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.

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.

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.

Open chromatin profiling identifies AP1 as a transcriptional regulator in oesophageal adenocarcinoma.

Oesophageal adenocarcinoma (OAC) is one of the ten most prevalent forms of cancer and is showing a rapid increase in incidence and yet exhibits poor survival rates. Compared to many other common cancers, the molecular changes that occur in this disease are relatively poorly understood. However, genes encoding chromatin remodeling enzymes are frequently mutated in OAC. This is consistent with the emerging concept that cancer cells exhibit reprogramming of their chromatin environment which leads to subsequent changes in their transcriptional profile. Here, we have used ATAC-seq to interrogate the chromatin changes that occur in OAC using both cell lines and patient-derived material. We demonstrate that there are substantial changes in the regulatory chromatin environment in the cancer cells and using this data we have uncovered an important role for ETS and AP1 transcription factors in driving the changes in gene expression found in OAC cells.

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.

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.

UK guidelines on oesophageal dilatation in clinical practice.

These are updated guidelines which supersede the original version published in 2004. This work has been endorsed by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG) under the auspices of the oesophageal section of the BSG. The original guidelines have undergone extensive revision by the 16 members of the Guideline Development Group with representation from individuals across all relevant disciplines, including the Heartburn Cancer UK charity, a nursing representative and a patient representative. The methodological rigour and transparency of the guideline development processes were appraised using the revised Appraisal of Guidelines for Research and Evaluation (AGREE II) tool.Dilatation of the oesophagus is a relatively high-risk intervention, and is required by an increasing range of disease states. Moreover, there is scarcity of evidence in the literature to guide clinicians on how to safely perform this procedure. These guidelines deal specifically with the dilatation procedure using balloon or bougie devices as a primary treatment strategy for non-malignant narrowing of the oesophagus. The use of stents is outside the remit of this paper; however, for cases of dilatation failure, alternative techniques-including stents-will be listed. The guideline is divided into the following subheadings: (1) patient preparation; (2) the dilatation procedure; (3) aftercare and (4) disease-specific considerations. A systematic literature search was performed. The Grading of Recommendations Assessment, Develop-ment and Evaluation (GRADE) tool was used to evaluate the quality of evidence and decide on the strength of recommendations made.

Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus.

BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations. METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls. RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)). CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.

Deregulation of the FOXM1 target gene network and its coregulatory partners in oesophageal adenocarcinoma.

BACKGROUND: Survival rates for oesophageal adenocarcinoma (OAC) remain disappointingly poor and current conventional treatment modalities have minimal impact on long-term survival. This is partly due to a lack of understanding of the molecular changes that occur in this disease. Previous studies have indicated that the transcription factor FOXM1 is commonly upregulated in this cancer type but the impact of this overexpression on gene expression in the context of OAC is largely unknown. FOXM1 does not function alone but works alongside the antagonistically-functioning co-regulatory MMB and DREAM complexes. METHODS: To establish how FOXM1 affects gene expression in OAC we have identified the FOXM1 target gene network in OAC-derived cells using ChIP-seq and determined the expression of both its coregulatory partners and members of this target gene network in OAC by digital transcript counting using the Nanostring gene expression assay. RESULTS: We find co-upregulation of FOXM1 with its target gene network in OAC. Furthermore, we find changes in the expression of its coregulatory partners, including co-upregulation of LIN9 and, surprisingly, reduced expression of LIN54. Mechanistically, we identify LIN9 as the direct binding partner for FOXM1 in the MMB complex. In the context of OAC, both coregulator (eg LIN54) and target gene (eg UHRF1) expression levels are predictive of disease stage. CONCLUSIONS: Together our data demonstrate that there are global changes to the FOXM1 regulatory network in OAC and the expression of components of this network help predict cancer prognosis.

BOB CAT: A Large-Scale Review and Delphi Consensus for Management of Barrett's Esophagus With No Dysplasia, Indefinite for, or Low-Grade Dysplasia.

OBJECTIVES: Barrett's esophagus (BE) is a common premalignant lesion for which surveillance is recommended. This strategy is limited by considerable variations in clinical practice. We conducted an international, multidisciplinary, systematic search and evidence-based review of BE and provided consensus recommendations for clinical use in patients with nondysplastic, indefinite, and low-grade dysplasia (LGD). METHODS: We defined the scope, proposed statements, and searched electronic databases, yielding 20,558 publications that were screened, selected online, and formed the evidence base. We used a Delphi consensus process, with an 80% agreement threshold, using GRADE (Grading of Recommendations Assessment, Development and Evaluation) to categorize the quality of evidence and strength of recommendations. RESULTS: In total, 80% of respondents agreed with 55 of 127 statements in the final voting rounds. Population endoscopic screening is not recommended and screening should target only very high-risk cases of males aged over 60 years with chronic uncontrolled reflux. A new international definition of BE was agreed upon. For any degree of dysplasia, at least two specialist gastrointestinal (GI) pathologists are required. Risk factors for cancer include male gender, length of BE, and central obesity. Endoscopic resection should be used for visible, nodular areas. Surveillance is not recommended for <5 years of life expectancy. Management strategies for indefinite dysplasia (IND) and LGD were identified, including a de-escalation strategy for lower-risk patients and escalation to intervention with follow-up for higher-risk patients. CONCLUSIONS: In this uniquely large consensus process in gastroenterology, we made key clinical recommendations for the escalation/de-escalation of BE in clinical practice. We made strong recommendations for the prioritization of future research.

Comparing outcome of radiofrequency ablation in Barrett's with high grade dysplasia and intramucosal carcinoma: a prospective multicenter UK registry.

BACKGROUND AND STUDY AIM: Mucosal neoplasia arising in Barrett's esophagus can be successfully treated with endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA). The aim of the study was to compare clinical outcomes of patients with high grade dysplasia (HGD) or intramucosal cancer (IMC) at baseline from the United Kingdom RFA registry. PATIENTS AND METHODS: Prior to RFA, visible lesions and nodularity were removed entirely by EMR. Thereafter, patients underwent RFA every 3 months until all visible Barrett's mucosa was ablated or cancer developed (end points). Biopsies were taken at 12 months or when end points were reached. RESULTS: A total of 515 patients, 384 with HGD and 131 with IMC, completed treatment. Prior to RFA, EMR was performed for visible lesions more frequently in the IMC cohort than in HGD patients (77 % vs. 47 %; P < 0.0001). The 12-month complete response for dysplasia and intestinal metaplasia were almost identical in the two cohorts (HGD 88 % and 76 %, respectively; IMC 87 % and 75 %, respectively; P = 0.7). Progression to invasive cancer was not significantly different at 12 months (HGD 1.8 %, IMC 3.8 %; P = 0.19). A trend towards slightly worse medium-term durability may be emerging in IMC patients (P = 0.08). In IMC, EMR followed by RFA was definitely associated with superior durability compared with RFA alone (P = 0.01). CONCLUSION: The Registry reports on endoscopic therapy for Barrett's neoplasia, representing real-life outcomes. Patients with IMC were more likely to have visible lesions requiring initial EMR than those with HGD, and may carry a higher risk of cancer progression in the medium term. The data consolidate the approach to ensuring that these patients undergo thorough endoscopic work-up, including EMR prior to RFA when necessary.

British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus.

These guidelines provide a practical and evidence-based resource for the management of patients with Barrett's oesophagus and related early neoplasia. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument was followed to provide a methodological strategy for the guideline development. A systematic review of the literature was performed for English language articles published up until December 2012 in order to address controversial issues in Barrett's oesophagus including definition, screening and diagnosis, surveillance, pathological grading for dysplasia, management of dysplasia, and early cancer including training requirements. The rigour and quality of the studies was evaluated using the SIGN checklist system. Recommendations on each topic were scored by each author using a five-tier system (A+, strong agreement, to D+, strongly disagree). Statements that failed to reach substantial agreement among authors, defined as >80% agreement (A or A+), were revisited and modified until substantial agreement (>80%) was reached. In formulating these guidelines, we took into consideration benefits and risks for the population and national health system, as well as patient perspectives. For the first time, we have suggested stratification of patients according to their estimated cancer risk based on clinical and histopathological criteria. In order to improve communication between clinicians, we recommend the use of minimum datasets for reporting endoscopic and pathological findings. We advocate endoscopic therapy for high-grade dysplasia and early cancer, which should be performed in high-volume centres. We hope that these guidelines will standardise and improve management for patients with Barrett's oesophagus and related neoplasia.

Radiofrequency ablation and endoscopic mucosal resection for dysplastic barrett's esophagus and early esophageal adenocarcinoma: outcomes of the UK National Halo RFA Registry.

BACKGROUND & AIMS: Patients with Barrett's esophagus (BE) and high-grade dysplasia (HGD) or early neoplasia increasingly receive endoscopic mucosal resection and radiofrequency ablation (RFA) therapy. We analyzed data from a UK registry that follows the outcomes of patients with BE who have undergone RFA for neoplasia. METHODS: We collected data on 335 patients with BE and neoplasia (72% with HGD, 24% with intramucosal cancer, 4% with low-grade dysplasia [mean age, 69 years; 81% male]), treated at 19 centers in the United Kingdom from July 2008 through August 2012. Mean length of BE segments was 5.8 cm (range, 1-20 cm). Patients' nodules were removed by endoscopic mucosal resection, and the patients then underwent RFA every 3 months until all areas of BE were ablated or cancer developed. Biopsies were collected 12 months after the first RFA; clearance of HGD, dysplasia, and BE were assessed. RESULTS: HGD was cleared from 86% of patients, all dysplasia from 81%, and BE from 62% at the 12-month time point, after a mean of 2.5 (range, 2-6) RFA procedures. Complete reversal dysplasia was 15% less likely for every 1-cm increment in BE length (odds ratio = 1.156; SE = 0.048; 95% confidence interval: 1.07-1.26; P < .001). Endoscopic mucosal resection before RFA did not provide any benefit. Invasive cancer developed in 10 patients (3%) by the 12-month time point and disease had progressed in 17 patients (5.1%) after a median follow-up time of 19 months. Symptomatic strictures developed in 9% of patients and were treated by endoscopic dilatation. Nineteen months after therapy began, 94% of patients remained clear of dysplasia. CONCLUSIONS: We analyzed data from a large series of patients in the United Kingdom who underwent RFA for BE-related neoplasia and found that by 12 months after treatment, dysplasia was cleared from 81%. Shorter segments of BE respond better to RFA; http://www.controlled-trials.com, number ISRCTN93069556.

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.

Structured gastroenterological intervention and improved outcome for patients with chronic gastrointestinal symptoms following pelvic radiotherapy.

PURPOSE: Fifty percent of patients develop chronic gastrointestinal (GI) symptoms following pelvic radiotherapy that adversely affect quality of life. Fewer than 20 % are referred to a gastroenterologist. We aimed to determine if structured gastroenterological evaluation is of benefit to this patient group. METHODS: Sixty patients with GI symptoms at ≥ 6 months after radical pelvic radiotherapy were identified prospectively from oncology clinics in this service evaluation. Those requiring urgent investigation were excluded. Patients were assessed at baseline using patient-reported questionnaires: inflammatory bowel disease questionnaire (IBDQ), Vaizey incontinence questionnaire, and the Common Terminology Criteria for Adverse Events (CTCAE) pelvis questionnaire. Participants were referred for gastroenterological evaluation using an algorithmic approach. Further assessments were made at 3 and 6 months. RESULTS: Twenty men and 36 women with primary gynecological (31), urological (17), or lower GI (8) tumors were included (mean age, 58.5 years). Median time from radiotherapy to baseline assessment was 3.0 years. Multiple GI symptoms were reported (median, 8; range, 4-16) including frequency, urgency, loose stool, fecal incontinence, flatulence, bloating/distension, and rectal bleeding. Common diagnoses included radiation proctopathy, bile acid malabsorption, diverticulosis, and colonic polyps. Statistically significant improvements in all questionnaire scores between baseline and 6 months were found: IBDQ (p = 0.014), Vaizey (p < 0.0005), and CTCAE rectum-bowel subset (p = 0.001). CONCLUSIONS: Gastroenterological evaluation identifies significant, potentially treatable diagnoses in patients who develop chronic GI symptoms following pelvic radiotherapy. Some findings are incidental and unrelated to previous cancer treatment. Radiation-induced GI symptoms have historically been considered "untreatable." We report the first data to show that structured gastroenterological assessment has the potential to improve outcome by identifying diagnoses and facilitating focused treatment.

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.

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.

Overview of bariatric surgery for the physician.

The worldwide pandemic of obesity carries alarming health and socioeconomic implications. Bariatric surgery is currently the only effective treatment for severe obesity. It is safe, with mortality comparable to that of cholecystectomy, and effective in producing substantial and sustainable weight loss, along with high rates of resolution of associated comorbidities, including type 2 diabetes. For this reason, indications for bariatric surgery are being widened. In addition to volume restriction and malabsorption, bariatric surgery brings about neurohormonal changes that affect satiety and glucose homeostasis. Increased understanding of these mechanisms will help realise therapeutic benefits by pharmacological means. Bariatric surgery improves long-term mortality but can cause long-term nutritional deficiencies. The safety of pregnancy after bariatric surgery is still being elucidated.

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.