Innovative monolateral approach for closed-chest atrial fibrillation surgery

Surgical treatment of atrial fibrillation recently gained new popularity since the introduction of different energy sources as an alternative to the original cut-and-sew technique. Recently an innovative approach for closed-chest thoracoscopic epicardial pulmonary veins isolation has been described for patients suffering from lone atrial fibrillation. Nevertheless in an effort to further reduce the invasiveness of closed-chest atrial fibrillation surgery, we developed a novel monolateral approach for thoracoscopic arrhythmia surgery.     

Dendritic cells and vascular endothelial growth factor in colorectal cancer: correlations with clinicobiological findings

OBJECTIVE: Dendritic cells (DC) are central to the development of immune system responses. In a cohort of 54 patients affected by colorectal cancer, we prospectively investigated the number of peripheral blood (PB) DC type 1 (DC1) and type 2 (DC2) and correlated their counts and functionality to the stage of the disease and to vascular endothelial growth factor (VEGF) levels. RESULTS: At diagnosis, compared with healthy controls, patients presented reduced PBDC1 and PBDC2 numbers (p < 0.001). Moreover, in cancer patients, PBDC showed low levels of DC-associated antigens (HLA DR, p = 0.004; CD11c, p < 0.001; CD83, p = 0.01; CD86, p = 0.007 and Mannose receptor, p = 0.029), an upregulation of CXCR4 (p = 0.017) and a reduced T cell stimulation capability (p < 0.001). DC1 and DC2 loss was higher in stage D versus stage ABC patients (p = 0.003 and p = 0.002, respectively); surgery and chemotherapy appeared to attenuate a DC defect, although the restoration of normal PBDC levels is completed only at 6 and 12 months after diagnosis, respectively. In this series of patients, PBDC1 and PBDC2 numbers inversely correlated with VEGF serum levels (p < 0.001), suggesting a possible effect of this cytokine on DC compartment. In culture, the exposure of monocyte-derived DC to VEGF produced a dramatic alteration of DC differentiation by (1) induction of apoptosis, (2) alteration of DC immunophenotypic profile and (3) increased CXCR4 expression. Exposure to anti-VEGF blocking antibodies reversed VEGF inhibitory effects in all cases. CONCLUSIONS: These findings suggest that in colorectal cancer patients there is a numerical and functional impairment of PBDC compartment possibly related to the stage of the disease and to VEGF levels.     

Alteration of the E-cadherin/beta-catenin cell adhesion system is common in pulmonary neuroendocrine tumors and is an independent predictor of lymph node metastasis in atypical carcinoids

BACKGROUND: To the authors' knowledge, little is known regarding the role of E-cadherin/beta-catenin system dysregulation in pulmonary neuroendocrine tumors. METHODS: E-cadherin and beta-catenin immunoreactivity was evaluated in 10 hyperplastic neuroendocrine tumorlets and 210 neuroendocrine tumors, including 96 typical carcinoids (CTs), 35 atypical carcinoids (ACTs), 49 large cell neuroendocrine carcinomas (LCNECs), and 30 small cell lung carcinomas (SCLCs). RESULTS: Normal and hyperplastic bronchial neuroendocrine cells expressed E-cadherin/beta-catenin with an orderly distribution along the cell membrane. Neuroendocrine tumors retained beta-catenin expression in all tumors and E-cadherin in most tumors, with the exception of 2% of LCNECs, 3% of SCLCs and 9% of ACTs. E-cadherin showed a prevalent membrane-associated, linear immunoreactivity in CTs, whereas membrane-disarrayed and cytoplasmic staining was seen in most ACTs, LCNECs, and SCLCs (P < 0.001). beta-Catenin exhibited similar immunoreactivity patterns according to tumor type and a close association with E-cadherin subcellular distribution (P < 0.001). Nuclear accumulation of beta-catenin was found only in seven LCNECs and in two SCLCs. In ACTs, disarrayed immunoreactivity for E-cadherin and/or beta-catenin was associated with a nontrabecular growth pattern, altered expression of the cell-motility marker fascin, and lymph node metastases. Furthermore, a disarrayed E-cadherin distribution pattern was associated with the pathologic lymph node classification and the number of involved lymph nodes. Multivariate analysis confirmed that a disarrayed E-cadherin or beta-catenin pattern was an independent predictor of lymph node metastases in patients with ACT. CONCLUSIONS: The subcellular compartmentalization of the E-cadherin/beta-catenin complex was altered in pulmonary neuroendocrine tumors. This likely affects the tumor growth pattern and cell motility of ACT and was correlated with the occurrence of lymph node metastases.     

Clinical role of tissue and serum levels of SCCA antigen in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most frequent cancer in the world and a common occurrence in patients with liver cirrhosis in western and North American countries. Ultrasound screening is a powerful technique for HCC diagnosis, whereas the only available serologic test, alpha-fetoprotein, has poor reliability. It has been reported that the squamous cell carcinoma antigen (SCCA) is overexpressed in HCC tissue. In our study, the expression of SCCA was investigated in tumoral and peritumoral tissues and in the serum of 52 HCC patients, as well as in the serum of 48 cirrhotic patients. The results show that SCCA expression is much stronger in the tumoral than in the peritumoral tissue of HCC. Moreover, it is also evident in metastatic nodules present in the peritumoral tissue. SCCA serum levels were significantly higher in HCC samples than in cirrhotic samples. However, no correlation was found between SCCA expression and the HCC histologic degree, nor did SCCA expression correlate with tumor size, presence of metastasis or clinical outcome. In conclusion, in HCC patients, the SCCA antigen could represent a useful marker for the detection of micro-metastasis in the tissues and for large-scale screening of serum in patients at risk.     

Characterization of the pharmacologic profile of a standardized soy extract in the ovariectomized rat model of menopause: effects on bone, uterus, and lipid profile

OBJECTIVE: This study was aimed to assess the effect of a standardized soy extract (SSE, Soyselect) in the ovariectomized rat model of menopause. DESIGN: Ovariectomized rats were treated for 6 weeks with the soy extract (50 or 100 mg/kg/day - PO), vehicle (distilled water), or 17beta-estradiol (0.5 mg/kg/day - PO). Tissue-specific estrogen agonist effects were examined using the endpoints bone mineral density, biochemical parameters of bone turnover, modulation of cytokines involved in the bone remodeling, uterine weight, uterine histology, uterine hormone receptor status, and serum lipid level. RESULTS: The SSE produced a bone-sparing effect associated with a slowing down in the increased bone turnover observed after ovariectomy (as indicated by measurements of serum osteocalcin levels and excretion ratio of deoxypyridinoline); changes in serum interleukin-6 levels observed after SSE suggested that this bone-sparing effect could be partly attributed to the modulation of osteoclastogenesis induced by interleukin-6. Remarkably, organ weight data and histopathologic analysis did not show any stimulatory activity of the SSE on the uterus. Immunohistochemical analysis showed a significant down-regulation of estrogen receptor-alpha (ERalpha) in uterine epithelium after 17beta-estradiol treatment, but not after treatment with the SSE; no significant differences among groups were observed in ER-alpha uterine stromal levels. After treatment with 17beta-estradiol, estrogen receptor-beta (ER-beta) expression was not modulated in the stroma or epithelium, whereas the SSE induced an up-regulation of ER-beta stromal expression. Collectively, these results suggest that the lack of stimulatory activity on the uterine epithelium using soy treatment could be due to a negligible stimulatory activity on estrogen receptor-alpha and/or to the enhanced expression observed in stromal ER-beta, the latter being considered as a negative modulator of ERalpha-mediated uterine proliferation. 17beta-estradiol, but not the SSE, down-regulated uterine epithelial progesterone receptor (PR), compared with ovariectomized rats. In the stromal compartment, progesterone receptor expression was fully up-regulated by 17beta-estradiol treatment and, to a lesser extent, by SSE treatment. The minor increase in lipid levels induced by ovariectomy was not affected by SSE administration. Finally, the lack of stimulatory activity on uterus was also confirmed in an immature female rat model. CONCLUSIONS: The results of this study demonstrated that the tested extract has an interesting profile of tissue-specific response, in that it is efficacious in preventing experimental osteoporosis without causing stimulation in uterus at doses that are effective in bone.     

Thoracoscopic epicardial pulmonary vein ablation for lone paroxysmal atrial fibrillation.

Surgical treatment of atrial fibrillation recently gained new popularity since the introduction of different energy sources for ablative therapy as an alternative to the original "cut-and-sew" techniques. However, most of the cases have been performed together with other cardiac surgical procedures and mainly through a standard median sternotomy approach. We report here the first European case of closed-chest thoracoscopic pulmonary vein isolation in a patient with lone paroxysmal atrial fibrillation.     

Echocardiographic evaluation of left ventricular end-systolic elastance in the elderly

BACKGROUND: The aging heart is characterized by structural changes, which are implicated in the development of left ventricular diastolic dysfunction. However, important changes in systolic function may also occur. Left ventricular end-systolic elastance (E(es)) is a major determinant of cardiac systolic function and ventricular-arterial interaction. AIM: To evaluate left-ventricular E(es) in elderly subjects compared with adult control subjects. METHODS: We studied dilated (DA, n=14) and hypertensive (HA, n=21) cardiomyopathy patients, and both adult control (A, n=25; age 55.6+/-6.6 years) and elderly (E, n=25; age 76.3+/-7.1 years) subjects without clinical-instrumental evidence of cardiovascular disease. M-mode, two-dimensional, and pulsed Doppler echocardiogram were performed. Doppler-derived indices of diastolic function were assessed and E(es) was calculated by a modified single-beat method. RESULTS: E(es) was reduced in dilated cardiomyopathy (1.32+/-0.10 mm Hg/ml) and increased in hypertensive cardiomyopathy (3.12+/-0.33 mm Hg/ml) patients compared to age-matched control subjects (1.96+/-0.26 mm Hg/ml; p<0.01 and p<0.05, respectively). More importantly, E(es) was higher in the elderly (2.52+/-0.70 mm Hg/ml) than in the adult control group (p<0.05) and was linearly correlated with age (r2=0.639; p<0.0001). CONCLUSION: Age-related increase in E(es), together with diastolic dysfunction, may lead to aging heart decompensation.     

Dendritic cell recovery after allogeneic stem-cell transplantation in acute leukemia: correlations with clinical and transplant characteristics

We have analyzed the kinetics of reconstitution of circulating dendritic cell (DC) subsets (myeloid-DC1 and lymphoid-DC2) in 19 patients affected by acute leukemia undergoing allogeneic hematopoietic stem-cell transplantation (HSCT). We have found that pretransplant DC1 and DC2 were lower in leukemic patients than in healthy subjects (P = 0.003 and P = 0.004, respectively) and that the number of DC2 (but not DC1) infused with the graft was higher in patients receiving peripheral blood stem cells (PBSC) (P = 0.03). Patients recovered to the pretransplant DC1 and DC2 levels within day +60; however, a normal DC1 number was reached on day +365, while DC2 remained lower than in controls up to 1 yr after transplant. DC1 reconstitution did not differ significantly between patients receiving bone marrow stem cells (BMSC) or PBSC, while patients receiving PBSC presented increased levels of DC2 on day +30 (P = 0.008) and +100 (P = 0.047) and a higher number of T lymphocytes and natural killer cells until day +365. The occurrence of graft vs. host disease (GVHD) was not influenced in our cases by DC1/DC2 graft composition, but patients with acute GVHD when compared with patients without acute GVHD presented a significantly less rapid DC recovery (DC1 P = 0.03, DC2 P = 0.009 on day +30, and DC1 P = 0.012, DC2 P = 0.006 on day +100). At the moment of relapse, a decrease of DC1/DC2 numbers was observed in four patients and the presence of two different DC populations one with a normal karyotype, and the other with the same cytogenetic abnormality as the malignant clone was detected by fluorescence in situ hybridization analysis. In conclusion, these observations suggest that in allogeneic HSCT recipients, DC recovery is a slow process possibly contributing to the high risk of infections in the post-transplant period and is possibly influenced by the source of HSC, the occurrence of GVHD and relapse. Further studies are warranted to investigate the significance of DC reconstitution in the transplant setting.     

Calcium sulfate: analysis of MG63 osteoblast-like cell response by means of a microarray technology

Calcium sulfate (CaS) is an highly biocompatible material that has the characteristic of being one of the simplest as well as one of the synthetic bone-like graft with the longest clinical history, spanning more than 100 years. Solidified or crystallized CaS is very osteogenic in vivo. As the surface CaS dissolves in body fluid, the calcium ions form calcium phosphate that reprecipitates on the surface forming an osteoblast "friendly" environment. How this "friendly" environment alters osteoblast activity to promote bone formation is poorly understood. We therefore attempted to address this question by using microarray techniques to identified genes that are differently regulated in osteoblasts exposed to CaS. By using DNA microarrays containing 19,200 genes, we identified in osteoblast-like cells line (MG-63) cultured with CaS (Surgiplaster, Classimplant, Roma, Italy) several genes that expression was significantly upregulated. The differentially expressed genes cover a broad range of functional activities: (a) immunity, (b) lysosomal enzymes production, (c) cell cycle regulation, (d) and signaling transduction. It was also possible to detect some genes whose function is unknown. The data reported are, to our knowledge, the first genetic portrait of CaS effects. They can be relevant to better understand the molecular mechanism of bone regeneration and as a model for comparing other materials with similar clinical effects.