Enteryx

Enteryx is a biocompatible polymer consisting of 8% ethylene vinyl alcohol mixed with tantalum powder that provided for radiographic opacification, in a solution of dimethyl sulfoxide. It is liquid before injection and becomes an inert spongy mass once injected into tissue. The procedure requires a special 4-mm, 23-gauge injector needle and the use of fluoroscopy. The standard procedure was placement of 1 mL or more of volume circumferentially around the GE junction until approximately 6 to 8 mL of Enteryx was implanted intramuscularly. The Enteryx procedure was repeatable if symptom control was inadequate but not reversible. Enteryx is no longer marketed or available for human clinical use.

An international multicenter study of 85 patients treated with Enteryx demonstrated cessation of PPI use in 74% of treated subjects at 6 months and, at 12-month follow-up, 70% of these subjects had significant improvements in objective measure of acid reflux (pH scores). pH normalization was encountered in 38.8% of patients at 12 months and the LES was approximately 1 cm longer after therapy. In the treated cohort, there was no effect on the incidence or severity of esophagitis after treatment. The GERD– health-related quality-of-life (HRQL) scores after Enteryx were comparable with those obtained on antisecretory medications. Complications included chest pain (92%) that resolved within l4 days in 83% of affected individuals and dysphagia (20%) that resolved within 2 to 12 weeks. There was one death related to Enteryx injection into the aortic wall that led to withdrawal of the device from the market.

Gatekeeper

The Gatekeeper Reflux Repair System (Medtronic, Minneapolis, Minnesota) restricts the diameter of the distal esophagus by submucosal implantation of a polyacrylonitrile-based hydrogel prosthesis. The device consists of a 16-mm overtube-type instrument through which a standard or pediatric-sized videogastroscope was passed, to monitor the procedure. Suction was used to draw mucosal tissue into multiple, shallow holes in the distal part of the Gatekeeper instrument and to place the hydrogel prostheses submucosally. A 1-mm diameter flexible endoscopic injector needle and a 1-mm trocar needle catheter were used through another channel in the overtube to prepare the submucosal region for implantation of the prosthesis. Usually, four to six implants were placed in a radial fashion during one treatment session. This implantation technique was repeatable and reversible.

A pilot study included 10 GERD patients and demonstrated successful implant placement in 97% of attempts. The procedures improved reflux symptom scores at 1 and 6 months’ follow-up. Four of 9 patients stopped their acid-suppressing medicines, whereas three reduced their PPI dosage by at least 50%. Pooled data from two prospective nonrandomized trials reported data for 68 patients treated with this method. At 6 months, time with pH less than 4 improved from 9.1% to 6.1% (n = 45, P <.05), LES pressure was slightly higher, and GERD-HRQL scores went from 24 to 5 ( P <.01). Two adverse events occurred: one patient suffered a pharyngeal perforation, and severe postprandial nausea was reported in another patient that resolved after endoscopic removal of the prostheses. An international, multicenter, sham-controlled trial was started for this device but was subsequently cancelled before completion, and the device is no longer available.

Durasphere

Durasphere (Carbon Medical Technologies, St Paul, Minnesota) is a Food and Drug Administration–approved injectable agent that has been used to treat urinary incontinence since 1999. It consists of carbon-coated beads ranging from 90 to 212 μm suspended in a water-based gel. The particles were specifically designed to prevent migration and are inert. This agent was recently used to treat 10 patients with objectively proved GERD on PPI therapy. The substance was injected submucosally at the Z-line in four quadrants using a standard endoscopic sclerotherapy needle. The patients were followed for 12 months and five of them were retreated within 90 days for poor symptom control. At the end of the study, the patients were found to have a significant reduction in DeMeester scores from 44.5 to 26.5. Four of the 9 patients followed had normal pH testing. The material and bulk effect was still in place at endoscopy 1 year later and adverse events, such as substernal pain and difficulty belching, were minor and transient. Further data are needed, including a randomized, controlled trial, but these initial results demonstrate a straightforward, safe technique with measurable symptom improvement.

Wilson-Cook Endoscopic Suturing Device

The Endoscopic Suturing Device (ESD) (Cook Medical, Bloomington, Indiana) consists of an external accessory channel, a flexible Sew-Right device, and a flexible Ti-Knot device. The external accessory channel is attached to a flexible endoscope and provides the pathway for the Sew-Right and Ti-Knot devices. The flexible Sew-Right device is a dual-needle system that uses a single suture loop to create the tissue plication. The target tissue is aspirated into a suction chamber. A needle with suture is then passed through the tissue collected within the chamber. A continuous single suture loop is used to stitch two adjacent areas in the proximal stomach to form the plication. With the ESD, no repeated endoscope withdrawals are required to create the gastric plication. Typically, two or three plications are placed during a single treatment. The ESD is no longer marketed or available for human clinical use.

Studies revealed early loss of the sutures. At 6 months, only 5% of the sutures were found in situ. No significant changes in reflux esophagitis or 24-hour pH monitoring were observed at 6 months (median pH <4/24 h, 9.9% vs 12.3% [therapy vs baseline]; P = .60). LES sphincter pressure was unchanged (median LES pressure 7.2 mm Hg vs 9.9 mm Hg; P = .22). PPI use was not improved either. A second uncontrolled study confirmed the same poor outcomes mainly related to early loss of the sutures.

BARD EndoCinch

The EndoCinch suturing device is inserted via an overtube. A sewing capsule is attached to the distal tip of a standard videogastroscope and has a cavity into which a tissue fold can be suctioned. A handle is attached to the biopsy port of the endoscope and controls the advance of a hollow-core suturing needle. A treasury-tag (t-tag) is back-loaded into the hollow-bore needle and is captured into the tip of the capsule after being driven forward by a stiff wire pushed through the hollow needle. It can be reloaded and a second area of tissue can be captured. The two captured areas are drawn together to create a tissue plication. A catheter cuts the suture ends as it cinches together the tag components at the luminal surface. Stitches to form plications can be placed in a linear, circumferential, or helical fashion. Typically two or three plications are created at a treatment session.

A sham-controlled, randomized study available published as an abstract demonstrated improved heartburn frequency at 3 months’ post treatment for the EndoCinch group (69% vs 31%, P = .03). There was no significant difference in heartburn severity (81% vs 50%), regurgitation (53% vs 56%), or bothersome scores (75% vs 50%). More subjects in the gastric plication group discontinued their daily acid-suppressing medications compared with sham treatment (75% vs 25%; P = .01). No difference was found comparing use of acid-suppressive medications (56% vs 25%), however. Acid exposure significantly improved in the EndoCinch versus sham groups (pH difference: -4.0 vs +1.0; P = .03) but normalized only in two (12.5%) treated patients. The study did not detect a difference between treated and sham patients on LES pressure or quality-of-life measures.

An uncontrolled, single-center study, including 70 patients, demonstrated long-term treatment failure mainly due to suture loss. Eighteen months after treatment, 56 of 70 patients (80%) did not improve their heartburn symptoms or PPI medication use by greater than 50%. Endoscopy exhibited all sutures in situ in 12 of 70 (17%) patients and no remaining sutures in 18 of 70 (26%). In 54 and 50 patients examined, no significant changes in 24-hour pH monitoring (median pH <4/24 h, 9.1% vs 8.5%; P = .82) or LES pressure (7.7 vs 10.3 mm Hg; P = .051) were observed respectively, whereas median LES length increased slightly (3.0 to 3.2 cm; P <.05).

A second sham-controlled study demonstrated reduced acid-inhibitory drug use and improved GERD symptoms and improved the quality of life at 3 months compared with a sham procedure. No difference in reduction of esophageal acid exposure was seen after endoscopic treatment compared with sham procedure. Due to suture loss, the effects only persisted up to 12 months.

NDO Plicator

The NDO Plicator was designed to create a transmural full-thickness placation at the angle of His. The plication is formed with a pretied, suture-based implant. The Plicator can be advanced into the stomach over a Savary guide wire and is retroflexed for placement of the full-thickness sutures at the GE junction. Visualization is accomplished using a 5.9-mm flexible endoscope inserted through a dedicated channel in the instrument. This plicating device remodels the antireflux barrier at the angle of His by fashioning a pleat of full-thickness tissue and permitting serosa-to-serosa apposition. The components of the system include the plicator instrument, a tissue retracting helical catheter, and pretied pledgeted suture implants. The plicator has a handle with wheels for opening/closing the arms and sliding/locking the pretied suture implant. The total procedure time is approximately 10 to 20 minutes to form a single plication. Newer data suggest that placement of 2 to 3 implants may be preferable to optimally restructure the GE junction.

A sham-controlled trial randomly assigned 159 patients to plication (n = 78) or a sham procedure (n = 81). The percentage reduction in esophageal pH time less than 4 was significantly improved in the plication group (7% vs 10% compared with baseline) but not in the sham group (10% vs 9%). There were no perforations or deaths. Four patients required hospitalization for postprocedure pain and one required exploratory laparoscopy 3 months after the procedure for persistent abdominal pain. Recent studies have used serial implants to improve restructuring of the angle of His and demonstrated significant reductions in esophageal acid exposure, esophagitis, and PPI use at 6 and 12 months. The NDO device is no longer available on for commercial use.

EsophyX

EsophyX (EndoGastric Solutions, Redmond, Washington) is a large overtube device with an insertion channel for a videogastroscope. It also includes a bending section, or elbow, which can articulate and retroflex to reach and manipulate tissue at the angle of His. The system is designed to create a 270° circumferential endoscopic plication at the angle of His. The technique uses a helical retractor to engage and manipulate tissue at the fundus and to create the correct angle. After tissue grasping and fixation, double-sided t-tags can be passed through a double layer full-thickness plication. The method involves the placement of approximately 6 to 14 sutures to create a near circumferential gastroplication of 180° to 260°. The device can be used to reduce small hiatal hernias. EsophyX is Conformite Europeenne marked and available in Europe and recently received Food and Drug Administration clearance in the United States.

No randomized controlled data are reported to date. Early clinical experience assessed the degree of postprocedural valve tightness relative to the gastroscope and reported the valves as tightly adherent in 14 and moderately adherent in 3 of 17 cases. The hiatal hernias present in 13 of 17 patients were all reduced. Adverse events reported include mild-to-moderate pharyngeal irritation and epigastric pain, which all resolved spontaneously. At 12-month follow-up (n = 16), the valve length had a mean of 3 cm (range 1 to 4 cm) and circumference of 200° (150° to 210°). Eighty-one percent of the valves retained their tightness. The hiatal hernias, present in 76% of subjects initially, were now found in 38%. The median GERD-HRQL scores improved by 67% and 9 of 17 patients (82%) were still off their PPI medications, whereas normalization of the pH was seen in 63%. Recent 2-year data were published by the same group, which included 14 of the initial 19 patients. The long-term safety profile of the device is good, and it seems as though the restructured anatomy is durable when examined endoscopically. Among the patients treated, 29% were completely relieved of GERD, 60% of hiatal hernias were reduced, and esophagitis was eliminated in 55% of individuals. This data must be interpreted with caution because they are essentially all from a single center, and a single, small cohort of patients. The only North American study using this device is a retrospective report of eight patients who underwent the procedure. Half of the patients did not benefit from the procedure, and one patient had clear disruption of the sutures. Two patients were off PPIs and the other two were on reduced doses of the medication. Much further study is needed, including a prospective RCT.

Syntheon Anti-Reflux Device

Using this device, a titanium implant is delivered into the cardia to create a serosa-to-serosa apposition similar to the Plicator. The Anti-Reflux Device (Syntheon, Miami, FL) instrument differs from the Plicator in that the device can be passed alongside the endoscope and controlled independently. A catheter-based tissue retractor through the endoscope biopsy channel is used to pull the gastric wall into the jaws of the Anti-Reflux Device. The titanium implant is deployed as the jaws close, to create a full-thickness pleat. Results of a multicenter clinical trial have been published in abstract form. Seventy GERD patients were treated, and 57 had been followed for a minimum of 6 months at the time of abstract publication. GERD-HRQL improved by 50% or more in 79% of the subjects. At 6 months, 33 of 52 individuals (63%) stopped all antisecretory therapy. The implants were all found in place on follow-up endoscopy and one gastric perforation occurred requiring surgical repair. Despite superior engineering, the Anti-Reflux Device was not brought forward to commercialization.

The His-Wiz Antireflux Procedure

Another overtube-based endoscopic suturing machine, coined the His-Wiz (Apollo Group/Olympus Optical, Tokyo, Japan), allows for full-thickness suturing and cutting in a single step. Two plications are performed, one anterior and the other posterior, just below the Z-line. A small clinical trial of seven patients with 1-year follow-up is available in abstract form. Subjective (heartburn scores) and objective (pH testing) improvements were observed, but the effect seemed to deteriorate slowly over time. Based on these preliminary data, the durability and effectiveness of this procedure are still unknown, and the device has not been brought forward to commercialization.

The Medigus Endoscopy System

Few data are available regarding this novel device (Medigus SRS, Omer, Israel), which consists of an ultrasonic video endoscope and an integrated surgical stapler. The cartridge is mounted onto the shaft of the scope and the anvil is at the tip. B-shaped, 4.8-mm staples are fired under ultrasound guidance to create an anterior, full-thickness, 180° fundoplication. One Medigus-sponsored survival porcine study has been published to date using this device. Twelve animals successfully underwent the procedure and survived for 6 weeks. The mean procedure time was 12 minutes, and all of the fundoplications seemed to be in place at the end of the study. More data will be available from a recently initiated international human clinical trial using this highly refined technology.