Eradication of Barrett’s neoplasia: endoscopy vs. laparoscopy

In the past 10 years, endoscopic therapy has replaced esophagectomy for the treatment of dysplasia and early cancer in Barrett’s esophagus. The spectrum of technologies used for the eradication of dysplastic Barrett’s mucosa is evolving: endoscopic resection (such as endoscopic mucosal resection [EMR] and endoscopic submucosal dissection), and radiofrequency ablation (RFA) are established endoscopic techniques; hybrid argon plasma coagulation and cryoablation are promising and currently under further investigation [1]; other techniques such as photodynamic therapy have been abandoned because of a lack of efficacy.

“Although stapler-assisted mucosectomy (SAM) includes a complete single resection that could facilitate pathological examination, only short segment Barrett’s can be removed.”

The cornerstone of treatment of dysplastic Barrett’s esophagus is a combined treatment of endoscopic resection with an ablation technique, of which RFA is the most extensively studied. In experienced hands these techniques are very effective and have a low complication rate. In a Dutch cohort study of patients who underwent RFA with or without endoscopic resection for neoplastic Barrett’s esophagus, 90 % of patients remained in remission at the 5 year follow-up, and the few recurrences found during follow-up were managed endoscopically [2]. So, this combined treatment approach has proven to be effective and durable, and presents a challenge to any novel techniques, which will need to demonstrate improvement on that outcome. Only 1 in 10 patients do not respond completely to the treatment, and this is often due to medically uncontrolled intractable reflux, which is implicated in the nature of the underlying pathophysiology of Barrett’s esophagus. A surgical contribution to overcome this problem in clinical practice may be laparoscopic Nissen fundoplication in selected cases.

In endoscopic therapy of Barrett’s esophagus, a learning curve has been defined for the acquisition of competence. This might in part be an explanation for the differences seen in outcomes in published studies. The results from the United Kingdom from a nationwide RFA study [3] differ from studies conducted exclusively at expert centers, for example in the Euro II study [4]: complete eradication of intestinal metaplasia was 76 % vs. 90 %, respectively. The variability in outcome again suggests the need for centralization of care of dysplastic Barrett’s esophagus, a process that is ongoing in some European countries. The recent European Society of Gastrointestinal Endoscopy guideline has clear advice on annual case load, with at least 10 new patients undergoing endoscopic treatment for high grade dysplasia or early carcinoma required per Barrett’s expert endoscopist [5]. Recommendations on the number needed to obtain competence in technical skills, management pathways, and the treatment of complications are also included in the guideline [5].

In this issue of Endoscopy, Steinemann et al. report on laparoscopic, transgastric, stapler-assisted mucosectomy (SAM) in a porcine model [6]. This technique enables the retrieval of a complete circumferential mucosal specimen of the distal esophagus. In the second part of the study, the SAM technique was compared with circumferential EMR, which is comparable to stepwise radical endoscopic resection (SRER), in a small randomized group in the same porcine model. SRER of dysplastic Barrett’s in humans has the disadvantage of a high risk of stenosing of the esophagus [7]. There are questions over whether comparison in this porcine experiment is completely appropriate. From a randomized trial it has been reported that SRER has a significant higher rate of stenosis (88 %) than the combination of endoscopic resection and RFA (14 %) [8]. So, if it ever comes to a randomized study in humans, a comparison of SAM with the best available or standard of care treatment seems more appropriate.

An extremely interesting observation from this SAM study is that covering of the denuded area with mucosa decreased the risk of stenosis. In endoscopic treatment, covering the resection wound with mucosa after a significant resection in the esophagus is not possible. However, in case of circumferential or extensive resection, stenosing can be prevented by corticosteroid injections. If, despite preventive action, stenosis occurs, treatment with endoscopic dilation is generally feasible.

In clinical practice endoscopists are familiar with hybrid transgastric laparoscopic approaches, usually in cooperation with surgeons, for indications such as endoscopic retrograde cholangiopancreatography after gastric bypass or removal of migrated LapBands in patients who have undergone bariatric procedures. Laparoscopic mucosal resection for high grade dysplasia by scissors via an anterior gastrotomy has been described before, but this has only been reported in small single-center series of patients [9]. This method is adapted and modified in SAM by using a stapler instead of scissors to remove the distal mucosa in the esophagus.

The drawbacks of this novel SAM technique seem to be invasiveness compared with endoscopic resection, the need for general anesthesia, prolonged hospital stay, and potential risk of complications. Although SAM includes a complete single resection that could facilitate pathological examination of the specimen, only short segments of Barrett’s can be removed. The median specimen length in the SAM pilot study was only 17 mm. From epidemiological studies, we know that longer Barrett’s segments have the higher risk of developing neoplasia (10 % increase per cm Barrett’s length) [10]. This raises the question of the potential usefulness of SAM in clinical practice. Can the upper margin of the Barrett’s segment be assessed accurately using only the laparoscopic view? (During endoscopy the border between columnar-lined and squamous tissue is clearly visible.) How are cases of remnant Barrett’s mucosa managed? Can SAM be repeated or does the patient require adjuvant endoscopic treatment? Leaving Barrett’s mucosa in a patient after EMR of dysplasia involves a high risk of metachronous recurrence of neoplasia of up to 30 % over the subsequent 3 years.

The value of performing an en bloc resection is overestimated in Barrett’s dysplasia. All essential histological parameters can be assessed on piecemeal specimens, with the exception of the certainty of the lateral margins. A repeat resection in cases of remnant disease is generally possible and uncomplicated. However, the depth of the resection specimen in early cancer needs to be at least into the submucosa, to get a free horizontal margin and perform a curative resection. In the two SAM experiments, only 50 % and 67 %, respectively, of the resection specimens had submucosal tissue available and therefore the depth of the resection does not seem to be very well controlled. Modification of the technique is essential, as indeed the authors suggest in their paper.

In conclusion, SAM is an interesting novel technique contributing to the evolving landscape of ablation techniques of dysplastic Barrett’s esophagus, but the procedure needs improvement. The more invasive character and shortcomings mentioned in its current form will make it difficult to prompt application in human studies, and it is yet far from ready for daily clinical practice.

• References

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• 2 Phoa KN, Pouw RE, van Vilsteren FG. et al. Remission of Barrett’s esophagus with early neoplasia 5 years after radiofrequency ablation with endoscopic resection: a Netherlands cohort study. Gastroenterology 2013; 145: 96-104
• 3 Haidry RJ, Dunn JM, Butt MA. et al. Radiofrequency ablation and endoscopic mucosal resection for dysplastic Barrett’s esophagus and early esophageal adenocarcinoma: outcomes of the UK National Halo RFA Registry. Gastroenterology 2013; 145: 87-95
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