Large European Multicenter Study Research Articles

Temperature guided high and very high-power short duration ablation for atrial fibrillation treatment - The peQasus multicentre study.

Temperature-controlled high-power short-duration (HPSD) radiofrequency catheter ablation for pulmonary vein isolation (PVI) utilizing a novel ablation catheter (QDOT Micro) with real-time assessment of catheter tip temperature aims for safer, more effective and faster procedures. The peQasus study is a large European multicenter study set up to assess safety, acute efficacy and outcomes of temperature-controlled HPSD based PVI. The primary endpoints were safety, efficacy and 12-months freedom from atrial tachyarrhythmias. Additionally, two strategies namely very HPSD (90W for 4 seconds) only and a hybrid approach (HPSD with maximum of 50W and vHPSD) were compared. A total of 1,023 AF patients in 15 centers from 9 European countries received PVI with the QDOT. Complete PVI was successfully achieved in all patients. In 699/1023 (68.3%) the vHPSD only approach (vHPSD group) and in 324/(31.7%) patients the hybrid approach (hybrid group) was utilized. The mean procedure duration was 98.4±37.4 min (vHPSD: 88.2±34.9min, hybrid: 117.4±32.7min, p<0.001). The first pass isolation rate of all PVs was 64% (vHPSD: 62.6%, hybrid: 67.1%, p=0.187). Severe adverse events were observed in 1.7% (vHPSD: 1.6%, hybrid: 1.9%, p=0.746). 12-month arrhythmia-recurrence free survival was 77.1% (vHPSD: 76.8%, hybrid: 77.8%, p=0.241). In this large multicentre study temperature-controlled HPSD and vHPSD ablation via a novel ablation catheter provides safe and effective PVI with a relatively short procedure duration. Despite a shorter procedure time no differences in terms of safety and freedom from arrhythmia-recurrence were found irrespective of utilizing vHPSD or the hybrid approach.

FRI-282 - Validation of serum biomarker panels for early HCC detection: results from a large prospective European and Latin American multicenter study

FRI-282 - Validation of serum biomarker panels for early HCC detection: results from a large prospective European and Latin American multicenter study

Real-world outcomes of patients with intrahepatic cholangiocarcinoma treated with trans-arterial radioembolization: Results from the CIRSE Registry for SIR-Spheres Therapy (CIRT), a large European prospective multi-center observational study.

308 Background: Trans-arterial radioembolization (TARE) is a treatment option for patients with intrahepatic cholangiocarcinoma (ICC). The CIRSE Registry for SIR-Spheres Therapy (CIRT) is the first European prospective multi-centre observational study designed to evaluate the clinical outcomes of patients treated with TARE with SIR-Spheres Y90 resin microspheres for ICC in the multi-institutional real-life clinical setting. The study was conducted by the Cardiovascular and Interventional Radiological Society of Europe (CIRSE). Methods: Patients were enrolled prospectively between Jan 2015 and 31 Dec 2017. Eligible patients were adults treated with TARE with Y90 resin microspheres for ICC. Data on baseline characteristics and treatment intention/clinical context and dosimetry were collected, as well as follow-up data (every 3 months; for 24 months after treatment), including overall survival (OS), (hepatic) progression-free survival [(h)PFS], safety and Global Health Status (GHS, using the European Organisation for the Research and Treatment of Cancer QLQ-C30). Results: 120 patients were included from 18 sites in 8 European countries. Median age was 63 years (range: 29-86) and 54.2% were male. Median tumour to liver percentage was 12.8%. Median prescribed activity was 1.32 GBq for whole liver treatments (n = 49), 1.20 GBq for right lobe treatments (n = 56) and 0.82 GBq for left lobe treatments (n = 51). 97.5% of the delivered activity was within 90% of the prescribed activity. TARE treatment as a first line (L1) global strategy was applied in 39.1%, 27.4% as second line (after systemic therapy). Treatment intention was predominantly palliative (69.2%) or tumour shrinkage (20.8%). Median OS was 14.7 months (95% confidence interval (CI) 10.9 – 17.9). Median PFS was 5.7 months (95% CI 3.9 – 7.5), whereas hPFS was 6.2 months (95% CI 4.1 – 8.5). Mean GHS was 59.3 at baseline, 61.0 after 3 months, 56.0 at 6 months, 54.4 at 9 months and 63.0 after 1 year. Severe adverse events (grade 3 and 4) were found in 13 (10.8%) patients: (abdominal pain 3.3%, fatigue 1.7%, gastrointestinal ulceration 0.8%, gastritis 0.8%, radiation cholecystitis 0.8%, radiation-induced liver disease 1.7%, other 5.8%). Detailed subgroup analyses are currently being performed. Updated data describing OS, PFS and hPFS for L1 TARE vs TARE after systemic chemotherapy, as well as prognostic factors for OS, PFS and hPFS will be shown. Conclusions: The results from this large prospective multi-centre observational study shows that in the real-world context, TARE is applied early and successfully in the treatment pathway. TARE is shown to be an effective and safe treatment with no meaningful deterioration of quality of life. Clinical trial information: NCT02305459.

Methylation markers FAM19A4 and miR124-2 as triage strategy for primary human papillomavirus screen positive women: A large European multicenter study.

In human papillomavirus (HPV) cervical cancer screening, cytology is used as triage to counter the low specificity of HPV testing. VALID‐SCREEN is a EU‐multicenter, retrospective study conducted to evaluate the clinical performance of the FAM19A4/miR124‐2 methylation‐based molecular triage test as a substitute or addition to cytology as reflex testing of HPV screen positive women. FAM19A4/miR124‐2 methylation test (QIAsure Methylation Test) was evaluated in 2384 HPV‐positive cervical screening samples, from women 29‐76 years of age, derived from four EU countries. Specimens were collected in ThinPrep or SurePath media, HPV‐status, concurrent cytology, and histology diagnosis were provided by the parent institutes. The control population consisted of women with no evidence of disease within 2 years of follow‐up. A total of 899 histologies were retrieved; 527 showed no disease, 124 CIN2 (5.2%), 228 CIN3 (9.6%) and 20 cervical cancers (0.8%); 19 of 20 screen‐detected cervical cancers were found methylation‐positive (sensitivity 95%). Overall specificity of FAM19A4/miR124‐2 methylation test was 78.3% (n = 2013; 95%CI: 76‐80). The negative predictive value of hrHPV positive, methylation‐negative outcomes were 99.9% for cervical cancer (N = 1694; 95%CI: 99.6‐99.99), 96.9% for ≥CIN3 (95%CI: 96‐98), and 93.0% for ≥CIN2 (95%CI: 92‐94). Overall sensitivity for CIN3 using FAM19A4/miR124‐2 methylation test was 77% (n = 228; 95%CI: 71‐82). CIN3 sensitivity was uniform between centers independent of sample collection medias, DNA extraction methods and HPV screening tests. Being objectively reported compared to the subjectivity of cytology, equally performing across settings and screening methods, the FAM19A4/miR124‐2 methylation constitute an alternative/supplement to cytology as triage method to be investigated in real‐life pilot implementation.

High/low-volume center experience predicts outcome of AMS 800 in male stress incontinence: Results of a large middle European multicenter case series.

To analyze the influence of implantation volume of artificial sphincters (AMS 800) on outcome in a large central European multicenter cohort study. As part of the DOMINO (Debates on Male Incontinence) project, the surgical procedures and outcomes were retrospectively analyzed in a total of 473 patients who received an artificial sphincter (AMS 800) between 2010 and 2012. Clinics that implanted at least 10 AMS 800 per year were defined as high-volume centers. Sixteen centers had a mean rate of 9.54 AMS 800/y of which five clinics were identified as high-volume centers. They implanted significantly more double cuffs (55% vs 12.1%; P < .001), used the perineal approach significantly more often (78% vs 67.7%; P = .003) and chose larger mean cuff sizes (4.63 cm vs 4.42 cm; P = .002). With a mean follow-up of 18 months, the revision rate was significantly higher at low-volume centers (38.5% vs 26.7%; P = .037), urethral erosion being the main reason for revision. Social continence (0-1 pads/24 h) was achieved significantly more often in high-volume centers (45.5% vs 24.2%; P = .002). Our study showed significantly better continence results and lower revision rates at high-volume centers, confirming earlier results that are still true in this decade. We, therefore, recommend surgery for male incontinence at qualified centers.

How do 66 European institutional review boards approve one protocol for an international prospective observational study on traumatic brain injury? Experiences from the CENTER-TBI study

BackgroundThe European Union (EU) aims to optimize patient protection and efficiency of health-care research by harmonizing procedures across Member States. Nonetheless, further improvements are required to increase multicenter research efficiency. We investigated IRB procedures in a large prospective European multicenter study on traumatic brain injury (TBI), aiming to inform and stimulate initiatives to improve efficiency.MethodsWe reviewed relevant documents regarding IRB submission and IRB approval from European neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI). Documents included detailed information on IRB procedures and the duration from IRB submission until approval(s). They were translated and analyzed to determine the level of harmonization of IRB procedures within Europe.ResultsFrom 18 countries, 66 centers provided the requested documents. The primary IRB review was conducted centrally (N = 11, 61%) or locally (N = 7, 39%) and primary IRB approval was obtained after one (N = 8, 44%), two (N = 6, 33%) or three (N = 4, 23%) review rounds with a median duration of respectively 50 and 98 days until primary IRB approval. Additional IRB approval was required in 55% of countries and could increase duration to 535 days. Total duration from submission until required IRB approval was obtained was 114 days (IQR 75–224) and appeared to be shorter after submission to local IRBs compared to central IRBs (50 vs. 138 days, p = 0.0074).ConclusionWe found variation in IRB procedures between and within European countries. There were differences in submission and approval requirements, number of review rounds and total duration. Research collaborations could benefit from the implementation of more uniform legislation and regulation while acknowledging local cultural habits and moral values between countries.

Predictors of oropharyngeal cancer survival in Europe

ObjectivesHPV16-positive oropharyngeal cancer (OPC) patients experience better outcomes compared to HPV16-negative patients. Currently, strategies for treatment de-escalation are based on HPV status, smoking history and disease stage. However, the appropriate cut-point for smoking and the role of other non-clinical factors in OPC survival remains uncertain. Materials and MethodsWe examined factors associated with OPC outcome in 321 patients recruited in a large European multi-center study. Seropositivity for HPV16 E6 was used as a marker of HPV16 positive cancer. Hazard ratios (HR) and confidence intervals (CI) were estimated using Cox proportional models adjusted for potential confounders. ResultsOverall 5-year survival following OPC diagnosis was 50%. HPV16-positive OPC cases were at significantly lower risk of death (aHR = 0.51, 95% CI: 0.32–0.80). A significant effect on OPC survival was apparent for female sex (aHR 0.50: 95% CI: 0.29–0.85) and being underweight at diagnosis (aHR: 2.41, 95% CI: 1.38–4.21). A 10 pack year smoking history was not associated with overall survival. Higher stage at diagnosis appeared as the only factor significantly associated with OPC recurrence (aHR: 4.88, 95% CI: 2.12–11.21). ConclusionThis study confirms that HPV16 status is an independent prognostic factor for OPC survival while female sex lowers risk of death and being underweight at diagnosis increases the risk of death. Smoking was not an independent predictor of OPC survival.

Estimation of the overall burden of cancers, precancerous lesions, and genital warts attributable to 9-valent HPV vaccine types in women and men in Europe

BackgroundIn addition to cervical cancer, human papillomavirus (HPV) is responsible for a significant proportion of cancers and precancerous lesions of the vulva, vagina, anus, penis, head and neck, as well as genital warts. We estimated the annual number of new cases of these diseases attributable to 9-valent HPV vaccine types in women and men in Europe.MethodsThe annual number of new cancers of the cervix, vulva, vagina, anus, penis, and selected head and neck sites in the population of the European Medicines Agency territory was estimated based on age-specific incidence rates extracted from Cancer Incidence in 5 Continents, Volume X and Eurostat population data for 2015. The annual number of new cancers attributable to 9-valent HPV vaccine types was estimated by applying the HPV attributable fraction from reference publications based on a large European multicenter study. For non-cervical cancers, HPV attributable fractions were based on oncogenically-active HPV infections only (i.e., detection of HPV DNA and either mRNA and/or p16 positivity). For precancerous lesions of the cervix, vulva, vagina, and anus, and for genital warts, previously published estimations were updated for the 2015 population.ResultsThe annual number of new cancers attributable to 9-valent HPV vaccine types was estimated at 47,992 (95% bound: 39,785-58,511). Cervical cancer showed the highest burden (31,130 cases), followed by head and neck cancer (6,786 cases), anal cancer (6,137 cases), vulvar cancer (1,466 cases), vaginal cancer (1,360 cases), and penile cancer (1,113 cases). About 81% were estimated to occur in women and 19% in men. The annual number of new precancerous lesions (CIN2+, VIN2/3, VaIN2/3, and AIN2/3) and genital warts attributable to 9-valent HPV vaccine types was estimated at 232,103 to 442,347 and 680,344 to 844,391, respectively.ConclusionsThe burden of cancers associated with 9-valent HPV vaccine types in Europe is substantial in both sexes. Head and neck cancers constitute a heavy burden, particularly in men. Overall, about 90% of HPV-related cancers, 80% of precancerous lesions, and 90% of genital warts are expected to be attributable to 9-valent HPV vaccine types each year, demonstrating the important preventive potential of the 9-valent HPV vaccine in Europe.

The role of neuromedin U in adiposity regulation. Haplotype analysis in European children from the IDEFICS Cohort.

Background and aimsNeuromedin U (NMU) is a hypothalamic neuropeptide with important roles in several metabolic processes, recently suggested as potential therapeutic target for obesity. We analysed the associations between NMU gene variants and haplotypes and body mass index (BMI) in a large sample of European children.Methods and resultsFrom a large European multi-center study on childhood obesity, 4,528 children (2.0–9.9 years, mean age 6.0±1.8 SD; boys 52.2%) were randomly selected, stratifying by age, sex and country, and genotyped for tag single nucleotide polymorphisms (SNPs; rs6827359, T:C; rs12500837, T:C; rs9999653,C:T) of NMU gene, then haplotypes were inferred. Regression models were applied to estimate the associations between SNPs or haplotypes and BMI as well as other anthropometric measures. BMI was associated with all NMU SNPs (p<0.05). Among five haplotypes inferred, the haplotype carrying the minor alleles (CCT, frequency = 22.3%) was the only associated with lower BMI values (beta = -0.16, 95%CI:-0.28,-0.04, p = 0.006; z-score, beta = -0.08, 95%CI:-0.14,-0.01, p = 0.019) and decreased risk of overweight/obesity (OR = 0.81, 95%CI:0.68,0.97, p = 0.020) when compared to the most prevalent haplotype (codominant model). Similar significant associations were also observed using the same variables collected after two years’ time (BMI, beta = -0.25, 95%CI:-0.41,-0.08, p = 0.004; z-score, beta = -0.10, 95%CI:-0.18,-0.03, p = 0.009; overweight/obesity OR = 0.81, 95%CI:0.66,0.99, p = 0.036). The association was age-dependent in girls (interaction between CCT haplotypes and age, p = 0.008), more evident between 7 and 9 years of age. The CCT haplotype was consistently associated with lower levels of fat mass, skinfold thickness, hip and arm circumferences both at T0 and at T1, after adjustment for multiple testing (FDR-adjusted p<0.05).ConclusionsThis study shows an association between a NMU haplotype and anthropometric indices, mainly linked to fat mass, which appears to be age- and sex-specific in children. Genetic variations within or in linkage with this haplotype should be investigated to identify functional variants responsible for the observed phenotypic variation.

Abstract 13512: Chemokines and Carotid Intima-Media Thickness in a European Population at High Risk for Cardiovascular Events: Results From the IMPROVE Study

Background: Experimental studies indicate that two archetype chemokines circulating in the blood, IL-8 and GRO-α, are critical for atherogenesis. However, their association with measures of subclinical atherosclerosis has not been investigated. Hypothesis: Here we test the hypothesis that circulating IL8 and GRO-α protein are associated with the carotid artery intima media thickness (c-IMT) in a large European multicenter study: the c-IMT and c-IMT Progression as Predictors of Vascular Events in a High Risk European Population ( IMPROVE ) study . Methods: IMPROVE study participants (n=3,703), recruited in 5 European Countries (Sweden, Finland, the Netherlands, France and Italy), had at least three cardiovascular (CV) risk factors but not prevalent CV diseases. C-IMT measures (mm) (c-IMT mean , c-IMT max and c-IMT mean-max ) were recorded at baseline. Each measurement represent the average of 8 (4 left and 4 right) carotid segments. IL8 and GRO-α were measured in plasma from 3,452 participants (women, n=1,784; men, n=1,668) using the Olink ProSeek CVD array I and expressed in arbitrary units. We evaluated the association, expressed as beta coefficient (β) and 95% confidence intervals (CI), between chemokines and c-IMT using median regression. Models were adjusted by sex, age, body mass index, hypertension, diabetes, current smokers, hypercholesterolemia and latitude. Results: Higher levels of IL8 and GRO-α were observed in participants from Northern Europe as compared to those from Southern Europe [IL8: 50 (41-62) vs 36 (28-49) and GRO-α 108 (70-176) vs 42(22-95)]. At multivariable analysis only in men, levels of IL8 were positively associated with c-IMT measures: c-IMT mean [1.0 x 10 -4 (6.5 x 10 -5 -1.4 x 10 -4 ), p&lt;0.01], c-IMT max [(6.5 x 10 -4 ,(4.8 x 10 -4 -8.2 x 10 -4 ), p&lt;0.01] and c-IMT mean-max [1.7 x 10 -4 , (1.3 x 10 -4 -2.2 x 10 -4 ), p&lt;0.01]. No corresponding association was observed for GRO-α and c-IMT measurements. Conclusions: The chemokine IL8, but not GRO-α, was associated with baseline c-IMT in men at high risk of CV events. Furthermore, our results suggest the presence of a European north-to-south gradient in chemokine levels. New studies are warranted to disentangle potential differences between IL8 and CV risk across sexes.

Pancreaticobiliary Maljunctions in European Patients with Bile Duct Cysts: Results of the Multicenter Study of the French Surgical Association (AFC).

Pancreaticobiliary maljunctions (PBMs) are congenital anomalies of the junction between pancreatic and bile ducts, frequently associated with bile duct cyst (BDC). BDC is congenital biliary tree diseases that are characterized by distinctive dilatation types of the extra- and/or intrahepatic bile ducts. Todani's types I and IVa, in which dilatation involves principally the main bile duct, are the most frequent. PBM induces pancreatic juice reflux into the biliary tract that is supposed to be one of the main factors of biliary cancer degeneration, although the diagnostic criteria of PBM that can be either morphological and/or functional are not well defined especially in Western series. The aim of this study was to assess the relative prevalence of PBM in BDC in a large European multicenter study, to analyze the characteristics of PBM and try to propose diagnostic criteria of PBMs based on morphological and/or functional criteria and define the positive, negative predictive values, sensibility and specificity of either criteria. From 1975 to 2012, 263 patients with BDC were analyzed. Among them, 190 (72.2%) were considered to present PBM. Types I and IVa had a similar rate of PBM association. According to the "AFC classification," 57.2% had a C-P type, 34.5% a P-C type and 8.3% a complex type ("anse-de-seau"). The median length of the common channel in patients with PBM was 15.8±6.8mm (range 5-40mm). The median intrabiliary amylase and lipase levels were 65,249 and 172,104UI/L, respectively. For the diagnostic of PBM, a common channel length of more than 8mm and an intrabiliary amylase level superior to 8000UI/L were associated with a predictive positive value and a specificity of more than 90%. Synchronous biliary cancer had an incidence of 8.7% in all patients with BDC and PBM 11.1% in adults. Compared to type IV, the type I BDC was associated with statistically more cancer patients in the presence of PBM. Characteristics of PBM associated with BDC in Western population are quite close to reported Eastern series. The results suggest considering both the intrabiliary value of amylase >8000UI/L and a length of a common channel >8mm as appropriate values for positive diagnosis of PBM.

Intraductal papillary mucinous neoplasms.

Our understanding of intraductal papillary mucinous neoplasm (IPMN) of the pancreas has remarkably grown within the last decade; nonetheless there is still an ongoing controversy if the majority of these potentially malignant neoplasms need to be resected or if observation in a subset is well tolerated. Novel cyst fluid biomarkers, like Gnas mutations or mab DAS-1, could play a pivotal role in the distinction of IPMN vs. other cystic lesions, in the sub-classification of IPMN and in the detection of IPMN with high-grade dysplasia or invasive cancer. Other recent studies focused on natural history of minimal- and extensive-mixed IPMN and the safety of the 2012 AIP guidelines. Small series also described that observation can be an option in selected frail patients with MD-IPMN. Further, data from a large European multicenter study analysis indicated that patients with IPMN do not have an increased frequency of extrapancreatic malignancies. Increasing knowledge about the nature of IPMN and their subtypes has resulted in an individualized approach in diagnosis and treatment. Owing to the availability of accurate diagnostic instruments, timing and indication for pancreatic resection have become more selective, sparing patients with harmless IPMN from major surgery.

P0661 : Prediction of HBeAg seroconversion in HBeAg-positive chronic hepatitis B patients treated with entecavir using ALT and platelet count: Results from a large european multi-center study

P0661 : Prediction of HBeAg seroconversion in HBeAg-positive chronic hepatitis B patients treated with entecavir using ALT and platelet count: Results from a large european multi-center study

Pattern of Postoperative Mortality After Esophageal Cancer Resection According to Center Volume: Results from a Large European Multicenter Study.

High center procedural volume has been shown to reduce postoperative mortality (POM); however, the cause of POM has been poorly studied previously. The aim of this study was to define the pattern of POM and major morbidity in relation to center procedural volume. Data from 2,944 consecutive adult patients undergoing esophagectomy for esophageal cancer in 30 centers between 2000 and 2010 were retrospectively collected. Data between patients who suffered 30-day POM were compared with those who did not. Factors associated with POM were identified using binary logistic regression, with propensity matching to compare low- (LV) and high-volume (HV) centers. The 30-day and in-hospital POM rates were 5.0 and 7.3%, respectively. Pulmonary complications were the most common, affecting 38.1% of patients, followed by surgical site infection (15.5%), cardiovascular complications (11.2%), and anastomotic leak (10.2%). Factors that were independently associated with 30-day POM included American Society of Anesthesiologists grade IV, LV center, anastomotic leak, pulmonary, cardiovascular and neurological complications, and R2 resection margin status. Surgical complications preceded POM in approximately 30% of patients compared to medically-related causes in 68%. Propensity-matched analysis demonstrated LV centers were significantly associated with increased 30-day POM, and POM secondary to anastomotic leak, and pulmonary- and cardiac-related causes. The results of this large, multicenter study provide further evidence to support the centralization of esophagectomy to HV centers, with a lower rate of morbidity and better infrastructure to deal with complications following major surgery preventing further mortality.

Contrast Echocardiography: Current Applications and Future Perspectives

Contrast echocardiography is an established imaging method and an essential tool in every state of the art echocardiographic laboratory. It has also been the subject of several major clinical and research studies during the last year. This article addresses the impact of these studies on the clinical use of contrast echocardiography. Most recent studies have been performed with commercially available ultrasound contrast agents, which cross the pulmonary vasculature and are used for assessment of the left heart. The principle licensed indication for these contrast media is the delineation of left ventricular (LV) borders, masses, and aneurysms. The superiority of 2-dimensional contrast echocardiography over nonenhanced 2-dimensional imaging has been confirmed for assessment of LV volumes and ejection fraction, and there is growing evidence for the use of contrast 3-dimensional echocardiography. Two studies have demonstrated the usefulness of contrast-enhanced TEE for detection of thrombi in the left atrial appendage. The improved endocardial definition seen with ultrasound contrast media can also be used for strain analysis on selected systems. In stress echocardiography, contrast has been used for myocardial perfusion imaging in addition to assessment of regional LV wall motion. A large European multicenter study has demonstrated Sonovue-enhanced myocardial contrast echocardiography to be more sensitive than nuclear single photon emission computed tomography (SPECT) for the detection of significant coronary artery disease. Two further studies are discussed, which have demonstrated the impact of isolated perfusion defects on patients’ outcome. In addition, several publications have supplemented existing evidence regarding the safety of commercially available contrast agents. Recent studies continue to establish the usefulness and safety of contrast echocardiography for the currently licensed indications. There is also now good evidence for the use of myocardial contrast echocardiography as an alternative to nuclear imaging.

Comparison of Sulfur Hexafluoride Microbubble (SonoVue)-Enhanced Myocardial Contrast Echocardiography With Gated Single-Photon Emission Computed Tomography for Detection of Significant Coronary Artery Disease: A Large European Multicenter Study

The purpose of this study was to compare sulfur hexafluoride microbubble (SonoVue)-enhanced myocardial contrast echocardiography (MCE) with single-photon emission computed tomography (SPECT) relative to coronary angiography (CA) for assessment of coronary artery disease (CAD).Small-scale studies have shown that myocardial perfusion assessed by SonoVue-enhanced MCE is a viable alternative to SPECT for CAD assessment. However, large multicenter studies are lacking.Patients referred for myocardial ischemia testing at 34 centers underwent rest/vasodilator SonoVue-enhanced flash-replenishment MCE, standard (99m)Tc-labeled electrocardiography-gated SPECT, and quantitative CA within 1 month. Myocardial ischemia assessments by 3 independent, blinded readers for MCE and 3 readers for SPECT were collapsed into 1 diagnosis per patient per technique and were compared to CA (reference standard) read by 1 independent blinded reader.Of 628 enrolled patients who received SonoVue (71% males; mean age: 64 years; >1 cardiovascular [CV] risk factor in 99% of patients) 516 patients underwent all 3 examinations, of whom 161 (31.2%) had ≥70% stenosis (131 had single-vessel disease [SVD]; 30 had multivessel disease), and 310 (60.1%) had ≥50% stenosis. Higher sensitivity was obtained with MCE than with SPECT (75.2% vs. 49.1%, respectively; p < 0.0001), although specificity was lower (52.4% vs. 80.6%, respectively; p < 0.0001) for ≥70% stenosis. Similar findings were obtained for patients with ≥50% stenosis. Sensitivity levels for detection of SVD and proximal disease for ≥70% stenosis were higher for MCE (72.5% vs. 42.7%, respectively; p < 0.0001; 80% vs. 58%, respectively; p = 0.005, respectively).SonoVue-enhanced MCE demonstrated superior sensitivity but lower specificity for detection of CAD compared to SPECT in a population with a high incidence of CV risk factors and intermediate-high prevalence of CAD. (A phase III study to compare SonoVue® enhanced myocardial echocardiography [MCE] to single photon emission computerized tomography [ECG-GATED SPECT], at rest and at peak of low-dose Dipyridamole stress test, in the assessment of significant coronary artery disease [CAD] in patients with suspect or known CAD using Coronary Angiography as Gold Standard-SonoVue MCE vs SPECT; EUCTR2007-003492-39-GR).

282 Radiofrequency Ablation Combined With Endoscopic Resection Is Highly Effective for Eradication of Early Barrett's Neoplasia: Final Results of a Large Prospective European Multicenter Study (EURO-II)

Radiofrequency Ablation Combined With Endoscopic Resection Is Highly Effective for Eradication of Early Barrett’s Neoplasia: Final Results of a Large Prospective European Multicenter Study (EURO-II) Nadine Phoa*, Roos E. Pouw, Raf Bisschops, Oliver Pech, Krish Ragunath, Bas L. Weusten, Brigitte Schumacher, Bjorn Rembacken, Alexander Meining, Helmut Messmann, Erik J. Schoon, Liebwin Gossner, Jayan Mannath, Cees a. Seldenrijk, Mike Visser, Antoon E. Lerut, Thomas RoSch, Stefan Seewald, Fiebo J. Ten Kate, Christian Ell, Horst Neuhaus, Jacques J. Bergman Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands; University Hospital Leuven, Leuven, Belgium; Dr. Horst-Schmidt-Kliniken, Wiesbaden, Germany; Nottingham Digestive Diseases Centre, Nottingham University Hospital, Nottingham, United Kingdom; Gastroenterology and Hepatology, St Antonius Hospital, Nieuwegein, Netherlands; Evangelisches Krankenhaus Dusseldorf, Dusseldorf, Germany; The General Infirmary at Leeds, Leeds, United Kingdom; Technical University of Munich, Munich, Germany; Klinikum Augsburg, Augsburg, Germany; Catharina Hospital, Eindhoven, Netherlands; Klinikum Karlsruhe, Karlsruhe, Germany; Pathology, St Antonius Hospital, Nieuwegein, Netherlands; Pathology, Academic Medical Center, Amsterdam, Netherlands; Universitatsklinikum HamburgEppendorf, Hamburg, Germany Background: Radiofrequency ablation (RFA) after prior endoscopic resection (ER) of focal lesions, has proven highly effective for Barrett’s esophagus (BE) containing high-grade dysplasia (HGD) or early cancer (EC), in a number of small-sized single center studies. Aim: To prospectively evaluate the efficacy of RFA combined with ER in case of focal lesions, for BE with HGD/EC in 13 European centers with expertise in BE neoplasia. Methods: Patients with BE 12 cm and HGD/EC on 2 separate endoscopies were included. Visible lesions ( 2cm length; 50% circumference) were removed with ER, residual EC was excluded on 2 mapping endoscopies post-ER. Subsequent RFA was scheduled every 3 months until clearance of BE was achieved, with max 5 RFA sessions allowed. Escape treatment was permitted for residual BE after RFA (max 2 APC sessions for islands 5mm, ER for islands 5mm or suspicious lesions). Followup (FU) endoscopy was scheduled at 3 9 mo after last treatment and annually thereafter, with 4Q/2cm biopsies from neosquamous epithelium and gastric cardia. Endpoints: complete eradication of neoplasia (CE-neo) and intestinal metaplasia (CE-IM); durability of CE-neo/CE-IM. To ensure uniformity and protocol compliance, investigators were trained at the coordinating site and a study monitor attended all treatments and first FU on-site. Central pathology review of all ER/biopsies was performed at the coordinating site. Results: 132 patients (107M, mean 65yrs, median BE C3M6) underwent en-bloc (n 63) or piecemeal ER (n 56); or no-ER (n 13). Worst ER histology: EC (n 78), HGD (n 31), LGD (n 7), no dysplasia (n 3). Worst grade post-ER/pre-RFA: HGD (n 36), LGD (n 45), no dysplasia (n 51). 124 pts completed the treatment phase, 8 discontinued due to unrelated causes. After a median of 3 (IQR 3-4) treatments, including ER (n 14) or APC (n 14), per intention-to-treat analysis (counting drop-outs as failures) CE-neo was reached in 122/132 (92%) and CEIM in 115/132 (87%) pts. In a per-protocol analysis (censoring for drop-outs) CEneo/CE-IM were achieved in 98% and 93%, respectively. Of 2 CE-neo failures, 1 was referred for surgery (T1bN0M0), 1 patient was treated endoscopically (offprotocol). Of 115 pts who reached CE-neo/CE-IM per-protocol, CE-neo was maintained in 112/115 (97%) pts during median 25 (IQR 18-34) mo FU since last treatment, with median 4 (2-5) FU endoscopies and 41 biopsies per patient. 3 pts with recurrent neoplasia (EC n 1; HGD n 2) were effectively re-treated by ER or APC. Conclusion: This is the largest prospective multicenter trial on RFA combined with ER for treatment of BE with HGD/EC. Our outcomes suggest that if performed by trained, expert endoscopists in carefully selected patients, this combined approach is highly effective, and appears durable in the majority (97%) of patients once complete eradication of neoplasia and IM is established. Fig 1. Inflammation score (range 0-13) of inflamed pediatric Crohn’s disease ileum increased compared to both non-inflammed Crohn’s diseae and control. Results expressed as mean SEM (*P 0.001).

Plasma Folate, Related Genetic Variants, and Colorectal Cancer Risk in EPIC

A potential dual role of folate in colorectal cancer (CRC) is currently subject to debate. We investigate the associations between plasma folate, several relevant folate-related polymorphisms, and CRC risk within the large European Prospective Investigation into Cancer and Nutrition cohort. In this nested case-control study, 1,367 incident CRC cases were matched to 2,325 controls for study center, age, and sex. Risk ratios (RR) were estimated with conditional logistic regression and adjusted for smoking, education, physical activity, and intake of alcohol and fiber. Overall analyses did not reveal associations of plasma folate with CRC. The RR (95% confidence interval; Ptrend) for the fifth versus the first quintile of folate status was 0.94 (0.74-1.20; 0.44). The polymorphisms MTHFR677C-->T, MTHFR1298A-->C, MTR2756A-->G, MTRR66A-->G, and MTHFD11958G-->A were not associated with CRC risk. However, in individuals with the lowest plasma folate concentrations, the MTHFR 677TT genotype showed a statistically nonsignificant increased CRC risk [RR (95% CI; Ptrend) TT versus CC=1.39 (0.87-2.21); 0.12], whereas those with the highest folate concentrations showed a nonsignificant decreased CRC risk [RR TT versus CC=0.74 (0.39-1.37); 0.34]. The SLC19A180G-->A showed a positive association with CRC risk [RR AA versus GG 1.30 (1.06-1.59); <0.01]. This large European prospective multicenter study did not show an association of CRC risk with plasma folate status nor with MTHFR polymorphisms. Findings of the present study tend to weaken the evidence that folate plays an important role in CRC carcinogenesis. However, larger sample sizes are needed to adequately address potential gene-environment interactions.

Congenital malformations after assisted reproduction: risks and implications for prenatal diagnosis and fetal medicine

Congenital malformations after assisted reproduction: risks and implications for prenatal diagnosis and fetal medicine

Plasma phospholipid fatty acid profiles and their association with food intakes: results from a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition

BackgroundPlasma phospholipid fatty acids have been correlated with food intakes in populations with homogeneous dietary patterns. However, few data are available on populations with heterogeneous dietary patterns. ObjectiveThe objective was to investigate whether plasma phospholipid fatty acids are suitable biomarkers of dietary intakes across populations involved in a large European multicenter study. DesignA cross-sectional study design nested to the European Prospective Investigation into Cancer and Nutrition (EPIC) was conducted to determine plasma fatty acid profiles in >3000 subjects from 16 centers, who had also completed 24-h dietary recalls and dietary questionnaires. Plasma fatty acids were assessed by capillary gas chromatography. Ecological and individual correlations were calculated between fatty acids and select food groups. ResultsThe most important determinant of plasma fatty acids was region, which suggests that the variations across regions are largely due to different food intakes. Strong ecological correlations were observed between fish intake and long-chain n–3 polyunsaturated fatty acids (r = 0.78, P < 0.01), olive oil and oleic acid (r = 0.73, P < 0.01), and margarine and elaidic acid (r = 0.76, P < 0.01). Individual correlations varied across the regions, particularly between olive oil and oleic acid and between alcohol and the saturation index, as an indicator of stearoyl CoA desaturase activity. ConclusionsThese findings indicate that specific plasma phospholipid fatty acids are suitable biomarkers of some food intakes in the EPIC Study. Moreover, these findings suggest complex interactions between alcohol intake and fatty acid metabolism, which warrants further attention in epidemiologic studies relating dietary fatty acids to alcohol-related cancers and other chronic diseases.