framework of personalized medicine strategies. Experience with this type of AAA detection is demonstrated by a cohort of 500 patients who underwent 18F-fluorometylcholine PET/CT examination due to the staging or restaging of prostate cancer. A total of 28 aneurysms were detected (26 aneurysms < 50 mm, 2 aneurysms > 50 mm). In 2 cases (diameter < 50 mm), serious complications were found (penetrating aortic ulcer). The detection and monitoring of AAA in patients undergoing 18F-fluorometylcholine PET/CT due to the prostate cancer offers the possibility of a secondary prevention of AAA, patient stratification, and common follow-up for both pathologies.

The Expression Profile of MicroRNAs in Small and Large Abdominal Aortic Aneurysms.

BACKGROUND: Abdominal aortic aneurysms (AAA) are relatively frequent in elderly population, and their ruptures are related with high mortality rate. There are no actually used laboratory markers predicting the AAA development, course, and rupture. MicroRNAs are small noncoding molecules involved in posttranscriptional gene expression regulation, influencing processes on cell and tissue levels, and are actually in focus due to their potential to become diagnostic or prognostic markers in various diseases. METHODS: Tissue samples of AAA patients and healthy controls were collected, from which miRNA was isolated. Microarray including the complete panel of 2549 miRNAs was used to find expression miRNA profiles that were analysed in three subgroups: small (N = 10) and large (N = 6) aneurysms and healthy controls (N = 5). Fold changes between expression in aneurysms and normal tissue were calculated including corresponding p values, adjusted to multiple comparisons. RESULTS: Six miRNAs were found to be significantly dysregulated in small aneurysms (miR-7158-5p, miR-658, miR-517-5p, miR-122-5p, miR-326, and miR-3180) and 162 in large aneurysms, in comparison with the healthy control. Ten miRNAs in large aneurysms with more than two-fold significant change in expression were identified: miR-23a-3p, miR-24-3p, miR-27a-3p, miR-27b-3p, miR-30d-5p, miR-193a-3p, miR-203a-3p, miR-365a-3p, miR-4291, and miR-3663-3p and all, but the last one was downregulated in aneurysmal walls. CONCLUSION: We confirmed some previously identified miRNAs (miR-23/27/24 family, miR-193a, and miR-30) as associated with AAA pathogenesis. We have found other, yet in AAA unidentified miRNAs (miR-203a, miR-3663, miR-365a, and miR-4291) for further analyses, to investigate more closely their possible role in pathogenesis of aneurysms. If their role in AAA development is proved significant in future, they can become potential markers or treatment targets.

Inflammatory cell infiltrates, hypoxia, vascularization, pentraxin 3 and osteoprotegerin in abdominal aortic aneurysms - A quantitative histological study.

Information about the tissue characteristics of abdominal aortic aneurysms (AAAs), some of which may be reflected in the serum, can help to elucidate AAA pathogenesis and identify new AAA biomarkers. This information would be beneficial not only for diagnostics and follow-up but also for potential therapeutic intervention. Therefore, the aim of our study was to compare the expression of structural proteins, immune factors (T and B lymphocytes, macrophages, neutrophils and pentraxin 3 (PTX3)), osteoprotegerin (OPG), microvessels and hypoxic cells in AAA and nonaneurysmal aortic walls. We examined specimens collected during surgery for AAA repair (n = 39) and from the abdominal aortas of kidney donors without AAA (n = 8). Using histochemical and immunohistochemical methods, we quantified the areas positive for smooth muscle actin, desmin, elastin, collagen, OPG, CD3, CD20, MAC387, myeloperoxidase, PTX3, and hypoxia-inducible factor 1-alpha and the density of CD31-positive microvessels. AAA samples contained significantly less actin, desmin, elastin and OPG, more collagen, macrophages, neutrophils, T lymphocytes, B lymphocytes, hypoxic cells and PTX3, and a greater density of vasa vasorum (VV) than those in non-AAA samples. Hypoxia positively correlated with actin and negatively correlated with collagen. Microvascular density was related to inflammatory cell infiltrates, hypoxia, PTX3 expression and AAA diameter. The lower OPG expression in AAAs supports the notion of its protective role in AAA remodeling. AAA contained altered amounts of structural proteins, implying reduced vascular elasticity. PTX3 was upregulated in AAA and colocalized with inflammatory infiltrates. This evidence supports further evaluation of PTX3 as a candidate marker of AAA. The presence of aortic hypoxia, despite hypervascularization, suggests that hypoxia-induced neoangiogenesis may play a role in AAA pathogenesis. VV angiogenesis of the AAA wall increases its vulnerability.