Krish Ragunath

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.

Radiofrequency Ablation vs Endoscopic Surveillance for Patients With Barrett Esophagus and Low-Grade Dysplasia: A Randomized Clinical Trial

IMPORTANCE Barrett esophagus containing low-grade dysplasia is associated with an increased risk of developing esophageal adenocarcinoma, a cancer with a rapidly increasing incidence in the western world. OBJECTIVE To investigate whether endoscopic radiofrequency ablation could decrease the rate of neoplastic progression. DESIGN, SETTING, AND PARTICIPANTS Multicenter randomized clinical trial that enrolled 136 patients with a confirmed diagnosis of Barrett esophagus containing low-grade dysplasia at 9 European sites between June 2007 and June 2011. Patient follow-up ended May 2013. INTERVENTIONS Eligible patients were randomly assigned in a 1:1 ratio to either endoscopic treatment with radiofrequency ablation (ablation) or endoscopic surveillance (control). Ablation was performed with the balloon device for circumferential ablation of the esophagus or the focal device for targeted ablation, with a maximum of 5 sessions allowed. MAIN OUTCOMES AND MEASURES The primary outcome was neoplastic progression to high-grade dysplasia or adenocarcinoma during a 3-year follow-up since randomization. Secondary outcomes were complete eradication of dysplasia and intestinal metaplasia and adverse events. RESULTS Sixty-eight patients were randomized to receive ablation and 68 to receive control. Ablation reduced the risk of progression to high-grade dysplasia or adenocarcinoma by 25.0% (1.5% for ablation vs 26.5% for control; 95% CI, 14.1%-35.9%; P < .001) and the risk of progression to adenocarcinoma by 7.4% (1.5% for ablation vs 8.8% for control; 95% CI, 0%-14.7%; P = .03). Among patients in the ablation group, complete eradication occurred in 92.6% for dysplasia and 88.2% for intestinal metaplasia compared with 27.9% for dysplasia and 0.0% for intestinal metaplasia among patients in the control group (P < .001). Treatment-related adverse events occurred in 19.1% of patients receiving ablation (P < .001). The most common adverse event was stricture, occurring in 8 patients receiving ablation (11.8%), all resolved by endoscopic dilation (median, 1 session). The data and safety monitoring board recommended early termination of the trial due to superiority of ablation for the primary outcome and the potential for patient safety issues if the trial continued. CONCLUSIONS AND RELEVANCE In this randomized trial of patients with Barrett esophagus and a confirmed diagnosis of low-grade dysplasia, radiofrequency ablation resulted in a reduced risk of neoplastic progression over 3 years of follow-up. TRIAL REGISTRATION trialregister.nl Identifier: NTR1198.

Consensus Statements for Management of Barrett's Dysplasia and Early-Stage Esophageal Adenocarcinoma, Based on a Delphi Process

BACKGROUND & AIMS Esophageal adenocarcinoma (EA) is increasingly common among patients with Barretts esophagus (BE). We aimed to provide consensus recommendations based on the medical literature that clinicians could use to manage patients with BE and low-grade dysplasia, high-grade dysplasia (HGD), or early-stage EA. METHODS We performed an international, multidisciplinary, systematic, evidence-based review of different management strategies for patients with BE and dysplasia or early-stage EA. We used a Delphi process to develop consensus statements. The results of literature searches were screened using a unique, interactive, Web-based data-sifting platform; we used 11,904 papers to inform the choice of statements selected. An a priori threshold of 80% agreement was used to establish consensus for each statement. RESULTS Eighty-one of the 91 statements achieved consensus despite generally low quality of evidence, including 8 clinical statements: (1) specimens from endoscopic resection are better than biopsies for staging lesions, (2) it is important to carefully map the size of the dysplastic areas, (3) patients that receive ablative or surgical therapy require endoscopic follow-up, (4) high-resolution endoscopy is necessary for accurate diagnosis, (5) endoscopic therapy for HGD is preferred to surveillance, (6) endoscopic therapy for HGD is preferred to surgery, (7) the combination of endoscopic resection and radiofrequency ablation is the most effective therapy, and (8) after endoscopic removal of lesions from patients with HGD, all areas of BE should be ablated. CONCLUSIONS We developed a data-sifting platform and used the Delphi process to create evidence-based consensus statements for the management of patients with BE and early-stage EA. This approach identified important clinical features of the diseases and areas for future studies.

Endoscopic tri-modal imaging for detection of early neoplasia in Barrett's oesophagus: a multi-centre feasibility study using high-resolution endoscopy, autofluorescence imaging and narrow band imaging incorporated in one endoscopy system

Objective: To investigate the diagnostic potential of endoscopic tri-modal imaging and the relative contribution of each imaging modality (i.e. high-resolution endoscopy (HRE), autofluorescence imaging (AFI) and narrow-band imaging (NBI)) for the detection of early neoplasia in Barrett’s oesophagus. Design: Prospective multi-centre study. Setting: Tertiary referral centres. Patients: 84 Patients with Barrett’s oesophagus. Interventions: The Barrett’s oesophagus was inspected with HRE followed by AFI. All lesions detected with HRE and/or AFI were subsequently inspected in detail by NBI for the presence of abnormal mucosal and/or microvascular patterns. Biopsies were obtained from all suspicious lesions for blinded histopathological assessment followed by random biopsies. Main outcome measures: (1) Number of patients with early neoplasia diagnosed by HRE and AFI; (2) number of lesions with early neoplasia detected with HRE and AFI; and (3) reduction of false positive AFI findings after NBI. Results: Per patient analysis: AFI identified all 16 patients with early neoplasia identified with HRE and detected an additional 11 patients with early neoplasia that were not identified with HRE. In three patients no abnormalities were seen but random biopsies revealed HGIN. After HRE inspection, AFI detected an additional 102 lesions; 19 contained HGIN/EC (false positive rate of AFI after HRE: 81%). Detailed inspection with NBI reduced this false positive rate to 26%. Conclusions: In this international multi-centre study, the addition of AFI to HRE increased the detection of both the number of patients and the number of lesions with early neoplasia in patients with Barrett’s oesophagus. The false positive rate of AFI was reduced after detailed inspection with NBI.

Chromoendoscopy and narrow-band imaging compared with high-resolution magnification endoscopy in Barrett's esophagus.

BACKGROUND & AIMS The aim of this study was to compare magnified still images obtained with high-resolution white light endoscopy, indigo carmine chromoendoscopy, acetic acid chromoendoscopy, and narrow-band imaging to determine the best technique for use in Barretts esophagus. METHODS We obtained magnified images from 22 areas with the 4 aforementioned techniques. Seven endoscopists with no specific expertise in Barretts esophagus or advanced imaging techniques and 5 international experts in this field evaluated these 22 areas for overall image quality, mucosal image quality, and vascular image quality. In addition, the regularity of mucosal and vascular patterns and the presence of abnormal blood vessels were evaluated, and this was correlated with histology. RESULTS The interobserver agreement for the 3 features of mucosal morphology with white light images ranged from kappa = 0.51 (95% confidence interval [CI]: 0.46-0.55) to kappa = 0.53 (95% CI: 0.50-0.57) for all observers, from kappa = 0.43 (95% CI: 0.33-0.54) to kappa = 0.53 (95% CI: 0.41-0.64) for experts, and from kappa = 0.51 (95% CI: 0.15-0.33) to kappa = 0.64 (95% CI: 0.58-0.70) for nonexperts. The interobserver agreement in these groups did not improve by adding one of the enhancement techniques. The yield for identifying early neoplasia with white light images was 86% for all observers, 90% for experts, and 84% for nonexperts. The addition of enhancement techniques did not improve the yield neoplasia. CONCLUSIONS The addition of indigo carmine chromoendoscopy, acetic acid chromoendoscopy, or narrow-band imaging to white light images did not improve interobserver agreement or yield identifying early neoplasia in Barretts esophagus.

Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers

Germline CDH1 mutations confer a high lifetime risk of developing diffuse gastric (DGC) and lobular breast cancer (LBC). A multidisciplinary workshop was organised to discuss genetic testing, surgery, surveillance strategies, pathology reporting and the patients perspective on multiple aspects, including diet post gastrectomy. The updated guidelines include revised CDH1 testing criteria (taking into account first-degree and second-degree relatives): (1) families with two or more patients with gastric cancer at any age, one confirmed DGC; (2) individuals with DGC before the age of 40 and (3) families with diagnoses of both DGC and LBC (one diagnosis before the age of 50). Additionally, CDH1 testing could be considered in patients with bilateral or familial LBC before the age of 50, patients with DGC and cleft lip/palate, and those with precursor lesions for signet ring cell carcinoma. Given the high mortality associated with invasive disease, prophylactic total gastrectomy at a centre of expertise is advised for individuals with pathogenic CDH1 mutations. Breast cancer surveillance with annual breast MRI starting at age 30 for women with a CDH1 mutation is recommended. Standardised endoscopic surveillance in experienced centres is recommended for those opting not to have gastrectomy at the current time, those with CDH1 variants of uncertain significance and those that fulfil hereditary DGC criteria without germline CDH1 mutations. Expert histopathological confirmation of (early) signet ring cell carcinoma is recommended. The impact of gastrectomy and mastectomy should not be underestimated; these can have severe consequences on a psychological, physiological and metabolic level. Nutritional problems should be carefully monitored.

Narrow band imaging for characterization of high grade dysplasia and specialized intestinal metaplasia in Barrett's esophagus: a meta-analysis.

BACKGROUND AND STUDY AIM Narrow band imaging (NBI), a novel endoscopic technique that highlights mucosal surface structures and microvasculature is increasingly advocated as a tool to detect and characterize neoplasia and intestinal metaplasia in patients with Barretts esophagus. We aimed to assess the diagnostic accuracy of NBI with magnification for the diagnosis of high grade dysplasia (HGD) and specialized intestinal metaplasia (SIM) in patients with Barretts esophagus. METHODS We performed a meta-analysis of studies which compared NBI-based diagnosis of HGD and SIM with histopathology as the gold standard. RESULTS Eight studies including 446 patients with 2194 lesions met the inclusion criteria. For diagnosing HGD, the pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.96 (95 % confidence interval [CI] 0.93-0.99), 0.94 (95 %CI 0.84-1.0), 342.49 (95 %CI 40.49 - 2896.89) and 0.99 (SE 0.01) on a per-lesion analysis with similar results on per-patient analysis.. For the characterization of SIM, the pooled sensitivity, specificity, DOR, and AUC were 0.95 (95 %CI 0.87-1.0), 0.65 (95 %CI 0.52-0.78), 37.53 (95 %CI 6.50-217.62) and 0.88 (SE 0.08) on a per-lesion analysis. CONCLUSION NBI with magnification is accurate with high diagnostic precision for diagnosis of HGD in Barretts esophagus on the basis of irregular mucosal pit patterns and/or irregular microvasculature. NBI has high sensitivity but poor specificity for characterizing SIM.

Meta‐analysis: the diagnostic yield of chromoendoscopy for detecting dysplasia in patients with colonic inflammatory bowel disease

Aliment Pharmacol Ther 2011; 33: 304–312

Endoscopic Tri-Modal Imaging Is More Effective Than Standard Endoscopy in Identifying Early-Stage Neoplasia in Barrett's Esophagus

BACKGROUND & AIMS Endoscopic tri-modal imaging (ETMI) incorporates high-resolution endoscopy (HRE), autofluorescence imaging (AFI), and narrow band imaging (NBI). A recent uncontrolled study found that ETMI improved the detection of high-grade dysplasia (HGD) and early carcinoma (Ca) in Barretts esophagus (BE). The aim was to compare ETMI with standard video endoscopy (SVE) for the detection of HGD/Ca with the use of a randomized cross-over design. METHODS Patients referred for work-up of inconspicuous HGD/Ca were eligible and underwent both SVE and ETMI in randomized order within an interval of 6-12 weeks. During ETMI, inspection with HRE was followed by AFI. Detected lesions were inspected in detail with NBI and biopsied, followed by random biopsies. During SVE, any visible lesion was biopsied followed by random biopsies. RESULTS Eighty-seven patients with BE underwent ETMI and SVE. No significant difference was observed in overall histologic yield between ETMI and SVE. ETMI had a significantly higher targeted yield compared with SVE because of AFI. However, the yield of targeted biopsies of ETMI was significantly inferior to the overall yield of SVE. Detailed inspection with NBI reduced the false-positive rate of HRE + AFI from 71% to 48% but misclassified 17% of HGD/Ca lesions as not suspicious. CONCLUSIONS ETMI statistically significant improves the targeted detection of HGD/Ca compared with SVE. Subsequent characterization of lesions with NBI appears to be of limited value. At this stage, ETMI cannot replace random biopsies for detection of lesions or targeted biopsies for characterization of lesions in a high-risk population.

High definition colonoscopy vs. standard video endoscopy for the detection of colonic polyps: a meta-analysis

BACKGROUND AND STUDY AIMS High definition colonoscopy may improve adenoma detection rates but studies report conflicting results. The aim of this meta-analysis was to compare the diagnostic yield of colonic polyps between high definition colonoscopy and standard video endoscopy (SVE). METHODS Various electronic databases were searched for articles reporting on high definition colonoscopy. The pooled incremental yield and pooled weighted mean difference of high definition colonoscopy over SVE for polyp detection was determined. RESULTS Five studies involving 4422 patients provided data on the total number of polyps detected. The incremental yield of high definition colonoscopy for the detection of any polyp was 3.8 % (95 % confidence interval [CI] 1 % - 6.7 %) with a number needed to treat (NNT) of 26. For the detection of adenomatous polyps the incremental yield was 3.5 % (95 %CI 0.9 % - 6.1 %) with an NNT of 28. There were no differences between high definition and SVE in the detection of high risk adenomas, with an incremental yield of -0.1 % (95 %CI -1.7 % to 1.6 %). When grouped according to the overall adenoma detection rate of the studies (> 50 % or < 50 %) the pooled weighted mean difference in small adenoma detection was better with high definition colonoscopy ( P = 0.035). CONCLUSIONS There were marginal differences between high definition colonoscopy and SVE for the detection of colonic polyps/adenomas. High definition colonoscopy did not improve the detection of high risk adenomas. Due to differences in the adenoma detection rate between the studies and the nonrandomized study design of three of the five studies, these results need to be interpreted with caution. Prospective randomized trials looking at long term outcomes such as rates of interval or missed cancers are needed to clarify the clinical implications.