Supplementary Figure from eQTL Set–Based Association Analysis Identifies Novel Susceptibility Loci for Barrett Esophagus and Esophageal Adenocarcinoma

BACKGROUND & AIMS:The Barrett's Oesophagus Surveillance Study (BOSS) was the first randomized study of surveillance. This study reports the costs and quality of life outcomes from the BOSS trial and models the outcomes and cost-effectiveness of surveillance beyond the follow-up period of the BOSS study. This trial showed similar stages and rates of esophageal cancer in both arms, but the regular surveillance arm did identify more high-grade dysplasia after a median of 12.8 years follow-up. METHODS:We used a decision tree model based on results from BOSS to conduct a cost-effectiveness analysis of costs and quality-adjusted life years (QALYs). A Markov model was used to extrapolate costs and outcomes over a further 10 years after the trial had ended, representing a 22.8-year time horizon. The proportion with high-grade dysplasia and QALYs was derived from the randomized trial. RESULTS:The total costs associated with 2-yearly surveillance was $5309 vs $3182 in the at-need arm. Total QALYs in the 2-yearly endoscopy arm were 8.647 compared with 8.629 in the at-need arm. Compared with at-need endoscopy, 2-yearly surveillance costs $115,563/QALY gained. In the sensitivity analyses around assumptions on the proportion of high-grade dysplasia that is undetected in the at-need endoscopy arm, surveillance had an incremental cost effectiveness ratio of $94,513/QALY for the best-case and $146,272/QALY for the worst-case scenario. CONCLUSION:Barrett's esophagus surveillance every 2 to 3 years is unlikely to be a cost-effective strategy. Guidelines should take this into account when deciding surveillance intervals.

BACKGROUND & AIMS:Barrett's esophagus (BE) is a precursor lesion for esophageal adenocarcinoma (EAC). Surveillance endoscopy aims to detect early malignant progression; although widely practiced, it has not previously been tested in a randomized trial. METHODS:BOSS (Barrett's Oesophagus Surveillance Versus Endoscopy at Need Study) was a randomized controlled trial at 109 centers in the United Kingdom. Patients with BE were randomized to 2-yearly surveillance endoscopy or "at-need" endoscopy, offered for symptoms only. Follow-up was a minimum of 10 years. The primary outcome was overall survival in the intention-to-treat population. Secondary outcomes included cancer-specific survival, time to diagnosis of EAC, stage of EAC at diagnosis, frequency of endoscopy, and serious adverse events related to interventions. RESULTS:There were 3453 patients recruited; 1733 patients were randomized to surveillance and 1719 to at-need endoscopy. Median follow-up time was 12.8 years for the primary outcome. There was no evidence of a difference in overall survival between the surveillance arm (333 deaths among 1733 patients) and the at-need arm (356 deaths among 1719 patients; hazard ratio, 0.95; 95% CI, 0.82-1.10; stratified log-rank P = .503). There was no evidence of a difference for surveillance vs at-need endoscopy in cancer-specific survival (108 vs 106 deaths from any cancer; hazard ratio, 1.01; 95% CI, 0.77-1.33; P = .926), time to diagnosis of EAC (40 vs 31 patients had a diagnosis of EAC; hazard ratio, 1.32; 95% CI, 0.82-2.11; P = .254), or cancer stage at diagnosis. Eight surveillance patients (0.46%) and 7 at-need patients (0.41%) reported serious adverse events. CONCLUSIONS:Surveillance did not improve overall survival or cancer-specific survival. At-need endoscopy may be a safe alternative for low-risk patients. (ClinicalTrials.gov, Number: NCT00987857.).

ObjectivesStrong recruitment and retention into randomised controlled trials involving invasive therapies is a matter of priority to ensure better achievement of trial aims. The BRIDE (Barrett's Randomised Intervention for Dysplasia by Endoscopy) Study investigated the feasibility of undertaking a multicentre randomised controlled trial comparing argon plasma coagulation and radiofrequency ablation, following endoscopic resection, for the management of early Barrett's neoplasia. This paper aims to identify factors influencing patients' participation in the BRIDE Study and determine their views regarding acceptability of a potential future trial comparing surgery with endotherapy.DesignA semistructured telephone interview study was performed, including both patients who accepted and declined to participate in the BRIDE trial. Interview data were analysed using the constant comparison approach to identify recurring themes.SettingInterview participants were recruited from across six UK tertiary centres where the BRIDE trial was conducted.ParticipantsWe interviewed 18 participants, including 11 participants in the BRIDE trial and 7 who declined.ResultsFour themes were identified centred around interviewees' decision to accept or decline participation in the BRIDE trial and a potential future trial comparing endotherapy with surgery: (1) influence of the recruitment process and participant-recruiter relationship; (2) participants' views of the design and aim of the study; (3) conditional altruism as a determining factor and (4) participants' perceptions of surgical risks versus less invasive treatments.ConclusionWe identified four main influences to optimising recruitment and retention to a randomised controlled trial comparing endotherapies in patients with early Barrett's-related neoplasia. These findings highlight the importance of qualitative research to inform the design of larger randomised controlled trials.

Abstract Aim Soft tissue sarcomas (STS) are a comparatively unusual cluster of tumours; they arise from mesenchymal tissues. Surgery remains the primary and the only potentially curative treatment for most STS subtypes. Existing intraoperative margin assessment techniques are inadequate and the current gold standard for resection margin assessment of STS is post-operative histopathology, but this takes weeks to finalize. Consequently, an augmented surgical technique established by real-time non-destructive recognition of clear margins is essential to diminish the risk of local relapse, decrease the resection area, and enhance the effectiveness of surgical resection of STS. Vibrational spectroscopy (VS) is a non-destructive evaluation of the atomic oscillation within a molecule. Every molecule has a unique set of vibrational modes called molecular fingerprint. We aim to use Raman spectroscopy to analyse biomolecular spectra of sarcoma and develop a potential tool for intra operative margin assessment Method Human sarcoma was tissue obtained from the biobank at QEHB. The samples were identified as Lipoma and Liposarcoma. The samples underwent spectral measurement with the Raman microscope and the tissue samples were then sent for histopathological analysis. Results The spectral evaluation clearly demonstrates the biomolecular difference between the two groups and has a potential to become an intraoperative tool. Conclusions A positive resection margin is the ultimate prognosticator of local relapse. There is a need for a rapid and reliable tool that can offer surgeons with instant feedback during primary procedure.

Pancreatic cancer claims over 460,000 victims per year. The carbohydrate antigen (CA) 19-9 test is the blood test used for pancreatic cancer’s detection; however, its levels can be raised in symptomatic patients with other non-malignant diseases, or with other tumors in the surrounding area. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy has demonstrated exceptional potential in cancer diagnostics, and its clinical implementation could represent a significant step towards early detection. This proof-of-concept study, investigating the use of ATR-FTIR spectroscopy on dried blood serum, focused on the discrimination of both cancer versus healthy control samples, and cancer versus symptomatic non-malignant control samples, as a novel liquid biopsy approach for pancreatic cancer diagnosis. Machine learning algorithms were applied, achieving results of up to 92% sensitivity and 88% specificity when discriminating between cancers (n = 100) and healthy controls (n = 100). An area under the curve (AUC) of 0.95 was obtained through receiver operating characteristic (ROC) analysis. Balanced sensitivity and specificity over 75%, with an AUC of 0.83, were achieved with cancers (n = 35) versus symptomatic controls (n = 35). Herein, we present these results as demonstration that our liquid biopsy approach could become a simple, minimally invasive, and reliable diagnostic test for pancreatic cancer detection.

BACKGROUND:Over 20 susceptibility single-nucleotide polymorphisms (SNP) have been identified for esophageal adenocarcinoma (EAC) and its precursor, Barrett esophagus (BE), explaining a small portion of heritability. METHODS:Using genetic data from 4,323 BE and 4,116 EAC patients aggregated by international consortia including the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON), we conducted a comprehensive transcriptome-wide association study (TWAS) for BE/EAC, leveraging Genotype Tissue Expression (GTEx) gene-expression data from six tissue types of plausible relevance to EAC etiology: mucosa and muscularis from the esophagus, gastroesophageal (GE) junction, stomach, whole blood, and visceral adipose. Two analytical approaches were taken: standard TWAS using the predicted gene expression from local expression quantitative trait loci (eQTL), and set-based SKAT association using selected eQTLs that predict the gene expression. RESULTS:Although the standard approach did not identify significant signals, the eQTL set-based approach identified eight novel associations, three of which were validated in independent external data (eQTL SNP sets for EXOC3, ZNF641, and HSP90AA1). CONCLUSIONS:This study identified novel genetic susceptibility loci for EAC and BE using an eQTL set-based genetic association approach. IMPACT:This study expanded the pool of genetic susceptibility loci for EAC and BE, suggesting the potential of the eQTL set-based genetic association approach as an alternative method for TWAS analysis.

Abstract Background Oesophageal cancer (OC) accounts for 3% of all new cancer diagnosis in the UK. Presentation is often late, reflected in a poor 5-year survival rate of 12%. The importance of identifying lymph node (LN) metastases has been demonstrated as the single biggest prognostic factor. The current ‘gold standard’ diagnosis of LN metastases is from histopathological assessment of the tissue after surgical resection of the primary tumour and surrounding tissue. The use of imaging techniques to try and gain this information preoperatively is standard practice but far from perfect. Raman spectroscopy (RS) has been investigated as a diagnostic tool to detect cancer and pre-cancerous change in the oesophagus, and preliminary work demonstrating the application of vibrational spectroscopy (Raman and FTIR) to LN analysis has been undertaken. The development of Raman needle probes (RNP) with potential for use in-vivo furthers the clinical impact. The DOLOMITE study started recruitment in the summer of 2022 to investigate the ability of RNP to identify the presence of malignant deposits in resected lymph nodes. Methods Patients identified by the clinical team as needing oesophagectomy to treat their OC were invited to participate in the study. After the specimen has been resected, prior to formalin fixation, three lymph nodes are dissected representing gastric, para-oesophageal and sub-carinal nodes. These are bisected longitudinally with half remaining with the specimen. The half for research is snap frozen in liquid nitrogen until needed for analysis. Adjacent sections are cut from the nodes to create slides for Raman mapping and conventional H&E staining. The bulk node left is used for Raman probe analysis. Spectral data is then analysed using MATlab. Results At this early stage, our initial measurements have provided information used for calibration in advance of completing recruitment. The Raman mapping has been assessed for correlation with the pathology identified in the H&E slides taken from the lymph node block. This data in turn has provided the background for developing interpretation of the Raman probe data, with further samples we will use this to create a classification model. Conclusions With ongoing recruitment the study will be able to fully report by September 2023. References 1. Stone N, Kendall C, Shepherd N, Crow P, Barr H Near-infrared Raman spectroscopy for the classification of epithelial pre-cancers and cancers 2002 33(7):564–573 2. Kong K, Kendall C, Stone N, Notingher I. Raman spectroscopy for medical diagnostics--From in-vitro biofluid assays to in-vivo cancer detection. Adv Drug Deliv Rev. 2015;89:121–34.

e16275 Background: Pancreatic cancer is the 7th most deadly cancer worldwide with over 460,000 victims per year. In the current diagnostic pathway, carbohydrate antigen (CA) 19-9 serum test is the blood assessment used for detection of pancreatic cancer; although, with poor positive predictive values reported, it is not specific for pancreatic tumors as its levels can be raised in symptomatic patients with other benign comorbidities and/or because of other tumors in the surrounding area. Attenuated total reflection–Fourier transform infrared spectroscopy (ATR-FTIR) has demonstrated exceptional potential in human blood serum analysis for cancer diagnostics and its implementation in the clinical environment could represent a significant step forward in the early detection of pancreatic cancer. This proof-of-concept study aimed to investigate the use of the Dxcover cancer liquid biopsy as a novel approach for pancreatic cancer detection. Methods: The study was focused on the discrimination between both cancer (n = 100) versus healthy control samples (n = 100), and cancer (n = 35) versus symptomatic non-malignant control samples (n = 35) from patients with comorbidities and/or confounding diseases. Various machine learning algorithms were applied to discriminate between the classes: random forest (RF), partial least squares-discriminant analysis (PLS-DA) and support vector machine (SVM). Receiver operating characteristic (ROC) analysis was also employed to evaluate the classes’ degree of diagnostic separability. Permutation tests were performed for each classification in order to ensure their statistical significance. Results: Cancer (n = 100) and healthy control samples (n = 100) were distinguished with excellent results, achieving results up to a sensitivity of 91.0 %, specificity of 87.6 %, and accuracy of 89.3 % with PLS-DA. Moreover, an area under the curve (AUC) equal to 0.954 was obtained through ROC analysis. When discriminating between cancer (n = 35) and symptomatic control samples (n = 35), accuracy values were recorded in the range between 70.6 and 77.3 % with ROC analysis showing a balanced sensitivity and specificity over 75 % with an AUC of 0.844. Both discriminations were proven statistically significant. Conclusions: Pancreatic cancer detection in early stages would be key in improving prognosis and survival rates of patients, through targeted earlier surgery and treatments. The Dxcover cancer liquid biopsy could represent a powerful tool in the clinical environment as an easy-to-use, minimally invasive and reliable spectroscopic blood test for detection of pancreatic cancer.

BACKGROUND:A promising approach to reduce the increasing costs of clinical trials is the use of routinely collected health data as participant data. However, the quality of this data could limit its usability as trial participant data. METHODS:The BOSS trial is a randomised controlled trial comparing regular endoscopies versus endoscopies at need in patients with Barrett's oesophagus with primary endpoint death. Data on death and cancer collected every 2 years after randomisation (trial-specific data) were compared to data received annually (all patients on one date) from the routinely collected health data source National Health Service (NHS) Digital. We investigated completeness, agreement and timeliness and looked at the implications for the primary trial outcome. Completeness and agreement were assessed by evaluating the number of reported and missing cases and any disparities between reported dates. Timeliness was considered by graphing the year a death was first reported in the trial-specific data against that for NHS Digital data. Implications on the primary trial outcome, overall survival, of using one of the data sources alone were investigated using Kaplan-Meier graphs. To assess the utility of cause of death and cancer diagnoses, oesophageal cancer cases were compared. RESULTS:NHS Digital datasets included more deaths and often reported them sooner than the trial-specific data. The number reported as being from oesophageal cancer was similar in both datasets. Due to time lag in reporting and missing cases, the event rate appeared higher using the NHS Digital data. CONCLUSION:NHS Digital death data is useful for calculating overall survival where trial-specific follow-up is only every 2 years from randomisation and the follow-up requires patient response. The cancer data was not a large enough sample to assess usability. We suggest that this assessment of registry data is done for more phase III RCTs and for more registry data to get a more complete picture of when RCHD would be useful in phase III RCT. TRIAL REGISTRATION:ISRCTN54190466 (BOSS) 1 Oct 2009.

Introduction Endoscopic resection (ER) and radiofrequency ablation (RFA) have become the standard of care worldwide for treatment of early Barrett’s neoplasia. Procedural outcomes are highly dependent on the operator skill and training. Validated tools for assessment of competency in these 2 procedures are currently lacking. We aimed to develop and validate ER and RFA tools for use in clinical practice. Methods A working group of 15 experts who met one or more of the predefined inclusion criteria was set up. Using published evidence-based criteria, the group devised a structured checklist of graded competency descriptors (scores ranged from 1=required maximal supervision to 4=competent). The latter were grouped into four main competency domains, namely: pre-procedural; specific skills; post-procedural; and endoscopic non-technical skills (ENTS). Consensus agreement and piloting was undertaken to ensure content validity. Construct validity was measured by independent assessment of 60 videos per procedure of ER and RFA by 7 assessors (selected from the working group) in a random manner. Procedures were performed by 15 operators with variable expertise including experts and trainees. Statistical analysis was performed using Generalizability theory, which analysed ‘variability components’ between: operators; cases; assessors; assessors across (x) operators; and unexplained variation. Results Data on a minimum of 45 videos per procedure were available for analysis. The mean (± standard deviation) competency scores were 3.4 (0.8) and 3.7 (0.6) for ER and RFA, respectively. The variability components for the analysis are detailed in table 1. Variation in scores between operators, assessors, and assessors across different operators was small accounting for <10% of the total variation suggesting good reliability. The majority of variance was explained by variation in cases or unexplained. Conclusions The DOBES assessment tools for ER and RFA appear to have good content and construct validity and were produced based on evidence and expert opinion. The analysis shows agreement on scores between expert assessors which strengthens the case for its adoption into clinical practice.

Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett’s esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analysis was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 single-nucleotide polymorphisms (SNPs) in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases and 3207 controls in the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17 159 controls). Global variation in the IGF pathway was associated with risk of BE (P = 0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; P = 0.00046, false discovery rate q = 0.0056) and IGF1R (IGF1 receptor; P = 0.0090, q = 0.0542). These gene-level signals remained significant at q < 0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.

We present the British Society of Gastroenterology (BSG) position statement on patient experience of GI endoscopy, recently published on the BSG website—www.bsg.org.uk/resource/patient-experience-of-gi-endoscopy-2019.html. The three dimensions of healthcare quality are patient safety, clinical effectiveness and patient experience, with much of healthcare practice focusing on the first two dimensions. Greater emphasis is now being given to the patient experience dimension in light of reports from Francis1 and Darzi2 highlighting the interaction between patient experience and quality of care. Clinical standards and safety in endoscopy are well reported and reviewed via the Joint Advisory Group on GI Endoscopy (JAG) accreditation programme. The Global Rating Scale3 used in JAG assessments includes a patient experience domain, but gives limited guidance available on how that should be measured or what standards should be …

Many problems in mechanobiology urgently require characterization of the micromechanical properties of cells and tissues. Brillouin light scattering has been proposed as an emerging optical elastography technique to meet this need. However, the information contained in the Brillouin spectrum is still a matter of debate because of fundamental problems in understanding the role of water in biomechanics and in relating the Brillouin data to low-frequency macroscopic mechanical parameters. Here, we investigate this question using gelatin as a model system in which the macroscopic physical properties can be manipulated to mimic all the relevant biological states of matter, ranging from the liquid to the gel and the glassy phase. We demonstrate that Brillouin spectroscopy is able to reveal both the elastic and viscous properties of biopolymers that are central to the structure and function of biological tissues.

We would like to respond to the editorial by van Munster et al,1van Munster S.N. Pouw R.E. Bergman J.J.G.H.M. Randomized studies for Barrett’s ablation: just because we can doesn’t mean we should.Gastrointest Endosc. 2019; 89: 690-692Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar which accompanied our pilot trial (BRIDE) comparing argon plasma coagulation (APC) with radiofrequency ablation (RFA) for the ablation of dysplastic Barrett’s esophagus (BE).2Peerally M.F. Bhandari P. Ragunath K. et al.Radiofrequency ablation compared with argon plasma coagulation after endoscopic resection of high-grade dysplasia or stage T1 adenocarcinoma in Barrett’s esophagus: a randomized pilot study (BRIDE).Gastrointest Endosc. 2019; 89: 680-689Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar They conclude that RFA is the established standard, modalities such as APC being reserved for special situations (strictures, refractory BE), and that comparative randomized controlled trials (RCTs) versus RFA are not warranted unless safety and efficacy have been established with large prospective trials, like EURO II for RFA.3Phoa K.N. Pouw R.E. Bisschops R. et al.Multimodality endoscopic eradication for neoplastic Barrett oesophagus: results of an European multicentre study (EURO-II).Gut. 2016; 65: 555-562Crossref PubMed Scopus (181) Google Scholar They believe that APC has not met this criterion. We disagree. The APC technique was standardized as part of BRIDE (despite less restrictive inclusion criteria on both endoscopic resection size, in keeping with current treatment guidelines,4Bennett C. Vakil N. Bergman J. et al.BADCAT consensus statements for management of Barrett's dysplasia and early-stage esophageal adenocarcinoma, based on a Delphi process.Gastroenterology. 2012; 143: 336-346Abstract Full Text Full Text PDF PubMed Scopus (331) Google Scholar,5Fitzgerald R.C. di Pietro M. Ragunath K. et al.British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus.Gut. 2014; 63: 7-42Crossref PubMed Scopus (842) Google Scholar and BE length than in EURO II). Together with the APE study by Manner et al,6Manner H. Rabenstein T. Pech O. et al.Ablation of residual Barrett’s epithelium after endoscopic resection: a randomized long-term follow-up study of argon plasma coagulation vs. surveillance (APE study).Endoscopy. 2014; 46: 6-12PubMed Google Scholar we believe there exist sufficient safety and efficacy data for a fully powered comparison with RFA. This is needed because of the cost saving we observed, although this was challenged; in fact, our health economist also included costs of sizing and energy delivery systems unique to RFA. We would like to respond to other points raised that question safety and efficacy: stricture rate was 8% (not 13%) with APC, similar to that in the APE study (9%).6Manner H. Rabenstein T. Pech O. et al.Ablation of residual Barrett’s epithelium after endoscopic resection: a randomized long-term follow-up study of argon plasma coagulation vs. surveillance (APE study).Endoscopy. 2014; 46: 6-12PubMed Google Scholar Complete BE eradication (CR-BE) at 12 months (not 24 months as the editorial implies) after 4 treatments is lower than in EURO II3Phoa K.N. Pouw R.E. Bisschops R. et al.Multimodality endoscopic eradication for neoplastic Barrett oesophagus: results of an European multicentre study (EURO-II).Gut. 2016; 65: 555-562Crossref PubMed Scopus (181) Google Scholar and APE6Manner H. Rabenstein T. Pech O. et al.Ablation of residual Barrett’s epithelium after endoscopic resection: a randomized long-term follow-up study of argon plasma coagulation vs. surveillance (APE study).Endoscopy. 2014; 46: 6-12PubMed Google Scholar (both allowed more treatments and time) although similar to a large RFA registry in the United States.7Gupta M. Iyer P.G. Lutzke L. et al.Recurrence of esophageal intestinal metaplasia after endoscopic mucosal resection and radiofrequency ablation of Barrett’s Esophagus: results from a US multicenter consortium.Gastroenterology. 2013; 145: 79-86Abstract Full Text Full Text PDF PubMed Scopus (189) Google Scholar BRIDE was a pilot study with time constraints limited by resources available to conduct the study; nevertheless, CR-BE was similar for APC/RFA, as shown in Figure 1. Finally, van Munster et al1van Munster S.N. Pouw R.E. Bergman J.J.G.H.M. Randomized studies for Barrett’s ablation: just because we can doesn’t mean we should.Gastrointest Endosc. 2019; 89: 690-692Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar criticize the primary endpoint in BRIDE (or for any proposed comparative RCT) of complete histologic remission of dysplasia, even though others have used this in RCTs of RFA (AIM,8Shaheen N.J. Sharma P. Overholt B.F. et al.Radiofrequency ablation in Barrett's esophagus with dysplasia.N Engl J Med. 2009; 360: 2277-2288Crossref PubMed Scopus (1123) Google Scholar SURF9Phoa K.N. van Vilsteren F.G. Weusten B.L. et al.Radiofrequency ablation vs endoscopic surveillance for patients with Barrett esophagus and low grade dysplasia: a randomized clinical trial.JAMA. 2014; 311: 1209-1217Crossref PubMed Scopus (453) Google Scholar) or APC versus surveillance (APE6Manner H. Rabenstein T. Pech O. et al.Ablation of residual Barrett’s epithelium after endoscopic resection: a randomized long-term follow-up study of argon plasma coagulation vs. surveillance (APE study).Endoscopy. 2014; 46: 6-12PubMed Google Scholar). Instead, they believe that CR-BE is more appropriate. Ablation after endoscopic resection, the most important staging and treatment step,4Bennett C. Vakil N. Bergman J. et al.BADCAT consensus statements for management of Barrett's dysplasia and early-stage esophageal adenocarcinoma, based on a Delphi process.Gastroenterology. 2012; 143: 336-346Abstract Full Text Full Text PDF PubMed Scopus (331) Google Scholar,5Fitzgerald R.C. di Pietro M. Ragunath K. et al.British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus.Gut. 2014; 63: 7-42Crossref PubMed Scopus (842) Google Scholar aims to reduce metachronous neoplasia, elegantly shown with the use of APC.6Manner H. Rabenstein T. Pech O. et al.Ablation of residual Barrett’s epithelium after endoscopic resection: a randomized long-term follow-up study of argon plasma coagulation vs. surveillance (APE study).Endoscopy. 2014; 46: 6-12PubMed Google Scholar Complete CR-BE is desirable, but BE recurred at 6% to 7% per year for as long as 8 years in large follow-up studies.7Gupta M. Iyer P.G. Lutzke L. et al.Recurrence of esophageal intestinal metaplasia after endoscopic mucosal resection and radiofrequency ablation of Barrett’s Esophagus: results from a US multicenter consortium.Gastroenterology. 2013; 145: 79-86Abstract Full Text Full Text PDF PubMed Scopus (189) Google Scholar,10Sami S.S. Ravindran A. Kahn A. et al.Timeline and location of recurrence following successful ablation in Barrett’s oesophagus: an international multicentre study.Gut. 2019; 68: 1379-1385Crossref PubMed Scopus (53) Google Scholar,11Krishnamoorthi R. Singh S. Ragunathan K. et al.Risk of recurrence of Barrett's esophagus after successful endoscopic therapy.Gastrointest Endosc. 2016; 83: 1090-1106Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar Therefore, annual surveillance is recommended indefinitely.10Sami S.S. Ravindran A. Kahn A. et al.Timeline and location of recurrence following successful ablation in Barrett’s oesophagus: an international multicentre study.Gut. 2019; 68: 1379-1385Crossref PubMed Scopus (53) Google Scholar We therefore disagree with CR-BE as the primary endpoint and the suggested noninferiority margin for a comparative RCT of 5% because CR-BE is not durable. Dr Lovat is the recipient of research support from Medtronic. Dr Ragunath is the recipient of educational grants from Erbe and Medtronic. The other authors disclosed no financial relationships. Randomized studies for Barrett’s ablation: just because we can doesn’t mean we shouldGastrointestinal EndoscopyVol. 89Issue 4PreviewBased on a convincing amount of data from high-quality studies, most guidelines on Barrett’s esophagus (BE) have adapted radiofrequency ablation (RFA) as the treatment of choice for BE with low-grade dysplasia (LGD) or high-grade dysplasia (HGD) and after endoscopic resection (ER) of visible lesions and mucosal cancer. In recent years, increasingly more attention has been given to alternative ablation techniques, such as (hybrid) argon plasma coagulation (APC) and cryo(balloon) ablation. Full-Text PDF ResponseGastrointestinal EndoscopyVol. 91Issue 5PreviewWe would like to respond to the letter of De Caestecker et al1 in reply to our editorial that reflected on the BRIDE study, a randomized pilot study comparing radiofrequency ablation with argon plasma coagulation for the treatment of Barrett’s esophagus (BE).2 Our main point of disagreement is that in the BRIDE study, complete eradication of dysplasia (CE-D) at 12 months was chosen as an endpoint. Although eradication of dysplasia may be the most relevant short-term outcome for the patient, we think that in light of a study comparing 2 ablation techniques, CE-D is a suboptimal endpoint, and its clinical relevance is questionable. Full-Text PDF

Abstract Background The aims of this study were to compare neoplasia detection rates for nontargeted biopsies (Seattle protocol) versus acetic acid-targeted biopsies (Portsmouth protocol) during Barrett’s surveillance and to explore feasibility, patient/clinician experience, acceptance, and barriers/enablers to study participation and implementation of the acetic acid technique. Methods This was a mixed-methods feasibility study including a pilot multicenter, randomized, crossover trial with qualitative interviews. Patients under Barrett’s surveillance with no history of neoplasia were included. Patients underwent two endoscopies, one with each protocol, 8 weeks apart. Outcomes included recruitment and retention rates, neoplasia yield, and number of biopsies. Results 200 patients were recruited from 6 centers, and 174 (87.0 %) underwent both procedures. Neoplasia prevalence was 4.7 % (9/192). High grade dysplasia and cancer were detected with both protocols. Five low grade dysplasias were detected (two with acetic acid, four with nontargeted biopsies; one lesion was detected with both techniques). A total of 2139 biopsies were taken in the nontargeted arm and 226 in the acetic acid arm. Both patients and clinicians found the acetic acid technique acceptable. Based on these data, a noninferiority, tandem, crossover trial would require an estimated 2828 patients. Conclusions We demonstrated the feasibility of performing a crossover endoscopy trial in Barrett’s surveillance. Low neoplasia yield makes this design necessary and qualitative results demonstrated patient and clinician acceptance. The reduced numbers of biopsies suggest that the acetic acid technique could result in cost savings, providing the lack of missed pathology can be proven in a fully powered definitive trial.

In addition, contributors who also aim at individually Pubmed indexed articles have to submit an extended abstract (less than 1500 words). Selected articles will be published: either in "Diagnostic Pathology" (editor-in-chief Klaus Kayser, co-chairs Catherine Bor, Philippe Camparo and Myriam Oger) or for computer science orientated articles in the "Computerized Medical Imaging and Graphics" Elsevier journal (editor-in-chief Daniel Racoceanu, co-chair Philippe Belhomme)