LADG seems to be safe and effective even for elderly patients, and their prognosis was satisfactory. However, careful monitoring for cardiovascular and pulmonary disease should be observed during the follow-up period.

Of these 51 patients, 21 (41.1%) had systemic disorders, including 4 (7.8%) with malignant diseases. Six patients (11.8%) had deep vein thrombosis (DVT) and five (9.8%) had pulmonary embolism (PE). All of the patients with DVT and/or PE had a thrombus in either the greater saphenous vein or the lesser saphenous vein; however, none of the patients with STP and a thrombus in the distal saphenous branch had either DVT or PE. The levels of coagulofibrinolytic markers such as fibrin degradation product-D dimer, plasmin alpha plasmin inhibitor complex, and thrombin antithrombin III complex were elevated in patients with STP or DVT, compared with those with varicose veins only. The level of C-reactive protein (CRP) was also elevated in the patients with STP or DVT. These findings indicate that STP is not necessarily a localized disease, but may be a symptom of systemic disease. In addition to duplex scanning, the measurement of coagulofibrinolytic markers as well as CRP may be useful for detecting STP and/ or DVT prior to the treatment of varicose veins.

2019) Chloride intracellular channel protein 2 in cancer and noncancer human tissues: relationship with tight junctions, Tissue Barriers, 7:1, 1593775, ABSTRACT Chloride intracellular channel protein 2 (CLIC2) belongs to the CLIC family of conserved metazoan proteins. Although CLICs have been identified as chloride channels, they are currently considered multifunctional proteins. CLIC2 is the least studied family member. We investigated CLIC2 expression and localization in human hepatocellular carcinoma, metastatic colorectal cancer in the liver, and colorectal cancer. Significant expression of mRNAs encoding CLIC1, 2, 4, and 5 were found in the human tissues, but only CLIC2 was predominantly expressed in non-cancer tissues surrounding cancer masses. Fibrotic or dysfunctional (aspartate aminotransferase ≥40) non-cancer liver tissues and advanced stage HCC tissues expressed low levels of CLIC2. Endothelial cells lining blood vessels but not lymphatic vessels in non-cancer tissues expressed CLIC2 as well as high levels of the tight junction proteins claudins 1 and 5, occludin, and ZO-1. Most endothelial cells in blood vessels in cancer tissues had very low expressions of CLIC2 and tight junction proteins. CD31 + /CD45 − endothelial cells isolated from non-cancer tissues expressed mRNAs encoding CLIC2, claudin 1, occludin and ZO-1, while similar cell fractions from cancer tissues had very low expressions of these molecules. Knockdown of CLIC2 expression in human umbilical vein endothelial cells (HUVECs) allowed human cancer cells to transmigrate through a HUVEC monolayer. These results suggest that CLIC2 may be involved in the formation and/or maintenance of tight junctions and that cancer tissue vasculature lacks CLIC2 and tight junctions, which allows the intravasation of cancer cells necessary for hematogenous metastasis. ARTICLE HISTORY

Angiogenesis, the formation of new blood vessels, is involved in a variety of diseases including the tumor growth. In response to various angiogenic stimulations, a number of proteins on the surface of vascular endothelial cells are activated to coordinate cell proliferation, migration, and spreading processes to form new blood vessels. Plasma membrane localization of these angiogenic proteins, which include vascular endothelial growth factor receptors and integrins, are warranted by intracellular membrane trafficking. Here, by using a siRNA library, we screened for the sorting nexin family that regulates intracellular trafficking and identified sorting nexin 9 (SNX9) as a novel angiogenic factor in human umbilical vein endothelial cells (HUVECs). SNX9 was essential for cell spreading on the Matrigel, and tube formation that mimics in vivo angiogenesis in HUVECs. SNX9 depletion significantly delayed the recycling of integrin β1, an essential adhesion molecule for angiogenesis, and reduced the surface levels of integrin β1 in HUVECs. Clinically, we showed that SNX9 protein was highly expressed in tumor endothelial cells of human colorectal cancer tissues. High‐level expression of SNX9 messenger RNA significantly correlated with poor prognosis of the patients with colorectal cancer. These results suggest that SNX9 is an angiogenic factor and provide a novel target for the development of new antiangiogenic drugs.

Pancreatic enzymes in the ischemic intestine are involved in the production of in vivo inflammatory mediators. These mediators stimulate cells in the cardiovascular system during shock and initiate multiorgan failure. An important aspect that controls the extent of the inflammation is the dispersion of these mediators from the ischemic intestine. In the past, two pathways for dispersion of these inflammatory mediators have been identified, absorption into the intestinal venous circulation and uptake into the lymphatics. We hypothesize here that the inflammatory mediators produced by pancreatic digestive enzymes in the lumen of the intestine may also be released directly into the peritoneal space. To assess the presence of inflammatory mediators in the peritoneal cavity in response to splanchnic arterial occlusion (90 min) and reperfusion (SAO shock), we measured the ability of fluid collected from this cavity to activate naive donor granulocytes. After SAO in control rats, peritoneal lavage fluid caused activation of naive donor granulocytes when tested in vitro. In contrast, when the lumen of the small intestine was flushed with a broad-acting pancreatic enzyme inhibitor (6-amidino-2-naphtyl p-guanidinobenzoate dimethanesulfate), the fluid no longer caused leukocyte activation. Reduction of the levels of inflammatory mediators in the peritoneal fluid was associated with an attenuation in the fall of blood pressure after SAO shock. These results indicate that the inflammatory mediators, which are produced by pancreatic digestive enzymes, can be absorbed directly into the systemic circulation via a transperitoneal route and play a part in the development of multiorgan failure.