High prevalence of abdominal aortic aneurysms in patients with lung cancer.

BACKGROUND: Lung cancer and abdominal aortic aneurysms (AAAs) possess multiple shared risk factors. Whereas both have screening guidelines in place, they vary in methodology despite having significant overlap in populations of patients screened. METHODS: Our hospital system's Lung Cancer Program database was used to identify patients diagnosed with primary lung cancer within the past 15 years. Demographic and risk factor data were obtained, and patients' original positron emission tomography-computed tomography scans were re-read for measurements of the abdominal aorta (aortic diameter ≥3.0 cm). A cancer-free control group was obtained for comparison. Multilinear regression modeling was used to evaluate the independent associations of multiple variables on the presence of AAA. RESULTS: Among 814 patients with primary lung cancer, 90 (11.1%; 95% confidence interval [CI], 8.9%-13.3%) had AAA compared with 4 of 200 (2%; 95% CI, 0.1%-3.9%) in the control group (P = .0001). Patients who smoked were more likely than nonsmokers to have AAA (11.9% [95% CI, 9.8-14.6] vs 2.2% [95% CI, 0.1-8.1]; P = .0021). In patients with AAA, 12% (11/90) had aneurysms that required treatment, and 76.6% had early-stage lung cancer. Women in our study also had a high prevalence of AAA (4.6%). Logistic regression analysis showed male sex (odds ratio [OR], 3.70; P <.001), increasing age (OR, 1.07 per year; P <.001), smoking amount (OR, 1.01 per pack-year; P = .004), and hypertension (OR, 2.30; P = .020) to be independent risk factors for AAA. CONCLUSIONS: Patients with lung cancer have a high prevalence of AAA. If future studies can demonstrate a reduction in AAA mortality by screening for AAA and lung cancer simultaneously, it may prove worthwhile to extend the low-dose computed tomography scan through the lower abdomen in select patients.

Development of In Vitro Bioengineered Vascular Grafts for Microsurgery and Vascular Surgery Applications.

INTRODUCTION: The use of vascular grafts is continuing to rise due to the increasing prevalence of coronary artery bypass grafting and microvascular flap-based tissue reconstructions. The current options of using native vessels (saphenous vein) or the synthetic grafts (Dacron) have been unable to manage current needs. In this study, we employed an original tissue engineering approach to develop a multi-layered vascular graft that has the potential to address some of the limitations of the existing grafts. MATERIALS AND METHODS: Biomaterials, gelatin and fibrin, were used to develop a two-layered vascular graft. The graft was seeded with endothelial cells and imaged using confocal microscopy. The graft's architecture and its mechanical properties were also characterized using histology, Scanning Electron Microscopy and rheological studies. RESULTS: Our methodology resulted in the development of a vascular graft with precise spatial localization of the two layers. The endothelial cells fully covered the lumen of the developed vascular graft, thus providing a non-thrombogenic surface. The elastic modulus of the biomaterials employed in this graft was found to be 5.186 KPa, paralleling that of internal mammary artery. The burst pressure of this graft was also measured and was found close to that of the saphenous vein (~2000 mm Hg). CONCLUSIONS: We were successfully able to employ a unique method to synthesize a multi-layered vascularized graft having adequate biological and mechanical properties. Studies are ongoing involving implantation of this developed vascular graft in the rat femoral artery and characterization of parameters such as vascular remodeling and patency.

The Effect of IL-26 on TNF-α-Induced CXCL8 Responses by Colonic Epithelial Cell Lines.

Th17 cells of the intestine and colon can produce several important cytokines during mucosal inflammation. However, few studies have focused on the role of IL-26 in intestinal inflammations. Colonic epithelial cells express receptors for IL-26, and this cytokine has been shown to induce the HT-29 colonic epithelial cell line to produce the chemokine CXCL8. However, epithelial cells would function in a cytokine network environment during mucosal inflammation and any effect of IL-26 on colonic epithelial cell chemokine responses could be affected by the presence of other potent pro-inflammatory cytokines like TNF-α and IL-1. Therefore, we investigated the effect of IL-26 with TNF-α or IL-1 on colonic epithelial cell line secretion of CXCL8. IL-26 alone had no effect on HT-29 or DLD1 cell line CXCL8 secretion. Yet, IL-26 was found to significantly enhance TNF-α-induced, but not IL-1-induced, CXCL8 secretion, but only at high levels of TNF-α. Similar results were seen with DLD1 cells. IL-26 did not enhance TNF-α-induced CXCL8 mRNA levels and did not affect TNF-α-induced IκBα phosphorylation or degradation. However, signaling through ERK and p38 MAPK were determined to be involved in the enhancing effect of IL-26 on the TNF-α-induced CXCL8 secretion, perhaps through known post-translational effects. These results suggest that the role of IL-26 in intestinal inflammation may be limited to enhancing CXCL8 secretion in the presence high levels of TNF-α, such as may occur in inflammatory bowel disease. Abbreviations: DMEM, Dulbecco's Modified Eagle's Medium; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IBD, inflammatory bowel disease; IL, interleukin; ITS, insulin, transferrin, selenium; TBS, Tris buffered saline; TNF, tumor necrosis factor.

IL-22 Enhances TNF-α- and IL-1-Induced CXCL8 Responses by Intestinal Epithelial Cell Lines.

IL-22 is known to induce intestinal epithelial cells (IECs) to produce the chemokine CXCL8. However, IECs exist in a cytokine network during mucosal inflammation, such that IL-22 must act in concert with potent pro-inflammatory cytokines like TNF-α and IL-1. Our studies show that IL-22 alone increased CXCL8 secretion from HT-29 cells, but the levels were minimal compared to that of the cells treated with TNF-α or IL-1 only. More significantly, co-stimulation with IL-22 and TNF-α enhanced both CXCL8 secretion and mRNA levels well over that of TNF-α stimulation alone. A similar enhancing effect was seen with IL-22- and IL-1-stimulated CXCL8 secretion. The enhancing effect of IL-22 on TNF-α-induced CXCL8 secretion was then determined to require the p38 MAPK, but not STAT1/3, PI3K, Akt, c-Jun N-terminal kinase, ERK, or IκBα. These experiments indicate that more significant effect of IL-22 on IECs responses may not be in inducing CXCL8 by itself, but in enhancing TNF-α- and IL-1-induced CXCL8 secretion to augment the contribution of IECs to local inflammatory responses.