Endoscopic submucosal dissection: the best way to deal with subsquamous metaplasia?

We read with great interest the article by Chevaux et al. reporting the results of a large prospective study of endoscopic submucosal dissection (ESD) for Barrett’s neoplasia [1].

The authors reported the technique to be feasible with a 90 % en bloc resection rate, and complications rates of 6.7 % for early and 60 % for late complications, however, with no 30-day mortality. ESD yielded an 85 % curative resection rate for early adenocarcinomas at risk of poor pathological assessment with conventional endoscopic mucosal resection (EMR). However, despite large mucosal resection specimens with a median size of 52.5 mm (interquartile range 43 – 71 mm), involving over three-fourths of the esophageal circumference in half of the patients, and safety margins of 3 – 5 mm, the curative resection rate for neoplasia was only 56 %.

Esophageal ESD is a technically challenging procedure, bearing relatively high complication rates as compared to EMR or ablation techniques. Therefore, one might expect that it would achieve two main goals: (i) curative resection of > 15-mm early adenocarcinomas, and (ii) one-stage, en bloc resection of all Barrett’s neoplasia, with optimal assessment of possible multifocal carcinomas, and low risk of residual or buried Barrett’s glands, given that the whole mucosa and submucosa are resected.

Buried metaplasia or subsquamous Barrett’s epithelium is defined by the presence of Barrett’s glands in the lamina propria. It has been reported to be present in a majority of patients with Barrett’s esophagus, either under the squamous epithelium at the squamocolumnar junction in previously untreated patients, or under the squamous neoepithelium after ablation therapies [2] [3] [4] [5]. Cases of buried adenocarcinoma have been reported as a possible complication of buried Barrett’s glands [6]. However, the actual importance of this condition is still unclear. Furthermore, some experts even cast doubt on the endoscopic and pathological definition of buried metaplasia [7].

According to a recent report, subsquamous Barrett’s epithelium extends to a mean of 3.3 mm under the squamous epithelium [4]. This finding might account for the high rate of histologically incomplete resection (62.5 %) due to positive horizontal margins in a previous study in which Barrett’s neoplasia was resected by ESD [5]. The authors concluded that safety margins during such ESD procedures should be set further away from the nearest endoscopically visible lesion than the usual cutoff of 1 – 2 mm.

The study by Chevaux et al. suggests that currently available endoscopic diagnostic tools do not allow for accurate delimitation of Barrett’s neoplasia. This could lead endoscopists either to consider en bloc resection of the entire Barrett’s mucosa, using larger security margins beyond the abnormality that the eye can see (possibly leading to high rates of esophageal stricture because of the extent of the resection required) or to consider systematic radiofrequency ablation (RFA) of residual Barrett’s esophagus after the resection by ESD of a visible lesion. In this case, rigorous histological follow-up would be required to search for buried metaplasia.

We would be interested to know the rate of subsquamous Barrett’s epithelium in the study by Chevaux et al., and whether this condition could account for the positive lateral margins observed in almost half of the patients. If so, en bloc resection of Barrett’s neoplasia by ESD might require even larger security margins than the 4 – 5 mm used by Chevaux et al.

• References

• 1 Chevaux JB, Piessevaux H, Jouret-Mourin A et al. Clinical outcome in patients treated with endoscopic submucosal dissection for superficial Barrett’s neoplasia. Endoscopy 2015; 47: 103-112
• 2 Cobb MJ, Hwang JH, Upton MP et al. Imaging of subsquamous Barrett’s epithelium with ultrahigh-resolution optical coherence tomography: a histologic correlation study. Gastrointest Endosc 2010; 71: 223-230
• 3 Zhou C, Tsai TH, Lee HC et al. Characterization of buried glands before and after radiofrequency ablation by using 3-dimensional optical coherence tomography (with videos). Gastrointest Endosc 2012; 76: 32-40
• 4 Anders M, Lucks Y, El-Masry MA et al. Subsquamous extension of intestinal metaplasia is detected in 98% of cases of neoplastic Barrett’s esophagus. Clin Gastroenterol Hepatol 2014; 12: 405-410
• 5 Neuhaus H, Terheggen G, Rutz EM et al. Endoscopic submucosal dissection plus radiofrequency ablation of neoplastic Barrett’s esophagus. Endoscopy 2012; 44: 1105-1113
• 6 Van Laethem JL, Peny MO, Salmon I et al. Intramucosal adenocarcinoma arising under squamous re-epithelialisation of Barrett’s oesophagus. Gut 2000; 46: 574-577
• 7 Pouw RE, Visser M, Odze RD et al. Pseudo-buried Barrett’s post radiofrequency ablation for Barrett’s esophagus, with or without prior endoscopic resection. Endoscopy 2014; 46: 105-109