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

How to select patients for anti-reflux surgery? The ICARUS guidelines (International Consensus regarding preoperative examinations and clinical characteristics assessment to select adult patients for AntiReflUx Surgery)

Objective: Anti-reflux surgery can be proposed in patients with gastro-esophageal reflux disease, especially when proton pump inhibitor use leads to incomplete symptom improvement. However, to date, international consensus guidelines on the clinical criteria and additional technical examinations used in patient selection for anti-reflux surgery are lacking. We aimed at generating key recommendations in the selection of patients for anti-reflux surgery. Design: We included 35 international experts (gastroenterologists, surgeons and physiologists) in a Delphi process and developed 37 statements that were revised by the Consensus Group, to start the Delphi process. Three voting rounds followed where each statement was presented with the evidence summary. The panel indicated the degree of agreement for the statement. When 80% of the Consensus Group agreed (A+/A) with a statement, this was defined as consensus. All votes were mutually anonymous.Results: Patients with heartburn with a satisfactory response to PPIs, patients with a hiatal hernia (HH), patients with esophagitis LA grade B or higher and patients with Barrett’s esophagus are good candidates for anti-reflux surgery. An endoscopy prior to anti-reflux surgery is mandatory and a barium swallow should be performed in patients with suspicion of a HH or short esophagus. Esophageal manometry is mandatory to rule out major motility disorders. Finally, esophageal pH (+/- impedance) monitoring off PPI is mandatory to select patients for anti-reflux surgery, if endoscopy is negative for unequivocal reflux esophagitis. Conclusion: With the ICARUS guidelines, we generated key recommendations for selection of patients for anti-reflux surgery

Colon cleansing efficacy and safety with 1 L NER1006 versus 2 L polyethylene glycol plus ascorbate: a randomized phase 3 trial

BACKGROUND: Polyethylene glycol (PEG)-based bowel preparations are effective cleansers but many require high-volume intake. This phase 3, randomized, blinded, multicenter, parallel-group, central reader-assessed study assessed the 1 L PEG NER1006 bowel preparation vs. standard 2 L PEG with ascorbate (2LPEG). METHODS: Patients undergoing colonoscopy were randomized (1:1:1) to receive NER1006, as an evening/morning (N2D) or morning-only (N1D) regimen, or evening/morning 2LPEG. Cleansing was assessed using the Harefield Cleansing Scale (HCS) and the Boston Bowel Preparation Scale (BBPS). Primary end points were overall bowel cleansing success and high-quality cleansing in the right colon. Modified full analysis set (mFAS) and per protocol (PP) analyses were performed. Mean cleansing scores were analyzed post hoc. RESULTS:  Of 849 randomized patients, efficacy was analyzed in the following patient numbers (mFAS/PP): total n = 822/670; N2D n = 275/220; N1D n = 275/218; 2LPEG n = 272/232. mFAS established noninferiority. PP showed superiority for N2D on overall success (97.3 % vs. 92.2 %; P = 0.014), and for N2D and N1D on right colon high-quality cleansing (N2D 32.3 % vs. 15.9 %, P < 0.001; N1D 34.4 % vs. 15.9 %, P < 0.001) vs. 2LPEG. Using HCS, N2D and N1D attained superior segmental high-quality cleansing (P ≤ 0.003 per segment). N2D showed superior mean segmental HCS scores (P ≤ 0.007 per segment). Both N2D and N1D achieved superior mean overall (P < 0.001 and P = 0.006) and right colon BBPS scores (P < 0.001 and P = 0.013). N2D demonstrated superior right colon polyp detection (P = 0.024). Adherence, tolerability, and safety were comparable between treatments. CONCLUSIONS: NER1006 is the first low-volume preparation to demonstrate superior colon cleansing efficacy vs. standard 2LPEG with ascorbate, with comparable safety and tolerability. European Clinical Trials Database (EudraCT)2014-002185-78TRIAL REGISTRATION: Multicenter, randomized, parallel group, phase 3 trial 2014-002185-78 at https://eudract.ema.europa.eu/.status: publishe

Incremental value of arterial and equilibrium phase compared to hepatic venous phase CT in the preoperative staging of colorectal liver metastases: an evaluation with different reference standards

To evaluate the incremental value of arterial and equilibrium phase compared to hepatic venous phase multidetector row CT (MDCT) in the preoperative staging of colorectal liver metastases (CLM) and to determine the influence of the reference standard. Fifty-three consecutive CLM patients underwent 16 detector row CT in hepatic arterial, venous, and equilibrium phase before surgery between March 2003 and January 2007. Detected lesions were characterized by three independent radiologists. The reference standard consisted of intraoperative palpation and ultrasound of the liver, and histopathological examination of the resected specimen. Additionally, data of follow-up CT was added. Statistical analysis was performed on a per-lesion basis. According to the reference standard 251 lesions were present, of which 203 (81%) were malignant (mean size: 29.4 ± 22.5 mm), and 41 (16%) were benign (mean size: 8.3 ± 7.7 mm). Sensitivity rates for CLM were comparable between triphasic and hepatic venous phase CT (P>0.05). Sensitivity for the detection of CLM lowered from 60-77% to 52-68% when follow-up CT was added to the reference standard. Arterial and equilibrium phase CT have no incremental value compared to hepatic venous phase MDCT in the detection of CLM. Sensitivity rates are, however, influenced by the type of reference standard use

Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (P combined = 4.09 × 10-9; odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (P combined = 2.74 × 10-10; OR = 1.14, 95% CI = 1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus. © 2012 Nature America, Inc. All rights reserved

Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined = 4.09 × 10−9; odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13–1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined = 2.74 × 10−10; OR = 1.14, 95% CI = 1.10–1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus