Injection Implantation of Biopolymers

Background

Endoscopic submucosal injection of bovine collagen (O'Connor and Lehman, 1998) or polytetrafluoroethylene (Shafik, 1996) into the zone of the EGJ has been attempted in the past with the goal of increasing tissue compliance and altering the dimensions and radial asymmetry of the LES. Clinical improvement was transient because collagen is biodegraded and polytetrafluoroethylene particles migrate from the implantation site.

A biodegradable polymer, ethylene-vinyl-alcohol copolymer (Enteryx, Boston Scientific, Natich, MA) has been used successfully for embolization of arteriovenous malformations (Terada et al, 1991). Enteryx is a biocompatible polymer (8% weight/volume [w/v] with a radiopaque contrast agent [30% w/v tantalum powder] dissolved in an organic liquid carrier (dimethyl sulfoxide [DMSO]). Upon injection and contact with tissue or body fluids, the DMSO rapidly diffuses into tissue and results in precipitation of the polymer as a spongy mass. The viscosity of Enteryx before tissue contact is quite low. This permits injection through a 23 to 25 gauge needle. The biopolymer is neither biodegradable nor antigenic and migration or shrinkage of the material has not been demonstrated. Biocompatibility tests have been approved by domestic and international standards organizations. Enteryx injection into the mini-pig model has demonstrated mature, well-delineated fibrous capsules surrounding the implants into muscle at the LES zone after 3 months (Mason et al, 2000).

Device

Enteryx (Boston Scientific, Natich, MA) Injection Therapy The injection therapy requires an upper gastrointestinal endoscope, a 4 mm needle (23 to 25 gauge) injection catheter, a catheter flush unit, and a vial of Enteryx solution (Figure 13-7).

Procedure

Enteryx injection is performed in a unit equipped with fluoroscopy. Prophylactic antibiotics are usually administered. The injection catheter is introduced through the biopsy channel of the endoscope. The needle catheter is flushed with DMSO and filled completely with Enteryx. The tip for the injection catheter was placed at or 1 to 2 mm below the SCJ. The mucosa is punctured and Enteryx solution injected along the muscle layer or deep submucosal layer of the cardia. If the polymer forms an arc, noted fluoro-scopically, additional material is injected at the same site. Otherwise, multiple separate 1 to 2 cc injections are performed in a circumferential (4-quadrant) fashion. Six to 8 cc total of Enteryx is injected although a 6 cc is associated with more chest pain. The injection rate is limited to 1 cc/min to allow for polymerization and heat dissipation, the needle remains in situ to avoid backflow of material. A gray surface color with a mass effect bulging into the lumen is indicative of a shallow submucosal injection. If this is observed, injection is stopped and a new injection site is chosen. The average procedure time was 33.8 ± 10 min in one report of 85 patients (Johnson et al, 2003). Total fluoroscopy time was 11.8 ± 7.9 min. Mucosal sloughs occur with submucosal injection causing superficial ulcers, which apparently heal without problems.

Effect

Enteryx injection does not appear to "bulk" the GEJ. Observations at follow-up endoscopy show no luminal narrowing or structural abnormalities. In one report, 9 patients with underlying esophageal disease received Enteryx injection 4 to 5 hours prior to esophagectomy. Subsequently, histologic exam of the resected esophagus demonstrated polymer substance implanted into the deep submocosa contiguous with the circular muscle and within the muscularis propria in all patients with implants occasionally extending into the subserosa (Peters et al, 2003). The primary effect of Enteryx may be alteration of distal esophageal compliance.

FIGURE 13-7. Enteryx (Boston Scientific, Natick, MA) injection solution and catheter delivery system.

Device:Plexiglas Implantation

Polymethylmethacrylate (PMMA) has been used for dental prosthesis and tissue expansion in plastic surgical operations for decades. The PMMA (100 |m) microspheres have a smooth completely rounded surface that permits injection through a needle. The substance used as a carrier for PMMA is a heated 3.5% bovine spongious encephalitis-free gelatin (1:3 suspension PMMA). Following implantation, the gelatin is phagocytized by macrophages (within 5 months) and replaced by fibroblasts and collagen fibers. The spheres are encapsulated by connective tissue and at

FIGURE 13-8. Plexiglas (PMMA) (Rohn & Hass, Philadelphia, PA) implantation. Appearance of distal esophagus following Plexiglas injections.

Pmma Injections

FIGURE 13-8. Plexiglas (PMMA) (Rohn & Hass, Philadelphia, PA) implantation. Appearance of distal esophagus following Plexiglas injections.

least two-thirds of the total volume of the implant remains at the injection site (Lemperle et al, 1995).

Procedure

Skin tests and antibody titers to gelatin are performed because of the large quantities of PMMA used for endoscopic therapy. In the only report to date using this injection therapy, a flexible sigmoidoscope was used (Feretis et al, 2001). The sterilized PMMA implant material is prepared in 3 mL syringes and injected into the submucosa 1 to 2 cm proximal SCJ through a shortened 90-cm catheter with a 4mm long, 21-gauge retractable needle. Five to six injections were performed in different sites until the swelling of the esophageal folds resulted in their close luminal approximation. The treatment was repeated a second or third time depending on patient's GERD symptoms (Figure 13-8).

Effect

Procedure time averaged between 10 to 30 minutes. Follow-up EUS demonstrated "continuing presence" of PMMA particle at all sites in the entire group of 10 patients (Feretis et al, 2001). The properties of PMMA implant make it a potential EGJ bulking agent. The product has not received FDA approval. Further publications or follow-up studies on the use of PMMA injection treatment have not appeared since the original report.

Device:Expandable Hydrogel Prosthesis

The Gatekeeper (Metronics, Minneapolis, MN) technique places miniature expandable hydrogel prosthesis at the GEJ during endoscopic observation. The hydrogel prosthesis expands over 75% volume in 24 hours following tissue place ment. The device includes a 16-mm overtube with a distal rigid segment containing a shelf-like structure, a 2.4-mm diameter hydrogel delivery system (needle, dilator, sheath), an injection catheter, and a packet of the hydrogel prosthesis.

Procedure

The upper gastrointestinal endoscope is inserted within the overtube and both devices passed into the distal esophagus over a guidewire to the GEJ. Suction applied from the endoscope retracts esophageal tissue into the bottom shelf of the overtube. Through a second channel in the overtube, a needle injection catheter is inserted. Saline is injected into the submucosa causing a bleb or pocket. The injection catheter is removed and the prosthesis delivery tube passed through the channel to the site of the bleb where a slit is formed. The sheath portion of the delivery system remains within the submucosal opening following removal of the needle/dilator mechanism. A dessicated 1.5-wide, 18-mm long hydrogel prosthesis is inserted into the proximal opening of the sheath and advanced by a push rod through the sheath into the submucosal slit. Following removal of the sheath, the esophageal fold is dislodged from the overtube shelf with air inflation and torque on the tube. Additional prosthesis can be placed simply by rotation of the overtube and repetition of placement technique(Figure 13-9).

Effect

Up to 12 prostheses have been placed at one time, but 6 appear to be the average number. The procedure takes approximately 15 minutes for initial prosthesis placement and 5 minutes for each additional insertion. The hydrogel

Enteryx Procedure Injection Bulking
FIGURE 13-9. Gatekeeper (Medtronic, Minneapolis, MN). Expandable hydrogel prosthesis placement.

prothesis will slough if placed superficially, however. In one recent preliminary multicenter report, the Gatekeeper technique was used in a group of 60 patients, 20% of prosthesis were lost in the first week. In 6 months follow-up of one-third of the group, 75% of prosthesis were retained (Fockens et al, 2003). The mechanism of Gatekeeper appears to be a "bulking" or "augmentation" of the LES zone.

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