[Retrosternal Giant Aortic Aneurysm;Report of Two Cases].

This is a 2-case report of successful aortic repair surgery for the retrosternal giant aortic aneurysm. Our surgical strategy is "deep hypothermia and left ventricular( LV) unloading under cardiopulmonary bypass before approaching to the aortic aneurysm" in case of possible catastrophic bleeding. Case 1, a 64-year-old woman, had a retrosternal pseudoaneurysm (80 mm) at the distal anastomosis of a Dacron graft used to replace the ascending aorta 7 years before. An LV vent tube was cannulated via the right upper pulmonary vein through an inferior T-shaped ministernotomy. Case 2, an 86-year-old woman, had a retrosternal chronic aortic dissecting aneurysm (66 mm). An LV vent cannula was inserted via the LV apex through a left minithoracotomy. Arch replacement and ascending aorta replacement were performed in Case 1 and 2, respectively, without cardiac, neurological, or any other complications. This strategy is safe and useful in a case with complex aortic disease.

Delayed perforation occurring on the 24th day after endoscopic submucosal dissection for early gastric cancer.

Delayed perforation occurs after 0.5% of endoscopic submucosal dissection (ESD) procedures for early gastric cancer (EGC). This complication can occur within a few hours or days after ESD. There are few reports in the English literature concerning patients who developed delayed perforation after ESD for EGC. An 81-year-old woman was referred to the emergency department of our hospital on the 24th day after ESD because of abdominal pain. We diagnosed her with delayed perforation with peritonitis after ESD for EGC using computed tomography (CT) and esophagogastroduodenoscopy (EGD). We performed primary closure with interrupted sutures covered via pedicled omentoplasty. The patient was discharged 13 days after surgery without any postoperative complications. Delayed perforation is generally treated with conservative, surgical, or endoscopic methods. Several benefits of endoscopic clipping have been reported. However, in the present case, we performed emergency surgery while considering possible fatal complications, such as severe peritonitis. It is important to recognize delayed perforation in the differential diagnosis. The decision to perform surgery should be made after carefully considering the degree of perforation based on EGD, CT findings, and patient conditions.

Delivery of microRNA-146a with polyethylenimine nanoparticles inhibits renal fibrosis in vivo.

Renal fibrosis is the final common pathway leading to end-stage renal disease. Although microRNA (miR) was recently shown to be involved in the development of renal fibrosis, few studies have focused on the effects on renal fibrosis of exogenous miR delivered in an in vivo therapeutic setting. The study reported here investigated the effects of miR-146a delivery using polyethylenimine nanoparticles (PEI-NPs) on renal fibrosis in vivo. PEI-NPs bearing miR-146 or control-miR (nitrogen/phosphate ratio: 6) were injected into the tail vein of a mouse model of renal fibrosis induced by unilateral ureteral obstruction. PEI-NPs bearing miR-146 significantly enhanced miR-146a expression in the obstructed kidney compared with the control group, while inhibiting the renal fibrosis area, expression of alpha-smooth muscle actin, and infiltration of F4/80-positive macrophages into the obstructed kidney. In addition, PEI-NPs bearing miR-146a inhibited the transforming growth factor beta 1-Smad and tumor necrosis factor receptor-associated factor 6-nuclear factor kappa B signaling pathways. Control-miR-PEI-NPs did not show any of these effects. These results suggest that the delivery of miR-146a attenuated renal fibrosis by inhibiting pro-fibrotic and inflammatory signaling pathways and that the delivery of appropriate miRs may be a therapeutic option for preventing renal fibrosis in vivo.

The interaction of LFA-1 on mononuclear cells and ICAM-1 on tubular epithelial cells accelerates TGF-ß1-induced renal epithelial-mesenchymal transition.

The epithelial-mesenchymal transition (EMT) of renal epithelial cells (RTECs) has pivotal roles in the development of renal fibrosis. Although the interaction of lymphocyte function-associated antigen 1 (LFA-1) on leukocytes and its ligand, intracellular adhesion molecule 1 (ICAM-1), plays essential roles in most inflammatory reactions, its pathogenetic role in the EMT of RTECs remains to be clarified. In the present study, we investigated the effect of the interaction of LFA-1 on peripheral blood mononuclear cells (PBMCs) and ICAM-1 on HK-2 cells after stimulation with TGF-ß(1) on the EMT of RTECs. ICAM-1 was highly expressed in HK-2 cells. After TGF-ß(1) stimulation, the chemokines CCL3 and CXCL12 increased on HK-2 cells. After co-culture of PBMCs and HK-2 cells pre-stimulated with TGF-ß(1) (0.1 ng/ml) (HK-2-TGF-ß(1) (0.1)), the expression of the active form of LFA-1 increased on PBMCs; however, total LFA-1 expression did not change. The expression of the active form of LFA-1 on PBMCs did not increase after co-culture with not CCL3 but CXCL12 knockdown HK-2-TGF-ß(1) (0.1). The expression of epithelial cell junction markers (E-cadherin and occludin) further decreased and that of mesenchymal markers (vimentin and fibronectin) further increased in HK-2-TGF-ß(1) (0.1) after co-culture with PBMCs for 24 hrs (HK-2-TGF-ß(1) (0.1)-PBMCs). The phosphorylation of ERK 1/2 but not smad2 and smad3 increased in HK-2-TGF-ß(1) (0.1)-PBMCs. The snail and slug signaling did not increase HK-2-TGF-ß(1) (0.1)-PBMCs. Although the migration and invasion of HK-2 cells induced full EMT by a high dose (10.0 ng/ml) and long-term (72-96 hrs) TGF-ß(1) stimulation increased, that of HK-2-TGF-ß(1) (0.1)-PBMCs did not increase. These results suggested that HK-2 cells stimulated with TGF-ß(1) induced conformational activation of LFA-1 on PBMCs by increased CXCL12. Then, the direct interaction of LFA-1 on PBMCs and ICAM-1 on HK-2 cells activated ERK1/2 signaling to accelerate the part of EMT of HK-2 cells induced by TGF-ß(1).