Exploring management and outcomes of elderly patients with glioblastoma using data from two randomised trials (GEINO1401/EX-TEM).

PURPOSE: The impact of age on optimal management of glioblastoma remains unclear. A recent combined analysis of two randomised trials, GEINO14-01 and EX-TEM, found no benefit from extending post-radiation temozolomide in newly diagnosed glioblastoma. Here, we explore the impact of age. METHODS: Relevant intergroup statistics were used to identify differences in tumour, treatment and outcome characteristics based on age with elderly patients (EP) defined as age 65 years and over. Survival was estimated using the Kaplan Meier method. RESULTS: Of the combined 205 patients, 57 (28%) were EP. Of these, 95% were ECOG 0-1 and 65% underwent macroscopic resection compared with 97% and 61% of younger patients (YP) respectively. There were numerically less MGMT-methylated (56% vs. 63%, p = 0.4) and IDH-mutated (4% vs. 13%, p = 0.1) tumours in EP vs. YP. Following surgery, EP were more likely to receive short course chemoradiation (17.5% vs. 6%, p = 0.017). At recurrence, EP tended to receive or best supportive care (28.3% vs. 15.4%, p = 0.09) or non-surgical options (96.2% vs. 84.6%, p = 0.06), but were less likely to receive bevacizumab (23.1% vs. 49.5%, p < 0.01). Median PFS was similar at 9.3months in EP and 8.5months in YP, with similar median OS at 20months. CONCLUSION: In this trial population of predominantly fit EP, survival was similar to YP despite a proportion receiving less aggressive therapy at diagnosis and recurrence. Advancing age does not appear to be an adverse prognostic factor for glioblastoma when patients are fit for treatment, and a less aggressive approach in selected patients may not compromise outcomes.

A combined analysis of two prospective randomised studies exploring the impact of extended post-radiation temozolomide on survival outcomes in newly diagnosed glioblastoma.

PURPOSE: The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data. METHODS: GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6 months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60% (80% power). Neither study recruited sufficient patients. We performed a combined analysis of individual patient data. RESULTS: 205 patients were recruited: 159 in GEINO14-01 (2014-2018) and 46 in EX-TEM (2019-2022). Median follow-up was 20.0 and 14.5 months. Baseline characteristics were balanced. There was no significant improvement in 6mPFS (57.2% vs 64.0%, OR0.75, p = 0.4), nor across any subgroups, including MGMT methylated; PFS (HR0.92, p = 0.59, median 7.8 vs 9.7 months); or OS (HR1.03, p = 0.87, median 20.1 vs 19.4 months). During treatment extension, 64% experienced any grade adverse event, mainly fatigue and gastrointestinal (both 54%). Only a minority required treatment changes: 4.5% dose delay, 7.5% dose reduction, 1.5% temozolomide discontinuation. CONCLUSION: For glioblastoma patients, extending post-radiation temozolomide from 6 to 12 months is well tolerated but does not improve 6mPFS. We could not identify any subset that benefitted from extended treatment. Six months should remain standard-of-care.

Hypermobility Assessment in 1,004 Adult Patients Presenting with Hip Pain: Correlation with Diagnoses and Demographics.

BACKGROUND: The strength of the association between hypermobility and developmental dysplasia of the hip (DDH) in adults is unknown. We sought to analyze this relationship in a prospective, blinded, institutional review board-approved, observational study. The hypothesis was that the prevalence of generalized joint hypermobility (GJH) would be significantly higher in patients with hip dysplasia than in those with other hip diagnoses on the basis of clinical observations of joint laxity. METHODS: One thousand and four consecutive new patients (390 males and 614 females) seen over a 4-year period were evaluated for hypermobility of the hip using 2 criteria: the Beighton 9-point physical examination criteria and the Hakim-Grahame 5-item history questionnaire. Diagnosis, age, sex, and race were tested as predictors of hypermobility. Patient-reported outcome scores from the International Hip Outcome Tool (iHOT-12) and the modified Harris hip score (mHHS) were also assessed. RESULTS: DDH was the primary diagnosis in 33.2% of the patient population. Patients who had dysplasia without osteoarthritis (OA) had a significantly elevated prevalence of GJH (77.9%) compared with those with nondysplastic hips (32.8%; p < 0.0001) or with patients who had dysplasia and OA (35.7%; p < 0.0001) according to either method. The odds ratio (OR) for patients with DDH versus those with other diagnoses was 7.1 (95% confidence interval [CI]: 5.1 to 10.0). The prevalence of hypermobility was significantly greater in females than in males (OR = 4.2 [95% CI: 3.2 to 5.5]; p < 0.0001). The prevalence of GJH was inversely proportional to age. There was a significantly reduced prevalence of GJH observed in Hispanic patients (p < 0.05) compared with other races. GJH was not a predictor of patient-reported outcome scores (p = 0.51 for iHOT-12 and p = 0.44 for mHHS). CONCLUSIONS: To our knowledge, this study is the first to establish a strong association between hypermobility and DDH in adults, confirming the hypothesis. We recommend utilizing both the Beighton and Hakim-Grahame scoring systems together as routine components of the history and physical examination for patients with hip dysplasia. Further research is warranted to explore the genetic basis and potential causal relationships between soft-tissue laxity and skeletal dysplasia, as well as improvements in assessment tools. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Clinicopathological features of squamous cell carcinoma of the oral cavity and oropharynx in young patients.

Our aim was to examine the clinicopathological features of squamous cell carcinoma (SCC) of the oral cavity and oropharynx in a group of young patients who were dignosed during a 15-year period (2000-2014). Patients' clinical details, risk factors, and survival were obtained from medical records. Formalin-fixed, paraffin-embedded, tissue was tested for high-risk human papillomavirus (HPV). The results were compared with those of a matching group of older patients. We identified 91 patients who were younger than 45 years old, and the 50 youngest patients were studied in detail. The male:female ratio was 2:1, with more tumours located in the oral cavity than in the oropharynx (35 compared with 15). HPV-related SCC was restricted to the oropharynx. When matched for site, stage and HPV status, five-year overall survival was similar in young and matched older patients (log-rank test, p=0.515). Our findings suggest that young patients with oral SCC have a disease profile similar to that of older patients with the condition. It is plausible that prognostic information generally available for oral cancers is applicable to young patients with the disease.

A quarter of patients with type 1 diabetes have co-existing non-islet autoimmunity: the findings of a UK population-based family study.

Individuals with type 1 diabetes (T1D) are at increased risk of coeliac disease (CD), autoimmune thyroiditis and autoimmune gastritis, but the absolute risks are unclear. The aim of this study was to investigate the prevalence of autoantibodies to tissue transglutaminase (TGA), thyroid peroxidase (TPOA) and gastric H+ /K+ -ATPase (ATPA) and their genetic associations in a well-characterized population-based cohort of individuals with T1D from the Bart's-Oxford family study for whom islet autoantibody prevalence data were already available. Autoantibodies in sera from 1072 patients (males/females 604/468; median age 11·8 years, median T1D duration 2·7 months) were measured by radioimmunoassays; HLA class II risk genotype was analysed in 973 (91%) using polymerase chain reaction with sequence specific primers (PCR-SSP). The prevalence of TGA (and/or history of CD), TPOA and ATPA in patients was 9·0, 9·6 and 8·2%, respectively; 3·1% had two or more autoantibodies. Females were at higher risk of multiple autoimmunity; TGA/CD were associated with younger age and TPOA with older age. ATPA were uncommon in patients under 5 years, and more common in older patients. Anti-glutamate decarboxylase autoantibodies were predictive of co-existing TPOA/ATPA. TGA/CD were associated with human leucocyte antigen (HLA) DR3-DQ2, with the DR3-DQ2/DR3-DQ2 genotype conferring the highest risk, followed by DR4-DQ8/DR4-DQ8. ATPA were associated with DR3-DQ2, DRB1*0404 (in males) and the DR3-DQ2/DR4-DQ8 genotype. TPOA were associated with the DR3-DQ2/DR3-DQ2 genotype. Almost one-quarter of patients diagnosed with T1D aged under 21 years have at least one other organ-specific autoantibody. HLA class II genetic profiling may be useful in identifying those at risk of multiple autoimmunity.

Genotype by random environmental interactions gives an advantage to non-favored minor alleles.

Fixation probability, the probability that the frequency of a newly arising mutation in a population will eventually reach unity, is a fundamental quantity in evolutionary genetics. Here we use a number of models (several versions of the Moran model and the haploid Wright-Fisher model) to examine fixation probabilities for a constant size population where the fitness is a random function of both allelic state and spatial position, despite neither allele being favored on average. The concept of fitness varying with respect to both genotype and environment is important in models of cancer initiation and progression, bacterial dynamics, and drug resistance. Under our model spatial heterogeneity redefines the notion of neutrality for a newly arising mutation, as such mutations fix at a higher rate than that predicted under neutrality. The increased fixation probability appears to be due to rare alleles having an advantage. The magnitude of this effect can be large, and is an increasing function of the spatial variance and skew in fitness. The effect is largest when the fitness values of the mutants and wild types are anti-correlated across environments. We discuss results for both a spatial ring geometry of cells (such as that of a colonic crypt), a 2D lattice and a mass-action (complete graph) arrangement.

Exposure-Response Analysis of Necitumumab Efficacy in Squamous Non-Small Cell Lung Cancer Patients.

We sought to describe the exposure-response relationship of necitumumab efficacy in squamous non-small cell lung cancer patients and evaluate intrinsic and extrinsic patient descriptors that may guide dosing. SQUIRE was a phase III study comparing necitumumab in combination with gemcitabine and cisplatin vs. gemcitabine and cisplatin alone in 1,014 patients. An integrated model for tumor size dynamics and overall survival was developed, where reduction in tumor size results in a decrease in survival hazard. The change in tumor size was characterized using linear growth and first-order shrinkage. Overall survival was described using a combination of a Weibull function and Gompertz function for the hazard, with dynamic tumor size being a predictor for the hazard. Although body weight resulted in higher clearance and lower exposure, simulations showed that an 800 mg flat dose provided optimal response regardless of body weight.

Mitochondrial stress-induced p53 attenuates HIF-1α activity by physical association and enhanced ubiquitination.

Retrograde signaling is a mechanism by which mitochondrial dysfunction is communicated to the nucleus for inducing a metabolic shift essential for cell survival. Previously, we showed that partial mitochondrial DNA (mtDNA) depletion in different cell types induced mitochondrial retrograde signaling pathway (MtRS) involving Ca+2-sensitive Calcineurin (Cn) activation as an immediate upstream event of stress response. In multiple cell types, this stress signaling was shown to induce tumorigenic phenotypes in immortalized cells. In this study we show that MtRS also induces p53 expression, which was abrogated by Ca2+ chelators and short hairpin RNA-mediated knockdown of CnAß mRNA. Mitochondrial dysfunction induced by mitochondrial ionophore, carbonyl cyanide m-chlorophenyl hydrazone and other respiratory inhibitors, which perturb the transmembrane potential, were equally efficient in inducing the expression of p53 and downregulation of MDM2. Stress-induced p53 physically interacted with hypoxia-inducible factor-1α (HIF-1α) and attenuated the latter's binding to promoter DNA motifs. In addition, p53 promoted ubiquitination and degradation of HIF-1α in partial mtDNA-depleted cells. The mtDNA depleted cells, with inhibited HIF-1α, showed upregulation of glycolytic pathway genes, glucose transporter 1-4 (Glut1-4), phosphoglycerate kinase 1 and Glucokinase but not of prolyl hydroxylase isoforms. For the first time we show that p53 is induced as part of MtRS and it renders HIF-1α inactive by physical interaction. In this respect, our results show that MtRS induces tumor growth independent of the HIF-1α pathway.

[Expression and significance of miR-210 in the epididymis in rats with varicocele and following varicocelectomy].

Objective: To investigate the expression of microRNA 210 (miR-210) in the epididymis of rats with varicocele and changes in miR-210 expression following high spermatic vein ligation, so as to explore the significance of the surgery in treating varicocele. Methods: A total of 21 male Sprague-Dawley (SD) rats aged 7 weeks were randomly divided into control group (n=7), experimental group (n=7), and surgical group (n=7). Varicocele model was established in both the experimental and surgical groups, while only vein isolation was performed in the control group. After 8 weeks, spermatic vein diameter were measured in the control and experimental rats, and collected the left epididymis (fixed in formaldehyde and frozen in refrigerator at -80 ℃). In the surgical group, left high spermatic vein ligation was performed, and the left epididymis was collected after 4 weeks as in the control and the experimental groups. The fixed epididymis tissues were treated with HE staining for observation of tissue injuries. The miR-210 expression in the epididymis was detected with reverse transcription-polymerase chain reaction (RT-PCR). At last every group had 5 rats. Results: The pathological examination showed that the number and distribution of mature sperms in epididymal duct in the experimental group were lower and less even compared to the control group, while the two indicators in the surgical group were better than those in the experimental group. The diameter of the left spermatic vein in the experimental group and pre-treatment surgical group were significantly enlarged than in the control group (P<0.01). The expression of miR-210 in the left epididymis in the experimental group was significantly higher compared with the control group(1.32±0.06 vs 0.98±0.14, P<0.01), while the expression of miR-210 in the left epididymis in the surgical group was significantly decreased compared with the experimental group (0.96±0.16 vs 1.32±0.06, P<0.01); the difference between the control group and the surgical group was not statistically significant (P>0.05). Conclusion: The expression of miR-210 in the epididymis may be increased by varicocele and reduced after high ligation of the affected spermatic vein.

Clinical characteristics and risk factors of postoperative pneumonia after hip fracture surgery: a prospective cohort study.

UNLABELLED: In this study, we attempt to determine the clinical characteristic and risk factors of postoperative pneumonia (POP) after hip fracture surgery in a well-defined hip fracture cohort. We find that intrinsic factors as well as major clinical interventions were all important risk factors of POP. INTRODUCTION: Postoperative pneumonia (POP) is one of the major complications following hip fractures surgery. However, the risk factors of POP are not well studied in hip fracture cohorts. We attempt to determine the clinical characteristic and risk factors of POP after hip fracture surgery in a well-defined hip fracture cohort. METHODS: Datasets from a prospective hip fracture cohort study with a 2-year follow-up period, from 2000 to 2011, were reanalyzed for characteristics of POP. Multivariate Cox proportional regression was used to evaluate the association between the incidence of POP and all-cause mortality. Multivariate logistic regression was used to screen for potential risk factors of POP by analyzing demographic factors, comorbidities, major clinical interventions, and hematological parameters. RESULTS: In 1429 patients who underwent hip surgery, the incidence of POP was 4.9 % (n = 70). All-cause mortality of patients with POP was significantly higher than that of patients without POP at 30 days (hazard ratio (HR) 3.05, 95 % confidence intervals (CI) 1.88-4.94), 1 year (HR 1.87, 95 % CI 1.41-2.48), and 2 years (HR 1.57, 95 % CI 1.23-1.99) postoperatively. Multivariate logistic regression showed that intrinsic factors (advanced age, anemia, diabetes, prior stroke, number of comorbidities, ASA score ≥III, and some laboratory biomarkers) as well as major clinical interventions were all significant risk factors for POP. CONCLUSION: Intrinsic factors and major clinical interventions were all important risk factors of POP in patients after hip fracture surgery. Targeted preventive measures to mitigate the above risk factors may help in reducing the incidence of POP.

Contact system revisited: an interface between inflammation, coagulation, and innate immunity.

The contact system is a plasma protease cascade initiated by factor XII (FXII) that activates the proinflammatory kallikrein-kinin system and the procoagulant intrinsic coagulation pathway. Anionic surfaces induce FXII zymogen activation to form proteolytically active FXIIa. Bacterial surfaces also have the ability to activate contact system proteins, indicating an important role for host defense using the cooperation of the inflammatory and coagulation pathways. Recent research has shown that inorganic polyphosphate found in platelets activates FXII in vivo and can induce coagulation in pathological thrombus formation. Experimental studies have shown that interference with FXII provides thromboprotection without a therapy-associated increase in bleeding, renewing interest in the FXIIa-driven intrinsic pathway of coagulation as a therapeutic target. This review summarizes how the contact system acts as the cross-road of inflammation, coagulation, and innate immunity.

Factor XII: a novel target for safe prevention of thrombosis and inflammation.

Plasma protein factor XII (FXII) activates the procoagulant and proinflammatory contact system that drives both the kallikrein-kinin system and the intrinsic pathway of coagulation. When zymogen FXII comes into contact with negatively charged surfaces, it auto-activates to the serine proteaseactivated FXII (FXIIa). Recently, various in vivo activators of FXII have been identified including heparin, misfolded protein aggregates, polyphosphate and nucleic acids. Murine models have established a central role of FXII in arterial and venous thrombosis. Despite its central function in thrombosis, deficiency in FXII does not impair haemostasis in animals and humans. In a preclinical cardiopulmonary bypass system in large animals, the FXIIa-blocking antibody 3F7 prevented thrombosis; however, in contrast to traditional anticoagulants, bleeding was not increased. In addition to its function in thrombosis, FXIIa initiates formation of the inflammatory mediator bradykinin. This mediator increases vascular leak, causes vasodilation, and induces chemotaxis with implications for septic, anaphylactic and allergic disease states. Therefore, targeting FXIIa appears to be a promising strategy for thromboprotection without associated bleeding risks but with anti-inflammatory properties.

Mitochondrial SOD2 regulates epithelial-mesenchymal transition and cell populations defined by differential CD44 expression.

Epithelial-mesenchymal transition (EMT) promotes cancer cell invasion, metastasis and treatment failure. EMT may be activated in cancer cells by reactive oxygen species (ROS). EMT may promote conversion of a subset of cancer cells from a CD44(low)-CD24(high) (CD44L) epithelial phenotype to a CD44(high)-CD24(-/low) (CD44H) mesenchymal phenotype, the latter associated with increased malignant properties of cancer cells. ROS are required for cells undergoing EMT, although excessive ROS may induce cell death or senescence; however, little is known as to how cellular antioxidant capabilities may be regulated during EMT. Mitochondrial superoxide dismutase 2 (SOD2) is frequently overexpressed in oral and esophageal cancers. Here, we investigate mechanisms of SOD2 transcriptional regulation in EMT, as well as the functional role of this antioxidant in EMT. Using well-characterized genetically engineered oral and esophageal human epithelial cell lines coupled with RNA interference and flow cytometric approaches, we find that transforming growth factor (TGF)-ß stimulates EMT, resulting in conversion of CD44L to CD44H cells, the latter of which display SOD2 upregulation. SOD2 induction in transformed keratinocytes was concurrent with suppression of TGF-ß-mediated induction of both ROS and senescence. SOD2 gene expression appeared to be transcriptionally regulated by NF-κB and ZEB2, but not ZEB1. Moreover, SOD2-mediated antioxidant activity may restrict conversion of CD44L cells to CD44H cells at the early stages of EMT. These data provide novel mechanistic insights into the dynamic expression of SOD2 during EMT. In addition, we delineate a functional role for SOD2 in EMT via the influence of this antioxidant upon distinct CD44L and CD44H subsets of cancer cells that have been implicated in oral and esophageal tumor biology.

EVERSUN: a phase 2 trial of alternating sunitinib and everolimus as first-line therapy for advanced renal cell carcinoma.

BACKGROUND: We hypothesised that alternating inhibitors of the vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin pathways would delay the development of resistance in advanced renal cell carcinoma (aRCC). PATIENTS AND METHODS: A single-arm, two-stage, multicentre, phase 2 trial to determine the activity, feasibility, and safety of 12-week cycles of sunitinib 50 mg daily 4 weeks on / 2 weeks off, alternating with everolimus 10 mg daily for 5 weeks on / 1 week off, until disease progression or prohibitive toxicity in favourable or intermediate-risk aRCC. The primary end point was proportion alive and progression-free at 6 months (PFS6m). The secondary end points were feasibility, tumour response, overall survival (OS), and adverse events (AEs). The correlative objective was to assess biomarkers and correlate with clinical outcome. RESULTS: We recruited 55 eligible participants from September 2010 to August 2012. DEMOGRAPHICS: mean age 61, 71% male, favourable risk 16%, intermediate risk 84%. Cycle 2 commenced within 14 weeks for 80% of participants; 64% received ≥22 weeks of alternating therapy; 78% received ≥22 weeks of any treatment. PFS6m was 29/55 (53%; 95% confidence interval [CI] 40% to 66%). Tumour response rate was 7/55 (13%; 95% CI 4% to 22%, all partial responses). After median follow-up of 20 months, 47 of 55 (86%) had progressed with a median progression-free survival of 8 months (95% CI 5-10), and 30 of 55 (55%) had died with a median OS of 17 months (95% CI 12-undefined). AEs were consistent with those expected for each single agent. No convincing prognostic biomarkers were identified. CONCLUSIONS: The EVERSUN regimen was feasible and safe, but its activity did not meet pre-specified values to warrant further research. This supports the current approach of continuing anti-VEGF therapy until progression or prohibitive toxicity before changing treatment. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12609000643279.

c-MYC is a radiosensitive locus in human breast cells.

Ionising radiation is a potent human carcinogen. Epidemiological studies have shown that adolescent and young women are at increased risk of developing breast cancer following exposure to ionising radiation compared with older women, and that risk is dose-dependent. Although it is well understood which individuals are at risk of radiation-induced breast carcinogenesis, the molecular genetic mechanisms that underlie cell transformation are less clear. To identify genetic alterations potentially responsible for driving radiogenic breast transformation, we exposed the human breast epithelial cell line MCF-10A to fractionated doses of X-rays and examined the copy number and cytogenetic alterations. We identified numerous alterations of c-MYC that included high-level focal amplification associated with increased protein expression. c-MYC amplification was also observed in primary human mammary epithelial cells following exposure to radiation. We also demonstrate that the frequency and magnitude of c-MYC amplification and c-MYC protein expression is significantly higher in breast cancer with antecedent radiation exposure compared with breast cancer without a radiation aetiology. Our data also demonstrate extensive intratumor heterogeneity with respect to c-MYC copy number in radiogenic breast cancer, suggesting continuous evolution at this locus during disease development and progression. Taken together, these data identify c-MYC as a radiosensitive locus, implicating this oncogenic transcription factor in the aetiology of radiogenic breast cancer.

Computed tomography follow-up of acute portal vein thrombosis.

PURPOSE: To assess the evolution of acute portal vein thrombosis by computed tomography (CT). PATIENTS AND METHODS: Retrospective single-centre study (2005-2011) including 23 patients who had an initial CT scan and a CT scan during the first year. The analysis compared the last CT scan available with that of the initial CT scan. Neoplastic thrombosis, extrinsic compressions and cavernomas were excluded. All patients received anticoagulant treatment. RESULTS: The causes included: cirrhoses (n = 6), blood disorders (n = 4), locoregional inflammations and infections (n = 8), abdominal surgery (n = 1). The thrombosis was idiopathic in 4 cases. After a mean follow-up of 7.7 months, 7 patients (30%) benefited from a restitutio ad integrum of the portal system, a stable or partially regressive thrombosis was noted in 12 patients (52%) and an aggravation of the thrombosis was noted in 4 patients (18%). In the sub-group of portal vein thrombosis, repermeabilisation was noted in 37.5% of the patients (6/16) and 6 cavernomas developed. CONCLUSION: CT monitoring helps follow the evolution of an acute portal vein thrombosis and demonstrates complete repermeabilisation of the portal vein in 30% of the patients.

Measurement of maximum diameter of native abdominal aortic aneurysm by angio-CT: reproducibility is better with the semi-automated method.

OBJECTIVES: We sought to identify the technique yielding the best reproducibility from among various measures of native maximum abdominal aortic aneurysm (AAA) diameter with computed tomography angiography (CTA). METHODS: Ten parameters of maximum diameter in 68 native AAA were measured double-blind by three radiologists on orthogonal planes, curved multiplanar reconstructions, and, finally, using semi-automated software. The semi-automated software creates the AAA lumen centreline and automatically provides cross sections perpendicular to this centreline. The maximum diameter in any direction is automatically calculated once the slice of interest has been selected. Intra- and inter-observer reproducibility and discordance >5 mm were analysed. RESULTS: Intra-observer reproducibility was high. The limits of agreement were within the clinically accepted range [-5; +5 mm] in 27/30 (90%) comparisons. The method common to all three observers that yielded the lowest values was the semi-automated method. Inter-observer reproducibility was poorer. The limits were outside the clinically accepted range in 26/30 (87%) comparisons. The semi-automated method led to lower intra- (0%) and inter-observer (5.88%) discordances rates. CONCLUSION: Even using precise methodology, the reproducibility of maximum diameter measurements of native AAA on CTA may exceed recommended thresholds. The semi-automatic method yielded the lower discordance rates and provided a more relevant anatomical approach for measuring the maximum diameter of an AAA.

Three-dimensional ultrasound improves the accuracy of diameter measurement of the residual sac in EVAR patients.

OBJECTIVES: Discrepancy between maximum diameters obtained with two-dimensional ultrasound and computed tomography (CT) after endovascular aneurysm repair (EVAR) is well known. The maximal diameter is ideally measured perpendicular to the centerline, a methodology so far only feasible with three-dimensional (3D) CT and magnetic resonance angiography (MRA). We aimed to investigate the agreement between 3D ultrasound and 3D CT and to determine reproducibility measures. METHODS: Prospective study comparing 3D ultrasound with 3D CT in 124 consecutive patients seen 3 or 12 month after EVAR. RESULTS: Replacing 2D with 3D ultrasound, the mean difference was improved from 6.0 mm to -1.3 mm (p < .001), and the range of variability was reduced from 9.4 mm to 6.6 mm (p = .009) using 3D CT as the gold standard. The mean difference between 3D ultrasound and 3D CT maximum diameter of the residual sac was -1.3 mm with upper and lower limits of agreement of 5.2 mm and -7.9 mm, respectively. Reproducibility measures of 3D ultrasound were ± 4 mm. CONCLUSION: 3D ultrasound correlate significantly better to 3D CT than the currently used 2D ultrasound method when assessing maximum diameter of the residual sac after EVAR, and reproducibility measures were within clinical acceptable values.