Clinical outcomes of prophylactic Damus-Kaye-Stansel anastomosis concomitant with bidirectional Glenn procedure

ObjectiveWe evaluated prophylactic Damus-Kaye-Stansel (DKS) anastomosis in association with the timing of a bidirectional Glenn (BDG) procedure as second-stage palliation aiming at Fontan completion to prevent late systemic ventricular outflow tract obstruction.MethodsBetween 1996 and 2005, 25 patients (14 boys; median age, 12 months) underwent a BDG procedure concomitant with DKS anastomosis. All had a systemic ventricular outflow tract through an intraventricular communication or morphologically developed subaortic conus and had previously undergone pulmonary artery banding. Enlargement of intraventricular communication and/or resection of a subaortic conus were not performed before or during the operation.ResultsTwenty-one (84%) patients subsequently underwent a Fontan operation, with a follow-up period of 6.8 ± 1.9 years (range, 4-11 years), with no mortalities after the Fontan operation. Cardiac catheterization showed that systemic ventricular end-diastolic volume was significantly decreased from 187% ± 74% of normal before BDG to 139% ± 35% after (P = .038) and to 73% ± 14% at 4.3 years after the Fontan operation (P < .001). However, the pressure gradient across the systemic ventricular outflow tract remained at 0.5 ± 0.8 mm Hg after DKS anastomosis and 0.6 ± 2.3 mm Hg at 4.6 years after the Fontan operation. None of the patients showed more than moderate aortic or neoaortic regurgitation, except 1 who progressed to pulmonary regurgitation after DKS anastomosis and required a reoperation for a systemic ventricular outflow tract. No anatomic properties affected late neoaortic valve function.ConclusionsRegardless of a significant reduction in systemic ventricular volume, DKS anastomosis concomitant with a BDG procedure shows promise for a nonobstructive systemic ventricular outflow tract after a Fontan operation

A Possible Anticancer Agent, Type III Interferon, Activates Cell Death Pathways and Produces Antitumor Effects

Recently identified interleukin-28 and -29 belong to a novel type III interferon (IFN) family, which could have distinct biological properties from type I and II IFNs. Type I IFNs, IFN-α/β, have been clinically applied for treating a certain kind of malignancies for over 30 years, but a wide range of the adverse effects hampered the further clinical applications. Type III IFNs, IFN-λs, have similar signaling pathways as IFN-α/β and inhibits proliferation of tumor cells through cell cycle arrest or apoptosis. Restricted patterns of type III IFN receptor expression in contrast to ubiquitously expressed IFN-α/β receptors suggest that type III IFNs have limited cytotoxicity to normal cells and can be a possible anticancer agent. In this paper, we summarize the current knowledge on the IFN-λs-mediated tumor cell death and discuss the functional difference between type I and III IFNs

Lipomatous Pseudohypertrophy of the Pancreas Taking the Form of Huge Massive Lesion of the Pancreatic Head

A 70-year-old woman presented with hypogastric pain. Computed tomography and magnetic resonance imaging revealed a retroperitoneal tumor 18.0 cm in diameter with fatty tissue density, ventrally compressing the pancreatic head. We suspected a well-differentiated liposarcoma compressing the pancreas. At laparotomy, the tumor mass was the size of an infant's head; its center was located in the area corresponding to the pancreatic uncus. It was continuous with the pancreatic parenchyma through a poorly demarcated border, and we resected as much of the tumor mass as possible while conserving the pancreatic capsule. Histopathological examination indicated lipomatous pseudohypertrophy of the pancreas with proliferation of mature fatty tissue as the main constituent. At the periphery, islands of acinar tissue were retained among the fatty infiltration, which also contained branches of the pancreatic duct and islets of Langerhans. Previous reports have stated that this disorder only causes fatty replacements throughout the pancreas or in the pancreatic body and tail; however, in this patient, imaging and macroscopic examination revealed no fatty replacements in the pancreatic body and tail. We report this case, which we consider extremely rare, along with a brief review of the literature

Pathological Vascular Invasion and Tumor Differentiation Predict Cancer Recurrence in Stage ia Non–Small-Cell Lung Cancer After Complete Surgical Resection

Introduction:The appropriate therapeutic strategy and postoperative management for patients with stage IA non–small-cell lung cancer (NSCLC) still remain a matter of debate because of the prognostic heterogeneity of this population, including the risk of cancer recurrence. The objective of the current study was to identify the clinicopathological factors that affect overall prognosis and cancer recurrence of stage IA NSCLC.Methods:We reviewed the data of 532 patients in whom complete resection of stage IA NSCLC had been performed. Overall survival and recurrence-free proportion (RFP) were estimated using the Kaplan–Meier method. RFP was estimated from the date of the primary tumor resection to the date of the first recurrence or last follow-up. We performed univariate and multivariate analyses to determine the independent prognostic factors.Results:On multivariate analyses, three variables were shown to be independently significant recurrence risk factors: histological differentiation (hazard ratio [HR] = 1.925), blood-vessel invasion (HR = 1.712), and lymph-vessel invasion (HR = 1.751). On subgroup analyses combining these risk factors, the 5-year RFP was 91.3% for patients with no risk factors, 79.5% for those with either poorly differentiated carcinoma or vascular invasion, (p < 0.001 for both), and 62.9% for those with both poorly differentiated carcinoma and vascular invasion (p = 0.068).Conclusion:These results indicated that vascular invasion and tumor differentiation have a significant impact on the prediction of cancer recurrence in patients with stage IA NSCLC. Patients with these predictive factors of recurrence may be good candidates for adjuvant chemotherapy

An image cytometric technique is a concise method to detect adenoviruses and host cell proteins and to monitor the infection and cellular responses induced

BackgroundGenetically modified adenoviruses (Ad) with preferential replications in tumor cells have been examined for a possible clinical applicability as an anti-cancer agent. A simple method to detect viral and cellular proteins is valuable to monitor the viral infections and to predict the Ad-mediated cytotoxicity.MethodsWe used type 5 Ad in which the expression of E1A gene was activated by 5′-regulatory sequences of genes that were augmented in the expression in human tumors. The Ad were further modified to have the fiber-knob region replaced with that derived from type 35 Ad. We infected human mesothelioma cells with the fiber-replaced Ad, and sequentially examined cytotoxic processes together with an expression level of the viral E1A, hexon, and cellular cleaved caspase-3 with image cytometric and Western blot analyses.ResultsThe replication-competent Ad produced cytotoxicity on mesothelioma cells. The infected cells expressed E1A and hexon 24 h after the infection and then showed cleavage of caspase-3, all of which were detected with image cytometry and Western blot analysis. Image cytometry furthermore demonstrated that increased Ad doses did not enhance an expression level of E1A and hexon in an individual cell and that caspase-3-cleaved cells were found more frequently in hexon-positive cells than in E1A-positive cells. Image cytometry thus detected these molecular changes in a sensitive manner and at a single cell level. We also showed that an image cytometric technique detected expression changes of other host cell proteins, cyclin-E and phosphorylated histone H3 at a single cell level.ConclusionsImage cytometry is a concise procedure to detect expression changes of Ad and host cell proteins at a single cell level, and is useful to analyze molecular events after the infection

Hypertension, hypertriglyceridemia, and impaired endothelium-dependent vascular relaxation in mice lacking insulin receptor substrate-1.

Insulin resistance is often associated with atherosclerotic diseases in subjects with obesity and impaired glucose tolerance. This study examined the effects of insulin resistance on coronary risk factors in IRS-1 deficient mice, a nonobese animal model of insulin resistance. Blood pressure and plasma triglyceride levels were significantly higher in IRS-1 deficient mice than in normal mice. Impaired endothelium-dependent vascular relaxation was also observed in IRS-1 deficient mice. Furthermore, lipoprotein lipase activity was lower than in normal mice, suggesting impaired lipolysis to be involved in the increase in plasma triglyceride levels under insulin-resistant conditions. Thus, insulin resistance plays an important role in the clustering of coronary risk factors which may accelerate the progression of atherosclerosis in subjects with insulin resistance

CA-ARBAC: privacy preserving using context-aware role-based access control on Android permission system

Existing mobile platforms are based on manual way of granting and revoking permissions to applications. Once the user grants a given permission to an application, the application can use it without limit, unless the user manually revokes the permission. This has become the reason for many privacy problems because of the fact that a permission that is harmless at some occasion may be very dangerous at another condition. One of the promising solutions for this problem is context-aware access control at permission level that allows dynamic granting and denying of permissions based on some predefined context. However, dealing with policy configuration at permission level becomes very complex for the user as the number of policies to configure will become very large. For instance, if there are A applications, P permissions, and C contexts, the user may have to deal with A × P × C number of policy configurations. Therefore, we propose a context-aware role-based access control model that can provide dynamic permission granting and revoking while keeping the number of policies as small as possible. Although our model can be used for all mobile platforms, we use Android platform to demonstrate our system. In our model, Android applications are assigned roles where roles contain a set of permissions and contexts are associated with permissions. Permissions are activated and deactivated for the containing role based on the associated contexts. Our approach is unique in that our system associates contexts with permissions as opposed to existing similar works that associate contexts with roles. As a proof of concept, we have developed a prototype application called context-aware Android role-based access control. We have also performed various tests using our application, and the result shows that our model is working as desired

NCRT with S-1 plus irinotecan for LALRC

Background and purpose: Preoperative 5-fluorouracil-based chemoradiotherapy is a standard treatment for locally advanced lower rectal cancer (LALRC). We performed a phase I study to develop a new regimen combining irinotecan and S-1. Materials and methods: Patients with LALRC (T3-4, N0-2) were studied. The radiation dose was 45 Gy in 25 fractions. S-1 (80 mg/m2/day) was administered on days 1–5, 8–12, 22–26, and 29–33. Irinotecan was administered on days 1, 8, 22, and 29. The dose of irinotecan was initially 60 mg/m2 (level 1). Surgery was performed 6–10 weeks after the chemoradiotherapy. Results: Twenty patients were enrolled, of whom 18 patients were analyzed. Dose-limiting toxicity (DLT) did not occur in the first 3 patients treated with irinotecan at 80 mg/m2 (level 2), but developed in 3 of the 6 patients who received irinotecan at 90 mg/m2 (level 3). Then DLT occurred in 3 other patients at level 2. At level 2 or 3, DLT comprised neutropenia, thrombocytopenia, and diarrhea. Level 2 was designated as the maximum tolerated dose, and level 1 as a recommended dose (RD). The pathological complete response rate was 28%, and the down-staging rate was 56%. Conclusions: Our results suggested that the RD of irinotecan when combined with preoperative S-1 and pelvic radiation was 60 mg/m2

Metformin produces growth inhibitory effects in combination with nutlin-3a on malignant mesothelioma through a cross-talk between mTOR and p53 pathways

BackgroundMesothelioma is resistant to conventional treatments and is often defective in p53 pathways. We then examined anti-tumor effects of metformin, an agent for type 2 diabetes, and combinatory effects of metformin and nutlin-3a, an inhibitor for ubiquitin-mediated p53 degradation, on human mesothelioma.MethodsWe examined the effects with a colorimetric assay and cell cycle analyses, and investigated molecular events in cells treated with metformin and/or nutlin-3a with Western blot analyses. An involvement of p53 was tested with siRNA for p53.ResultsMetformin suppressed cell growth of 9 kinds of mesothelioma including immortalized cells of mesothelium origin irrespective of the p53 functional status, whereas susceptibility to nutlin-3a was partly dependent on the p53 genotype. We investigated combinatory effects of metformin and nutlin-3a on, nutlin-3a sensitive MSTO-211H and NCI-H28 cells and insensitive EHMES-10 cells, all of which had the wild-type p53 gene. Knockdown of p53 expression with the siRNA demonstrated that susceptibility of MSTO-211H and NCI-H28 cells to nutlin-3a was p53-dependent, whereas that of EHMES-10 cells was not. Nevertheless, all the cells treated with both agents produced additive or synergistic growth inhibitory effects. Cell cycle analyses also showed that the combination increased sub-G1 fractions greater than metformin or nutlin-3a alone in MSTO-211H and EHMES-10 cells. Western blot analyses showed that metformin inhibited downstream pathways of the mammalian target of rapamycin (mTOR) but did not activate the p53 pathways, whereas nutlin-3a phosphorylated p53 and suppressed mTOR pathways. Cleaved caspase-3 and conversion of LC3A/B were also detected but it was dependent on cells and treatments. The combination of both agents in MSTO-211H cells rather suppressed the p53 pathways that were activated by nutrin-3a treatments, whereas the combination rather augmented the p53 actions in NCI-H28 and EHMES-10 cells.ConclusionThese data collectively indicated a possible interactions between mTOR and p53 pathways, and the combinatory effects were attributable to differential mechanisms induced by a cross-talk between the pathways