Praful Patel

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 Barretts 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 Barretts 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 Barretts oesophagus and related neoplasia.

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

Background & Aims Barretts 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 Barretts 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.

Cost-effectiveness of population screening for Helicobacter pylori in preventing gastric cancer and peptic ulcer disease, using simulation

OBJECTIVES To evaluate the cost-effectiveness of population screening for Helicobacter pylori in preventing gastric cancer and peptic ulcer disease in England and Wales. METHODS A discrete event simulation model used parameter estimates, derived from peer-reviewed literature, routine data and statistical modelling. Population screening was compared with no screening but with opportunistic eradication in patients presenting with dyspepsia. Costs included screening, eradication and costs averted to provide costs per life years saved (cost/LYS) for preventing gastric cancer and peptic ulcer disease. Sensitivity analyses were undertaken. RESULTS The cost/LYS from screening at age 40 years was Uk pounds 5860 at discount rates of 6%. The outcomes were sensitive to H. pylori prevalence, the degree of opportunistic eradication, the discount rate, the efficacy of eradication on gastric cancer risk, the risk of complicated peptic ulcer disease and gastric cancer associated with H. pylori infection, and the duration of follow-up. In sensitivity analyses, the cost/LYS rarely exceeded UK pounds 20000 over an 80-year follow-up, but did for shorter periods. CONCLUSIONS H. pylori screening may be cost-effective in the long term. However, before screening can be recommended further evidence is needed to resolve some of the uncertainties, particularly over the efficacy of eradication on risk of gastric cancer, the risk associated with complicated peptic ulcers, and the effect of more widespread opportunistic testing of patients with dyspepsia.

Improvement over time in outcomes for patients undergoing endoscopic therapy for Barrett's oesophagus-related neoplasia: 6-year experience from the first 500 patients treated in the UK patient registry

Background Barretts oesophagus (BE) is a pre-malignant condition leading to oesophageal adenocarcinoma (OAC). Treatment of neoplasia at an early stage is desirable. Combined endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA) is an alternative to surgery for patients with BE-related neoplasia. Methods We examined prospective data from the UK registry of patients undergoing RFA/EMR for BE-related neoplasia from 2008 to 2013. Before RFA, visible lesions were removed by EMR. Thereafter, patients had RFA 3-monthly until all BE was ablated or cancer developed (endpoints). End of treatment biopsies were recommended at around 12 months from first RFA treatment or when endpoints were reached. Outcomes for clearance of dysplasia (CR-D) and BE (CR-IM) at end of treatment were assessed over two time periods (2008–2010 and 2011–2013). Durability of successful treatment and progression to OAC were also evaluated. Results 508 patients have completed treatment. CR-D and CR-IM improved significantly between the former and later time periods, from 77% and 56% to 92% and 83%, respectively (p<0.0001). EMR for visible lesions prior to RFA increased from 48% to 60% (p=0.013). Rescue EMR after RFA decreased from 13% to 2% (p<0.0001). Progression to OAC at 12 months is not significantly different (3.6% vs 2.1%, p=0.51). Conclusions Clinical outcomes for BE neoplasia have improved significantly over the past 6 years with improved lesion recognition and aggressive resection of visible lesions before RFA. Despite advances in technique, the rate of cancer progression remains 2–4% at 1 year in these high-risk patients. Trial registration number ISRCTN93069556.

Prognostic significance of cyclooxygenase-2 (COX-2) expression in patients with surgically resectable adenocarcinoma of the oesophagus.

BackgroundCOX-2 expression in tumour cells has been associated with poor prognosis in gastrointestinal and non-gastrointestinal cancers. The aim of our study was to test the hypothesis that higher levels of COX-2 expression are prognostically related to poor clinico-pathologic features in adenocarcinoma of the oesophagus.MethodsWe reviewed the records of 100 consecutive patients undergoing resection for adenocarcinoma of the oesophagus to collect data on T-stage, N-stage, tumour recurrence and survival. T & N-stage was further confirmed by histological examination. COX-2 protein expression was assessed by immunohistochemistry in all patients and COX-2 m-RNA expression was measured by quantitative RT-PCR in a small group of patients.ResultsHigher levels of COX-2 expression were associated with higher T stage (p = 0.008), higher N stage (p = 0.049), increased risk of tumour recurrence (p = 0.01) and poor survival (p = <0.001). A COX-2 score of >200 was associated with a median survival of 10 months compared to 26 months with a score of <200 (p = <0.001).ConclusionHigher levels of COX-2 expression are associated with poor clinico-pathologic features and poor survival in patients with oesophageal adenocarcinoma.

A Simulation to Evaluate Screening for Helicobacter Pylori Infection in the Prevention of Peptic Ulcers and Gastric Cancers

A discrete event simulation model has evaluated a screening programme for Helicobacter pylori infection (H. pylori) in which individuals under the age of 50 years would be screened once. Eradication of H. pylori would reduce the peptic ulcer risk immediately and the gastric cancer risk after a fixed delay. The data were derived from published databases and peer reviewed papers. The simulation model, using variance reduction techniques, predicted that a screening programme would reduce morbidity and deaths but could cost around £19 million for England and Wales in the first year of screening. A factorial design analysis showed the sensitivity of key variables. An increase in the opportunistic testing was found significantly to reduce the impact of screening.

A UK-based cost-utility analysis of radiofrequency ablation or oesophagectomy for the management of high-grade dysplasia in Barrett's oesophagus.

Aliment Pharmacol Ther 2010; 32: 1332–1342

Mucosal expression of cyclooxygenase isoforms 1 and 2 is increased with worsening damage to the gastric mucosa

Aims : To test the hypothesis that both COX‐1 and COX‐2 expression in human gastric mucosa is up‐regulated in the presence of inflammation as seen in patients with gastritis and gastric ulcers.

Premedication with N-acetylcysteine and simethicone improves mucosal visualization during gastroscopy: a randomized, controlled, endoscopist-blinded study.

Objectives Diagnostic gastroscopy provides a unique opportunity to diagnose early oesophagogastric neoplasia; however, intraluminal mucus and bile can obscure mucosal visualization. The aim of this study was to determine whether the use of a premedication solution containing the mucolytic agent N-acetylcysteine and the surfactant simethicone improves mucosal visualization within a UK diagnostic gastroscopy service. Materials and methods A total of 75 consecutive patients were recruited from a single (S.J.) endoscopist’s diagnostic gastroscopy list. They were randomized into three treatment groups: (a) standard control=clear fluids only for 6 h, nil by mouth for 2 h; (b) water control=standard control+100 ml sterile water (given 20 min before gastroscopy); and (c) solution=standard control+100 ml investigated solution (20 min before gastroscopy). The endoscopist was blinded to patient preparation. Inadequate mucosal visualization was defined as fluid/mucus during gastroscopy that could not be suctioned and required flushing with water. The volume of flush, the site at which it was used and the total procedure times were recorded. Results All three groups showed no statistical difference for age, sex ratio, procedure priority or indication. The mean volume of flush required to obtain clear mucosa was significantly less in the solution group compared with the other groups. The mean overall procedure time was also less in the solution group compared with the other groups. Discussion Premedication with N-acetylcysteine and simethicone markedly improves mucosal visibility during gastroscopy. It also reduces the time taken for the procedure. This low-cost and well-tolerated intervention may improve detection of early neoplasia.

A randomised controlled trial of structured nurse-led outpatient clinic follow-up for dyspeptic patients after direct access gastroscopy

BackgroundDyspepsia is a common disorder in the community, with many patients referred for diagnostic gastroscopy by their General Practitioner (GP). The National Institute of Clinical Excellence (NICE) recommends follow-up after investigation for cost effective management, including lifestyle advice and drug use. An alternative strategy may be the use of a gastro-intestinal nurse practitioner (GNP) instead of the GP. The objective of this study is to compare the effectiveness and costs of systematic GNP led follow-up to usual care by GPs in dyspeptic patients following gastroscopy.ResultsDirect access adult dyspeptic patients referred for gastroscopy; without serious pathology, were followed-up in a structured nurse-led outpatient clinic. Outcome measurement used to compare the two study cohorts (GNP versus GP) included Glasgow dyspepsia severity (Gladys) score, Health Status Short Form 12 (SF12), ulcer healing drug (UHD) use and costs. One hundred and seventy five patients were eligible after gastroscopy, 89 were randomised to GNP follow-up and 86 to GP follow-up. Follow-up at 6 months was 81/89 (91%) in the GNP arm and 79/86 (92%) in the GP arm. On an intention to treat analysis, adjusted mean differences (95%CI) at follow-up between Nurse and GP follow-up were: Gladys score 2.30 (1.4–3.2) p < 0.001, SF12 140.6 (96.5–184.8) p =< 0.001 and UHD costs £39.60 (£24.20–£55.10) p =< 0.001, all in favour of nurse follow-up.ConclusionA standardised and structured follow-up by one gastrointestinal nurse practitioner was effective and may save drug costs in patients after gastroscopy. These findings need replication in other centres.