Comparing the effectiveness of endoscopic full-thickness plication and endoscopic radiofrequency treatments for patients with GERD

Keywords::

• antireflux
• Barrett’s esophagus
• endoluminal
• full-thickness plication
• fundoplication gastroesophageal junction
• gastroesophageal reflux
• lower esophageal sphincter
• radiofrequency

Gastroesophageal reflux disease (GERD) is a significant health concern, with millions of Americans experiencing weekly heartburn and the resulting significant impairment in quality of life. Even more concerning is the increased prevalence of more advanced GERD, as evidenced by rising numbers of patients with Barrett’s esophagus, including an increasing rise in the incidence of Barrett’s esophagus with high-grade dysplasia and esophageal adenocarcinoma.

An ongoing dissatisfaction with the traditional therapies for GERD, antisecretory medications or antireflux surgery, has driven the development of new therapies hoping to incorporate the best of both therapies – a noninvasive way to establish a mechanical antireflux barrier. Endoluminal antireflux surgery includes a new group of therapies that promise the use of an endoscopic technique in order to create an effective antireflux valve. Currently, the endoluminal techniques that have gained traction rely on two quite different mechanisms to enhance the antireflux barrier: full-thickness plication (FTP) and delivery of radiofrequency energy (RFe) to the area of the lower esophageal sphincter (LES) and gastroesophageal junction (GEJ).

Historically, endoluminal techniques have focused on three different ways of providing an effective antireflux barrier: fixation techniques to tighten the area of the LES or effect an esophagogastric plication (EndoCinch™, NDO™, Esophyx™); radiofrequency application to the area of the LES, thereby increasing the bulk and decreasing the compliance of the LES while also altering the neurological mediated transient LES relaxations (Stretta^®, Mederi Therapeutics, CT, USA); and submucosal injection or implantation of a prosthetic into the area of the LES to enhance the LES volume and/or the compliance of the LES (Enteryx™, Gatekeeper™).

Some historic perspective will be helpful before getting into the specific comparison of FTP with RFe delivery to the LES. Approved in April 2000 as the first system to promote flexible endoscopic suturing within the GI tract, the Bard EndoCinch remains on the market today. This suture technique plicates the area of the LES, thereby tightening the GEJ to create a more effective valve. The Bard EndoCinch has been subjected to multiple studies, including a prospective randomized sham-controlled trial [1], and comparisons to surgical fundoplication [2,3]. Despite this very innovative technique coming to market first, it has failed to demonstrate effectiveness and durability as an antireflux technique, largely because this technique does not typically produce a full-thickness stitch. In our opinion, the great contribution of the Bard EndoCinch was to teach us the importance of full-thickness sutures when suturing within the GI tract.

Two other endoluminal techniques sought to create a more effective antireflux barrier by introducing a prosthetic into the area of the LES, thereby creating a mechanical ‘road bump’ of artificial material (Gatekeeper) and/or altering the compliance of the LES (Enteryx). Of course, this is an oversimplification of the mechanism of action, but it suffices for this article.

The Gatekeeper System utilizes a soft, pliable, expandable, radiopaque prosthesis made of a polyacrylonitrile-based hydrogel [4]. The prosthesis is implanted into the esophageal submucosa at or near the squamocolumnar juncion, and with time the prosthesis absorbs water, thereby expanding and creating bulk in the region of implantation. The prosthesis is removable if necessary. This technique was subjected to a prospective randomized sham-controlled trial; however, this trial was stopped early owing to a lack of effectiveness. The development of this technique has since been stopped by the company. The Enteryx technique [5] injects a biocompatible copolymer under fluoroscopic guidance into the muscle layer at or below the GEJ to provoke a chronic foreign body reaction, thereby adding bulk and altering the compliance of the GEJ and creating a better barrier to reflux. While the technique had early promising results, there were several adverse events reported to the US FDA, including several deaths. The company electively removed the product from the market and it is not currently an available option.

The techniques that remain the subject of this article are FTP, as effected by the NDO Plicator (NDO Surgical Inc., MA, USA) or Esophyx (EndoGastric Solutions, WA, USA), and radiofrequncy ablation at the LES, as applied by Stretta.

NDO Plicator

The NDO Plicator creates FTP of the gastric cardia to the esophagus, thereby creating a valve similar to a partial fundoplication, while at the same time tightening the outlet of the distal esophagus to the diameter of the shaft of the device. Several studies, including a prospective randomized sham-controlled trial, have been published. Rothstein and colleagues compared FTP to a sham procedure through a randomized, single-blind, prospective, multicenter trial. Upon assignment, 78 patients on proton pump inhibitor (PPI) therapy for GERD underwent endoscopic FTP. In the other arm, 81 patients underwent a sham procedure. At 3 months follow-up, 56% of patients in the treatment arm achieved at least a 50% improvement in GERD health-related quality of life score. This was significantly greater than the sham group (18.5%; p < 0.001). In addition, 50% of treatment patients stopped their PPI use, while only 24% stopped in the sham group (p = 0.002) [6].

To summarize the results with NDO FTP, early experience with 3-year follow-up and then further follow-up on the same patients at 5 years showed improvements in health-related quality of life scores and decreased use of PPIs, thereby showing efficacy for the instrument and technique [7]. In a study with a shorter follow-up and a sham-controlled design, Rothstein demonstrated superiority of the NDO Plicator in a prospective, randomized, multicenter trial [6]. While there remains interest in further study of the long-term effects of NDO plication, NDO Surgical closed its doors for business in June of 2008 owing to poor financial performance and, therefore, the device and technique is no longer available.

Esophyx endoluminal fundoplication

Using transoral tissue suction and transmural fasteners, the Esophyx device has been shown to be capable of deploying fasteners directly into tissue and forming an interrupted suture line at the base of the LES. Also known as transoral incisionless fundoplication, the manufacturer claims that this technique reproduces a partial fundoplication typically only able to be performed surgically. In a prospective, multicenter trial, Cadiere and colleagues reported results from 84 patients with PPI-dependent GERD, who underwent endoluminal fundoplication with Esophyx. All 49 patients with associated hiatal hernia had their hernias reduced. In addition, neoesophageal valves measuring 4 cm in length (range: 2–6 cm) and 230° in diameter (range: 160–300°) were constructed. The device is touted to help restore the angle of His while reducing small hiatal hernias up to 2 cm in size. At 12 months follow-up, 79 total patients were retained in the study. For all 79 patients, 81% completely stopped using PPIs, while 85% either stopped any use or discontinued daily PPI use. LES resting pressure improved by 53% (p < 0.001). Based on symptom improvement and PPI discontinuation, the authors concluded that Esophyx endoscopic plication cured GERD in 56% of the patients [8].

In summary, Esophyx is the newest of the FTP techniques and has shown promise as an effective and relatively durable antireflux technique. No prospective comparative data exist to substantiate its effectiveness relative to any existing technique. Because it most closely creates an equivalent to surgical fundoplication, there remains a strong interest in the future of this technique, and given the positive results, further investigation of Esophyx, in comparison with other endoscopic techniques, must be carried out to determine its role in endoluminal antireflux procedures.

Radiofrequency energy: Stretta

Perhaps the most studied and scrutinized of the endoluminal techniques has been Stretta. Stretta utilizes the delivery of low-power, temperature-controlled RFe to the GEJ with a balloon-basket catheter with 4 Nickel–Titanium needles. The proposed mechanisms for which RFe affects the LES include heat-induced collagen contraction, fibroblast and collagen deposition, and wound remodeling at the LES and gastric cardia [9]. Owing to the fact that inappropriate transient lower esophageal sphincter relaxations (TLESRs) via the afferent vagal pathway are believed to be a cause of GERD, it is believed that RFe may disturb aberrant intraluminal or intramuscular vagal nerve fibers within the cardia, thereby reducing the number of these TLESRs.

The previously mentioned research has included animal research, testing the use of fluoroscopic guidance [10]; large case series; use in gastroparesis or failed surgical fundoplication [11]; and sham-controlled prospective trials. Results have been promising in all areas. Despite these results, the first company to commercialize Stretta, Curon (CA, USA), was not able to remain financially viable and thus folded. Recently, the technology has been reintroduced by Mederi Therapeutics. With this recent remarketing of Stretta, further research will ensue for this technology that likely develops the LES, making it anatomically more resistant to reflux. This should continue to correlate with post-procedural patient satisfaction.

Stretta was the first endoluminal technique subjected to a prospective, randomized, sham-controlled trial, and set the standard for the validation of future techniques. Corley and colleagues published this prospective, randomized sham-controlled trial in 2003. The study design followed patients post-procedure for 12 months, with crossover allowed at 6 months. At 6 months, patients in the treatment group experienced improved heartburn scores (61 vs 33%; p = 0.05) and quality of life scores (61 vs 30%). At 12-months follow-up, symptomatic improvement was maintained in the treatment group [12].

So, what about the comparison of FTP techniques with radiofrequency ablation at the LES? Looking at each technique separately, it appears that these techniques are comparable, with each working through a different mechanism of action. There are some data that allow a more direct comparison of FTP with RFe.

Radiofrequency (Stretta) versus FTP (NDO Plicator)

Prior to the failure of the company responsible for Stretta, an outcomes comparison was published that investigated endoluminal FTP and RFe treatments for GERD [13]. Based on prospective data from 126 patients, Jeansonne and colleagues used pre- and post-procedural questionnaires and esophageal pH analyses to compare RFe (Stretta) to FTP (NDO Plicator). The results showed that the patients in the RFe group had less post-procedural dysphagia, dysphonia and cough. In addition, the RFe patients with moderate-to-severe heartburn decreased from 55 to 22% (p < 0.01), and the number of subjects using PPI therapy decreased from 84 to 50% (p = 0.01). The percentage of time that the pH was less than 4 was unchanged.

Meanwhile, the patients in the FTP group had improvement in dysphagia, dysphonia and regurgitation. In addition, there was a nonsignificant decrease in heartburn from 53 to 43% (p = 0.3), with a significant decrease in PPI use from 95 to 43% (p = 0.01). Most importantly, for the FTP patients there was a decrease in the percentage of time for which the pH was less than 4, from 10.0 to 6.1% (p = 0.05). Based on pH analysis and differences in post-procedural regurgitation, the authors concluded that FTP may be preferred for those with regurgitation as their chief complaint [13].

Later that year, White and colleagues looked at the same two modalities in the obese patient population to determine which patients were optimal candidates for endoluminal therapy [14]. Based on a ‘failure’ defined as a patient having either no symptomatic improvement in any of the symptom scores or the need for subsequent antireflux surgery, the resultant failure rate for the 12 patients who underwent Stretta was higher (42%) than for the ten patients who underwent NDO plication (10%). Despite some patient failures, an improvement in moderate-to-severe symptoms was demonstrated for all study patients with regard to chest pain, cough, dysphonia and dysphagia. Additionally, only 45% of postoperative patients were on PPI, compared with 81% of patients in the preoperative setting (p = 0.1).

Our conclusion from these data, and after nearly a decade of experience with every endoluminal technique available commercially in the USA, is that FTP and RFe are both reasonable offerings to select patients with GERD. We would lean to Stretta for patients with predominantly upright GERD and an LES that demonstrates retention of adequate tone and function on esophageal motility testing. The change in compliance of the LES and potential for altering the neurologically mediated TLESRs should result in a reasonable chance of a good outcome with Stretta in these patients. Conversely, patients with regurgitation, night-time GERD and a small hiatal hernia should hypothetically show greater benefit from the more directly mechanical effects of FTP. Finally, with a 30–40% failure rate for any of the endoluminal techniques, a well-done laparoscopic 360° fundoplication should be considered for all patients with GERD severe enough to warrant procedural intervention [15].

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.