Risk Factor Analysis of Recanalization Timing in Coiled Aneurysms: Early versus Late Recanalization.

BACKGROUND AND PURPOSE: Long-term documentation of anatomic and angiographic characteristics pertaining to the timing of recanalization in coiled aneurysms has been insufficient. Our intent was to analyze and compare early and late-phase recanalization after coiling, identifying respective risk factors. MATERIALS AND METHODS: A total of 870 coiled saccular aneurysms were monitored for extended periods (mean, 30.8 ± 8.3 months). Medical records and radiologic data were also reviewed, stratifying patients as either early (n = 128) or late (n = 52) recanalization or as complete occlusion (n = 690). Early recanalization was equated with confirmed recanalization within 6 months after the procedure, whereas late recanalization was defined as verifiable recanalization after imaging confirmation of complete occlusion at 6 months. A multinomial regression model served to assess potential risk factors, the reference point being early recanalization. RESULTS: Posterior circulation (P = .009), subarachnoid hemorrhage at presentation (P = .011), second attempt for recanalized aneurysm (P < .001), and aneurysm size >7 mm (P < .001) emerged as variables significantly linked with early recanalization (versus complete occlusion). Late (versus early) recanalization corresponded with aneurysms ≤7 mm (P = .013), and in a separate subanalysis of lesions ≤7 mm, aneurysms 4-7 mm showed a significant predilection for late recanalization (P = .008). However, the propensity for complete occlusion in smaller lesions (≤7 mm) increased as the size diminished. CONCLUSIONS: Although long-term complete occlusion after coiling was more likely in aneurysms ≤7 mm, such lesions were more prone to late (versus early) recanalization, particularly those of 4-7 mm in size. Long-term follow-up imaging is thus appropriate in aneurysms >4 mm to detect late recanalization of those formerly demonstrating complete occlusion.

Do Contrast-Fill Patterns Immediately After Coil Embolization of Small Saccular Aneurysms Impact Long-Term Results?

PURPOSE: It is generally accepted that filling of a saccular aneurysm with contrast immediately after coil embolization predisposes to later recanalization. However, not all such scenarios evolve similarly over time. We investigated outcomes of small (≤ 7 mm) aneurysms with contrast-filled sacs immediately after coil embolization, evaluating the impact of pattern and degree of filling on subsequent recanalization. METHODS: Between January, 2008 and December, 2010, 186 small (≤ 7 mm) saccular aneurysms that retained contrast after coil embolization accrued for this study. Lesions were categorized by pattern (eccentric vs. concentric) and degree of filling on working projections. Clinical and morphologic factors were also analyzed to assess impact on subsequent recanalization. Morphologic outcomes at 6 months or more were assessed. RESULTS: In 93.5 % (174/186) of aneurysms with visible contrast retention, complete occlusion was evident on follow-up imaging studies at 6 months. Multiple logistic regression analysis indicated that eccentric (vs. concentric) contrast filling carried greater risk of subsequent recanalization (p = 0.020). Stent placement and progressive occlusion were also linked, falling short of statistical significance (p = 0.089). Of 166 progressively occluded aneurysms followed for more than 12 months (mean, 30.8 ± 7.3 months), 158 (95.2 %) exhibited stable occlusion. CONCLUSION: Small (≤ 7 mm) aneurysms that retain contrast immediately after coil embolization are more likely to become completely occluded over time through progressive thrombosis. However, an eccentric fill pattern may predispose to recanalization.

Fate of Coiled Aneurysms with Minor Recanalization at 6 Months: Rate of Progression to Further Recanalization and Related Risk Factors.

BACKGROUND AND PURPOSE: Minor recanalization in coiled aneurysms may remain stable with time or may progress to major recanalization. Our aim was to monitor the aneurysms displaying minor recanalization in imaging studies at 6 months, gauging major recanalization rates and related risk factors through extended follow-up. MATERIALS AND METHODS: Sixty-five aneurysms (in 65 patients) showing minor recanalization in follow-up imaging at 6 months were reviewed retrospectively. Medical records and radiologic data accruing during extended monitoring (mean, 24.8 ± 8.2 months) were assessed. Univariate and multivariate analyses were conducted to identify risk factors for progression from minor-to-major recanalization. RESULTS: Progression to major recanalization was observed in 24 (36.9%) of the initially qualifying aneurysms during a follow-up of 112.5 aneurysm-years, for an annual rate of 17.84% per aneurysm-year. Progression was determined chronologically as follows: 14 (58.3%) at 6 months, 8 (33.3%) at 18 months, and 2 (8.4%) at 30 months. Stent deployment significantly decreased the occurrence of major recanalization (OR = 0.22, P = .03), whereas antiplatelet therapy (OR = 0.82, P = .75), posterior location (OR = 0.24, P = .20), and second coiling for recanalized aneurysms (OR = 0.96, P = .96) were unrelated. CONCLUSIONS: Our analysis determined a 36.9% rate of major recanalization during a follow-up of 112.5 aneurysm-years in coiled aneurysms showing minor recanalization at 6 months. Stent deployment alone conferred a protective effect, preventing further recanalization without additional treatment. Given the fair probability of late major recanalization, aneurysms showing minor recanalization at 6 months should be monitored diligently, particularly in the absence of stent placement.

MicroRNA signatures associated with immortalization of EBV-transformed lymphoblastoid cell lines and their clinical traits.

OBJECTIVE: MicroRNAs (miRNAs) are negative regulators of gene expression that play important roles in cell processes such as proliferation, development and differentiation. Recently, it has been reported that miRNAs are related to development of carcinogenesis. The aim of this study was to identify miRNAs associated with terminal immortalization of Epstein-Barr virus (EBV)-transformed lymphoblastoid cell line (LCL) and associated clinical traits. MATERIAL AND METHODS: Hence, we performed miRNA microarray approach with early- (p6) and late-passage (p161) LCLs. RESULTS AND CONCLUSION: Microarray data showed that nine miRNAs (miR-20b*, miR-28-5p, miR-99a, miR-125b, miR-151-3p, miR-151:9.1, miR-216a, miR-223* and miR-1296) were differentially expressed in most LCLs during long-term culture. In particular, miR-125b was up-regulated in all the tested late-passage LCLs. miR-99a, miR-125b, miR-216a and miR-1296 were putative negative regulators of RASGRP3, GPR160, PRKCH and XAF1, respectively, which were found to be differentially expressed in LCLs during long-term culture in a previous study. Linear regression analysis showed that miR-200a and miR-296-3p correlated with triglyceride and HbA1C levels, respectively, suggesting that miRNA signatures of LCLs could provide information on the donor's health. In conclusion, our study suggests that expression changes of specific miRNAs may be required for terminal immortalization of LCLs. Thus, differentially expressed miRNAs would be a potential marker for completion of cell immortalization during EBV-mediated tumorigenesis.

Expression phenotype changes of EBV-transformed lymphoblastoid cell lines during long-term subculture and its clinical significance.

OBJECTIVES: The EBV-transformed lymphoblastoid cell line (LCL) is a useful resource for population-based human genetic and pharmacogenetic studies. The principal objective here was to assess expression phenotype changes during long-term subculture of LCLs, and its clinical significance. MATERIALS AND METHODS: We searched for genes that were differentially expressed in 17 LCLs at late (p161) passage compared to early passage (p4) using microarray assay, then validated them by real-time RT-PCR analysis. In addition, we estimated correlations between expression phenotypes of 20 LCL strains at early passage and 23 quantitative clinical traits from blood donors of particular LCL strains. RESULTS: Transcript sequences of 16 genes including nuclear factor-kappaB (NF-kappaB) pathway-related genes (such as PTPN13, HERC5 and miR-146a) and carcinogenesis-related genes (such as XAF1, TCL1A, PTPN13, CD38 and miR-146a) were differentially expressed (>2-fold change) in at least 15 of the 17 LCL strains. In particular, TC2N, FCRL5, CD180, CD38 and miR-146a were downregulated in all 17 of the evaluated LCL strains. In addition, we identified clinical trait-associated expression phenotypes in LCLs. CONCLUSION: Our results showed that LCLs acquired expression phenotype changes involving expression of NF-kappaB pathway- and carcinogenesis-related genes during long-term subculture. These differentially expressed genes can be considered to be a gene signature of LCL immortalization or EBV-induced carcinogenesis. Clinical trait-associated expression phenotypes should prove useful in the discovery of new candidate genes for particular traits.

Identification of tumor necrosis factor signaling-related proteins during Epstein-Barr virus-induced B cell transformation.

Epstein-Barr virus (EBV) infection in vitro transforms primary B cells into continuously proliferating lymphoblastoid cell lines (LCLs) that have been widely used as a genomic resource for variety of immunological and genetic studies. However, the biochemical and biological characteristics that distinguish LCLs from the B cells have not been thoroughly investigated. Our proteomic approach showed that EBV infection induced changes in the profiles of tumor necrosis factor (TNF) signaling-related proteins in LCLs including heat shock protein family members TNF receptor-associated protein 1 (TRAP-1), heat shock 70-kDa protein 9 (HSPA9)) and superoxide dismutase 2 (SOD2). In addition, our literature co-occurrence study placed TNF at the center of a gene cluster network of differentially expressed proteins in LCLs. This study suggested that deregulation of TNF signaling pathway could contribute to the cellular transformation and immortalization of the EBV-infected B cells.

Identification of stathmin 1 expression induced by Epstein-Barr virus in human B lymphocytes.

INTRODUCTION: The Epstein-Barr virus transforms resting B cells into proliferating lymphoblastoid cells, the origin of cell lines. METHOD AND RESULTS: Our cDNA microarray analyses led to the identification of 232 up-regulated and 112 down-regulated genes with more than a 3-fold difference in lymphoblastoid cell lines compared to resting B cells. The functional classification of these genes exhibited the distinct expression signature for cell proliferation, cell cycle and an immune response. Among them, we verified the differential expression of several oncogenes such as stathmin 1 (STMN1), RAB27A, RAB9A, BACH1 and BACH2 using quantitative real-time reverse transcriptase-polymerase chain reactions or Western blot analysis. Expression of STMN1 (which is involved in regulation of the microtubule filament system, cell growth and S-phase of cell cycle) was increased in lymphoblastoid cell line as well as in 7-day post-Epstein-Barr virus infection B cells, compared to resting B cells. CONCLUSION: Thus, this study suggests that Epstein-Barr virus infection induces STMN1 expression, which play a role in cell cycle progression and proliferation in the human B lymphocyte.