Carotid ultrasound findings as a predictor of long-term survival after abdominal aortic aneurysm repair: a 14-year prospective study

AbstractPurposeSeveral factors have been related to long-term survival after open abdominal aortic aneurysm (AAA) repair. The effect of carotid stenosis on outcome has not yet been examined. We performed an open prospective study to evaluate the prognostic significance of carotid stenosis on long-term survival of patients who had undergone elective operative repair of AAA.MethodsTwo hundred eight patients who underwent elective open AAA repair in our department between March 1987 and December 2001 were included in the study. All patients were evaluated preoperatively with color duplex ultrasound (US) scanning of the carotid arteries, and were followed up with clinical examination and carotid duplex US scanning 1 month after the operation and every 6 months thereafter. Median duration of follow-up was 50 months (range, 5-181 months). Cardiovascular morbidity and mortality, as well as all causes of mortality, were recorded and analyzed with regard to traditional risk factors and carotid US findings.ResultsTwenty-seven fatal and 46 nonfatal cardiovascular events were recorded. Both univariate and multivariate analysis showed that carotid stenosis 50% or greater and echolucent plaque were significantly associated with cardiovascular mortality and morbidity. Carotid stenosis was a stronger predictor of cardiovascular death than was ankle/brachial index. Age, hypercholesterolemia, coronary artery disease, and diabetes mellitus were also associated with higher mortality and morbidity from cardiovascular causes.ConclusionPatients electively operated on for AAA repair and with stenosis 50% or greater and echolucent plaque at duplex US scanning are at significantly increased risk for cardiovascular mortality and morbidity. Carotid US can therefore be used to select a subgroup of patients with AAA who might benefit from medical intervention, including antiplatelet and lipid-lowering agents

Application of adipose-derived stromal cells in fat grafting: Basic science and literature review

Autologous fat is considered the ideal material for soft‑tissue augmentation in plastic and reconstructive surgery. The primary drawback of autologous fat grafting is the high resorption rate. The isolation of mesenchymal stem cells from adipose tissue inevitably led to research focusing on the study of combined transplantation of autologous fat and adipose derived stem cells (ADSCs) and introduced the theory of ʻcell‑assisted lipotransferʼ. Transplantation of ADSCs is a promising strategy, due to the high proliferative capacity of stem cells, their potential to induce paracrine signalling and ability to differentiate into adipocytes and vascular cells. The current study examined the literature for clinical and experimental studies on cell‑assisted lipotransfer to assess the efficacy of this novel technique when compared with traditional fat grafting. A total of 30 studies were included in the present review. The current study demonstrates that cell‑assisted lipotransfer has improved efficacy compared with conventional fat grafting. Despite relatively positive outcomes, further investigation is required to establish a consensus in cell‑assisted lipotransfer

FAK, CD44v6, c-Met and EGFR in colorectal cancer parameters: tumour progression, metastasis, patient survival and receptor crosstalk

Research for reliable and patient-specific markers in colorectal cancer (CRC) is based on solid evidence that staging alone is not informative enough. Employing four cellular receptors, we embarked to identify aggressive tumour behaviour and impact of surrogate marker expression on patient prognosis. One-hundred eighty-three CRC patients were enrolled in our investigation that focused on an array of biological markers, namely epidermal growth factor receptor (EGFR), c-Met, focal adhesion kinase (FAK) and CD44v6. Tissue samples, clinicopathological data and patient’s follow-up information were collected, and immunohistochemical assays evaluated the levels of the aforementioned molecules. All available data were correlated with tumour grade, stage, patient age, gender and survival. Expression of all receptors correlated closely with tumour stage (P < 0.01) exhibiting a connection with cancer’s invasiveness and progress. Survival also proved to depend significantly on molecular expression (log-rank test for Kaplan-Meier; EGFR P = 0.030, c-Met P = 0.050, FAK P < 0.001, CD44v6 P < 0.001). Stage, FAK and CD44v6 emerged as independent predictors of survival in a stepwise regression analysis (FAK P = 0.001 Exp(B) = 2.517, 95 % confidence interval (CI) = 1.704-5.831 and CD44v6 P = 0.005, Exp(B) = 2.299, 95 % CI = 1.287-4.110). T-stage, nodal metastasis, all metastatic types (N/M) and size correlated with at least one of the receptors or their co-expression. Notably, increased staining for each receptor was followed by statistically significant expression elevation of at least one of the other markers. Our results suggest that the selected cellular receptors are suitable for use as biomarkers of survival and tumour progression in CRC. Furthermore, we provide additional evidence for receptor interaction, properly clarifying their importance, which could potentially lead to more effective anti-CRC regimens

Vascular endothelial growth factor receptors 1,3 and caveolin-1 are implicated in colorectal cancer aggressiveness and prognosis-correlations with epidermal growth factor receptor, CD44v6, focal adhesion kinase, and c-Met

Vascular endothelial growth factor receptor-1 (VEGFR-1) and caveolin-1 have been shown to act both as tumor-promoting and tumor-suppressing proteins in various malignancies as well as in colorectal cancer (CRC), while VEGFR-3’s lymphagiogenic involvement and connection to tumor parameters has yielded heterogenic results. This study was designed to investigate the expression of these molecules in 183 human CRC tissue specimens and explore their effect in both clinicopathological parameters and disease prognosis. We also utilize our previous results regarding epidermal growth factor receptor (EGFR), c-Met, CD44v6, and focal adhesion kinase, in an attempt to further clarify their distinct role in tumor prognosis and their crosstalk. Caveolin-1 was more freely distributed in the neoplasms of the right colon and restricted towards the left and the rectal cancer samples (p = 0.022); VEGFR-3 was associated with higher nodal metastasis’ status (p = 0.001) and staging (p = 0.006), and loss of VEGFR-1 predicted distant metastasis (p = 0.026) and advanced stage (p = 0.049). Prompted by previous reports, we performed all analyses also in the patient group of early (I and II) tumor stage where it was evident that VEGFR-1 was more frequently expressed in patients under 60 years old (p = 0.014) and VEGFR-3 was significantly elevated in left colon cancers (p = 0.039) and female patients (p = 0.038). Within the advanced stage (III and IV), the absence of VEGFR-1 exhibited a tendency for higher M status (p = 0.067) and lack of caveolin-1 signified worse AJCC classification (p = 0.053). Additionally, patient survival was influenced from VEGFR-3 (p = 0.019) for the whole sample, whereas subgroup analyses provided a correlation between caveolin-1 expression and improved survival in the early detection group of patients (p = 0.022). Using Cox regression for all available markers, EGFR, CD44v6, and VEGFR-1 emerged in this study as potential surrogate markers, the latter having positive prognostic significance. We further explored the multiple receptor correlations that were identified

Prognostic significance of transforming growth factor beta (TGF-beta) signaling axis molecules and E-cadherin in colorectal cancer

The transforming growth factor beta (TGF-beta) signaling pathway has been considered both a tumor suppressor and a cancer promoter. Additionally, downregulation of cell adhesion molecules such as E-cadherin plays an important role in the metastatic potential of colorectal cancer (CRC). The aim of the present study was to evaluate TGF-beta, TGF-beta type I receptor (TGF-beta R1), TGF-beta type II receptor (TGF-beta R2), Smad4, pSmad2/3, and E-cadherin expression in colorectal carcinoma and to correlate the obtained data with other standard prognostic parameters, such as disease stage, metastases, and patient survival. TGF-beta, TGF-beta R1, TGF-beta R2, Smad4, pSmad2/3, and E-cadherin expression was evaluated immunohistochemically in 195 unrelated CRC specimens and the results subjected to various statistical analyses. TGF-beta was expressed in 71.28%, TGF-beta R1 in 61.0%, TGF-beta R2 in 54.4%, Smad4 in 61.5%, pSmad2/3 in 71.3%, and E-cadherin in 50.26% of the colorectal carcinoma samples tested. The correlation of immunoexpression with the clinicopathological parameters of CRC revealed that the high expression of TGF-beta and low expression of TGF-beta R1, TGF-beta R2, Smad4, pSmad2/3, and E-cadherin were correlated with tumor-node-metastasis (TNM) stage of disease. High TGF-beta expression and low TGF-beta R1, TGF-beta R2, Smad4, and pSmad2/3 expression were also correlated with lymph node metastasis. The Kaplan-Meier survival curves demonstrated a clear association of cancer-specific overall survival with high TGF-beta, as well as low TGF-beta R1, TGF-beta R2, Smad4, pSmad2/3, and E-cadherin expression. Our results suggest that TGF-beta, TGF-beta R1, TGF-beta R2, Smad4, pSmad2/3, and E-cadherin are closely related to TNM stage of CRC. Moreover, TGF-beta, TGF-beta R2, Smad4, pSmad2/3, and E-cadherin emerge as valuable independent biomarkers of prognosis in CRC patients

TGF-beta signalling in colon carcinogenesis

Colorectal cancer remains the most common cancer and the second leading cause of cancer mortality in Europe. There are a number of pathways that have been implicated in colorectal carcinogenesis, including TGF-beta (TGF-beta)/Smad signalling pathway. The TGF-beta pathway is involved in several biological processes, including cell proliferation, differentiation, migration and apoptosis. Here we review the role of TGF-beta signalling cascade in colorectal carcinogenesis and provide some new molecular insights that may aid efforts towards targeted antitumor therapies. (C) 2011 Elsevier Ireland Ltd. All rights reserved

Correlation between oxidative stress and immunosuppressive therapy in renal transplant recipients with an uneventful postoperative course and stable renal function

Background Reactive oxygen species (ROS) are important mediators of cellular damage and lipid peroxidation is the most important expression of ROS-induced oxidative stress. Recent studies have suggested that increased plasma malondialdehyde (MDA) levels are a consequence of specific immunosuppressive therapies. This study aims at investigating the relation between oxidative stress and immunosuppressive therapies in renal transplant patients with stable renal function and uneventful postoperative course. Methods The study group included 26 renal patients. Two groups of renal transplant recipients, treated with a different combination of immunosuppressive agents were studied (Group A: CyA, MMF, Steroids and Basiliximab, Group B: Tacrolimus, MMF, Steroids and Daclizumab). All patients had an uneventful postoperative course. Plasma MDA levels were measured before transplantation, 1 and 6 months after. Plasma concentration of endogenous creatinine (Cr) was used as a measure of stable renal function. Results Levels of MDA were increased before the transplantation in all renal patients (MDA: 7.81 +/- 4.81, normal levels: 2.23-1.08 nmol/ml, P < 0.05). Combined therapy with CYA was associated with high values of MDA at 6 months measurement after transplantation. However this tendency of increased MDA levels did not achieve a statistical significance (Group A: 6.97 vs. 9.06 nmol/ml, P > 0.05). On the contrary, statistically significant diminution of MDA levels was observed in Group B patients (Tacrolimus-MMF-steroids) at 6 months measurement after transplantation. (Group B: 8.61 vs. 4.11 nmol/ml, P < 0.02 < 0.05). Conclusions Immunosuppressive combined therapy with CyA was associated with the high values of MDA that were measured posttransplantly. Our study provides strong evidence that Tacrolimus is significantly associated with improved free radical metabolism

The role of liquid-based cytology in the investigation of colorectal lesions: a cytohistopathological correlation and evaluation of diagnostic accuracy

Background amd aims: The role of cytologic techniques is not widely accepted even if it is well documented that the cytologic investigation of colorectal tract could complement the biopsy and increase the correct diagnosis of carcinomas. This study aims to evaluate the role of Thin-Prep (R) liquid-based cytology in the investigation of colorectal lesions. Materials and methods: We compared the diagnostic accuracy of Thin-Prep (R) with that of biopsy in 158 patients with signs and symptoms of the lower gastrointestinal tract. Each patient underwent colonoscopy, followed by tissue biopsy and brush cytology. Brushing material was obtained and prepared according to the operating manual of Thin-Prep (R). Results: The rate of unsatisfactory smears was 5% (8/158) with liquid-based technique and appeared to be slightly higher than the respective of biopsy [3.2% (5/158) (5 vs 3.2%, P = 0.18)]. Based on the final diagnosis, 89 out of 93 total malignant cases and 53 out of 53 total benign cases were correctly diagnosed with Thin-Prep (R) technique (four false negatives). Accurate diagnosis with biopsy was performed in 87 out of 93 total malignant cases and 53 out of 53 total benign cases with biopsy (six false negatives). Neither in Thin-Prep (R) technique nor in biopsy were false-positive cases observed. The sensitivities of detecting malignancy by Thin-Prep (R) and biopsy were 95.7, and 93.5%, respectively (no significant difference, P = 0.239). The sensitivity was augmented (98.9%) when the two techniques were combined, and this difference was found to be statistically significant (98.9 vs 92.9, P = 0.01, and 98.9 vs 95.7, P = 0.039). Conclusions: Liquid-based cytology appears to be an easy, highly accurate, and reliable cytologic method for the diagnostic approach of colorectal diseases and could be applied as complementary to biopsy for the improvement of the diagnosis. Moreover, could be used for DNA ploidy analysis and immmunohistochemical studies

Application of adipose-derived stromal cells in fat grafting: Basic science and literature review (Review)

Autologous fat is considered the ideal material for soft-tissue augmentation in plastic and reconstructive surgery. The primary drawback of autologous fat grafting is the high resorption rate. The isolation of mesenchymal stem cells from adipose tissue inevitably led to research focusing on the study of combined transplantation of autologous fat and adipose derived stem cells (ADSCs) and introduced the theory of `cell-assisted lipotransfer'. Transplantation of ADSCs is a promising strategy, due to the high proliferative capacity of stem cells, their potential to induce paracrine signalling and ability to differentiate into adipocytes and vascular cells. The current study examined the literature for clinical and experimental studies on cell-assisted lipotransfer to assess the efficacy of this novel technique when compared with traditional fat grafting. A total of 30 studies were included in the present review. The current study demonstrates that cell-assisted lipotransfer has improved efficacy compared with conventional fat grafting. Despite relatively positive outcomes, further investigation is required to establish a consensus in cell-assisted lipotransfer