Endovascular repair for concomitant multilevel aortic disease.

OBJECTIVE: Patients with multilevel aortic disease represent a small subgroup with the need for extensive surgical treatment at considerable risk. We present our experience of endovascular exclusion for simultaneous thoracic and abdominal aortic disease in four patients. METHODS: Between January 2002 and January 2005, four patients underwent endovascular repair for simultaneous thoracic and abdominal aortic disease. Mean age was 69+/-10 years (range, 60-81). Thoracic lesions included penetrating aortic ulcer (n=2, ruptured=1), atherosclerotic aneurysm (n=1), and chronic type B dissection (n=1). Abdominal aortic disease included atherosclerotic infrarenal (n=3) and juxtarenal (n=1) aortic aneurysms. Thoracic aortic stent-grafts had been the following: Excluder/TAG (n=3) or Talent (n=1) straight tube devices. Abdominal aortic stent-grafts used were as following: Excluder (n=3) or Zenith (n=1). All patients were followed-up with CT-angiography and chest X-rays 1, 4, 12 months after the procedure, and once per year thereafter. RESULTS: Stent-graft deployment was technically successful in all cases. Intraoperative mortality was not observed. Mean procedure time was 94+/-34 min (range, 70-145). Early postoperative complications occurred in one patient that developed acute renal failure but dialysis was not required. Mean hospitalisation was 8+/-5 days (range, 4-15). Late death occurred in one patient for an undetected ruptured thoracic type 1 endoleak. All three survivors are currently well 16.5 months (range, 3-36) after surgery. No neurological complications developed. CONCLUSION: Simultaneous abdominal and thoracic endovascular repair for multilevel aortic disease is feasible and could be a viable alternative in high-risk patients, who otherwise may not be suitable candidates for conventional repair.     

Pituitary corticotroph adenoma with crooke’s hyalinization

The diagnosis of pituitary corticotroph adenoma relies on the demonstration of a loss of the normal feedback control of adrenocorticotropic hormone (ACTH) biosynthesis by cortisol. The marked variability in the degree of ACTH suppression by glucocorticoids in these tumors, however, greatly enhances the difficulty in distinguishing Cushing’s disease from other syndromes of glucocorticoid excess. To illustrate this variability, we describe the clinical, biochemical, and morphological characteristics of a pituitary corticotroph adenoma in a 63-year-old woman, who presented with symptoms of a sellar mass but did not initially have florid Cushing’s disease. Light and electron microscopy of the pituitary tumor showed a corticotroph adenoma with Crooke’s hyalinization of the tumor cells, characterized by the accumulation of keratin immunoreactive microfilaments similar to those observed in normal corticotrophs in the presence of excess glucocorticoids. This case illustrates an unusual clinical presentation that may be associated with pituitary corticotroph adenoma showing Crooke’s hyalinization.     

E-cadherin germline missense mutations and cell phenotype: evidence for the independence of cell invasion on the motile capabilities of the cells

In Hereditary Diffuse Gastric Cancer syndrome, E-cadherin germline mutations of the missense type harbour significant functional consequences. In this study, we have characterised the effect of T340A, A617T, A634V and V832M E-cadherin germline missense mutations on cell morphology, motility and proliferation. Wild-type E-cadherin and A617T expressing cells have an epithelial-like morphology, with polarised cells migrating unidirectionally. T340A and A634V expressing cells, fibroblast-like, have a high motile phenotype. We show that this phenotype is dependent on an increased level of active RhoA. V832M expressing cells grow in piled-up structure of round cells, as an effect of the disturbance of the binding between alpha-catenin and beta-catenin. The destabilisation of the adhesion complex is shown to hamper the motile capabilities of these cells. We did not observe any effect of the E-cadherin mutations on cell proliferation. We show the existence of a genotype-phenotype correlation between different E-cadherin mutations and cell behaviour. However, we demonstrate that the ability of cells expressing the different E-cadherin mutations to invade is independent on their motile capabilities, providing evidence that motility is neither necessary nor sufficient for cells to invade. Our data give new insights into the understanding of the mechanisms linking invasion and E-cadherin mutations in diffuse gastric cancer.     

Expression of Epstein-Barr virus latent membrane protein-1 in Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma: associations with presenting features, serum interleukin 10 levels, and clinical outcome.

PURPOSE: EBV-latent membrane protein-1 (LMP-1) is often expressed in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin's lymphoma (cHL), but its clinical significance is controversial. We correlated LMP-1 with presenting features, including serum interleukin 10 levels and clinical outcome. EXPERIMENTAL DESIGN: Patients were eligible if they had biopsy-proven cHL, were untreated, HIV-1 negative, and had available archival tissue. LMP-1 expression was determined by immunohistochemistry. RESULTS: We identified 577 patients with cHL with a median age of 30 years, 55% of whom were male. LMP-1 was expressed in HRS cells of 124 patients (21%) and was detected in 78 of 461 (17%) patients with nodular sclerosis compared with 44 of 112 (39%) with mixed cellularity (P < 0.001 by Fisher's exact test). Patients with tumors with LMP-1-positive HRS cells had higher serum interleukin 10 levels (P = 0.009 by Mann-Whitney test). For the 303 patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalent regimens, the 5-year failure-free survival (FFS) for those with LMP-1-positive tumors was 74% compared with 81% for those with LMP-1-negative tumors (P = 0.23, by log-rank test). Overall survival (OS) at 5 years for patients with LMP-1-positive tumors was 90 versus 91% for patients with LMP-1-negative tumors (P = 0.8 by log-rank test). Expression of LMP-1 was not associated with different FFS and OS in patients treated with other regimens or with radiotherapy alone. CONCLUSIONS: LMP-1 was expressed by HRS cells in 21% of cHL and correlated with mixed cellularity type and higher serum interleukin 10 levels. The presence of LMP-1 was not associated with FFS or OS in uniformly treated patients.     

Survivin in Brain Tumors: An Attractive Target for Immunotherapy

Survivin, a member of the inhibitor of apoptosis proteins gene family, was recently shown to be expressed by tumors originating from different cell lineages. There are also cumulative evidences that spontaneous immune response against survivin derived epitopes may occur. Here, using RT-PCR, Western-blot analysis and immunohistochemistry, we show that survivin is widely expressed by gliomas, meningiomas and schwannomas, both in vitro and in vivo. These data indicate that survivin may serve as an attractive target for immunotherapies designed for brain tumors.     

p15INK4b, p14ARF, and p16INK4a inactivation in sporadic and neurofibromatosis type 1-related malignant peripheral nerve sheath tumors.

PURPOSE: Malignant peripheral nerve sheath tumor (MPNST) can arise sporadically or in association with neurofibromatosis type 1. Deletions at the 9p21 locus have been reported in these tumors. To additionally characterize the status of this chromosomal region, in this study we performed a comprehensive, mostly PCR-based molecular analysis of the three tumor suppressor genes p15(INK4b), p14(ARF) and p16(INK4a) located at the 9p21 locus in 26 cryopreserved MPNSTs. EXPERIMENTAL DESIGN: Fourteen neurofibromatosis type 1-related and 12 sporadic cases were investigated for homozygous deletion coupled with fluorescent in situ hybridization, promoter methylation, and mutational analysis, as well as m-RNA expression. RESULTS: The results showed that an inactivation of one or more genes occurred in 77% of MPNSTs and was mainly achieved through homozygous deletion (46%), which, in turn, encompassed all of the three tandemly linked genes in 83% of the deleted cases. Promoter methylation was at a less extent involved in gene silencing (18%), and no mutations were found. Loss of function at DNA level strongly correlated with loss of mRNA expression accounting for 80% of the cases. Because of the close relationship between p14(ARF) and TP53 and between p15(INK4b)/p16(INK4a) and Rb, these results support a model of a coinactivation of TP53 and Rb pathways in 75% of MPNSTs, with functional consequences on cell growth control and apoptosis. CONCLUSIONS: The inactivation of the 9p21 locus is a frequent and peculiar hallmark of MPNST genetic profile leading also to an impaired apoptosis that could be taken into account in treatment planning of these tumors.     

Intensity and duration of in‐vitro antibacterial activity of different adhesives used in orthodontics

This work investigated the antibacterial activity of 14 bonding agents to predict their ability to inhibit white‐spot development during orthodontic treatment. Standardized, sterilized disks of each material were continuously rinsed (for up to 180 d) in a flow of sterile saline. At predetermined time points, the residual ability of each material to inhibit bacterial growth (determined by measuring the size of inhibition halos around disks placed onto appropriate culture media seeded with Streptococcus gordonii DSM6777, Streptococcus sanguinis DSM20567, Streptococcus mutans DSM20523, or Lactobacillus acidophilus DSM20079) and biofilm formation (determined by measuring the numbers of bacteria adherent to disks following incubation in appropriate broths) was tested in triplicate and compared with the baseline activities of freshly prepared materials. Overall antibacterial and anti‐biofilm activities, adjusted for exposure time and strain of bacteria, were assessed. The decrease of antibacterial activity was faster (30–60 d) and complete for fluoride‐enriched materials, but slower (90 d) and partial for antimicrobial‐containing materials (benzalkonium chloride, zinc oxide, chlorexidine, or MDPB). Materials enriched with benzalkonium chloride, chlorexidine, or MDPB showed the highest antibacterial activities. Anti‐biofilm assays yielded similar results. These data could be helpful for clinicians in the choice of the best performing bonding agent also in light of duration of the clinical application.