Development and validation of a novel Barrett's oesophagus patient reported outcome measure (B-PROM).

Background: Patients with Barrett's oesophagus (BO) carry significant cancer worry, burden of symptoms, and lack disease-specific knowledge. Currently there is no validated BO patient reported outcome measure (PROM) to measure these factors for use in clinical practice and research, hence the aim of this study was to devise a novel, validated BO-specific tool, B-PROM. Methods: Literature review, quantitative and qualitative research informed the initial item generation. The item bank was refined through a modified Delphi process between May and August 2021. The PROM was then tested through cognitive interviews and validated via multicentre testing between September 2021 and February 2023 with the aim to create a succinct tool which addresses the key important factors to BO patients and has strong psychometric properties. Findings: B-PROM covers key themes of disease-specific knowledge, trust in clinicians, burden of symptoms, cancer worry and burden of surveillance. Validation results from 387 participants (response rate 40.8%) showed 93.3% of participants completed >95% of B-PROM. All individual items scored a completion rate of >95%. Mean completion time was 5 mins 34s for a sample group. Nineteen items showed a ceiling effect, 3 items showed a floor effect. Internal consistency overall demonstrated a Cronbach Alpha of 0.846, while predetermined subsections showed Cronbach alphas of 0.335, 0.718, 0.736, and 0.896. Inter-item analysis found 2 pairs of items with strong correlation, with only 6 items correlating weakly. Item-total correlation showed 19 items correlated well. Exploratory Factor analysis (EFA) with principal component analysis produced 5 components with Eigenvalues >1 of which 4/5 had satisfactory Cronbach alphas. Test-retest reliability showed no significant differences across single and average measures (p ≤ 0.001). Interpretation: B-PROM is the first BO-specific PROM to be systematically evaluated. Validation findings show strong internal consistency, short completion time, low missingness and excellent test-retest reliability. Funding: Medtronic Limited ISR-2016-1077.

Dedicated service for Barrett's oesophagus surveillance endoscopy yields higher dysplasia detection and guideline adherence in a non-tertiary setting in the UK: a 5-year comparative cohort study.

Objective: Barrett's oesophagus (BO) endoscopic surveillance is performed to varying quality, dedicated services may offer improved outcomes. This study compares a dedicated BO service to standard care, specifically dysplasia detection rate (DDR), guideline adherence and use of advanced imaging modalities in a non-tertiary setting. Design/method: 5-year retrospective comparative cohort study comparing a dedicated BO endoscopy service with surveillance performed on non-dedicated slots at a non-tertiary centre in the UK. All adult patients undergoing BO surveillance between 1 March 2016 and 1 March 2021 were reviewed and those who underwent endoscopy on a dedicated BO service run by endoscopists with training in BO was compared with patients receiving their BO surveillance on any other endoscopy list. Endoscopy reports, histology results and clinic letters were reviewed for DDR and British society of gastroenterology guideline adherence. Results: 921 BO procedures were included (678 patients). 574 (62%) endoscopies were on a dedicated BO list vs 348 (38%) on non-dedicated.DDR was significantly higher in the dedicated cohort 6.3% (36/568) vs 2.7% (9/337) (p=0.014). Significance was sustained when cases with indefinite for dysplasia were excluded: 4.9% 27/533 vs 0.9% 3/329 (p=0.002). Guideline adherence was significantly better on the dedicated endoscopy lists.Factors associated with dysplasia detection in regression analysis included visible lesion documentation (p=0.036), use of targeted biopsies (p=<0.001), number of biopsies obtained (p≤0.001). Conclusions: A dedicated Barrett's service showed higher DDR and guideline adherence than standard care and may be beneficial pending randomised trial data.

Quality of life measures in dysplastic Barrett's oesophagus are comparable to patients with non-dysplastic Barrett's oesophagus and do not improve after endoscopic therapy.

OBJECTIVE: Barrett's oesophagus (BO) is a precursor lesion, via dysplastic phases, to oesophageal adenocarcinoma. Although overall risk from BO is low, it has been shown to adversely affect health-related quality of life (HRQOL). The aim was to compare dysplastic BO patients' HRQOL pre-endoscopic therapy (pre-ET) and post-ET. The pre-ET BO group was also compared with other cohorts: non-dysplastic BO (NDBO), those with colonic polyps, gastro-oesophageal reflux disease (GORD) and healthy volunteers. DESIGN: Participants in the pre-ET cohort were recruited prior to their endotherapy and HRQOL questionnaires provided pre-ET and post-ET. Wilcoxon rank test was used to compare the pre-ET and post-ET findings. The Pre-ET group was compared to the other cohorts' HRQOL results using multiple linear regression analysis. RESULTS: Pre-ET group of 69 participants returned the questionnaires prior to and 42 post-ET. Both the pre-ET and post-ET group showed similar levels of cancer worry, despite the treatment. No statistical significance was found for symptoms scores, anxiety and depression or general health measures with the Short Form-36 (SF-36) Score. Education for the BO patients was overall lacking with many of the pre-ET group still reporting unanswered questions about their disease.The Pre-ET group was compared with NDBO group (N=379), GORD (N=132), colonic polyp patients (N=152) and healthy volunteers (N=48). Cancer worry was similar between the NDBO group and the Pre-ET group, despite their lower risk of progression. GORD patients had worse symptom scores from a reflux and heartburn perspective. Only the healthy group has significantly better scores in the SF-36 and improved hospital anxiety and depression scores. CONCLUSION: These findings suggest that there is a need to improve HRQOL for patients with BO. This should include improved education and devising-specific patient-reported outcome measures for BO to capture relevant areas of HRQOL in future studies.

Barrett's oesophagus with indefinite for dysplasia shows high rates of prevalent and incident neoplasia in a UK multicentre cohort.

AIMS: Barrett's oesophagus with indefinite for dysplasia (IDD) carries a risk of prevalent and incident dysplasia and oesophageal adenocarcinoma. This study seeks to determine the risk of neoplasia in a multicentre prospective IDD cohort, along with determining adherence to British Society of Gastroenterology (BSG) guidelines for management and histology reporting. METHODS: This was a cohort study using prospectively collected data from pathology databases from two centres in the North West of England (UK). Cases with IDD were identified over a 10-year period. Data were obtained on patient demographics, Barrett's endoscopy findings and histology, outcomes and histological reporting. RESULTS: 102 biopsies with IDD diagnosis in 88 patients were identified. Endoscopy was repeated in 78/88 (88%) patients. 12/78 progressed to low-grade dysplasia (15% or 2.6 per 100 person years), 6/78 (7.7%, 1.3 per 100 person years) progressed to high-grade dysplasia and 6/78 (7.7%, 1.3 per 100 person years) progressed to oesophageal adenocarcinoma. The overall incidence rate for progression to any type of dysplasia was 5.1 per 100 person years. Cox regression analysis identified longer Barrett's segment, multifocal and persistent IDD as predictors of progression to dysplasia. Histology reporting did not meet 100% adherence to the BSG histology reporting minimum dataset prior to or after the introduction of the guidelines. CONCLUSIONS: IDD carries significant risk of progression to dysplasia or neoplasia. Therefore, careful diagnosis and management aided by clear histological reporting of these cases is required to diagnose prevalent and incident neoplasia.

The current use of ultrasound to measure skeletal muscle and its ability to predict clinical outcomes: a systematic review.

Quantification and monitoring of lean body mass is an important component of nutrition assessment to determine nutrition status and muscle loss. The negative impact of reduced muscle mass and muscle function is increasingly evident across acute and chronic disease states but is particularly pronounced in patients with cancer. Ultrasound is emerging as a promising tool to directly measure skeletal muscle mass and quality. Unlike other ionizing imaging techniques, ultrasound can be used repeatedly at the bedside and may compliment nutritional risk assessment. This review aims to describe the current use of skeletal muscle ultrasound (SMUS) to measure muscle mass and quality in patients with acute and chronic clinical conditions and its ability to predict functional capacity, severity of malnutrition, hospital admission, and survival. Databases were searched from their inception to August 2021 for full-text articles in English. Relevant articles were included if SMUS was investigated in acute or chronic clinical contexts and correlated with a defined clinical outcome measure. Data were synthesized for narrative review due to heterogeneity between studies. This review analysed 37 studies (3100 patients), which met the inclusion criteria. Most studies (n = 22) were conducted in critical care. The clinical outcomes investigated included functional status at discharge (intensive care unit-acquired weakness), nutritional status, and length of stay. SMUS was also utilized in chronic conditions such as chronic obstructive pulmonary disease, chronic heart failure, and chronic renal failure to predict hospital readmission and disease severity. Only two studies investigated the use of SMUS in patients with cancer. Of the 37 studies, 28 (76%) found that SMUS (cross-sectional area, muscle thickness, and echointensity) showed significant associations with functional capacity, length of stay, readmission, and survival. There was significant heterogeneity in terms of ultrasound technique and outcome measurement across the included studies. This review highlights that SMUS continues to gain momentum as a potential tool for skeletal muscle assessment and predicting clinically important outcomes. Further work is required to standardize the technique in nutritionally vulnerable patients, such as those with cancer, before SMUS can be widely adopted as a bedside prognostic tool.

Developing patient-orientated Barrett's oesophagus services: the role of dedicated services.

INTRODUCTION: Barrett's oesophagus (BO) is common and is a precursor to oesophageal adenocarcinoma with a 0.33% per annum risk of progression. Surveillance and follow-up services for BO have been shown to be lacking, with studies showing inadequate adherence to guidelines and patients reporting a need for greater disease-specific knowledge. This review explores the emerging role of dedicated services for patients with BO. METHODS: A literature search of PubMed, MEDLINE, Embase, Emcare, HMIC, BNI, CiNAHL, AMED and PsycINFO in regard to dedicated BO care pathways was undertaken. RESULTS: Prospective multicentre and randomised trials were lacking. Published cohort data are encouraging with improvements in guideline adherence with dedicated services, with one published study showing significant improvements in dysplasia detection rates. Accuracy of allocation to surveillance endoscopy has been shown to hold cost savings, and a study of a dedicated clinic showed increased discharges from unnecessary surveillance. Training modalities for BO surveillance and dysplasia detection exist, which could be used to educate a BO workforce. Qualitative and quantitative studies have shown patients report high levels of cancer worry and poor disease-specific knowledge, but few studies have explored follow-up care models despite being a patient and clinician priority for research. CONCLUSIONS: Cost-benefit analysis for dedicated services, considering both financial and environmental impacts, and more robust clinical data must be obtained to support this model of care in the wider health service. Greater understanding is needed of the root causes for poor guideline adherence, and disease-specific models of care should be designed around clinical and patient-reported outcomes to address the unmet needs of patients with BO.

COVID-19-induced sarcopenia and physical deconditioning may require reassessment of surgical risk for patients with cancer.

BACKGROUND: The long-term physiological consequences of SARS-CoV-2 (severe acute respiratory syndrome coronavirus) infection are not known. The ability of COVID-19 to cause chronic illness, sarcopenia, and physical deconditioning may be underestimated and go beyond the anticipated respiratory sequelae. Myalgia, lethargy, and anorexia are common symptoms even in mild to moderate cases and have the potential to exacerbate frailty. How this impacts on risk-stratification for patients requiring surgery for time-critical conditions, such as malignancy, requires further urgent investigation. MAIN BODY: The deleterious effect of sarcopenia and poor physical capacity are well recognised in cancer surgery. This review commentary highlights current evidence which suggests skeletal muscle as an under recognised cause of COVID-19-related functional deconditioning. The mechanisms behind this are via direct (viral induced myositis, nutritional decline, cytokine-mediated myopathy) and indirect mechanisms (social isolation, inactivity, and psychological consequences). CONCLUSION: Further mechanistic research is required to explore the processes behind the deconditioning effects of SARS-CoV-2 infection and how this impacts on treatment of malignant disease.

Repurposing of KLF5 activates a cell cycle signature during the progression from a precursor state to oesophageal adenocarcinoma.

Oesophageal adenocarcinoma (OAC) is one of the most common causes of cancer deaths. Barrett's oesophagus (BO) is the only known precancerous precursor to OAC, but our understanding about the molecular events leading to OAC development is limited. Here, we have integrated gene expression and chromatin accessibility profiles of human biopsies and identified a strong cell cycle gene expression signature in OAC compared to BO. Through analysing associated chromatin accessibility changes, we have implicated the transcription factor KLF5 in the transition from BO to OAC. Importantly, we show that KLF5 expression is unchanged during this transition, but instead, KLF5 is redistributed across chromatin to directly regulate cell cycle genes specifically in OAC cells. This new KLF5 target gene programme has potential prognostic significance as high levels correlate with poorer patient survival. Thus, the repurposing of KLF5 for novel regulatory activity in OAC provides new insights into the mechanisms behind disease progression.

Acid fluids present in the gut can sometimes 'go up' and damage the oesophagus, the pipe that connects the mouth and the stomach. As a result, a small number of individuals can develop Barrett's oesophagus, a condition where cells in the lining of the lower oesophagus show abnormal shapes. In certain patients, these cells then become cancerous, but exactly how this happens is unknown. This lack of understanding contributes to late diagnoses, limited treatment and low survival rates. Many cancers feature 'signature' mutations in a set of genes that controls how a cell can multiply. Yet, in the case of cancers of the lower oesophagus, known genetic changes have had a limited impact on our understanding of the emergence of the disease. Here, Rogerson et al. focused instead on non-genetic changes and studied transcription factors, the proteins that bind to regulatory regions of the DNA to switch genes on and off. A close inspection of cancer cells in the lower oesophagus revealed that, in that state, a transcription factor called KLF5 controls the abnormal activation of genes involved in cell growth. This is linked to the transcription factor adopting a different pattern of binding onto regulatory regions in diseased cells. Crucially, when the cell growth genes regulated by KLF5 are activated, patients have lower survival rates. Further work is now required to examine whether this finding could help to identify patients who are most at risk from developing cancer. More broadly, the results from the work by Rogerson et al. demonstrate how transcription factors can be repurposed in a disease context.

Tele-Monitoring of Cancer Patients' Rhythms during Daily Life Identifies Actionable Determinants of Circadian and Sleep Disruption.

The dichotomy index (I < O), a quantitative estimate of the circadian regulation of daytime activity and sleep, predicted overall cancer survival and emergency hospitalization, supporting its integration in a mHealth platform. Modifiable causes of I < O deterioration below 97.5%-(I < O)low-were sought in 25 gastrointestinal cancer patients and 33 age- and sex-stratified controls. Rest-activity and temperature were tele-monitored with a wireless chest sensor, while daily activities, meals, and sleep were self-reported for one week. Salivary cortisol rhythm and dim light melatonin onset (DLMO) were determined. Circadian parameters were estimated using Hidden Markov modelling, and spectral analysis. Actionable predictors of (I < O)low were identified through correlation and regression analyses. Median compliance with protocol exceeded 95%. Circadian disruption-(I < O)low-was identified in 13 (52%) patients and four (12%) controls (p = 0.002). Cancer patients with (I < O)low had lower median activity counts, worse fragmented sleep, and an abnormal or no circadian temperature rhythm compared to patients with I < O exceeding 97.5%-(I < O)high-(p < 0.012). Six (I < O)low patients had newly-diagnosed sleep conditions. Altered circadian coordination of rest-activity and chest surface temperature, physical inactivity, and irregular sleep were identified as modifiable determinants of (I < O)low. Circadian rhythm and sleep tele-monitoring results support the design of specific interventions to improve outcomes within a patient-centered systems approach to health care.

Comparative quantitative survey of patient experience in Barrett's oesophagus and other gastrointestinal disorders.

Objective: To assess health-related quality of life in patients with non-dysplastic Barrett's oesophagus (NDBO) and endoscopically treated dysplastic Barrett's oesophagus (DBO). Design: This quantitative, self-administered questionnaire study was conducted across three National Health Service hospitals. Data were collected from three other cohorts; gastro-oesophageal reflux disease (GORD), colonic polyp surveillance and healthy individuals. Fisher's exact and Spearman's rank correlation tests were used for analysis. Propensity score matching adjusted for age, sex and comorbidities. Results: 687 participants were eligible for analysis (NDBO n=306, DBO n=49, GORD n=132, colonic polyps n=152 and healthy n=48). 53% of NDBO participants reported similarly high cancer worry, comparable to DBO (50%, p=0.933) and colonic polyp participants (51%, p=0.355). Less cancer worry was reported in GORD participants (43.4%, p=0.01 vs NDBO). NDBO participants reported anxiety in 15.8% and depression in 8.6% of cases, which was similar to the other disease cohorts. Moderate or severe heartburn or acid regurgitation was found in 11% and 10%, respectively, in the NDBO cohort, comparable to DBO participants (heartburn 2% p=0.172, acid regurgitation 4% p=0.31) but lower (better) than GORD participants (heartburn 31% p=<0.001, acid regurgitation 25% p=0.001). NDBO participants with moderate or severe GORD symptoms were associated with higher rates of anxiety (p=<0.001), depression (p=<0.001) and cancer worry (p=<0.001). NDBO patients appropriately perceiving their cancer risk as low had lower rates of cancer worry (p=<0.001). Conclusion: This study provides insight into the problems Barrett's oesophagus patients may face. Future care pathways must be more patient focussed to address misconceptions of cancer risk, oesophageal cancer related worry and GORD symptom control.

Endoscopic resection of early squamous neoplasia of the oesophagus: long-term follow-up in a UK population from a tertiary hospital.

AIM: To review the efficacy and outcomes of endoscopic resection in the diagnosis and treatment of oesophageal squamous dysplasia and early neoplasia. METHODS: This was a retrospective study between May 2012-2018. Twenty-one patients were treated with or considered for treatment with endoscopic resection at a tertiary hospital in the UK. The primary outcome was curative resection, defined as histologically proven complete resection of the lesion with deep/vertical margin ≥1 mm from neoplasia. Secondary outcomes were changes in staging from endoscopic resection histology, whether there was a complete reversal of dysplasia at 12-months or the latest endoscopic follow-up and 5-year overall survival rate. RESULTS: Seventeen patients (mean age = 66.5 years) with 20 lesions (35% en-bloc; 65% piecemeal resections) had endoscopic resection performed. Complete resection was achieved in 90% of lesions by endoscopic criteria, but this was confirmed in fewer lesions histologically. Curative resection was achieved histologically in 60% of lesions (11 patients) and noncurative resection in 40% of lesions (6 patients). Changes in staging from endoscopic resection histology were found in 79.2% of lesions (41.7% upstaged; 37.5% downstaged). No patients were found to have recurrence at their 12-month endoscopic follow-up. Eight of the 11 patients (72.7%) with curative resection remained clear of dysplasia/neoplasia throughout their follow-up (mean, 24.3 months; median, 19 months). The five-year overall survival rate was 64%. CONCLUSION: In UK, endoscopic resection is useful in the management of early squamous neoplasia both for staging and (by piecemeal endoscopic resection in elderly unfit) for medium- to long-term disease clearance.

Long-term follow-up of endoscopic submucosal dissection of gastric dysplasia and early neoplasia in a United Kingdom Caucasian population - a tertiary centre experience.

Introduction: Endoscopic submucosal dissection (ESD) is extensively performed for the treatment of early gastric cancer (EGC) in the Eastern countries due to its favourable outcomes compared to gastrectomy in terms of lower complication rates, shorter hospital stays, better quality of life, with similar 5-year survival rate. Yet, its use is still limited in the UK.Aim: A long-term follow-up study to evaluate the outcome of ESD in the treatment of EGC in a Caucasian population at a tertiary referral centre in the United Kingdom.Methods: Data for the 35 Caucasian patients, who underwent ESD in a tertiary referral centre between May 2012 and June 2017 were collected. The selected patients were followed-up until May 2018. Curative resection (CR) and survival rates were used to measure the efficacy of ESD.Results: ESD was attempted on 46 lesions and completed on 37. En-bloc and CR rates of 57% and 19% were achieved, respectively. 24% of the lesions were non-CR and 57% were indefinite for non-CR/CR and 41% of the lesions showed change in histological grade post-ESD. Complete reversal of dysplasia/neoplasia was seen in 60% of the 'indefinite' group and 100% of the CR group at latest FU (18 months, mean). Recurrence was seen in 23% of the patients at latest FU. Seventy-one months' survival rate was 77%, while the disease-specific mortality was 0%.Conclusions: This study demonstrates the positive long-term outcome of ESD for gastric neoplasia in a UK Caucasian population, encouraging further development and implementation of ESD in the UK.

Accuracy of the revised Vienna Classification for predicting postendoscopic resection outcomes for gastric and oesophageal neoplasms: a retrospective cohort study of patients from a UK tertiary referral centre.

AIMS: To review the effectiveness of the revised Vienna classification (rVC) at predicting histological outcome and defining the postendoscopic resection (ER) clinical management plan of gastro-oesophageal dysplasia and early neoplasia in a UK tertiary-centre population. METHODS: This was a retrospective cohort study between November 2011 and May 2018. 157 patients from Salford Royal NHS Foundation Trust in the UK were included. The primary outcome was the histological results of postsurgical resection (SR) specimens compared with their post-ER rVC. The secondary outcome was overall survival rates of patients with category 4.4 and 5 of the rVC. RESULTS: One-hundred and thirteen patients were diagnosed with category ≥4 of the rVC. 23 patients (20.4%) were referred for additional surgery, whereas 69 patients (61.1%) were on endoscopic surveillance only. 60.9% of post-SR specimens (14/23) revealed no residual neoplasia. 78.6% of these cancer-free specimens were classed as category 5 rVC. The overall 7-year survival rate of 25 patients with category ≥4.4 was 68% with causes of mortality not linked to upper gastrointestinal neoplasia. The overall 7-year and 3-year survival rates of category 4.4 and 5 were 73.6% and 50%, respectively, although age and comorbid state played a role. CONCLUSIONS: This study provides evidence of outcomes comparable to other reported cohorts for cases after ER in a single-centre UK population even at rVC 4.4/5. It suggests surgery may not be necessary in all cases due to the lack of residual disease and further refinement of the rVC category 5 may help guide management.

Dedicated service improves the accuracy of Barrett's oesophagus surveillance: a prospective comparative cohort study.

OBJECTIVES: Standards for Barrett's oesophagus (BO) surveillance in the UK are outlined in the British Society of Gastroenterology (BSG) guidelines. This study aimed to assess the quality of current surveillance delivery compared with a dedicated service. DESIGN: All patients undergoing BO surveillance between January 2016 and July 2017 at a single National Health Service district general hospital were included. Patients had their endoscopy routed to a dedicated BO endoscopy list or a generic service list. Prospective data were analysed against the BSG guidelines and also compared with each patient's prior surveillance endoscopy. RESULTS: 361 patients were scheduled for surveillance of which 217 attended the dedicated list, 78 attended the non-dedicated list and 66 did not have their endoscopy. The dedicated list adhered more closely to the BSG guidelines when compared with the non-dedicated and prior endoscopy, respectively; Prague classification (100% vs 87.3% vs 82.5%, p<0.0001), hiatus hernia delineation (100% vs 64.8% vs 63.3%, p<0.0001), location and number of biopsies recorded (99.5% vs 5.6% vs 6.9%, p<0.0001), Seattle protocol adherence (72% vs 42% vs 50%, p<0.0001) and surveillance interval adherence (dedicated 100% vs prior endoscopy 75%, p<0.0001). Histology results from the dedicated and non-dedicated list cohorts revealed similar rates of intestinal metaplasia (79.8% vs 73.1%, p=0.12) and dysplasia/oesophageal adenocarcinoma (4.3% vs 2.6%, p=0.41). CONCLUSIONS: The post-BSG guideline era of BO surveillance remains suboptimal in this UK hospital setting. A dedicated service appears to improve the accuracy and consistency of surveillance care, although the clinical significance of this remains to be determined.

Identification of a primitive intestinal transcription factor network shared between esophageal adenocarcinoma and its precancerous precursor state.

Esophageal adenocarcinoma (EAC) is one of the most frequent causes of cancer death, and yet compared to other common cancers, we know relatively little about the molecular composition of this tumor type. To further our understanding of this cancer, we have used open chromatin profiling to decipher the transcriptional regulatory networks that are operational in EAC. We have uncovered a transcription factor network that is usually found in primitive intestinal cells during embryonic development, centered on HNF4A and GATA6. These transcription factors work together to control the EAC transcriptome. We show that this network is activated in Barrett's esophagus, the putative precursor state to EAC, thereby providing novel molecular evidence in support of stepwise malignant transition. Furthermore, we show that HNF4A alone is sufficient to drive chromatin opening and activation of a Barrett's-like chromatin signature when expressed in normal human epithelial cells. Collectively, these data provide a new way to categorize EAC at a genome scale and implicate HNF4A activation as a potential pivotal event in its malignant transition from healthy cells.

Author Correction: Authentication and characterisation of a new oesophageal adenocarcinoma cell line: MFD-1.

A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Barrett's oesophagus: A qualitative study of patient burden, care delivery experience and follow-up needs.

BACKGROUND: Barrett's oesophagus (BO), a precursor to oesophageal adenocarcinoma, requires long-term endoscopic surveillance. The rising incidence of this chronic disease has implications for service provision and patient burden. Few studies have explored BO patients' personal burden, care delivery experience and participation in health-care delivery decisions. OBJECTIVE: To identify and explore factors impacting BO patients' health-related quality of life, follow-up needs and views on new models of follow-up care. DESIGN: An exploratory qualitative approach was adopted using semi-structured, in-depth, one-to-one interviews, audio-recorded and transcribed verbatim. Patients undergoing BO surveillance, at a single NHS hospital, were recruited using purposive sampling with the aim of achieving maximum variation. Data were analysed using framework analysis approach, supported by NVivo Pro 11. RESULTS: Data saturation occurred after 20 participant interviews. Ten subthemes and three main themes emerged from the analysis: (a) burden of disease-symptom control, worry of oesophageal cancer and surveillance endoscopy; (b) follow-up experiences-follow-up care, at this NHS hospital, was found to be inconsistent and often inadequate to meet patients' needs, in particular a lack of disease-specific information; and (c) follow-up needs-participants sought enhanced communication, organization and structure of care. They highly valued face-to-face interaction with a specialist, and the concept of direct secondary care access in-between endoscopies was reassuring to participants. CONCLUSIONS: This qualitative research provides an in-depth account of the patients' perspective of BO, the effectiveness of follow-up care and patient opinion on new follow-up systems.

Esomeprazole and aspirin in Barrett's oesophagus (AspECT): a randomised factorial trial.

BACKGROUND: Oesophageal adenocarcinoma is the sixth most common cause of cancer death worldwide and Barrett's oesophagus is the biggest risk factor. We aimed to evaluate the efficacy of high-dose esomeprazole proton-pump inhibitor (PPI) and aspirin for improving outcomes in patients with Barrett's oesophagus. METHODS: The Aspirin and Esomeprazole Chemoprevention in Barrett's metaplasia Trial had a 2 × 2 factorial design and was done at 84 centres in the UK and one in Canada. Patients with Barrett's oesophagus of 1 cm or more were randomised 1:1:1:1 using a computer-generated schedule held in a central trials unit to receive high-dose (40 mg twice-daily) or low-dose (20 mg once-daily) PPI, with or without aspirin (300 mg per day in the UK, 325 mg per day in Canada) for at least 8 years, in an unblinded manner. Reporting pathologists were masked to treatment allocation. The primary composite endpoint was time to all-cause mortality, oesophageal adenocarcinoma, or high-grade dysplasia, which was analysed with accelerated failure time modelling adjusted for minimisation factors (age, Barrett's oesophagus length, intestinal metaplasia) in all patients in the intention-to-treat population. This trial is registered with EudraCT, number 2004-003836-77. FINDINGS: Between March 10, 2005, and March 1, 2009, 2557 patients were recruited. 705 patients were assigned to low-dose PPI and no aspirin, 704 to high-dose PPI and no aspirin, 571 to low-dose PPI and aspirin, and 577 to high-dose PPI and aspirin. Median follow-up and treatment duration was 8·9 years (IQR 8·2-9·8), and we collected 20 095 follow-up years and 99·9% of planned data. 313 primary events occurred. High-dose PPI (139 events in 1270 patients) was superior to low-dose PPI (174 events in 1265 patients; time ratio [TR] 1·27, 95% CI 1·01-1·58, p=0·038). Aspirin (127 events in 1138 patients) was not significantly better than no aspirin (154 events in 1142 patients; TR 1·24, 0·98-1·57, p=0·068). If patients using non-steroidal anti-inflammatory drugs were censored at the time of first use, aspirin was significantly better than no aspirin (TR 1·29, 1·01-1·66, p=0·043; n=2236). Combining high-dose PPI with aspirin had the strongest effect compared with low-dose PPI without aspirin (TR 1·59, 1·14-2·23, p=0·0068). The numbers needed to treat were 34 for PPI and 43 for aspirin. Only 28 (1%) participants reported study-treatment-related serious adverse events. INTERPRETATION: High-dose PPI and aspirin chemoprevention therapy, especially in combination, significantly and safely improved outcomes in patients with Barrett's oesophagus. FUNDING: Cancer Research UK, AstraZeneca, Wellcome Trust, and Health Technology Assessment.

Glasgow Blatchford Score and risk stratifications in acute upper gastrointestinal bleed: can we extend this to 2 for urgent outpatient management?

Upper gastrointestinal (GI) bleeds are a common presentation to emergency departments in the UK. The Glasgow Blatchford score (GBS) predicts the outcome of patients at presentation. Current UK and European guidelines recommend outpatient management for a GBS of 0. In the current study, our aim was to assess whether extending the GBS allows for early discharge while maintaining patient safety. We also analysed whether pathologies could be missed by discharging patients too early. Data were retrospectively collected on patients admitted with symptoms of an upper GI bleed between 1 October 2013 and 10 June 2016. The GBS was calculated and gastroscopy reports were obtained for each patient. In total, 399 patients were identified, 63 of whom required therapy. The negative predictive value (NPV) for excluding the need for endoscopic intervention with a GBS score up to 1 was 100%. Extending the score to 2 and 3 reduced the NPV to 98.53% and 98.77%, respectively. The NPV of GBS in excluding any diagnosis at 0 was 43.55%. Two patients died as a result of GI bleeding, with a GBS score of 3. Therefore, we can conclude that, for non-variceal bleeds, the GBS can be extended to 2 for safe outpatient management, thereby reducing the number of bed days and pressure for urgent endoscopies.