Most endoscopic therapies have focused on trying to increase the resistance at the gastroesophageal (GE) junction.
The Stretta system uses radiofrequency ablation of the GE junction. This method utilizes a flexible catheter with a balloon. Four electrodes are placed into the surrounding tissue at the level of the LES. The probes reach the level of the submucosa and radiofrequency energy is applied, elevating the submucosal temperature to 85°C whereas a cold water infusion in the balloon keeps the mucosal temperature at 50°C. The procedure is repeated. The energy creates thermal lesions in the submucosa which cause scarring and tightening around the LES. In essence, a stricture is created at the LES, increasing resistance at the GE junction. Unfortunately, a randomized sham trial did not demonstrate any difference in any objective measure of reflux in these patients, although some did report a reduction in heartburn symptoms.4
Additional studies, to date, all have been characterized by short-term follow-ups of 6 to 12 months, small numbers of patients, and variable improvements in objective symptoms.5 Aziz et al.6 in 2010 reported on 30 patients with improvement in health-related quality-of-life (HRQL) scores, LES pressure, and pH scores of those patients off medication, although some patients experienced some delayed gastric emptying. Coron et al.7 in 2008 demonstrated that 18 of 20 patients were able to stop proton pump inhibitor (PPI) use, although there was no change in esophageal acid exposure.
One prospective nonrandomized comparison of the Stretta system with laparoscopic fundoplication demonstrated a superior outcome with the laparoscopic procedure. Patients in both groups had improvement of their quality of life and symptoms, but only 58% of patients in the Stretta group were able to discontinue medication compared to 97% of patients following the laparoscopic procedure, despite the fact that the Stretta group patients had less severe disease.8
Bard Endocinch and the NDO Plication System use sutures placed with a proprietary device to tighten the LES. Although some studies have demonstrated some efficacy, there have been concerns about its durability. Schwartz conducted a double-blind randomized sham-controlled trial with the Endocinch that demonstrated less PPI in the treatment group (65%) compared to the observation group (0%), but there was no difference in esophageal acid exposure in the treatment group versus the sham group.9 Montgomery et al.,10 in a randomized placebo controlled trial, likewise determined that there was no difference in esophageal acid exposure at 3 and 12 months.
With regard to the plication system, results have been more promising. A randomized single blind prospective multicenter trial in 2006 did demonstrate greater cessation of PPI treatment in the treatment arm compared to sham (50% vs. 20%, p = 0.002) and with greater improvement in esophageal pH compared to sham.11 von Renteln in 2009 demonstrated 63% of patients had symptomatic improvement.12 Daily PPI use was eliminated in 69% of patients at 12 months. Khajanchee performed a meta-analysis of 266 patients that demonstrated a decreased in DeMeester score with 32% of patients resulting in a normal range. However, the company lost funding, and the device is no longer available.13
Injection of inert products into the LES also has been tried. Plexiglas, Gatekeeper Reflux Repair System, and the Enteryx are some of the products in this category. Plexiglas inserted polymethylmethacrylate (PMMA) into the submucosa of the LES to decrease transient relaxation of the sphincter. Enteryx injected 8% ethylene vinyl alcohol in dimethyl sulfoxide and micronized tantalum powder into the muscular layer of the LES.14 The compound hardened after injection. This procedure was associated with serious complications including injection into the mediastinum, embolization to the kidney, pericarditis, and aortoesophageal fistula, which resulted in withdrawal from the market. The Gatekeeper used a soft, pliable, biocompatible, hydrophilic prosthesis into the submucosa of the LES. Upon insertion, it absorbs water and expands, creating bulk and decreasing compliance of the LES. A randomized sham-controlled blinded multicenter study demonstrated no improvement in outcomes at 6 months.15 This, too, was withdrawn from the market.
Endoscopic Partial Fundoplication
The most recent entry into the endoscopic antireflux therapy is the EsophyX device by endogastric solutions. The goal of this device is to produce a 270-degree partial fundoplication. A large tubular device is placed over the endoscope and through the mouth into the esophagus. Once in the stomach, the end of the device is advanced and the tip closed such that it is facing the GE junction. A helical device is anchored to the Z-line. Using this anchor, the GE junction is then pulled into the open device and closed. The gastric fundus is approximated to the distal intra-abdominal lumen by the device. Two stylets are used to deploy two polypropylene H-shaped fasteners that are supposed to traverse from the gastric mucosa to the esophageal mucosa, thereby securing the shape. The device is opened and then rotated, and the sequence repeated until fasteners are placed from the posterior lesser curvature to the anterior lesser curvature and an omega-shaped 270-degree wrap is formed, ideally of 2 cm length. Small hiatal hernias can also reportedly be reduced by using suction traction on the device.
Over 30 peer-reviewed publications have evaluated the EsophyX device. Cadiere et al.16 were the first to publish their experience in a prospective multicenter trial of 84 patients in 2008. At 12 months, they demonstrated that 73% of patients had greater than or equal to 50% improvement of the GERD-HRQL score, 85% discontinuation of daily PPI use, and 37% normalization of esophageal acid exposure. Resting LES pressure was improved by 53%. There were two esophageal perforations during the insertion of the device and one patient required a four unit blood transfusion from postoperative bleeding. GERD was considered cured in 56% of patients. Pre- and postoperative esophageal pH monitoring demonstrated a significant reduction in DeMeester score from 34 to 28 (p < 0.001) at 12-month follow-up. A 2-year feasibility follow-up of 14 patients by the same group in 2009 indicated that the GERD-HRQL score remained favorable and 86% of patients were satisfied with the outcome of the procedure. Ten of fourteen patients remained successfully off of PPI.17
Hoppo et al. published a multicenter study involving one American and two Australian institutions in 2010 and 19 patients with GERD. At 10.8 months, 5 of 19 patients had discontinued their PPI and 3 of 19 had reduced their dose. However, 10 of 19 eventually underwent laparoscopic Nissen fundoplication for recurrent reflux symptoms. Three major complications occurred including an esophageal perforation, bleeding requiring transfusions, and one permanent numbness of the tongue.18
Demyttenaere et al. reported on 26 patients that demonstrated that only 45% of patients had ≥50% decreased in the GERD-HRQL score and of 45% of patients were satisfied with the procedure while 30% were dissatisfied. Three patients required conversion to a laparoscopic Nissen procedure. Repici in 2010 reported on 20 patients after the transoral incisionless fundoplication (TIF) procedure. Four patients required conversion to a laparoscopic Nissen fundoplication in the first year and only 16.6% of patients demonstrated improved in esophageal acid exposure while in 66.7% it worsened.19
Velanovich in 2010 reported on 26 patients. In two patients, the device was not able to be passed. Four patients had a prior Nissen fundoplication and had recurrent symptoms. At 7 weeks follow-up, 19 of 24 patients were satisfied with symptom control and the mediastinal GERD-HRQL scores improved from 25 to 5 (p = 0.0004).20
Barnes et al. in 2011 reported a US multicenter retrospective evaluation of endoscopic fundoplication in 110 patients at a median follow-up of 7 months. Median GERD-HRQL scores were significantly reduced from 28 to 2 (p < 0.001), and median reflux symptom index scores were reduced from 29 to 4 (p < 0.001). There were significant benefits for the typical symptoms of heartburn, regurgitation, and dysphagia as well as the atypical symptoms of hoarseness, clearing of the throat, cough, and globus sensation. A total of 102 of 110 patients were able to get off PPI treatment.21
Bell and Freeman in 2011 reported their retrospective experience of 37 patients. At 6 months follow-up, 64% of patients with atypical symptoms and 70% of typical patients demonstrated improvement. Five patients required additional intervention including two with redo endoscopic fundoplication and three with a laparoscopic Nissen fundoplication.22
A single-center randomized trial comparing the TIF to laparoscopic Nissen fundoplication was published from the Czech republic. The TIF arm had a combined experience of the plicator and the EsophyX. Both arms demonstrated significant improvement in the GERD-HRQL scores although the mean hospital stay was shorter for the endoscopic arm at 2.9 days compared to 6.4 days, p < 0.0001.23
Muls reported a 3-year follow-up of 66 patients. In all, 61% of patients discontinued daily PPI use. However, only 9 of 23 patients on intention to treat analysis demonstrated a normal pH.24 Likewise Witteman et al.25 reported 38 patients at 36 months follow-up and demonstrated that 56% had hiatal hernia reduction and 47% has resolution of esophagitis. However, there was no improvement in esophageal acid exposure. Multiple additional studies have demonstrated improvement in patient symptoms, about 60% to 80% of patients mostly off of PPI medication, and improvement in GERD-HRQL scores. However, the objective esophageal acid exposure data have remained lacking or unchanged. Comparison of pH exposure following EsophyX versus laparoscopic Nissen fundoplication demonstrated only 50% of cases with normalized esophageal acid exposure compared to 100% in the Nissen group.26