A New ‘Look’ at Barrett’s Esophagus

Barrett’s esophagus, a precursor to esophageal adenocarcinoma, is the focus of current efforts to combat the rapidly rising incidence of this deadly cancer. Barrett’s esophagus is thought to progress from nondysplastic Barrett’s esophagus through low-grade dysplasia and high-grade dysplasia before becoming adenocarcinoma. The risk of esophageal adenocarcinoma is assessed by sampling the affected mucosa through biopsies for the detection of dysplasia and mucosal cancer. The current recommendation from all major gastrointestinal societies is to survey Barrett’s esophagus with random biopsies: four quadrants of the esophagus every one-to-two centimeters for the entire length of Barrett’s. This is a tedious, expensive and time-consuming protocol, and there is good evidence to show that endoscopists do not routinely adhere to this.1


“Advanced endoscopic imaging technologies have been evaluated and hold the potential to reshape the way we survey Barrett’s esophagus.”


To address several of these shortcomings, advanced endoscopic imaging technologies have been evaluated and hold the potential to reshape the way we survey Barrett’s esophagus. High-definition white light endoscopy (HD-WLE) has essentially replaced standard definition white light endoscopy (SD-WLE). For Barrett’s esophagus, studies have found that high-definition white light endoscopy increases the yield in targeted biopsies over standard definition white light endoscopy2 and that spending one minute per centimeter of Barrett’s esophagus on examination of the affected mucosa increases the detection of suspicious lesions for targeted biopsy.3 Such a ‘quality examination’ could be easily implemented and should be the minimal standard in surveillance of patients with Barrett’s.

Chromoendoscopy is the endoscopic application of a solution (examples include indigo carmine, acetic acid, etc.) to enhance mucosal details. These can be applied by introducing a spray catheter through the channel of an endoscope that allows for the detection of suspicious lesions for targeted biopsies. A recent meta-analysis of 843 patients from 14 studies evaluated chromoendoscopy with targeted biopsies versus white light endoscopy with random biopsies and found chromoendoscopy increases the yield for detecting dysplasia or cancer by 35 percent over white light endoscopy.4 Chromoendoscopy is easily implemented without having to purchase expensive equipment or new endoscopes, but it can be time consuming to prepare and is limited by the subjective interpretation of mucosal patterns.

Virtual chromoendoscopy is the enhancement of endoscopic images to enhance mucosal details, much like chromoendoscopy. There are several forms of virtual chromoendoscopy: narrow-band imaging, iScan and flexible spectral imaging color enhancement. One study compared narrow-band imaging with targeted biopsies to high-definition white light endoscopy with random biopsies and found narrow-band imaging required fewer biopsies (3.6 compared to 7.6) but maintained the same sensitivity of 92 percent.z5 A system for identifying suspicious mucosal patterns is required to ensure consistent and reliable examinations between different providers. The BING (Barrett’s International NBI group) consortium developed a system using expert consensus, which has a sensitivity of 92 percent, a negative predictive value of 95 percent and a specificity of 88 percent for dysplasia when images are interpreted with confidence. This system also had a significant inter-user agreement.6

Confocal laser endomicroscopy visualizes a plane of tissue in vivo at the cellular level. This procedure will allow the endoscopist to see the goblet cells as well as features of dysplasia. A multi-center study comparing high-definition white light endoscopy using random biopsies with confocal laser endomicroscopy using targeted biopsies found that confocal laser endomicroscopy increases the yield of biopsies for the diagnosis of neoplasia to 34 percent compared to 7 percent with random biopsies, and allows the endoscopist to avoid biopsies in as much as 65 percent of patients with nondysplastic Barrett’s esophagus.7 This technique requires specialized endoscopes or probes through the working channel of endoscopes.

Volumetric laser endomicroscopy also visualizes a plane of tissue at the cellular level, but uses a balloon to generate a circumferential image over a 6 centimeter segment of the esophagus and has a greater depth of view than confocal laser endomicroscopy. Preliminary studies have shown this to be safe and effective in patients with Barrett’s esophagus.8,9

While we are still struggling with random biopsy protocols, the next generation of technology for Barrett’s esophagus surveillance is here. How should we apply this to clinical practice? ASGE’s Preservation and Incorporation of Valuable Endoscopic Interventions (PIVI) initiative has proposed that if any tool is to replace random biopsies, it must have a sensitivity greater than 90 percent, a negative predictive value greater than 98 percent and specificity greater than 80 percent.10 Based on published evidence to date, narrow-band imaging and confocal laser endomicroscopy have met the PIVI requirements. And a recent expert consensus whitepaper from the AGA Center for GI Innovation and Technology proposed that those endoscopists with expertise in any of these tools, such that they can meet the standards set by the PIVI initiative, could start applying these technologies in practice.11 Once the tools and training are available, endoscopists will have to choose between the current protocol for random biopsies or the more efficient targeted biopsies with advanced imaging. We believe the majority will favor this new, advanced way of ‘looking’ at Barrett’s esophagus.

Dr. Thomas has no conflicts to disclose.

Dr. Sharma has no conflicts to disclose.

References

1. Abrams JA, Kapel RC, Lindberg GM, et al. Adherence to Biopsy Guidelines for Barrett’s Esophagus Surveillance in the Community Setting in the United States. Clin Gastroenterol Hepatol 2009;7:736–742.

2. Sami SS, Subramanian V, Butt WM, et al. High definition versus standard definition white light endoscopy for detecting dysplasia in patients with Barrett’s esophagus. Dis Esophagus 2014:742–749.

3. Gupta N, Gaddam S, Wani SB, et al. Longer inspection time is associated with increased detection of high-grade dysplasia and esophageal adenocarcinoma in Barrett’s esophagus. Gastrointest Endosc 2012;76:531–8.

4. Qumseya BJ, Wang H, Badie N, et al. Advanced imaging technologies increase detection of dysplasia and neoplasia in patients with barrett’s esophagus: A meta-analysis and systematic review. Clin Gastroenterol Hepatol 2013;11:1562–1570.

5. Sharma P, Hawes RH, Bansal A, et al. Standard endoscopy with random biopsies versus narrow band imaging targeted biopsies in Barrett’s oesophagus: a prospective, international, randomised controlled trial. Gut 2013;62:15–21.

6. Sharma P, Bergman JJGHM, Goda K, et al.Development and Validation of a Classification System to Identify High-Grade Dysplasia and Esophageal Adenocarcinoma in Barrett’s Esophagus Using Narrow-Band Imaging. Gastroenterology 2015.

7. Canto MI, Anandasabapathy S, Brugge W, et al. In vivo endomicroscopy improves detection of Barrett’s esophagus-related neoplasia: A multicenter international randomized controlled trial (with video). Gastrointest Endosc 2014;79:211–221.

8. Leggett CL, Gorospe EC, Chan DK, et al.Comparative diagnostic performance of volumetric laser endomicroscopy and confocal laser endomicroscopy in the detection of dysplasia associated with Barrett’s esophagus. Gastrointest Endosc 2015.

9. Wolfsen HC, Sharma P, Wallace MB, et al. Safety and feasibility of volumetric laser endomicroscopy in patients with Barrett’s esophagus (with videos). Gastrointest Endosc 2015;82:631–640.

10. Sharma P, Savides TJ, Canto MI, et al. The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on imaging in Barrett’s Esophagus. Gastrointest Endosc 2012;76:252–254.

11. Sharma P, Brill J, Canto M, et al. White Paper AGA: Advanced Imaging in Barrett’s Esophagus. Clin Gastroenterol Hepatol 2016;13:2209–2218.

12. Daly C, Vennalaganti P, Soudagar S, et al. Randomized controlled trial of self-directed versus in-classroom teaching of narrow-band imaging for diagnosis of Barrett’s esophagus-associated neoplasia. Gastrointest

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