Vascular Thrombus Research Articles

Factor Xa Inhibitor Attenuates Leukocyte Adhesion and Thrombus Formation in an Experimental Mouse Model of the Metabolic Syndrome

In a model of acute inflammation, Factor Xa inhibitors have been reported not only to suppress the coagulation system but also to exert anti-inflammatory effects. However, this has not been experimentally demonstrated in a model of chronic inflammation. Recent studies demonstrated that vascular inflammation in the metabolic syndrome plays major roles in the development of thrombotic diseases. Therefore, we examined the anti-inflammatory effects of fondaparinux, a Factor Xa inhibitor, in a mouse model of the metabolic syndrome, looking at both leukocyte adhesion on the vascular endothelium and thrombus formation. Following clamping of the mesenteric vein for 20 min in the KK-A(y) mouse, mice were administered by subcutaneous injection either low-dose or high-dose fondaparinux or placebo (n = 10 in each group. Microscopic observation of the intestinal microcirculation was carried out. In another series, blood samples were taken and measured for blood cell counts and organ damage markers (n = 6 in each). Both leukocyte adherence and thrombus formation were inhibited by treatment with fondaparinux. Red blood cell and white blood cell counts were maintained better in high-dose group. Levels of alanine aminotransferase (ALT) were significantly reduced in both low-dose and high-dose groups (P < 0.05 and 0.01, compared with control, respectively). Factor Xa inhibitor attenuates leukocyte adhesion and leukocyte-platelet conjugate formation in a mouse model of the metabolic syndrome. These effects appeared to be related to both inhibition of thrombus formation and reduction in markers of organ damage.

Cigarette smoking induces vascular damage of both conduit arteries and small vessels and persistent elevation of plasma serotonin unresponsive to 8 weeks of smoking cessation

Purpose: Cigarette smoking is one of the major risk factors of cardiovascular diseases and induces deleterious vascular damages. Whereas serotonin released to plasma upon platelet activation modulates vascular tonus and thrombus formation. The purpose of this study was to examine the plasma levels of serotonin in habitual cigarette smokers and the kinetics of plasma serotonin after smoking cessation, and their association with endothelial function. Methods: In study 1, clinical profiles including endothelial function were compared between apparently healthy male smokers (n=27, 40±8 years) and age-adjusted non-smokers (n=21, 40±7 years). In study 2, smokers were instructed to stop smoking and clinical profiles and laboratory findings including serum level of cotinine, principal metabolite of nicotine, were investigated before and after 8 weeks of smoking cessation. Strict precautions were taken to obtain platelet poor plasma (PPP). Serotonin levels in PPP were measured by HPLC. Endothelial function was assessed by 2 distinct techniques, namely flow-mediated dilation (FMD) using ultrasound system for conduit arteries and peripheral arterial tonometry (PAT) using End-PAT 2000 for peripheral small vessels. Results: In Study 1, levels of PPP serotonin and serotonin corrected by platelets number (serotonin/plt) in smokers were higher than those in non-smokers (6.90±2.91 vs 4.60±2.32 nmol/L, P<0.01; and 31.3±16.6 vs 20.6±11.9 x10-9 pmol/plt, P<0.05; respectively), and FMD in smokers was lower than that in non-smokers (3.12±1.15 vs 4.11±1.93%, P<0.05). In study 2, serotonin/plt in PPP (33.5±19.4 x10-9 pmol/plt) correlated positively with serum level of cotinine (152±140 ng/ml, r=0.45, P<0.05) and inversely with HDL cholesterol (61±16 mg/dl, r=-0.46, P<0.05) and PAT ratio (0.25±0.10, r=-0.45, P<0.05). Smokers who completely attained smoking cessation indicated significantly increased PAT ratio (P<0.05) although serotonin and serotonin/plt in PPP were not significantly changed. Conclusions: Cigarette smoking is associated with increase of plasma serotonin and impaired endothelial function in middle-aged healthy subjects. Moreover, the change was unresponsive to 8 weeks of smoking cessation, suggesting that caution should be taken during plasma serotonin levels are not decreased even after improvement of endothelial function.

Sputum Plasminogen Activator Inhibitor-1 Elevation by Oxidative Stress-Dependent Nuclear Factor-κB Activation in COPD

Plasminogen activator inhibitor-1 (PAI-1) is an important regulator of fibrinolysis at sites of vascular injury and thrombus formation. Recently, sputum PAI-1 was reported to be elevated in COPD. However, the mechanism of PAI-1 elevation in COPD has yet to be clarified. Here, we show that PAI-1 elevation in COPD is closely associated with oxidative stress-induced nuclear factor κB (NF-κB) activation. Patients and control subjects were recruited from the outpatient department of Royal Brompton Hospital, local general practice, and the National Heart and Lung Institute. Sputum samples were obtained, and sputum sample processing was performed to obtain sputum supernatants and sputum macrophages. The mean PAI-1 level in COPD sputum (1.92 ± 3.11 ng/mL, n = 32) was higher than that of both age-matched smokers without COPD (0.48 ± 0.63 ng/mL, n = 11) and healthy nonsmokers (0.55 ± 1.11 ng/mL, n = 9). Sputum PAI-1 significantly correlated with sputum malondialdehyde (MDA) in COPD (r = 0.59, P &lt; .001). In addition, NF-κB activity in sputum macrophages (three control and seven COPD subjects) significantly correlated with both sputum PAI-1 (r = 0.72, P &lt; .05) and sputum MDA (r = 0.78, P &lt; .01). An in vitro study showed that both hydrogen peroxide and cigarette smoke-conditioned medium induced PAI-1 production in A549 cells, and the production was inhibited by an inhibitor of I κB kinase-β in a concentration-dependent manner. Furthermore, histone deacetylase 2 (HDAC2) knockdown by RNA interference, a mimic of oxidative-stress-dependent HDAC2 reduction, enhanced tumor necrosis factor-α-induced PAI-1 induction (half maximal effective concentration [EC50], 0.64 ± 0.19 ng/mL in HDAC2-KD, 7.64 ± 3.70 ng/mL in control) concomitant with enhancement of NF-κB p65 acetylation and NF-κB DNA-binding activity. Oxidative stress, directly or indirectly via HDAC reduction, plays a role in PAI-1 expression in COPD via activation of NF- κ B.

Analysis of lymph node dissection range-related factors for early gastric cancer operation.

The purpose of comprehensive treatment for early gastric cancer (EGC) is curing tumor, prevention of recurrence or metastasis. The aim of the present study was to analyze the clinical pathological characteristics of EGC, and to find out factors which influence lymph node metastasis. Records of 417 patients with EGC who underwent surgery from January 1996 to December 2006 were collected. The information including general characteristics, tumor relevant factors, surgical complications, clinical manifestations and pathological features, were evaluated. EGC accounted for 6.03% of total gastric cancer (GC) cases. In EGC subjects, mucosal cancer and sub-mucosal cancer accounted for 55.2% and 44.8%, respectively; 11.5% (48/417) of patients were found with positive lymph nodes metastasis, the incidence of lymph node metastasis was 5.64% (168/2979); 6 cases were found with liver metastasis; 96.64% of patients undertook radical surgical treatment; 5 cases with positive upper incisal margin (1.2%). Logistic regression analysis showed that multiple original tumors, lesions of over 2cm, tumor invasion to the submucosa, poor differentiation, and vascular tumor thrombus, were independent risk factors for lymph node metastasis in EGC. The risk factors of lymph node metastasis should be noticed and evaluated in EGC treatment.

Anti-thrombotic Effects of Modified using a FeCl-induced Carotid Arterial Thrombosis Model

Objectives: The aim of this study was to examine the antithrombotic effects of the four herbal ingredients (Mume Fructus, MF; Santali Albi Lignum, SAL; Amomi Tsao-Ko Fructus, ATF; and Amomi Fructus, AF) of modified Jeho-tang (MJHT) in a ferric chloride (FeCl₃)-induced carotid arterial thrombosis model. Methods: Thirty minutes prior to a 35% FeCl₃ application, Sprague-Dawley (SD) rats were injected with saline, MF, SAL, ATF or AF (100 mg/kg, intraperitoneal injection), respectively. The effect of the MJHT ingredients was examined for time to occlusion (TTO) and thrombus weight (TW) in a FeCl₃-induced thrombosis model. Histological analysis was performed to examine the effect of the MJHT ingredients on collagen fiber damage using hematoxylin & eosin and Masson’s trichrome staining. Results: Compared with vehicle treatment, MF, SAL and ATF treatment delayed TTO (vehicle, 8.11 ± 0.60 min; MF, 16.67 ± 1.03 min; SAL, 17.50 ± 1.52 min and ATF, 13.33 ± 1.21 min; P Conclusions: Altogether, these results are the first evidence that the MJHT ingredients MF, SAL and ATF have the ability to prevent vascular damage and thrombus formation in FeCl₃-induced carotid arterial thrombosis.

A popliteal artery entrapment syndrome after by-pass surgery.

A 36-year-old male was admitted to our radiology department with a presentation of claudication on the left side for two weeks after femoral artery to tibial artery by-pass surgery. Upon physical examination, the left leg appeared pale and cold. Left magnetic resonance angiography (MRA) with gadolinium was performed from the superficial femoral arteries through the proximal portion of the popliteal fossa. The images included the bilateral popliteal arteries during dorsiflexion, plantar extension and neutral positions. There appeared to be a left venous graft that was patent. It arose from the proximal popliteal artery and traveled to the anterior tibial artery. The graft was patent at the visualized aspect. There appeared to be a mild to moderate degree of stenosis of the popliteal artery in the neutral position. There was severe stenosis of the same segment of the popliteal artery during knee extension. The popliteal artery was compressed by the slip of the medial head of the gastrocnemius, which arose more laterally than normal (Figure 1 A–C). Figure 1. 3D gadolinium-enhanced MRA images reveal the mild degree of stenosis of the popliteal artery in the neutral and dorsiflexion positions (A, B); there is severe stenosis of the same segment of the popliteal artery in the extension position (C). These images ... Popliteal artery entrapment syndrome (PAES) is a rare congenital vascular pathology caused by a compression of the popliteal artery by adjacent muscle and tendon structures. This condition is most commonly observed in young men with ischemic symptoms of the lower extremities. Extrinsic arterial compression causes chronic vascular micro trauma, early arteriosclerosis and thrombus formation, leading to distal ischemia [1, 2]. The classic presentation, which includes calf or foot claudication or pain on exertion, can have many other etiologies, including atherosclerosis, exertional compartment syndrome, and other musculoskeletal or neurogenic disorders. The most commonly used classification of PAES was described by Love and Whalen [3]. Our case had type III PAES. The incidence of popliteal entrapment has been described to be between 0.165% and 3.5% [2, 4]. Noninvasive tests, such as duplex ultrasound and axial imaging, including multi detector computed tomography angiography (MDCTA) or MRA, can help identify the anatomical abnormalities [1, 4]. In conclusion, MRA MDCTA is a safe, rapid, and noninvasive diagnostic imaging technique that enables clinicians to determine the underlying pathology and the complications of PAES.

Abstract 3854: Novel hematopoietic neoplasms in prkar2a- deficient mice.

Abstract Background: Histiocytic sarcoma (HS) is an aggressive hematological neoplasm that responds poorly to therapy. The molecular etiology and pathology of this disease remain unclear, hampering the development of an effective therapy. Therefore, a need for more, and more realistic, animal models remains. Lymphoproliferative disorders have been reported in mice deficient for the prkar1a gene coding for the regulatory subunit type 1A of protein kinase A (PKA), but nothing is known about the role of type II PKA regulatory subunits in hematologic malignancies. Methods: Mice deficient for the Prkar1a and Prkar2a alleles were previously reported (Kirschner et al, 2005 και Burton et al, 1997) and were kept on a mixed genetic background (C57BL/129Sv). Mice were crossed to create prkar2a+/- and prkar2a-/-. Mice were phenotyped at the ages of 3-6-9-12-18 months or when they exhibited signs of advanced disease. Tissues were collected for histological and molecular analysis. Results: Unexpectedly, mice deficient for the prkar2a allele(s) developed lymphomas, with significant higher incidence compared to the prkar1a+/- mice [8/13 (61.5%) of the prkar2a+/- and 5/8 (62.5%) of the prkar2a-/- vs. 3/21(14.2%) of the prkar1a+/-, Fisher's exact test p=0.02]. Histology studies of sections stained with H&amp;E revealed a variety of pathologic changes in lymphoid and non-lymphoid tissues. Lesions characteristic of histiocytic sarcoma (HS) were found in spleen and abdominal lymph nodes, sometimes associated with leukemic infiltrates in lung and bone marrow (BM). Abnormal megakaryopoiesis in spleen and BM was associated with cells actively phagocytosing red cells, others with a pseudo Gaucher-like appearance and increased immature forms. Erythropoiesis was reduced in BM and spleen. Vascular thrombi were associated with schistocytosis. Accumulations of mostly mature plasma cells and some plasmablasts were present in the splenic red pulp together with large, active germinal centers. Cells with characteristics of diffuse large B cell lymphoma often occupied expanded splenic follicles and lymph nodes. Kidneys exhibited degenerative changes in glomeruli and tubules. Median age at presentation was 18 months (range 16-25 months). FACS analysis of BM cells revealed a decrease in late pro-B cells in the prkar2a deficient mice compared to the wild-type, indicating a developmental block at this stage of early B cell differentiation. Interestingly, Southern blot analysis of these B cell lymphomas showed that in most cases they were monoclonal with either one or both IgH alleles rearranged. Conclusions: Our data indicate that PRKAR2a may be involved in the development of malignant lesions of the hematologic lineage. The presented mouse model can be used to gain insights into the molecular and cellular origins of this rare neoplasm and provide a preclinical model in which to test novel therapeutic strategies. Citation Format: Emmanouil Saloustros, Paraskevi Salpea, Lina Gugglioti, Kittman Tsang, Anelia Horvath, Maria Nesterova, Chen-Feng Qi, Herbert C. Morse III, Constantine A. Stratakis. Novel hematopoietic neoplasms in prkar2a- deficient mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3854. doi:10.1158/1538-7445.AM2013-3854

Real-time Imaging of Heterotypic Platelet-neutrophil Interactions on the Activated Endothelium During Vascular Inflammation and Thrombus Formation in Live Mice

Real-time Imaging of Heterotypic Platelet-neutrophil Interactions on the Activated Endothelium During Vascular Inflammation and Thrombus Formation in Live Mice

Real-time Imaging of Heterotypic Platelet-neutrophil Interactions on the Activated Endothelium During Vascular Inflammation and Thrombus Formation in Live Mice

Interaction of activated platelets and leukocytes (mainly neutrophils) on the activated endothelium mediates thrombosis and vascular inflammation. During thrombus formation at the site of arteriolar injury, platelets adherent to the activated endothelium and subendothelial matrix proteins support neutrophil rolling and adhesion. Conversely, under venular inflammatory conditions, neutrophils adherent to the activated endothelium can support adhesion and accumulation of circulating platelets. Heterotypic platelet-neutrophil aggregation requires sequential processes by the specific receptor-counter receptor interactions between cells. It is known that activated endothelial cells release adhesion molecules such as von Willebrand factor, thereby initiating platelet adhesion and accumulation under high shear conditions. Also, activated endothelial cells support neutrophil rolling and adhesion by expressing selectins and intercellular adhesion molecule-1 (ICAM-1), respectively, under low shear conditions. Platelet P-selectin interacts with neutrophils through P-selectin glycoprotein ligand-1 (PSGL-1), thereby inducing activation of neutrophil β2 integrins and firm adhesion between two cell types. Despite the advances in in vitro experiments in which heterotypic platelet-neutrophil interactions are determined in whole blood or isolated cells, those studies cannot manipulate oxidant stress conditions during vascular disease. In this report, using fluorescently-labeled, specific antibodies against a mouse platelet and neutrophil marker, we describe a detailed intravital microscopic protocol to monitor heterotypic interactions of platelets and neutrophils on the activated endothelium during TNF-α-induced inflammation or following laser-induced injury in cremaster muscle microvessels of live mice.

Radiotherapy for Hepatocellular Carcinoma With Tumor Vascular Thrombus: Ready for Prime Time?

Radiotherapy for Hepatocellular Carcinoma With Tumor Vascular Thrombus: Ready for Prime Time?

Wilms Tumor With Renal Vein Tumor Thrombus Treated With Only 3-port Retroperitoneal Laparoscopic Technique

Wilms tumor is the most common malignant renal tumor in childhood, but it is rarely associated with a vascular tumor thrombus. We present a case of Wilms tumor with renal vein tumor thrombus treated with only a 3-port retroperitoneal laparoscopic technique in a 10-year-old girl. The patient was alive at the 12-month follow-up examination with adjuvant chemotherapy. To our knowledge, we present the first case of Wilms tumor with renal vein tumor thrombus treated with pure retroperitoneal laparoscopic management. Our technique can be recommended owing to the benefitsof the superior recovery profile, a safer surgical route, and cosmetically more acceptable incisions.

Analysis of the relationship between clinicopathological factors and lymph node matastasis of pancreatic adenocarcinoma

To investigate retrospectively the relationship between clinicopathological factors and lymph node matastasis of pancreatic adenocarcinoma. The clinicopathological factors, including gender, age, preoperative CA-19-9 level etc. of 71 patients with pancreatic adenocarcinoma were summarized to analyze the relationship between those factors and lymph node matastasis. Among the 71 cases, there were 49 males (69.0%) and 22 females (31.0%). Forty-eight were ≥ 60 (67.6%) and 23 were < 60 (32.4%) years old. Twenty patients had normal preoperative CA-19-9 level (28.2%) and 51 had elevated level (71.8%). The tumor in 43 (60.6%) cases located in the pancreatic head and neck, and 28 (39.4%) in the body and tail. The tumors in 8 patients were well-differentiated (11.3%), 27 were moderately differentiated (38.0%), and 36 were poorly differentiated (50.7%). The maximum diameter of the tumor was ≤ 2 cm in 11 cases (15.5%), 2 - 5 cm in 45 cases (63.4%), and > 5 cm in 15 cases (21.1%). Ten patients had tumor confined to the pancreas (14.1%), and 61 invaded peripancreatic tissues (85.9%). Vascular tumor thrombus was found in 48 cases (67.6%), and 23 cases were absent (32.4%). Thirty-six cases had lymph node matastasis (50.7%). Univariate chi-square test revealed that differentiation and range of local infiltration were significantly associated with lymph node meatstasis (P < 0.05). Multivariate logistic regression analysis also showed that differentiation and range of local infiltration were significantly associated with lymph node meatstasis (P < 0.05). The differentiation of tumor and range of local infiltration of pancreatic adenocarcinoma are significantly associated with lymph node metastasis. There is no significant relationship of location of the tumor, maximum diameter, presence or absence of vascular tumor thrombus with lymph node metastasis. Therefore, special attention should be paid to lymph node dissection in cases with a poorly differentiated pancreatic adenocarcinoma invading into peripancreatic tissues.

FHIT and RASSF1A promoter hypermethylation in plasma and tumor tissues from patients with hepatocellular carcinoma

Objective To detect aberrant methylation in the promoter of FHIT and RASSFIA genes in peripheral plasma and tumor tissues from patients with hepatocellular carcinoma （HCC） and to determine its clinical significance. Methods The methylation status of FHIT and RASSFIA genes in peripheral plasma and tumor tissues from 36 patients with HCC were detected by methylation-spe- cific polymerase chain reaction（MSP）. The correlation between methylation status in plasma and clini- copathological features was analyzed. Results The frequency of promoter methylation of FHIT in tis- sues was 75% （27/36） and in plasma 52.8% （19/36）, and the correlation coefficient was r=0. 482 （P= 0. 003）. The frequency of promoter methylation of RASSFIA in tumor tissues was 83.3% （30/36） and in plasma 61.1% （22/36）, and the correlation coefficient was r=0. 561 （P=0. 0004）. Aberrant methylation of FHIT, RASSFIA gene in the plasma and tissues had no correlation with the patients＇ clinicopathological features such as gender, age, HBV/HCV infection, hepatic cirrhosis, tumor size, alpha-fetoprotein （AFP） level, pathological grade, staging, vascular tumour thrombus and recurrence. The sensitivity of AFP ≥400 μg/L was 44. 4%, and AFP ≥20 μg/L 69.4M. The sensitivity of FHIT and RASSF1A gene promoter hypermethylation in 36 HCC patients was 72.2%. In 20 patients whose AFP 〈400 μg/L, the frequency of hypermethylation of the two genes together was 80%. When AFP 〈20 μg/L, the frequency of hypermethylation of the two genes together was54.50%. Conclusions There was a significant concordance between plasma and tumor tissue methyla tion profiles. The methylation status in plasma and tumor tissues had no correlation with the patients clinicopathological features. Combining promoter methylation of FHIT and RASSF1A genes was supe riot to AFP in the diagnosis of HCC. Key words: Hepatocellular carcimona; Methylation; Tumor tissue; Plasma

TREATMENT OF VASCULITIS AND DERMATITIS IN A 59-YR-OLD NILE HIPPOPOTAMUS (HIPPOPOTAMUS AMPHIBIUS)

A 59-yr-old female Nile hippopotamus (Hippopotamus amphibius) was diagnosed and treated for severe dermatitis. Lesions included large areas of depigmentation, erosions, and ulcerations on glabrous skin areas, limbs, and perineal region. Histopathologic lesions included a markedly edematous, focally eroded, ulcerative to necrotic epidermis; foci of keratinocyte apoptosis; and a mixed suppurative dermatitis. Most of the dermal vessels had variable hyalinized walls with plump endothelial cells and frequent intramural neutrophils, and some vessels had vascular thrombi consistent with vasculitis. Culture of the lesions yielded beta-hemolytic Streptococcus, Morganella morgannii, and Enterococcus sp. The hippopotamus was successfully treated with sulfamethoxazole and trimethoprim, amoxicillin, and pentoxifylline for more than 2 mo, and the condition did not recur over the subsequent 16 mo.

Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

Stereotactic body radiotherapy (SBRT), in which highly conformal potent radiation doses are delivered in fewer fractions than traditional radiation therapy (RT), is an increasingly popular treatment for hepatocellular carcinoma (HCC). The great majority of HCCs smaller than 6 cm and with Child-Pugh A liver function are controlled with SBRT with limited toxicity. Long-term local control is reduced in larger tumors, and toxicity is increased in patients with Child-Pugh B or C liver function. SBRT is an effective treatment for tumor vascular thrombi and can lead to sustained vascular recanalization. The first site of recurrence following SBRT is most often within the liver, away from the high dose volume, providing rationale for combining SBRT with regional or systemic therapies. Randomized trials of SBRT are warranted.

ULTRASONOGRAPHIC IDENTIFICATION OF VASCULAR INVASION BY ADRENAL TUMORS IN DOGS

Adrenalectomy is the treatment of choice for adrenal tumors that are producing adverse clinical signs. Surgical planning prior to adrenalectomy is aided by identifying tumors with invasion into adjacent vessels or the presence of a tumor thrombus extending into the caudal vena cava. In this paper, we evaluated the sensitivity and specificity of ultrasound in determining if vascular invasion or tumor thrombus is present. Thirty-four dogs with 36 adrenal tumors were reviewed retrospectively. Overall, 36% of tumors had vascular invasion. Abdominal ultrasound was 100% sensitive and 96% specific in identifying the presence of a tumor thrombus in the caudal vena cava. The sensitivity and specificity was 76% and 96%, respectively, when all forms of vascular invasion were evaluated and included patients with vascular wall invasion without concurrent thrombus. Abdominal ultrasound is a good screening tool for identifying vascular invasion or tumor thrombus associated with adrenal tumors in dogs.

Edge Effect From Drug-Eluting Stents as Assessed With Serial Intravascular Ultrasound

Several studies have demonstrated effective reduction of intimal hyperplasia within a drug-eluting stent (DES) when compared with a bare metal stent (BMS), thereby resulting in a lower incidence of target lesion revascularization.1–3 Restenosis at the stent edges, however, is not appreciably reduced by DES. Thus, to understand stent edge effect in DES, it is important to improve the efficacy of this technology. The concern that stent edge effects alter intimal hyperplasia in the stent but not at the edges has existed for many years, and often is described as the “candy wrapper phenomenon.” This phenomenon was first described in radioactive stents4,5 and is due to local inhibition of intimal growth and endothelial healing6 only within the stent. Many DES trials, therefore, sought to better understand the edge effect using intravascular ultrasound (IVUS) to assess the vessel response post stent implantation. Many studies have documented DES edge effect in older- and newer-generation DES. One challenge facing IVUS studies that assess DES edge effect is a high degree of patient-to-patient variability, along with potential variability among the different DES types. Because of these variables and the relatively small size of most sequential IVUS studies, there is no general consensus regarding stent edge effect in DES. We therefore reviewed the literature to find common findings and tendency. This review focused on 4 DES types approved by the United States Food and Drug Administration: the Cypher sirolimus-eluting stent (SES) (Cordis), the Taxus paclitaxel-eluting stent (PES) (Boston Scientific), the Endeavor zotarolimus-eluting stent (ZES) (Medtronic CardioVascular Inc.), and the XIENCE V everolimus-eluting stent (EES) (Abbott Vascular). ### Mechanical Edge Effect Post Stent Implantation Edge stenosis can occur from several different mechanisms: a vascular response from peri-stent vascular injury, plaque shift, and thrombus or hematoma formation post stent implantation. Before discussing DES and the impact of adding …

A efficacy analysis of intensity-modulated radiotherapy or three-dimensional conformal radiotherapy for resected thoracic esophageal squamous cell carcinoma

Objective To analyze retrospectively the clinical therapeutic effect and toxicities of three-dimensional conformal radiotherapy ( 3DCRT) or intensity modulated radiotherapy ( IMRT) for resected stage Ⅱ/Ⅲ thoracic esophageal squamous cell carcinoma ( TESCC). Methods A total of 251patients with resected TESCC underwent 3DCRT or IMRT at the Cancer Hospital ( Institute) , Chinese Academy of Medical Sciences between 2004. 1 t0 2009. 7 enrolled. Postoperative radiotherapy applied via 3DCRT ( 20 patients) or IMRT (231 patients) with a median total dose of 60 Gy. The Kaplan-Meier methodwas used to calculate the survival rates, and the log-rank test was used for univariate analysis. The Cox proportional model was used for multivariate analysis. Results The follow-up rate was 98. 8％ . 159 and 57 patients were followed t0 3 and 5 years, respectively. The 1-, 3-and 5-year overall survival ( OS) rates for all the patients were 90. 8％ , 56. 1％ and 45. 8％ , respectively. For the stage Ⅱa, Ⅱb, and Ⅲ stage patients , the 5-year OS rates were 65. 0％ , 53. 8％ and 38. 4％ , respectively ( X2 = 7. 30 , P = 0. 026) . The 5-year OS rates were 64. 9％ and 40. 4％ for the patients with negative and positive lymph node metastasis ( X2 =7. 04 , P = 0. 008 ) . Univariate analysis showed that the significant prognostic factors include UICC 2002 stage, the degree of differentiation, lymphatic metastasis and vascular carcinomatous thrombus ( X2 =7. 30 ,7. 04 , 8. 34 ,9. 40 , P = 0. 026 , 0. 008 , 0. 004 ,0.002 ) . Multivariate analysis revealed that the grade of differentiation, lymphatic metastasis and vascular carcinomatous thrombus were independent prognostic factors ( X2 = 6. 86, 5. 27, 4. 24, P= 0. 009, 0. 022, 0. 040 ). Treatment failure occurred in 58 patients because of systemic metastases , 14 cervical lymph node recurrence , 17 abdominal lymph node metastases, and 31 0f intrathoracic recurrence. Five patients had grade 2 0r worse late treatment-related anastomotic stenosis , and 8 patients died from late treatment-related gastrointestinal bleeding. Conclusions Postoperative prophylactic 3DCRT or IMRT of TESCC can provide a favorable local control rate and acceptable toxicity. Postoperative radiotherapy should be included into the standard treatment of Stage ⅢTESCC or TESCC with lymph node metastasis. Key words: Esophageal neoplasms/surgery; Intensity-modulated radiotherapy,postoperative; Three-dimensional conformal radiotherapy,postoperative; Prognosis

Orai1 calcium channels in the vasculature

Orai1 was discovered in T cells as a calcium-selective channel that is activated by store depletion. Recent studies suggest that it is expressed and functionally important also in blood vessels, not only because haematopoietic cells can incorporate in the vascular wall but also because Orai1 is expressed and functional in vascular smooth muscle cells and endothelial cells. This article summarises the arising observations in this new area of vascular research and debates underlying issues and challenges for future investigations. The primary focus is on vascular smooth muscle cells and endothelial cells. Specific topics include Orai1 expression; Orai1 roles in store-operated calcium entry and ionic currents of store-depleted cells; blockade of Orai1-related signals by Synta 66 and other pharmacology; activation or regulation of Orai1-related signals by physiological substances and compartments; stromal interaction molecules and the relationship of Orai1 to other ion channels, transporters and pumps; transient receptor potential canonical channels and their contribution to store-operated calcium entry; roles of Orai1 in vascular tone, remodelling, thrombus formation and inflammation; and Orai2 and Orai3. Overall, the observations suggest the existence of an additional, previously unrecognised, calcium channel of the vascular wall that is functionally important particularly in remodelling but probably also in certain vasoconstrictor contexts.

Adiuvant huaier on long-term survivals after curative hepatectomy for primary liver cancer

Objective To study the effects of adjuvant Huaier on long-term survivals after curative partial hepatectomy for primary liver cancer.Methods 175 patients with primary liver cancer who received curative partial hepatectomy from January 2002 to January 2006 were divided into two groups:the treatment group (group A,n =87) and the control group (group B,n=88).Group A was treated with Huaier (60 g per day for 6 months) after the operation while group B received no Huaier treatment.Results The overall 1-,3- and 5 year survival rates and disease-free survival rates were 91.90％,73.90％,and 56.0％ and 68.1％,48.4％ and 40.2％,respectively.The overall 1-,3-and 5-year survival rates in group A were significantly higher than group B (91.80％,79.30％,65.2％ vs 92.0％,68.3％,46.6％,P 0.038).In addition,the 1-,3-and 5-year survival rates after tumor recurrence in group A was also significantly higher than group B (78.6％,46.9％,38.2％ vs 69.0％,16.8％,12.6％,P=0.040).Multivariate analysis showed that the use of Huaier,hepatitis infection,severity of cirrhosis,vascular cancer thrombus were the most important prognostic factors for overall long-term survival (P＜0.05).Blood transfusion and histological grade were independent risk factors for disease free survival.The use of Huaier and the clinicopathological type were significantly co-related to the survival from recurrence/metastasis to death.Conclusion The use of Huaier improved disease free survival and the survival from recurrence or metastasis for patients with primary liver cancer following curative hepatectomy. Key words: Primary liver cancer; Huaier; Recurrence; Metastasis