Joseph Burnette, MD1, Alvin Zfass, MD2, Alexandra M Roch, MD, MS3, John Bagnato, MD1. 1Department of Surgery, Coliseum Northside Hospital, Macon, GA, USA, 2Division of Gastroenterology, Commonwealth University Medical Center, Richmond, VA, USA, 3Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
Objective of the technology
The replacement of normal squamous epithelium by specialized columnar epithelium with goblet cells (intestinal metaplasia), also known as Barrett’s esophagus, is a well-established esophageal precancerous lesion that commonly occurs after a long-standing history of gastroesophageal reflux disease (GERD).
High-definition eso-gastro-duodenoscopy (EGD) with biopsies according to the Seattle protocol (4 quadrants every 1-2cm and mucosal abnormalities) is the current standard of care for Barrett’s esophagus screening. Because intestinal metaplasia may not be clearly identified macroscopically, this protocol is subject to sampling error.
We hypothesized that using probe-based Confocal Laser Endomicroscopy (pCLE) in screening high-risk individuals for Barrett’s esophagus yielded a better accuracy than the current tissue biopsy protocol.
Description
pCLE (GastroFlex UHD, Cellvizio; Mauna Kea Technologies, Paris, France) is a probe-based flexible microscope that fits through the channel of any videoendoscope. pCLE involves a scanning laser light coupled with a fluorescent agent to generate highly-magnified (1000-fold, 1 micron-resolution) cell-level images of the gastrointestinal mucosa, providing real-time microscopy.
After high-definition EGD evaluation of the esophagus, and injection of fluorescein, the pCLE probe is introduced through the accessory channel of the endoscope and placed in gentle contact with the esophageal mucosa. pCLE enables easy pattern recognition of intestinal metaplasia, reduces the need for tissue biopsy, and facilitates application of focal endoscopic therapy during the time of actual endoscopy.
Preliminary results
A total of 108 consecutive patients with GERD were referred to a single medical center for endoscopic surveillance and screening of Barrett’s esophagus. Of them, 55 were actively treated with proton-pump inhibitor (PPI) therapy. During the same endoscopic procedure, all patients underwent standard protocol biopsies and real-time pCLE evaluation of the mucosa by the gastroenterologist. All tissue biopsies were reviewed by a dedicated gastrointestinal pathologist with extensive experience in Barrett’s esophagus histology, who was blinded to pCLE evaluation.
The incidence of Barrett’s esophagus based on pathology from random tissue biopsies and pCLE was 12% and 28%, respectively. The 25 cases that showed discrepancy between the 2 methods were reviewed post-hoc by a pCLE expert, with an interobserver agreement (between real-time evaluation and expert post-hoc review) using Kappa statistic of 0.7.
In patients under PPI therapy (n=55), the incidence of Barrett’s esophagus using tissue biopsy was 16%, compared to 40% with pCLE.
The sensitivity for diagnosis of Barrett’s esophagus of random tissue biopsy and pCLE was 40% and 92%, respectively (p=0.0002). Similarly, the negative predictive value of random tissue biopsy for diagnosis of intestinal metaplasia was 81%, and 99% for pCLE.
Conclusion
The current standard of care for screening of patients with Barrett’s esophagus is suboptimal, with low sensitivity (40%) and underestimation of the incidence. With an excellent negative predictive value, pCLE, if negative, reduces the need for additional biopsies, and is thereby a useful addition to standard EGD. Due to the quick learning curve on image interpretation and real-time application, the addition of pCLE to the screening work-up improves diagnostic accuracy of Barrett’s esophagus in patients with GERD compared to the current standard of care.
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