A prospective multicenter study using a new multiband mucosectomy device for endoscopic resection of early neoplasia in Barrett's esophagus.

BACKGROUND AND AIMS: Early neoplasia in Barrett's esophagus (BE) can be effectively and safely removed by endoscopic resection (ER) using multiband mucosectomy (MBM). This study aimed to document performance of a novel MBM device designed for improved visualization, easier passage of accessories, and better suction power compared with other marketed MBM devices. METHODS: This international, single-arm, prospective registry in 14 referral centers (Europe, 10; United States, 3; Canada, 1) included patients with early BE neoplasia scheduled for ER. The primary endpoint was successful ER defined as complete resection of the delineated area in 1 procedure. Secondary outcomes were adverse events and procedure time. RESULTS: A total of 332 lesions was included in 291 patients (248 men; mean age, 67 years [standard deviation, 9.6]). ER indication was high-grade dysplasia in 64%, early adenocarcinoma in 19%, lesion with low-grade dysplasia in 11%, and a lesion without definite histology in 6%. Successful ER was reached in 322 of 332 lesions (97%; 95% confidence interval [CI], 94.6%-98.4%). A perforation occurred in 3 of 332 procedures (.9%; 95% CI, .31%-2.62%), all were managed endoscopically, and patients were admitted with intravenous antibiotics during days 2, 3, and 9. Postprocedural bleeding requiring an intervention occurred in 5 of 332 resections (1.5%; 95% CI, .65%-3.48%). Dysphagia requiring dilatation occurred in 11 patients (3.8%; 95% CI, 2.1%-6.6%). Median procedure time was 16 minutes (interquartile range, 12.0-26.0). CONCLUSIONS: In expert hands, the novel MBM device proved to be effective for resection of early neoplastic lesions in BE, with successful ER in 97% of procedures. Severe adverse events were rare and were effectively managed endoscopically or conservatively. (Clinical trial registration number: NCT02482701.).

Correction: Periconception Maternal Folate Status and Human Embryonic Cerebellum Growth Trajectories: The Rotterdam Predict Study.

[This corrects the article DOI: 10.1371/journal.pone.0141089.].

Simplified versus standard regimen for focal radiofrequency ablation of dysplastic Barrett's oesophagus: a multicentre randomised controlled trial.

BACKGROUND: For focal radiofrequency ablation of Barrett's oesophagus, a simplified regimen (3 × 15 J/cm2, without cleaning) has proven to be as effective as the standard regimen (2 × 15 J/cm2, followed by cleaning, followed by 2 × 15 J/cm2). However, this simplified regimen seemed to be associated with a higher stenosis rate. Therefore, we lowered the radiofrequency energy and hypothesised that this new simplified regimen would be as effective and safe as the standard regimen. METHODS: This randomised non-inferiority trial included patients with dysplastic Barrett's oesophagus or residual Barrett's oesophagus after endoscopic resection or circumferential radiofrequency ablation, in five European tertiary referral centres. Patients were randomly assigned (1:1) to the new simplified regimen (3 × 12 J/cm2, without cleaning) or the standard regimen, with variable block sizes of four, six, and eight patients, stratified by participating hospital. Focal radiofrequency ablation was done every 3 months, up to a maximum of three treatments, until all Barrett's oesophagus was eradicated. The primary outcome was complete endoscopic and histological regression of dysplasia and intestinal metaplasia after two focal radiofrequency ablation treatments, assessed in the intention-to-treat population. Non-inferiority was assessed on the basis of the difference between groups in the median percentage of Barrett's oesophagus surface regression, with a non-inferiority margin of -15%. This study is registered with www.trialregister.nl, number NTR4994, and is completed. FINDINGS: Between March 25, 2015, and July 25, 2016, 84 patients were randomly assigned to treatment: 44 to receive the simplified regimen and 40 to receive the standard regimen. One patient assigned to the simplified regimen and four assigned to the standard regimen were excluded because they weree found not to be eligible; therefore the final intention-to-treat population consisted of 43 patients in the simplified ablation group and 36 in the standard ablation group. Complete endoscopic and histological regression of dysplasia and intestinal metaplasia after two focal radiofrequency ablation treatments was achieved in 32 (74%, 95% CI 59-87) patients treated with the simplified protocol, versus 30 (83%, 95% CI 67-94) patients treated with the standard protocol (p=0·34). Median Barrett's oesophagus surface regression after two focal radiofrequency ablation sessions was 98% (IQR 95-100) in the simplified regimen group and 100% (97-100) in the standard regimen group. The difference between medians was 2% (95% CI -0·562 to 3·162); thus the simplified regimen was deemed non-inferior to the standard regimen. Stenoses requiring dilatation were observed in four (9%) of 43 patients in the simplified regimen group and four (11%) of 36 in the standard regimen group. Post-procedural bleeding requiring repeat endoscopy occurred in one (2%) patient in the simplified ablation group and three (8%) patients in the standard ablation group. One patient (2%) in the simplified treatment group died 36 days after the second radiofrequency ablation procedure, due to an unknown cause. INTERPRETATION: Based on the results of this study, we conclude that the simplified regimen is the preferred regimen for focal radiofrequency ablation of Barrett's oesophagus. FUNDING: None.

Periconception Maternal Folate Status and Human Embryonic Cerebellum Growth Trajectories: The Rotterdam Predict Study.

We aimed to investigate whether periconceptional maternal folate status affects human embryonic cerebellar size and growth trajectories. In a prospective periconceptional cohort participants filled out questionnaires and received weekly transvaginal 3D-ultrasounds between 7+0 and 12+6 weeks gestational age (GA). Viable non-malformed singleton pregnancies were selected for cerebellar measurements; transcerebellar diameter, (TCD), left and right cerebellar diameters (LCD, RCD). Linear mixed models were performed to estimate associations between questionnaire data on the timing of maternal folic acid supplement initiation and longitudinal cerebellar measurements as a function of crown-rump length (CRL) and GA. Maternal red blood cell folate concentrations were analysed before 8 weeks GA to validate the associations. A total of 263 serial high quality three-dimensional ultrasound scans of 135 pregnancies were studied. Preconceptional compared to postconceptional initiation of folic acid use was associated with slightly larger cerebellar diameters per millimetre increase of CRL (TCD: ß = 0.260mm, 95%CI = 0.023-0.491, p<0.05; LCD: ß = 0.171mm, 95%CI = 0.038-0.305, p<0.05; RCD: ß = 0.156mm, 95%CI = 0.032-0.280, p<0.05) and with proportional cerebellar growth (TCD/CRL:ß = 0.015mm/mm, 95%CI = 0.005-0.024, p<0.01; LCD/CRL:ß = 0.012mm/mm, 95%CI = 0.005-0.018, p<0.01; RCD/CRL:ß = 0.011mm/mm, 95%CI = 0.005-0.017, p<0.01). Cerebellar growth was significantly highest in the third quartile of maternal red blood cell folate levels (1538-1813 nmol/L). These first findings show that periconceptional maternal folate status is associated with human embryonic cerebellar development. Implications of these small but significant variations for fetal cerebellar growth trajectories and the child's neurodevelopmental outcome are yet unknown and warrant further investigation.