Esophageal adenocarcinoma is the fastest growing cancer in Westernized countries and has grown over 600% since the introduction of the first anti-secretory medication (Cimetidine) in the 1970s. Despite advances in medical therapy to control acid reflux, the occurrence rates of esophageal adenocarcinoma as a result of uncontrolled GERD continues to rise. Barrett’s esophagus is the number one risk factor for the development of esophageal adenocarcinoma. Intestinal metaplasia of the esophagus, or Barrett’s esophagus (BE), comes from uncontrolled GERD. Gastroesophageal reflux disease (GERD) affects nearly 10% of the US population and Westernized countries. The diagnosis of GERD is associated with a 10-15% risk of developing Barrett’s esophagus. Compared to the general population, patients with BE have a 30-50% increased risk of developing esophageal adenocarcinoma. Despite these alarming numbers regarding the rise of esophageal cancer, Barrett’s esophagus continues to be an underdiagnosed and undertreated condition.
Visible columnar metaplasia is characterized by replacement of normal squamous epithelium with columnar epithelium in the esophagus as a response to uncontrolled GERD. The presence of goblet cells defines BE and can be considered a risk factor for cancer.
Current ASGE guidelines recommend that tissue samples be obtained to confirm endoscopically suspected Barrett’s esophagus for diagnosis and surveillance. The Seattle Protocol for Barrett’s esophagus recommends four-quadrant random biopsies at 2-cm intervals (1-cm intervals if suspected high grade intraepithelial neoplasia).1 This random biopsy protocol can be time-consuming, expensive, and prone to sampling error, as very little of the esophageal surface area is actually sampled.
Diagnosis of BE remains difficult. The White Paper AGA addresses this issue by stating, “BE (specifically shorter disease) is often misdiagnosed during endoscopy. This misdiagnosis is often attributed to 1 of 2 reasons: (1) inability to differentiate columnar mucosa of the proximal stomach (cardia) from metaplastic epithelium in the distal esophagus or (2) lack of goblet cells in biopsies obtained from columnar lined epithelium in the esophagus.” 2
Probe-based Confocal Laser Endomicroscopy (pCLE) generates digital biopsies, providing physicians with microscopic images of tissue in real time and in a minimally invasive manner. This provides endoscopists with dynamic microscopic views of gastrointestinal mucosa, allowing for real-time diagnosis of intestinal metaplasia. It also allows a greater esophageal surface area to be examined as compared to the random physical biopsy method. Finally, pCLE allows for directed biopsies when clinically appropriate of specific high risk areas.
In the DONT BIOPCE trial, a 2.7-fold increase in the diagnostic yield of BE and a 4.8-fold decrease in the number of biopsies by using pCLE and targeted biopsies have been observed. 3
As AGA White Paper published in December 2015, “…the workshop panelists agreed that in the hands of endoscopists who have met the preservation and incorporation of valuable endoscopic innovation thresholds (diagnostic accuracy) with enhanced imaging techniques (specific technologies), use of the technique in Barrett’s esophagus patients is appropriate”.2 This AGA White paper is also supported by the consensus statements developed by a group of 26 international experts in the United European Gastroenterology Journal. 6
General surgeons are integral to the care of the GERD patient. To appropriately diagnose and treat patients there are multiple studies that are required to perform that comprehensive assessment. Cellvizio®, very clearly is integral to the comprehensive assessment of patients suffering from reflux disease. In fact, it fills a much needed diagnostic gap in patients at risk for Barrett’s esophagus and or have Barrett’s. Clinicians and patients alike need and deserve access to Cellvizio® (pCLE) in order to obtain a comprehensive assessment of the extent of disease and to make real-time therapeutic treatment decisions. Employing Cellvizio® has the additional advantage of being cost effective by potentially eliminating the need for tissue biopsies, allowing for fewer biopsies. In addition to improving diagnostic yield, Cellvizio® can also be used to map an area of Barrett’s prior to treatment and evaluate completeness of therapy upon follow-up.
Appendix
Extract from the Consensus
- Use of probe-based confocal laser endomicroscopy (pCLE) in gastrointestinal applications. A consensus report based on clinical evidence. Wang KK, Carr-Locke DL, Singh SK, Neumann H, Bertani H, Galmiche JP, Arsenescu RI, Caillol F, Chang KJ, Chaussade S, Coron E, Costamagna G, Dlugosz A, Ian Gan S, Giovannini M, Gress FG, Haluszka O, Ho KY, Kahaleh M, Konda VJ, Prat F, Shah RJ, Sharma P, Slivka A, Wolfsen HC, Zfass A. United European Gastroenterol J. 2015 Jun;3(3):230-54 :
- CLE should be considered in the evaluation of BE [Agreement: 95%];
- CLE should be combined with red-flag techniques (e.g. chromoendoscopy) [Agreement: 95%];
- CLE is clinically indicated in patients with BE dysplasia in lesions initially identified with red flag techniques (i.e. NBI) [Agreement: 95%];
- CLE is clinically indicated in patients with BE dysplasia in lesions initially identified endoscopically in surveillance [Agreement: 100%];
- CLE is able to distinguish cardia (non-intestinal) from intestinal metaplasia, based on the presence or absence of goblet cells [Agreement: 75%];
- CLE is superior to WLE in identifying intestinal metaplasia [Agreement: 100%];
- A negative CLE random sampling in an endoscopically benign-appearing esophagus is sufficient to reduce the need for a physical biopsy in patients with known BE [Agreement: 85%];
- CLE can improve the yield for neoplasia compared with standard WLE and random biopsies [Agreement: 95%];
- CLE and WLE-targeted biopsies are superior to WLE-targeted biopsies alone in the detection of dysplasia [Agreement: 100%];
- A positive CLE random sampling in an endoscopically neoplastic-appearing esophagus is sufficient for therapeutic intervention [Agreement: 80%];
- CLE can be used to define the location and lateral extent of neoplasia prior to therapy [Agreement: 85%].
Literature-
1. ASGE Standards of Practice Committee, Muthasamy et al. The Role of endoscopy in the management of GERD. Gastrointestinal endoscopy. 2015; 81 (6): 1305-1310.
2. Sharma, et al. White Paper AGA: Advanced Imaging in Barrett’s Esophagus. Clinical Gastroenterol Hepatol. 2015 Dec; 13(13)” 2209-18.
3. Sharma, et al, Real-time increased detection of neoplastic tissue in Barrett’s esophagus with probe- based confocal laser endomicroscopy; final results of an international multi-center, prospective, randomized, controlled trial. GIE, 2011
4. Bertani, et al. Improved Detection of Incident Dysplasia by Probe-based Confocal Laser Endomicroscopy in a Barrett’s Esophagus Surveillance Program. Digestive Diseases and Sciences, 2013
5. Canto et al., Confocal Endomicroscopy for Barrett’s Esophagus or Confocal Endomicroscopy for Barrett’s Esophagus (CEBE) Trial Group. In vivo endomicroscopy improves detection of
Barrett’s esophagus-related neoplasia: a multicenter international randomized controlled trial (with video). Gastrointest Endosc, 2014
6. Use of probe-based confocal laser endomicroscopy (pCLE) in gastrointestinal applications. A consensus report based on clinical evidence. Wang et al. United European Gastroenterol J. 2015 Jun;3(3):230-54