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ENDOSCOPIC TREATMENT MODALITIES FOR GASTRO-OESOPHAGEAL REFLUX DISEASE : A Review
PANKAJ DHAWAN*
*Consultant Gastroenterologist, Jaslok Hospital and Research Center, Mumbai. *Chief of Endoscopy, Digestive Diseases and Endoscopy Center, Motiben Dalvi Hospital, Mumbai.
INTRODUCTION
Gastro-oesophageal reflux disease (GORD) is a common disease in the West and is increasing in our country as well. The spectrum of symptoms varies from heartburn and regurgitation to persistent oesophageal tissue damage with subsequent development of serious complications such as oesophageal stricture and Barrett's oesophagus.[1] Persistent, severe symptoms can seriously hamper the quality of life of the patient.[2] The mainstay of treatment includes life style modifications, which are most often disagreeable for the patient, and long-term treatment with potent acid suppressing drugs.[3] More recently interventional endoscopic treatment modalities have been used for treating these patients. These new therapeutic options offer an exciting new avenue for both clinical application and research in patients with GORD. This review covers the available endoscopic treatment modalities including some procedural aspects, probable mechanisms of action, results and also discusses future trends.
PATIENT SELECTION FOR ENDOSCOPIC TREATMENT
Endoscopic treatment is offered to patients with established GORD based on symptoms (oesophageal or extraoesophageal), endoscopy and pH studies. Patients should have at least partial response to proton pump inhibitors (PPIs) but do not wish to take long-term medication. Patients with complicated GORD including Barrett's oesophagus and stricture are not suitable candidates for endoscopic treatment. Also those patients with severe oesophagitis, a large hiatal hernia (> 3 cm) or short oesophagus are not suitable for currently available endoscopic techniques. Patients who are obese have sub-optimal results and have been excluded from most trials with currently available devices.
Advantages of Endoscopic Treatment Modalities
The two modalities which have been approved by the US Food and Drug Administration (FDA) are the endoluminal gastric plication (Endocinch) and the radio frequency energy delivery (Stretta system). Both these methods can be technically performed in all selected patients, can be done as an outpatient procedure under sedation, have little complications and are efficacious in the short term. Moreover they do not hamper future surgical treatment if required. It is particularly useful for patients with no insurance cover requiring long-term medications.
Endoscopic Methods for GORD
The three basic principles on which endoscopic treatment modalities have been developed are to either tighten the region of the lower oesophageal sphincter (LOS) by sutures or clips, cause collagenization at the gastro-oesophageal junction (GOJ) by application of heat energy or by augmenting the GOJ by injecting substances. These methods and their results are reviewed below.
ENDOLUMINAL GASTRIC PLICATION (ENDOSCOPIC SEWING)
The first endoscopic sewing machine was developed by Paul Swain.[4] This was a cumbersome device, the use of which was technically demanding and time consuming. Since then, the device has undergone considerable refinement. The currently used device called Endocinch (CR Bard, Murray Hill, NJ) is the first device to be approved by the US FDA for endoscopic treatment of GORD.
Procedure
The procedure is usually performed on an outpatient basis under sedation and requires two endoscopes. Upper endoscopy is first performed and the distance from the incisor and the Z line is measured. A wire is left behind over which an over tube is placed. A capsule with a wide aperture (resembling the Crosby intestinal biopsy capsule) containing a needle loaded with the suture (Prolene 3-0) is inserted at the tip of the endoscope. A handle attached at the biopsy port of the endoscope triggers the needle. The endoscope loaded with the capsule is inserted into the oesophagus through the over tube and tissue is sucked into the aperture. The needle is then fired into the sucked tissue. The procedure is repeated at another site. The two threads are then sutured (4-6 square knots) creating a plication. Using a suture cutter, the threads are then cut. The second generation Endocinch device incorporates a catheter loaded with a ceramic plug and ring used to tighten the sutures. Using the same catheter the threads can be cut thus reducing the number of intubations and procedure time. Usually two or three such plications are taken one above the other along the lesser curvature within 1 cm of the squamocolumnar junction. Usually, the depth of the plications is upto the submucosa. The procedure takes about 45 minutes to complete.
Mechanism of action
The precise mechanism by which endoscopic suturing achieves benefit in patients with GORD is under evaluation. By tightening the lax LOS within the lesser curve the procedure accentuates the angle of His. However, future studies will help address this issue better.
Results
The initial trial with the BARD Endocinch was a multi-center study, which recruited 64 patients.[5] A significant reduction in reflux scores was noted and there was a significant improvement in the quality of life scores of patients undergoing endoscopic suturing. Sixty-two per cent of the patients in this trial either stopped or significantly reduced their reflux medications. The beneficial results persisted till 6 months of follow-up. In another multicentre study,[6] 88 patients were recruited for endoscopic suturing of which 82.5% of patients had complete resolution of their heartburn. Seventy-four per cent of the study patients had discontinued their medication, 17% continued intermittent medication and 9% showed no improvement in their symptoms. The longest follow-up of 2 years (mean, 25 months) after endoscopic suturing has been recently reported.[7] In this multicentre study, 33 patients were recruited. Heartburn and regurgitation scores (severity and frequency) significantly improved compared to baseline. About 25% of patients were completely off PPIs whereas 35% were taking only intermittent medication. Forty per cent were taking full dose PPIs and 6% underwent fundoplication due to treatment failure. In one study from Mayo Clinic,[8] out of 21 patients, 24% required a repeat procedure over the first 1 to 2 months; complete relief was seen in only 3 patients with partial relief in 9 patients. At 6 months follow-up, only 35% of patients had discontinued PPIs. The poor results with some of the studies have been partially attributed to the complexity of the procedure and the learning curve, which the endoscopist has had to go through.[9] Minor complications such as sore throat, chest pain, mucosal trauma, bleeding, transient dysphagia, anaesthesia related hypoxia and contained perforation have been reported in a small proportion of patients (1-2%). None of these complications required surgical intervention.
RADIOFREQUENCY ENERGY DELIVERY
Recently, the US FDA has approved the radio frequency delivery of energy for treatment of GERD. This is performed using the Stretta system (Curon Medical, Sunnyvale, CA).
Procedure
Upper gastrointestinal endoscopy is first performed to measure the distance between the incisor and the Z line. Over a guide-wire the Stretta catheter is advanced and the wire removed. The catheter is positioned 1 cm above the Z line. The catheter has a 6 mm shaft with a balloon-basket at the distal end, which inflates to 3 cm diameter (2.5 PSI) and deploys four nickel-titanium needle electrodes in the muscle layer of the GOJ. The catheter is attached to a radio frequency generator. Using a computer algorithm, automatic, temperature-controlled rediofrequency is delivered to the target tissue. A special suction and irrigation system maintains the mucosal temperature. Lesion sets are created by rotating the catheter and varying its linear position between 1 cm above and 2 cm below the Z line. A total of 14 such lesion sets are created. Immediately after the procedure, check endoscopy is performed which typically shows tightening of the GOJ due to collagen contraction.
Mechanism of action
The two probable mechanisms of action are mechanical and neurological. In a porcine reflux model, radio frequency increased the gastric yield pressure by 75% and LOS pressure by 21%.[10] In animal studies, an increase in the muscular wall thickness was observed histologically and on endoscopic ultrasonography.[11,12] In a recent human trial an increase in the LOS pressure has been reported.[13] Decrease in transient lower oesophageal sphincter relaxations (TLOSRs) has been reported in animal as well as human studies implying a neurological mechanism of action.[13,14]
Results
In a recent open-label trial, 118 patients were recruited for treatment of GORD using the Stretta system.[15] The long-term (12 months) effect on GORD symptoms, quality of life, medication use, oesophageal pH and motility studies as well as complications was studied. The Stretta procedure significantly improved the GORD symptoms, quality of life scores and oesophageal acid exposure time in treated patients. At 12 months follow-up 60% of patients were not using any PPIs. Only 6 patients (5%) failed the procedure and were subjected to laparoscopic fundoplication. Another study evaluated a modified Stretta procedure (ante grade ablation) in 10 patients with either a failed Nissen fundoplication or a greater than 3 cm sliding hiatal hernia.[16] Symptom of regurgitation disappeared in all the 10 patients, 6 discontinued their medication and 4 had mild heartburn controlled with once daily PPI treatment. Complications such as sore throat, fever, chest pain, transient dysphagia, minor bleeding, mucosal ulceration, contained perforation, sedation-related hypotension and hypoxia have been infrequently (1-2%). Amongst 1200 Stretta procedures, the complication rates were 0.83%.[17] Aspiration and death have been reported in a very small percentage of patients (0.17%). Patient selection and technical expertise will help reduce the number of complications.
ENDOSCOPIC INJECTION THERAPY
Methods to augment the LOS using low-viscosity bulking agents are being evaluated since many years. Initial trials in animals used polytetrafluroethylene (PTFE) paste and bovine dermal collagen.[18] More recently, ethinyl-vinyl alcohol (Enteryx, Enetric Medical Technologies, Palo Alto), an inert polymer has been evaluated in humans.[19] However, US FDA has not approved this as yet.
Procedure
A sclerotherapy needle is used to inject this substance circumferentially near the Z line. A small diameter needle (23 to 27 gauge) is used to inject the substance because it is easy to manipulate and atruamatic preventing back leak of the injected substance from the puncture site. The depth of implant may be submucosal (bulge appears at site of injection) or deep in the muscle layer (under fluoroscopy guidance). The material tends to flow 1-2 cm proximally or distally from injection site.
Results
In the multi-centre European and North American open-label trial,[19] 75 patients were included. Intramuscular injection of the polymer was done under fluoroscopic guidance. At 1, 3 and 6 months, 35, 21 and 9 patients could be analysed respectively. For each of the time points, symptoms improved by 64%, 83% and 82% respectively. At 1-month follow-up, 32 of 35 patients, at 3 months 18 of 21 and at 6 months, 7 of 9 patients were off medications. Other than chest pain there were no serious complications.
ENDOSCOPIC MICROSPHERE IMPLANTATION
Another method of bulking the GOJ barrier has been to inject inert polymer micro spheres (polymethylacrylate dispersed in gelatin solution) into the mucosa of the LOS region.[20] These microspheres have a property of resisting phagocytosis and not migrating away from the injected site. In one study,[20] 10 patients underwent this treatment and at 7 months follow-up, 7 were off medications. Further studies using larger number of patients and longer follow-up are needed.
Expandable Hydrogen Prosthesis Implantation
Under endoscopic guidance, miniature hydrogen prosthesis (Gatekeeper, Endonetics, San Diego, CA) has been implanted submucosally in the region of the GOJ. After placement, the prosthesis expands and bulks the LOS region. In one pilot study,[21] significant improvement in quality-of-life scores was observed in 9 patients at 1-month follow-up. Endoscopic ultrasound confirmed proper placement of the prosthesis in 8 of 9 patients. Minimal complications were reported. However, more data is awaited on this treatment method.
Endoscopic Full-thickness Plication System
One of the limitations of the Endocinch system is that the depth of the suture is only up to submucosa. To overcome this limitation, the endoscopic plication system (NDO Surgical, Mansfield, MA) is being developed. This method fuses the full-thickness of the gastric wall at the GOJ, thus accentuating the angle of His. A small calibre endoscope and the plication device are introduced into the stomach and retroflexed to view the cardia at the greater curvature side, 1 cm below the Z line. After proper positioning, a set of jaws is opened, and a catheter with a corkscrew tip is screwed into the muscularis propria, bringing the gastric wall into the span of the jaws. The jaws are then closed and a plication is achieved using a double-pronged, rivet-like implant opposing two full-thickness portions of the gastric wall which over time fuse and tighten the cardia.[22]
Peroral Endoscopic Fundoplication
The technique if successfully developed will be the endoscopic equivalent of the laparoscopic fundoplication in the long-term. Using a special device (Boston Scientific / Microvasive, Natick, MA), the distal oesophagus and proximal fundus are grasped, folded and remodelled to create a nipple-valve at the LOS.[23] Bioabsorbable clips are then used to fasten the oesophageal and gastric tissue together creating a result comparable to the Nissen fundoplication. A small calibre endoscope is introduced through the lumen of the grasping device so that the entire procedure is done under endoscopic guidance. This new device is currently being evaluated in adult baboons.
CONCLUSION
The endoscopic sewing machine and the Stretta system are the only US FDA approved products. These two modalities have shown promising results in the short-term. Certainly design modifications and newer devices will improve the long-term results. Large number of patients will need to be enrolled in well-designed randomised clinical trials comparing endoscopic treatment to drugs as well as laparoscopic fundoplication. Technological advances along with wider applications promises to make endoscopic treatment for GORD the modality of choice in future. However, till such a time, laparoscopic fundoplication will continue to be the gold standard for interventional treatment modalities for GORD.
REFERENCES
1.Lagergren J, Bergstrom R, Lindgren A, Nyren O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999; 340 : 825-831.
2.Locke GR, Talley NJ, Fett SL, et al. Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota. Gastroenterology 1997; 112 : 1448-1456.
3.Chiba N, DeGara CJ, Wilkinson JM, et al. Speed of healing and symptom relief in grade II-IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology 1997; 112 : 1798-1810.
4.Swain P, Park PO, Kjellin T, et al. Endoscopic gastroplasty for gastroesophageal reflux disease [abstract]. Gastrointest Endosc 2000; 51 : A144.
5.Filipi CJ, Lehman GA, Rothstein RI, et al. Transoral, flexible endoscopic suturing for treatment of GERD: a multicenter trial. Gastrointest Endosc 2001; 53 : 416-422.
6.Raijman I, Ben-Menachem T, Reddy G, et al. Symptomatic response to endoluminal gastroplication (ELGP) in patients with gastroesophageal reflux disease (GERD): a multicenter experience [abstract]. Gastrointest Endosc 2001; 53 : A74.
7.Rothstein RI, Pohl H, Grove M, et al. Endoscopic gastric plication for the treatment of GERD: two year follow-up results. Am J Gastroenterol 2001; 96 : S35.
8.Maple JT, Alexander JA, Gostout CJ, et al. Endoscopic gastroplasty for GERD: Not as good as billed? A single-center, 6-moth report. Am J Gastroenterol 2001; 96 : S22.
9.Filipi CJ. Why endoscopic suturing for GERD is appropriate. Gastrointest Endosc 2002; 55 : 300-302.
10.Utley DS, Kim MS, Vierra MA, Triadafilopoulos G. Augmentation of lower esophageal sphincter pressure and gastric yield pressure after radiofrequency energy delivery to the gastroesophageal junction: a porcine model. Gastrointest Endosc 2000; 52 : 81-86.
11.Kim MS, Dent J, Holloway R, Utley DS. Radiofrequency energy delivery to the gastric cardia inhibits triggering of transient lower esophageal sphincter relaxation in a canine model [abstract]. Gastroenterology 2000; 188 : A4790.
12.Chang KJ, Utley DS. Endoscopic ultrasound (EUS) in-vivo assessment of radiofrequency (RF) energy delivery to the gastroesophageal (GE) junction in a porcine model [abstract]. Gastrointest Endosc 2001; 53 : A2001.
13.DiBaise JK, Quigley EM. Efficacy of radiofrequency energy delivery to the lower esophageal sphincter in the treatment of GERD [abstract]. Gastrointest Endosc 2000; 51 : A3454.
14.Tam WCE, Schoeman MN, Zhang Q, et al. Delivery of radiofrequency energy (RFe) to the lower esophageal sphincter (LES) and gastric cardia inhibits transient LES relaxations and gastroesophageal reflux in patients with reflux disease [abstract]. Gastroenterology 2001; 120 : A16.
15.Triadafilopoulos G, Dibaise JK, Nostrant TT, et al. The Stretta procedure for the treatment of GERD: 6 and 12 month follow-up of the U.S. open label trial. Gastrointest Endosc 2002; 55 : 149-156.
16.Noar MD, Igari Y, Mulock D, Bidlack D. The large hiatal hernia and failed Nissen fundoplication: initial report of successful treatment using modified radiofrequency ablation (Stretta) technique. Am J Gastroenterol 2001; 96 : S27.
17.Food and Drug Administration : Medical Device Reports. Washington, DC: FDA; 2001.
18.O'Connor KW, Lehman GA. Endoscopic placement of collagen at the lower esophageal sphincter to inhibit gastroesophageal reflux: a pilot study of 10 medically intractable patients. Gastrointest Endosc 1988; 34 : 106-112.
19.Lehman GA, Deviere J, Haber G, et al. Lower esophageal sphincter (LES) augmentation therapy for GERD with Enteryx, a biocompatible inert polymer: initial multicenter human trial results [abstract]. Gastrointest Endosc 2001; 53 : A123.
20.Feretis C, Benakis P, Dimopoulos C, et al. Endoscopic implantation of plexiglass (PMMA) microspheres for the treatment of GERD. Gastrointest Endosc 2001; 53 : 423-426.
21.Fockens P, Bruno MJ, Hirsch DP, et al. Endoscopic augmentation of the lower esophageal sphincter: pilot study of the Gatekeeper system in patients with gastroesophageal reflux disease. Am J Gastroenterol 2001; 96 (suppl) : 37.
22.Chuttami R, Kozarek R, Lo S, et al. A novel endoscopic full thickness plicator for the treatment of GERD: demonstration of safety in pigs [abstract]. Gastrointest Endosc 2001; 53 : A132.
23.Mason RJ, DeMeester TR, Schurr MO, et al. Peroral endoscopic Nissen fundoplication: the introduction of a new era [abstract]. Gastrointest Endosc 2001; 53 : A74.
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