Biased assessment of 3D optical coherence tomography in a single post-radiofrequency ablation patient without histological correlation

A case report entitled “Three-dimensional optical coherence tomography of Barrett’s esophagus and buried glands beneath neosquamous epithelium following radiofrequency ablation,” was recently published by Adler et al. in Endoscopy [1]. Based on the title and abstract, we fully expected the authors to present evidence showing that three-dimensional optical coherence tomography (3D-OCT) was able to detect buried Barrett’s after radiofrequency ablation (RFA) that was otherwise not detectable with conventional methods. Unfortunately, the authors report a single ablation-naïve case where it seems that buried glands were detected on biopsy yet not specifically detected with 3D-OCT or explicitly described in their findings, followed by a single (separate) post-ablation case where structures near the gastroesophageal junction (GEJ) imaged with 3D-OCT were deemed “buried Barrett’s glands” by the authors, yet not confirmed histologically with biopsy. In our opinion, the title of this report is misleading, and the authors’ conclusions are far-reaching and not supported by the reported findings.

The authors state that after ablation therapy “buried Barrett’s beneath regenerative neosquamous epithelium are often found.” Multiple recent reports however have shown that a histological finding of buried Barrett’s is actually a common finding in as many as 25 % of ablation-naïve Barrett’s patients (as seen in the ablation-naïve patient reported by the authors), and that ablative therapy with RFA results in a significant reduction or elimination of the prevalence of buried Barrett’s [2] [3] [4]. Furthermore, in a recent histology study on the properties of neosquamous epithelium after RFA, no buried glands were found in standard biopsies, double-depth keyhole biopsies, or endoscopic resection specimens, which sampled deeply into the submucosa [5].

The authors claim that 3D-OCT found deeply buried glands at the GEJ in a single post-RFA patient. These buried glands were interpreted by the authors as being buried Barrett’s glands, but biopsies from these sites demonstrated “gastric mucosa and GEJ tissue” without evidence of buried Barrett’s glands. The 3D-OCT image of this patient is labeled as “?Barrett’s esophagus” (Fig. 6), indicating that the authors are uncertain as to what these structures are. Furthermore, no endoscopic resection was performed to correlate the 3D-OCT findings with histopathology. This means that this case report lacks any form of histological correlation to deem these structures imaged on 3D-OCT as buried Barrett’s glands.

Another confounding variable is the GEJ location where the authors report a 3D-OCT finding of buried glands in this post-ablation patient. Histology studies on esophagectomy and autopsy specimens have demonstrated that there is a mean overlap of 4 mm of squamous and gastric mucosa at the GEJ [6]. Thus the structures detected on 3D-OCT may actually be undermined gastric mucosal glands representing a normal finding at the GEJ. In fact, we would like to ask the authors if biopsies from the post-ablation patient in the area of 3D-OCT indeed contained glandular structures consistent with undermined gastric mucosa, as their description of the histology is vague. The authors argue that similar 3D-OCT structures were absent in their single control case without Barrett’s esophagus. This is however not very surprising, as the authors limited OCT assessment to the mid-esophagus in this case and did not perform OCT at the GEJ as would have been appropriate for comparing the findings in these patients.

To make matters even more confusing, the authors found buried Barrett’s in biopsies in the ablation-naïve patient (Fig. 5) yet fail to explicitly describe 3D-OCT findings of Barrett’s glands buried beneath squamous epithelium. Instead, they report “densely packed Barrett’s glands beneath 300 – 500 microns of superficial tissue were discernable.” If the superficial tissue is glandular on 3D-OCT, this appears to be a false-negative finding for 3D-OCT versus the gold standard of histology.

Finally, the authors suggest that 3D-OCT may be used for enhanced detection of buried Barrett’s during post-ablation follow-up. This presumes that there is a clinical need for such second-tier detection and implies that an aggressive post-ablation biopsy regimen misses occult buried Barrett’s. The aforementioned recent histology study has provided proof that this is highly unlikely; in other words, we do not have evidence to support the premise that occult buried glands are a common occurrence after ablation [5]. The authors fail to mention any limitations that might be associated with imaging an entire esophagus after ablative therapy with a small probe. In our opinion, it is more efficient and more effective to use high-quality endoscopes with narrow-band imaging or comparable techniques along with biopsy to detect residual or recurrent Barrett’s mucosa during post-ablative follow-up.

In conclusion, we think that the authors’ report is a rather biased view on the application of 3D-OCT in post-RFA patients. Although this imaging technique may be useful in other fields, we feel that this single patient finding of buried structures at the GEJ without histological correlation and proper control is irrelevant and rather misleading, and does not justify the authors’ conclusion that a highly experimental imaging technique such as 3D-OCT may find a future use to enhance detection of buried glands after ablation therapy.

Competing interests: Dr Bergman has received restricted grants to conduct research at the AMC from BÂRRX Medical, Sunnyvale, California, USA.

References

• 1 Adler D C, Zhou C, Tsai T H. et al . Three-dimensional optical coherence tomography of Barrett’s esophagus and buried glands beneath neosquamous epithelium following radiofrequency ablation.  Endoscopy. 2009;  41 773-776
• 2 Fleischer D E, Overholt B F, Sharma V K. et al . Endoscopic ablation of Barrett’s esophagus: a multicenter study with 2.5-year follow-up.  Gastrointest Endosc. 2008;  68 867-876
• 3 Shaheen N J, Sharma P, Overholt B F. et al . Radiofrequency ablation in Barrett’s esophagus with dysplasia.  N Engl J Med. 2009;  360 2277-2288
• 4 Bronner M P, Overholt B F, Taylor S L. et al . Squamous overgrowth is not a safety concern for photodynamic therapy for Barrett’s esophagus with high-grade dysplasia.  Gastroenterology. 2009;  136 56-64
• 5 Pouw R E, Gondrie J J, Rygiel A M. et al . Properties of the neosquamous epithelium after radiofrequency ablation of Barrett’s esophagus containing neoplasia.  Am J Gastroenterol. 2009;  104 1366-1373
• 6 Takubo K, Aida J, Sawabe M. et al . The normal anatomy around the oesophagogastric junction: a histopathologic view and its correlation with endoscopy.  Best Pract Res Clin Gastroenterol. 2008;  22 569-583