The earliest endoscopic approach involved the injection of bovine dermal collagen into the LES in an attempt to reinforce the barrier function by enhancing the LES thickness both from a “bulking effect and also due to an inflammatory reaction” [5, 6]. Since then, several devices including Enteryx^™ (Boston Scientific Corporate, Natick, MA) and Gatekeeper^™ Reflux Repair System (Medtronic, Minneapolis, MN) had been introduced in the market and investigated.

Enteryx^™ used a radio-opaque copolymer (Ethylene vinyl alcohol), which is an embolization agent, and which was injected into the distal esophageal wall under endoscopic and fluoroscopic guidance to create a permanent implant and a chronic foreign body reaction in the LES muscle layer (Fig. 14.1). An initial open-label, multicenter, international trial of Enteryx demonstrated sustained efficacy in the reduction of PPI use and esophageal acid exposure compared to baseline up to 2 years [7, 8]. This promising data led to a randomized sham-controlled multicenter trial involving 64 patients (Enteryx, n = 32; control, n = 32), which demonstrated that PPI cessation was achieved in 70 % of the Enteryx group compared to 40 % in the control group at a follow-up of 6 months. Interestingly enough, there was no significant difference in objective measurements of pH testing or LES pressure compared to baseline in both groups [9]. Because of reports of severe complications involving the mediastinum due to transmural injection or nearby inflammatory reaction that occurred after early large-scale commercialization, Enteryx was withdrawn from the market in 2005 [10–12].

Gatekeeper^™ Reflux Repair System uses small hydrogel cylindrical prostheses, which are implanted into the submucosa at the level of GEJ. Similar to Enteryx, initial data was excellent, leading to a sham-controlled randomized study (Gatekeeper, n = 96; sham, n = 48), which resulted in an early termination due to lack of compelling efficacy with symptomatic control and objective measures of pH testing such as distal esophageal acid exposure [11]. Because of serious complications including esophageal perforation (n = 2), pulmonary fistula related to perforation (n = 1), and severe chest pain (n = 1) [6, 13], the Gatekeeper^™ Reflux Repair System was withdrawn from the market in 2009.

The application of radiofrequency to the GEJ creates a controlled thermal injury and possibly nerve ablation at the muscular layer of GEJ, producing fibrosis that decreases the compliance of the GEJ and has been shown to decrease the occurrence of transient LES relaxation [14, 15]. The Stretta System (Mederi Therapeutics, Greenwich, CT), which was reintroduced in the United States in April 2010 and is currently available for clinical use, is a transoral device used to deliver radiofrequency energy at the GEJ to treat GERD. This device uses a single-use, flexible catheter along with a balloon basket assembly with electrode needle sheaths. The catheter is inserted transorally proximal to the squamocolumnar junction, and the balloon is then inflated. Nickel–titanium electrodes are deployed into the muscular layer of the GEJ. Radiofrequency energy at 465 kHz and 2–5 W is delivered while microcircuitry monitors the mucosal temperature [16]. Serial thermal ablations are applied to the muscular layer every 0.5 cm extending from 1.5 cm distal to 2 cm proximal to the squamocolumnar junction. The consequent fibrotic tissue, and perhaps collagen contraction, reactions that can be seen for up to 12 month, result in a reinforcement of the LES [17]. Aberrant nerve pathways may also be ablated, as observed in cardiac arrhythmia ablation. It is possible that radiofrequency treatments may delay gastric emptying due to accidental thermal damage of the vagal nerves [18–20].

Although previous studies have demonstrated the safety and potential efficacy of the Stretta system, the therapeutic outcomes have been somewhat conflicting. A case series of 109 patients who had undergone the Stretta procedure demonstrated a significant improvement of GERD-HRQL score and reduction in the need for daily antisecretory medications at a follow-up period of 4 years. Furthermore, a second session of ablation was proposed for those with GERD-HRQL scores that did not improve by 75 % at the end of 4 months and showed additional response [21]. A randomized controlled study involving 64 patients with GERD (Stretta, n = 32; control, n = 32) demonstrated that the Stretta procedure improved clinical symptoms such as heartburn and GERD-HRQL score at 6 months after intervention compared to the placebo group; however there was no significant difference in antisecretory medication use or esophageal acid exposure at 6 months [22]. Another randomized controlled study involving 40 patients (Stretta, n = 20; control, n = 20) demonstrated that PPIs were discontinued in 3 patients and reduced in 15 patients at 12 months after intervention in the Stretta group, whereas none in the control group reduced their dose of PPIs [23]. However, there was no difference in objective measurements of acid exposure by pH testing. In the most recent prospective, sham-controlled randomized trial, 36 patients with chronic GERD were randomly assigned to single-dose Stretta group (n = 12), double-dose Stretta group (n = 12), or sham group (n = 12). The Stretta procedure significantly reduced GERD-HRQL scores, PPI use, distal esophageal acid exposure, and grade of esophagitis compared to the sham procedure at a 12-month follow-up. Double-dose Stretta appeared to have superior outcomes to single-dose Stretta, although this was not a significant difference [24].

Overall, the Stretta system appears to improve GERD symptoms and quality of life, and potentially reduces the need for PPIs during intermediate follow-up; however the impact of Stretta on objective measurements of GERD such as distal esophageal acid exposure remains unpredictable.

Devices that are applied transorally and attempt tissue approximation by deploying nonabsorbable sutures, staples, or plastic fasteners through the gastric and/or esophageal wall have a long history. Some devices such as the EndoCinch use a suctioning chamber for mucosa-to-mucosa approximation, whereas the NDO System and EsophyX use a grasping tool (e.g., a screw-shaped needle) to retract the tissue for subsequent serosa-to-serosa full-thickness plication. The primary goal of these suturing and plication devices is to restore the impaired gastroesophageal flap valve by recreating the acute angle of His with either stitches or fasteners, thus leading to the reduction of esophageal acid exposure [25–29]. In addition an attempt is made with some approaches to envelop the distal esophagus with the proximal stomach so as to replicate the nipple valve seen with a Nissen.