A Feasibility Trial to Evaluate Endoscopic Removal of early esophageal neoplasia using Endoscopic Submucosal Dissection with LumenR Esophageal RetractorTM (LER), a Modified Esophageal Overtube

Barrett's esophagus is a condition in which a normal esophageal epithelium is replaced with the intestinal epithelium, which may transform into dysplasia or adenocarcinoma. The Barrett's esophagus is diagnosed with upper gastrointestinal (GI) endoscopy and biopsy. The exact prevalence of the Barrett’s esophagus is unknown, but it is estimated that it affects 1.6 to 6.8 percent of people.1 Men develop Barrett’s esophagus twice as often as women, and Caucasian men develop this condition more often than men of other races.2 The average age at diagnosis is 55.3 The exact cause of Barrett's esophagus is not known. However, gastroesophageal reflux disease (GERD) increases the chances of developing the condition.4. Treatment options for Barrett's esophagus include a surveillance endoscopy, endoscopic ablative therapies, endoscopic mucosal or submucosal resection, and surgery. When Barrett’s esophagus is found to harbor a high dysplasia or an early adenocarcinoma endoscopic treatment is preferred over surgical treatment. Endoscopic treatment consists of endoscopic resection of endoscopically visible abnormalities supplemented with ablation therapy for flat type residual Barrett’s mucosa. The purpose of the endoscopic resection is to remove the most involved part of Barrett’s segment with histological correlation and to render the residual Barrett’s segment flat for subsequent ablation therapy. Histological staging is imperative for optimal patient selection: only well/moderately differentiated mucosal cancers without lymphovascular invasion are amendable for curative endoscopic treatment whereas patients with submucosal invading lesions, poorly differentiated cancers, or lymphovascular invasion should be treated by additional esophagectomy given their risk for local lymph node metastasis. Endoscopic resection of early neoplasia in Barrett’s esophagus is mainly performed using cap-based techniques. These resection techniques allow en bloc resection of lesions up to approximately 15-mm in diameter. Larger lesions require removal in multiple pieces (i.e. piecemeal resection). After piecemeal resection assessment of the radicality of the lateral margins is generally not feasible. From an oncological standpoint complete resection in one piece (i.e. en bloc resection) is preferred since it allows optimal histological staging including the assessment of the lateral resection margins. Despite these theoretical advantages of en bloc resection over piecemeal resection, most early Barrett’s lesions are still removed by the cap based resection techniques in piecemeal. There are two reasons for this: 1) endoscopic resection en bloc of larger lesions requires the use of a technique known as endoscopic submucosal dissection (ESD). ESD is technically complicated procedure in which the outer margin of the lesion is incised followed by careful dissection of submucosal space underneath the lesion until it can be removed en bloc.5-8 The ESD technique has been developed in Japan but in the Western world experience with this technology is limited. Compared to piecemeal resection, ESD is more time consuming and carries a higher risk of complications. In addition, ESD in Barrett’s esophagus is considered to be more difficult and risky than standard ESD indications (i.e. esophageal squamous neoplasia and early gastric cancer) because of the movement of distal esophagus due to respiration, esophageal motility and the contractions of the heart, the higher rate of scarring of the submucosal compartment due to longstanding gastroesophageal reflux, and the larger diameter of the submucosal blood vessels; 2) large scale multicenter studies have shown that piecemeal resection combined with endoscopic ablation therapy results in high success rates for eradicating neoplasia (>95%) with a low 5-year recurrence rate of neoplasia (<5%)9,10; 3) most of the histological staging that is so important for proper risk assessment can be just as well done on piecemeal resection specimens as on specimens obtained en bloc. For these reasons, recent European guidelines on the use of ESD in the gastrointestinal tract have considered ESD in Barrett’s to be only an optional resection technique. For squamous neoplastic lesions of the esophagus, ESD is the preferred resection technique. Most Barrett’s expert centers therefore, currently restrict the use of ESD to lesions to the following indications 1) lesions with a bulky intraluminal component; 2) lesions with a large area suspicious for invasive cancer; or 3), or lesions suspected of submucosal invasion. In these lesions, cap-based endoscopic piecemeal resection may compromise the radicality of the deeper resection margin and/or the histological assessment of the cancer. Despite the conservative adaption of ESD for Barrett´s neoplasia, most experts agree that if ESD of Barrett’s lesions would be just as easy, safe and effective as current piecemeal techniques, all Barrett’s lesions would be resected en bloc by ESD. The challenge therefore is in developing an ESD technique to overcomes the technical challenges of ESD: the lack of triangulation and counter traction during dissection of the submucosal space, the instability of the working field do to peristalsis, respiration and heartbeat, and the lack of independent maneuverability of devices and optical inspection. LumenR RetractorTM (LER) is a modified esophageal overtube, which has expandable chamber on its distal end. This overtube is loaded on top of regular endoscope and when it is expanded inside the esophagus, it creates a stable platform improving visualization and access to the target lesion. In addition, the expandable chamber has an extra working channel, allowing use of commercially available grasping forceps to retract the tissue in various directions and creating effects of triangulation. In addition, the expandable chamber, retraction tools and endoscope can operate independently, which significantly facilitate dissection of the target tissue and could make endoscopic resection of early Barrett’s neoplasia and early squamous esophageal neoplasia simple and safe. Our hypothesis is that the use of the modified esophageal overtube (LumenR) will simplify endoscopic removal of the target tissue with clear margins, will decrease the time needed to complete the procedure and will decrease the rate of complications (i.e. bleeding, perforation, etc).

Our hypothesis is that the use of the modified esophageal overtube (LumenR) will simplify endoscopic removal of the target tissue with clear margins, will decrease the time needed to complete the procedure and will decrease the rate of complications (i.e. bleeding, perforation).

day 0, 3, 10 and 90.

Endoscopic submucosal dissection using the LumenR-overtube