Gastroesophageal reflux disease (GERD) is a common condition requiring considerable medical resources. The mainstay of therapy is proton pump inhibitors (PPIs), which are effective at reducing acid reflux. In patients who have refractory acid reflux and esophagitis despite high-dose PPI, or are intolerant of the side effects of PPI therapy, surgical fundoplication is the primary therapy. The risk and cost gap between medical therapy and surgery has resulted in substantial interest in less-invasive endoscopic therapies. In this review, we discuss the underlying physiology of GERD along with the anatomic hurdles that must be overcome to develop an effective antireflux procedure. We also review the current published literature and assess the clinical efficacy of the devices that have been studied or currently are being investigated. Despite promising early studies, many of the devices fall short in high-quality randomized controlled trials. Furthermore, the physiologic aberration resulting in GERD oftentimes is addressed inadequately. Although there is certainly a need for less-invasive, safe, and effective therapy for reflux, therapy will need to withstand the established clinical efficacy of both PPI and surgical fundoplication. At present, we have the luxury of time to wait for such a device to become available.

Gastroesophageal reflux disease (GERD) is the most common upper gastrointestinal disorder seen in the elderly. The worldwide incidence of GERD is increasing as the incidence of Helicobacter pylori is decreasing. Although elderly patients with GERD have fewer symptoms, their disease is more often severe. They have more esophageal and extraesophageal complications that may be potentially life threatening. Esophageal complications include erosive esophagitis, esophageal stricture, Barrett's esophagus and adenocarcinoma of the esophagus. Extraesophageal complications include atypical chest pain that can simulate angina pectoris; ear, nose, and throat manifestations such as globus sensation, laryngitis, and dental problems; pulmonary problems such as chronic cough, asthma, and pulmonary aspiration. A more aggressive approach may be warranted in the elderly patient, because of the higher incidence of severe complications. Although the evaluation and management of GERD are generally the same in elderly patients as for all adults, there are specific issues of causation, evaluation and treatment that must be considered when dealing with the elderly.

Due to its large prevalence, gastro-oesophageal reflux disease is an ideal target for companies developing medical devices designed to cure reflux. Indeed, because medications leave part of the patients unsatisfied, there is a potential place for alternative therapies, capable of restoring an efficacious anti-reflux barrier, but without the drawbacks of surgery. For more than a decade, several novel endoluminal therapies were developed, clinically evaluated, put on the market and, for many of them, withdrawn due to economic considerations, lack of efficacy or complications. These therapies were designed to act on the gastro-oesophageal junction and reinforce mechanically the anti-reflux barrier by three different ways: suturing, radiofrequency energy application, or implantation of foreign materials. Most of the published data come from open uncontrolled studies with short-term enthusiastic results. There are a few randomized control trials assessing the true efficacy of these modalities, showing often less impressive results than the open studies did, due to a high placebo effect in mild gastro-oesophageal reflux disease. Although endoscopic treatment of gastro-oesophageal disease is still an interesting topic of investigation, one can draw some lessons from the recent experiences and foresee which place these techniques could find in the management of patients suffering from reflux.

Heartburn is the most common symptom associated with gastroesophageal reflux disease, and life-long proton pump inhibitor therapy is often required to control symptoms. Antireflux surgery is an alternative, but there may be significant side effects and the duration of therapeutic effect is variable. Several endoscopic antireflux techniques (E-ARTs) have been developed to enhance the function of the lower esophageal sphincter or alter the structure of the angle of His with the goal of recreating or augmenting the reflux barrier. Many methods are no longer available, and some await regulatory approval. This article reviews available data for the most common E-ARTs.

Endoscopic therapies to treat gastroesophageal reflux disease have been developed as another option for patients with reflux symptoms who do not want to continue medications indefinitely or are unwilling to undergo surgical intervention. The endoscopic treatments can be divided into those that pleat or plicate the upper stomach, deliver thermal energy into the lower esophageal sphincter, or inject or implant biopolymers into the gastroesophageal junction. Although capable to improve reflux symptoms for the majority of treated patients for a short while, durability has been variable among the various treatments, and there have been safety issues with some of the therapies. Although symptom improvement has been universally shown in short-term follow-up, there has been variable outcome for reduced need of antisecretory medications and pH studies show normalization of the distal esophageal acid exposure for only the minority of treated patients. Patients with significant reflux esophagitis or Barrett esophagus are not typically candidates for this antireflux intervention. Except for the NDO Plicator, in sham-controlled studies, there have been no significant differences between treated and sham-treated individuals for ability to discontinue medications or normalize pH. One issue in interpreting the results of these preliminary studies is the influence of the learning curve of a new technology. Another is that the devices and techniques have not been optimized. Currently, only the Davol/Bard EndoCinch and the NDO Plicator are available for commercial use. There are several newer devices under study or in development, and further testing and experience will demonstrate their capabilities in the treatment of gastroesophageal reflux disease.

During the last few decades many endoscopic interventions have been developed as an alternative for the treatment of gastro-oesophageal reflux disease (GORD). In many countries, these interventions are thus being performed in the general clinical setting. The aim of this study is to systematically review the evidence on the effect of endoscopic therapies for GORD. A systematic search of the literature on this subject in English, indexed in MEDLINE (1966 to May 2007) and in the Cochrane Library, was carried out. For the study selection, retrospective and prospective open-label and randomized, sham-controlled trials were taken into account. The exclusion criteria included the following: case series that included fewer than 10 patients, abstracts, studies involving children or those with a follow-up shorter than 3 months. For data extraction, two reviewers, using standardized forms, independently abstracted data on study design and methods, population, sample size, function studies (e.g. pH-metry), type of endoscopic treatment, follow-up, health-related and quality of life scores, outcomes and complications. Data synthesis involved the following: 43 studies, including four randomized, sham-controlled trials that met the inclusion criteria, out of 4182 citations. The primary end point in most studies was the reduction of the use of proton pump inhibitors (PPIs) by more than 50%. In view of these findings, the majority of studies suggested the efficacy of endoluminal therapies for the control of symptoms in GORD. In the sham-controlled studies, the effect of placebo was, nevertheless, as high as 50%. Most studies were small feasibility studies, with follow-ups of less than 1 year. No study comparing endoscopic techniques with other established treatment options such as PPIs existed. All endoscopic therapies were associated with a small but important percentage of mild to severe complications, which included perforation, abscess and death. In conclusion, the data from most of the short-term follow-up and the few sham-controlled studies demonstrate that subgroups of patients experienced improvement or resolution of typical GORD symptoms and decreased PPI usage. Currently, however, there are not enough scientific and clinical data on safety, efficacy and durability to support the use of endoluminal therapies for GORD in routine clinical practice.

A novel endoluminal fundoplication (ELF) technique using a trans-oral and fastener-deploying device (EsophyX, EndoGastric Solutions) was developed and evaluated for feasibility, safety and the treatment of gastroesophageal reflux disease (GERD) in a series of bench, animal, human (phase 1, phase 2, commercial registry) studies. The studies verified biological compatibility, durability and non-toxicity of the polypropylene fasteners as well as the feasibility of the ELF technique. The results of the preclinical testing indicated that the EsophyX device was shown to be safe, and capable of deploying fasteners directly into tissue and forming an interrupted suture line at the base of the gastro-esophageal valve (GEV). Moreover, the studies demonstrated that the ELF technique performed using the EsophyX device resulted in the creation of new GEVs of 3-5 cm in length and a circumference of 200 degrees -310 degrees , which maintained their anatomical aspects at six months. The ELF-created GEVs appeared similar to those created by laparoscopic anti-reflux surgery (LARS). The ELF procedure also resulted in reduction of all small hiatal hernias (2 cm in size) and restoration of the angle of His. The ELF procedure provides an anatomical approach similar to that of LARS for the treatment of GERD.

In recent years, various endoscopic treatments have become available to treat gastroesophageal reflux disease (GERD) in Western countries. The Stretta procedure, which uses radiofrequency energy, is one type of safe and effective endoluminal treatment for GERD. However, the feasibility, safety, and efficacy of the Stretta procedure in Japanese patients with GERD, who differ from Western peoples in their physiological characteristics, are not known. In 2006, we imported a Stretta system from the United States and investigated important clinical aspects of the system in Japanese patients with GERD.

This study was an open-label trial that enrolled patients with GERD who desired to undergo the Stretta procedure. Heartburn scores, medication use, overall satisfaction with the procedure, and adverse events were evaluated.

Nine patients received the Stretta treatment between February and September 2006. Esophagogastroduodenoscopy just after treatment revealed a remarkable reduction in the expansion of the gastric cardia and small erosions in all patients. At 3 or 6 months after treatment, heartburn scores were significantly improved compared with pretreatment scores (5.0 +/- 1.7 pretreatment vs. 0.7 +/- 1.4 posttreatment, P=0.007). In six of nine patients (66.7%), treatment significantly (P=0.009) decreased medication use. There were no major adverse events. All patients were satisfied with this treatment.

The Stretta procedure safely reduced GERD symptoms and decreased medication use in Japanese patients with GERD. This treatment may thus be very useful for such patients, and it is hoped that a nationwide trial will be undertaken in Japan to obtain more extensive data.

Gastroesophageal reflux disease (GERD) is a very common chronic disorder manifesting itself as heartburn, regurgitation, or dysphagia, possibly leading to esophagitis, Barrett's esophagus and adenocarcinoma, and has a major impact on the patient's quality of life. Both medical treatment and surgery are well-established methods with several limitations. Recently, three types of endoscopic methods in several modifications have been developed: (1) Radiofrequency therapy (Stretta procedure) is available both in Europe and USA and more than 5,000 patients have been treated to date. (2) Injection therapy requires the injection of bulking agents or implantation of bioprosthesis into the lower esophageal sphincter (LES) zone. Both Enteryx was withdrawn from the market in 2005, and Gatekeeper was suspended before FDA approval. (3) Suturing/plication therapy is based on the plication at the level of the LES, and most of all techniques resemble the principle of surgical treatment. Despite sophisticated technologies and promising short-term results, all these techniques are associated with inconsistencies, controversies, and relevant adverse affects. According to current practice, use of endoscopic methods is justifiable only as part of clinical trials. Many aspects, including commercial ones, will influence future developments in this area, which are difficult to predict.

The high prevalence of gastroesophageal reflux disease (GERD) in Western societies has accelerated the need for new modalities of treatment. Currently, medical and surgical therapies are widely accepted among patients and physicians. New potent antisecretory drugs and the development of minimally invasive surgery for the management of GERD are at present the pivotal and largely accepted approaches to treatment. The minimally invasive treatment revolution, however, has stimulated several new endoscopic techniques for GERD. Up to now, the data is limited and further studies are necessary to compare the advantages and disadvantages of the various endoscopic techniques to medical and laparoscopic management of GERD. New journal articles and abstracts are continuously being published. The Food and Drug Administration has approved 3 modalities, thus gastroenterologists and surgeons are beginning to apply these techniques. Further trials and device refinements will assist clinicians. This article will present an overview of the various techniques that are currently on study. This review will report the efficacy and durability of various endoscopic therapies for gastroesophageal reflux disease (GERD). The potential for widespread use of these techniques will also be discussed. Articles and abstracts published in English on this topic were retrieved from Pubmed. Due to limited number of studies and remarkable differences between various trials, strict criteria were not used for the pooled data presented, however, an effort was made to avoid bias by including only studies that used off-PPI scoring as baseline and intent to treat.

Enteryx (Boston Scientific Corp, Natick, Mass) is an injectable polymer used for the treatment of GERD. Current use of Enteryx requires fluoroscopy for accurate placement into the deep esophageal wall (ie, the deep submucosa or muscularis propria). In this study, we assessed the use of a new double-lumen, double-needle injection catheter for accurate placement of Enteryx into the deep esophageal wall, without fluoroscopy, in a porcine model.

All procedures were performed by using a new injection catheter (GZ Medical, LLC, Minnetonka, Minn), which allows for tissue depth assessment via the flow of gas through one lumen and the injection of a therapeutic substance (Enteryx) via a second lumen. Endoscopy was performed on 5 consecutive pigs by using the new catheter alone, without fluoroscopy, and attempting deep injections. Four injections of Enteryx were made at the gastroesophageal junction, 10 cm above the junction, and 15 cm above the junction. A total of 60 sites (12 per animal) were injected. The animals were sacrificed and each esophagus was harvested. The mediastinal cavity was searched for extravasated Enteryx material, and the esophagus was examined grossly for Enteryx adherent to the outside wall. Injection sites then were classified morphologically as superficial (mucosa or submucosa), deep (muscularis propria or deep submucosa contiguous to muscularis), subadventitial (between muscle and adventitia), or transmural. Only deep injections were considered adequate.

No extravasated Enteryx was found in the mediastinum in 60 injected sites. One area of transmural injection had Enteryx adherent to the outside esophageal wall (1.7%). Fifty-one injected sites (85%) were adequate deep injections, 4 injections (6.7%) were subadventitial, 1 injection (1.7%) was superficial, and 3 injections (5%) could not be assessed. There were no complications observed in any animal.

By using a new injection device without fluoroscopy, Enteryx can be deposited consistently into the deep esophageal wall with a high degree of accuracy, avoiding mediastinal extravasation. Additional clinical trials are necessary to determine the relative accuracy and role of the new technique compared to standard radiographically guided placement.

The aim of this study was to compare and determine the efficiency and safety of two newly introduced endoscopic antireflux procedures in the treatment of gastroesophageal reflux disease (GERD).

In a prospective, randomized trial, endoluminal gastroplasty (EndoCinch) was compared with polymer injection (Enteryx) employing 51 consecutive patients dependent on proton pump inhibitor therapy. Follow-up evaluation included drug consumption, symptoms, quality-of-life scoring, endoscopy, pH monitoring, manometry, and documentation of adverse events.

Twenty-six patients were assigned to EndoCinch treatment, 23 patients received Enteryx implantation, and two patients dropped out before applying endoscopic therapy. At 6 months, proton pump inhibitor therapy could be stopped or dosage was reduced by > or =50% in 20 of 26 (77%) EndoCinch-treated patients and in 20 of 23 patients treated by Enteryx (87%, p= 0.365), which differed significantly in both groups compared to the pre-interventional status (p < 0.0001). Esophageal acid reflux (pH < 4) decreased from 14.5% to 9.6% in EndoCinch-treated patients (p= 0.071) and from 15.5% to 13.9% in patients treated by Enteryx (p= 0.930). Heartburn symptom score, modified DeMeester score, gastrointestinal life quality index, and SF-36 physical health survey score improved significantly in both groups postinterventionally (p < 0.0001). Approximately 25% of the patients in both groups required retreatment in an attempt to achieve symptom control.

This is the first prospective, randomized study directly comparing two endoscopic anti-GERD techniques. EndoCinch and Enteryx seem to be equally successful in the treatment of GERD significantly reducing the proton pump inhibitor dosages, and also by improving symptoms of patients. Both endoluminal antireflux procedures may be promising therapeutic options; long-term evaluation will have to show if the positive initial results can be maintained.

Gastro-oesophageal reflux disease (GORD) is a chronic condition affecting up to one-quarter of the Western population. GORD is characterized by heartburn and acid regurgitation, but is reported to be associated with a spectrum of extra-oesophageal symptoms.

The aim of this systematic review was to critically evaluate postulated extra-oesophageal symptoms of GORD.

Extra-oesophageal symptoms were identified from population-based studies evaluating their association with GORD (either defined as heartburn and/or acid regurgitation, or diagnosed in general practice). The response of these symptoms to acid-suppressive therapy was investigated using randomized, double-blind, placebo-controlled studies. Pathogenic mechanisms were evaluated using clinical and preclinical studies.

An association between GORD and symptoms or a diagnosis of chest pain/angina, cough, sinusitis and gall-bladder disease was evident from three eligible population-based studies of GORD. Randomized placebo-controlled studies (n=20) showed that acid-suppressive therapy provides symptomatic relief of chest pain, asthma and, potentially, chronic cough and laryngitis. Mechanistic models, based on direct physical damage by refluxate or vagally mediated reflexes, support a causal role for GORD in chest pain and respiratory symptoms, but not in gall-bladder disease.

GORD is likely to play a causal role in chest pain and possibly asthma, chronic cough and laryngitis. Further investigation is desirable, particularly for other potential extra-oesophageal manifestations of GORD such as chronic obstructive pulmonary disease, sinusitis, bronchitis and otitis. Acid-suppressive therapy is likely to benefit patients with non-cardiac chest pain, but further placebo-controlled studies are needed for other symptoms comprising the extra-oesophageal spectrum of GORD.

The problem of eliminating gastroesophageal reflux (GER) with simple, effective and devoid of unpleasant side effects procedures is still unresolved. We tried to settle this problem with a magnetic device that should be applied to the distal end of the esophagus.

Two plastoferrite magnets of 2 x 4 x 0.5cm(1) were applied, on the opposite sides of a flaccid polyethylene tube mimicking the physical characteristics of the terminal esophagus. The two magnets attracting themselves compressed the tube, creating an artificial high-pressure zone that divided the tube in two segments. Both segments of the tube were connected to pressure transducers and a polygraph and one of them was connected to a hydraulic pump. The pressure was progressively increased in this segment up to a value sufficient to detach the magnets with consequent flowing of the water in the other segment of the tube.

The progressive increase of the pressure in a segment of the tube detached the magnets allowing a free flow into the other segment when the pressure reached an average value of 9.75+/-1.05 mmHg (mean+/-SD).

A couple of magnets clamping a tube with the characteristics of the distal esophagus is able to prevent the passage of liquid with a pressure value near to that of a normal lower esophageal sphincter. This magnetic device could be useful to maintain closed a sphincter unable to prevent gastroesophageal reflux.

Within the last 15 years, novel endoscopic therapies have been developed as options for patients who have gastroesophageal reflux disease (GERD). These approaches can provide long-term relief of GERD, or can be used to "bridge" patients to future therapy, because undergoing treatment does not preclude one from future medical or surgical therapy. These therapies continue to bean active source of research and investigation. Although they are undergoing rapid development, there are only a few peer-reviewed articles detailing original studies with short-term follow-up. Future success in this arena will depend on sham-controlled trials, long-term outcome studies, and cost-effectiveness analyses. This article describes available endoscopic therapies, discusses their effectiveness and duration of response, and reviews their failures and complications.

Endoscopic therapies for the control of GERD offer the potential for significant symptomatic improvement while obviating many of the potential drawbacks associated with long-term medical therapy with acid suppressive or neutralizing medications and traditional antireflux surgery. Such endoluminal therapies are intended to be safe with a brief learning curve, easily administered in an outpatient setting without the need for general anesthesia, reproducible, and durable. LES injection therapies share the common theoretic method of action of bulking at the GEJ, leading to loss of sphincter compliance and distensibility. In the case of Enteryx, this sustained effect has been demonstrated to be secondary to chronic inflammation, fibrosis, and encapsulation resulting from a foreign body response to the injectate. Available data suggest that a majority of patients respond to LES injection therapies, as demonstrated by a decreasing usage of PPIs after implantation, the ability of many patients to terminate PPI use completely, and improved GERD-HRQOL scores. Responses seem reasonably durable in follow-up assessment up to 24 months post treatment. Although there may be some placebo effect associated with treatment, patients injected with Enteryx respond better than a control group of sham-treated subjects. Individuals treated with LES injections, however, represent a select subgroup of the overall population of refluxers. Study subjects, by and large, have had uncomplicated GERD with typical reflux symptoms of heartburn or regurgitation that have responded to PPIs. Patients who have severe anatomic derangements, such as esophageal strictures, persistent esophagitis, Barrett's esophagus, or sizeable hiatal hernias, are excluded from clinical trials, as are patients who have severe motility disorders or significant comorbid conditions. Similarly, patients who have responded poorly to PPIs and those who have primarily extraesophageal manifestations of GERD have not been studied. Outcomes to date have been assessed over the short to medium term; long-term outcome studies are lacking. The durability of response, therefore, remains largely unknown, as does the incidence of any long-term complications or side effects. A postmarket study to assess the long-term safety and durability of Enteryx therapy up to 36 months is under way, as required by the FDA, with a target enrollment of 300 patients. Detailed cost analyses have yet to be reported. Such data are important not only for comparing the various endoluminal therapies but also for comparison to standard medical therapy and antireflux surgery. At present, no randomized trials are completed that compare injection therapies to other accepted treatments of GERD. The ability to perform fundoplication safely and effectively after failed LES injection therapy is not well known, in that the number of subsequent surgical cases is small and the results largely anecdotal to date. Likewise, the ability to use LES injection as salvage therapy after failed fundoplication has not been tested. The data regarding endoluminal injection therapies are similar to those after endoscopic plication and radiofrequency application to the LES, in that a definite symptomatic response is observed, but the objective documentation of diminished esophageal acid exposure lags behind. Esophageal acid exposure is normalized in a minority of treated subjects and improved in an additional subgroup, whereas the rate of symptomatic response exceeds these objective improvements. The reasons for this disconnect are the subject of much speculation and controversy. A placebo effect has been discussed, but clearly more factors are at play. Perhaps a study effect also is important, in that patients enrolled in clinical trials for GERD control may be more likely to modify their dietary and lifestyle habits in an effort to bring about symptom relief. Maybe the understanding of the perception of reflux events is lacking, and these endoluminal therapies work mainly by altering the perception of reflux more than the amount of reflux itself. A recent technologic review of injection therapies for GERD concludes that the "data for Enteryx are as compelling as those of any other open-label evaluation of an endoluminal therapy for GERD". There is much to be learned about all endoluminal techniques. For now, LES injections are promising therapies lacking supportive evidence of long-term safety and efficacy. The available data justify their use only in patients who have GERD symptoms responsive to PPIs and who do not have significant comorbidities or complications associated with GERD. Whether or not the role of LES injection techniques will be expanded to include more complicated cases, patients who are partially responsive to PPIs, combination therapy with other endoluminal techniques, or salvage therapy after failed fundoplication awaits further study.

Endoscopic therapies for gastroesophageal reflux disease represent a minimally invasive alternative to medical or surgical treatment. These devices include suturing, radiofrequency energy, and bulking agent technologies. Research into the use of these technologies in gastroesophageal reflux disease continues to accelerate, and the last 2 years have witnessed significant developments that may affect current and future clinical practice.

Long-term data from nonrandomized clinical trials have become available in the last 2 years for many gastroesophageal reflux disease endotherapies, providing some insight into their durability. Furthermore, two multicenter and one single-center sham-controlled trials were published recently, allowing comparison between groups.

Although it is premature to propose the superiority of any individual approach, emerging data in this rapidly evolving field may inform current and future directions in the research and treatment of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a chronic condition affect-ing over 7% of the US population. The primary objective of therapy is symptom relief, with secondary goals to heal esophagitis, prevent reflux-related complications, and maintain remission. There are several new endoscopic therapies (ETs) for treatment of GERD, generating considerable interest. An outpatient procedure, performed without an incision and general anesthesia, is attractive to patients and these therapies are being rapidly introduced, despite lack of long-term follow-up and randomized trials. In this article, the authors review endoscopic procedures, including technical aspects, mechanisms of action, safety, efficacy, and tolerability. Patient selection and relevant human studies are reviewed to clarify advantages and disadvantages of ET compared with conventional procedures.

Over the past decade, a number of endoscopic techniques have been developed as alternatives to medical and surgical treatment of gastroesophageal reflux disease (GERD). The driving force was to provide an outpatient transoral, endoscopic procedure effective in controlling reflux in a portion of patients with GERD. Three major technologies emerged, although each use different approaches to augment the barrier function of the lower esophageal sphincter, mechanisms may be similar. These include Endocinch which tightens the gastroesophageal junction via a set of suture plications around the lower esophageal sphincter, Stretta, which delivers radiofrequency energy at the cardia, and Enteryx, which is an inert polymer injected into the muscle layer of the gastroesophageal junction. To date, the underlying mechanism of action of these procedures has not been completely elucidated, although each alters the compliance of the GEJ and thus its ability to respond to a "refluxogenic stress". The target population currently consists of proton pump inhibitor-dependent GERD patients, with little or no hiatal hernia and without severe esophagitis or Barrett's. The Stretta procedure is the only procedure to date to be subjected to a sham-controlled trial. Registries of complications suggest that these techniques are relatively safe, but serious morbidity including rare mortality have been reported. All can be performed on an outpatient basis. Future comparative studies with predetermined end points, validated outcome measures, prolonged follow-up, and complete complication registries are needed to determine the role of endoscopic procedures in the clinical practice of patients with GERD. Evolution of the current technologies will almost certainly occur, and a commonly performed, efficacious endoscopic antireflux procedure is likely to emerge.

Enteryx implantation in the esophagus is an alternative therapy for patients with proton pump inhibitor (PPI) dependent GERD. Although this treatment resulted in highly significant improvement at 6 and 12 months, longer follow-up is needed to more fully assess the durability of these positive effects.

An open-label, international clinical trial was conducted in 144 PPI-dependent patients with GERD with follow-up at 6 and 12 months. In addition, the durability and the safety of the treatment were assessed for 24 months in 64 patients enrolled in a postapproval study. The primary study outcome measure was usage of PPI. Secondary outcomes in the multicenter trial were GERD health-related quality of life (GERD-HRQL) symptom score and esophageal acid exposure.

At 12 months, PPI use was reduced > or =50% in 84%: 95% confidence interval (CI) [76%, 90%] and was eliminated in 73%: 95% CI[64%, 81%] of evaluable patients (intent-to-treat analysis 78%: 95% CI[70%, 84%] and 68%: 95% CI[60%, 76%], respectively). A GERD-HRQL < or =11 was attained in 78%: 95% CI[69%, 85%] of evaluable patients. Esophageal acid exposure (total time pH <4) was reduced by 31%: 95% CI[17%, 43%]. At 24 months, a > or =50% or greater reduction in PPI use was achieved in 72%: 95% CI[59%, 82%] and PPI use was eliminated in 67%: 95% CI[54%, 78%] of patients.

This investigation provides evidence for sustained effectiveness and safety of implantation of Enteryx in the esophagus in PPI-dependent patients with GERD.

The aim of this study was to assess the intermediate-term (12-month) safety and efficacy of endoscopic full-thickness plication in patients with symptomatic GERD.

Sixty-four patients with chronic heartburn that required maintenance antisecretory therapy received a single, endoscopically placed, full-thickness plication in the gastric cardia 1 cm distal to the gastroesophageal junction. At baseline and 12 months after plication, patients completed the GERD Health Related Quality of Life questionnaire, Gastrointestinal Symptom Rating Scale, and SF-36 Health Survey, as well as a medication use diary. Ambulatory 24-hour pH monitoring and esophageal manometry were obtained at baseline and 3 months after plication. At 6 months after plication, the 24-hour pH study was repeated.

Of the 57 patients who completed the 12-month follow-up, 40 (70%) were no longer taking a proton pump inhibitor. Median GERD Health Related Quality of Life scores were improved compared with baseline while taking medication (19.0 vs. 5.0; p < 0.0001) and while not taking medication (13.0 vs. 5.0; p < 0.002). At 6 months after the procedure, an improvement in distal esophageal acid exposure was demonstrated in 40 of 51 patients (80%), with a decrease of 39% in the median percentage of time the pH was less than 4 (p < 0.0001). Normal pH scores were observed in 30% of patients. All procedure-related adverse events occurred acutely, as previously reported, and no new adverse event was observed during extended follow-up.

Full-thickness plication at the gastroesophageal junction is an effective endoscopic procedure for treatment of patients with symptoms caused by GERD. It reduces reflux symptoms and antisecretory medication use over at least a 1-year period.

Endoluminal gastroplication has shown promise for the treatment of GERD in short-term studies. Until now, long-term outcome data have been lacking.

A prospective, multicenter trial enrolled 85 patients with GERD to be treated with endoluminal gastroplication. Inclusion criteria were 3 or more heartburn or regurgitation episodes per week, >4.2% time in 24 hours with esophageal pH < 4, and dependency on antisecretory medications. Exclusion criteria were the presence of varices, achalasia, aperistalsis, or previous gastric resection. Patients underwent manometry, 24-hour pH monitoring, and symptom severity scoring before and after the procedure. Patient diaries were used to assess medication use and to estimate annual medication cost.

At 1- and 2-year follow-up, patients had significant reductions in median heartburn symptom scores (72 at baseline [interquartile range (IQR) 90-48] vs. 4 at 12 months [IQR 43-0] and 16 at 24 months [IQR 53-3.5]; p < 0.0001 vs. baseline) and median regurgitation symptoms (2 at baseline [IQR 3-1] vs. 0 at 12 months (IQR 1-0) and 1 at 24 months [IQR 1-0]; p < 0.0001 vs. baseline). Of all patients, 59% and 52% showed heartburn symptom resolution at 12 and 24 months, respectively ( p < 0.0001 vs. baseline). Also, 83% and 77% had regurgitation symptom resolution at 12 and 24 months, respectively (p < 0.0001 vs. baseline). Proton pump inhibitor use also was significantly reduced at 12 and 24 months after the procedure. At 2-year follow-up, median annualized medication costs were reduced by 88% (1381 US dollars) (p < 0.0001). Endoluminal gastroplication significantly reduced the duration and the number of episodes of esophageal acid exposure (p < 0.0001 vs. baseline). Only 7 patients experienced adverse events.

Endoscopic gastroplication is safe and effective, and is associated with symptom reductions in patients with GERD for at least 24 months.

Gastroesophageal reflux disease (GERD) typically requires lifelong medical therapy or surgery for the management of patients with frequent symptoms. The current standard of care is to prescribe medical therapy using proton pump inhibitors. Patients with moderate-to-severe GERD require extended/maintenance therapy. Until recently, the only alternative to this approach was surgical intervention. Endoscopic therapy for GERD has emerged as a second alternative strategy. Primary endpoints for all interventions have aimed at symptomatic control and reduction/discontinuance of medication use. For surgical and endoscopic therapies, however, there are other physiologic endpoints that have attempted to define changes in lower esophageal sphincter pressure and esophageal acid exposure. For patients being evaluated for endoscopic GERD therapy, the author recommends comprehensive esophageal testing and pH testing.

Tube-based ambulatory pH testing has rapidly evolved in the past 3 decades to become the standard by which other diagnostic approaches to gastroesophageal reflux disease are judged. Acid exposure 5 cm above the manometrically determined lower esophageal sphincter is the standard for documentation of pathologic acid exposure of the distal esophagus. Proximal esophageal or hypopharyngeal monitoring is an evolving technique that may shed light on patients with supraesophageal symptoms. The ability to simultaneously monitor esophageal and gastric acidity (usually in patients with persistent symptoms despite therapy) is another advantage of this technique. Whether the new system that allows simultaneous pH and impedance monitoring and the system that uses an implantable tubeless monitoring capsule will supplant this older but well-established technology remains to be determined.

The need is well recognized for additional data on endoluminal therapies for gastroesophageal reflux disease (GERD). This prospective multicenter clinical trial was designed to assess safety and effectiveness of Enteryx, a nonresorbable copolymer implanted into the lower esophagus, in reducing usage of proton pump inhibitors (PPIs) and improving reflux symptoms and quality of life.

Enteryx implantation was performed under fluoroscopic visualization without general anesthesia in 93 patients with symptomatic GERD responsive to and relapsing upon cessation of PPI therapy. Subjective and objective data were collected up to 12 months postprocedure. The criterion for treatment success was reduction in PPI dosage of > or =50%.

At 12 months, treatment success was attained in 86% (confidence interval, 77%-93%) of 74 evaluable patients and elimination of PPI therapy in 65% (confidence interval, 53%-76%). The treatment success rate by intent-to-treat analysis was 69% (confidence interval, 58%-78%). Reflux-related heartburn (P < 0.0001), regurgitation symptoms (P = 0.0005), and physical (P < 0.0001) and mental quality of life (P = 0.0012) scores improved. The most frequent complications were chest pain (77%), dysphagia/odynophagia (27%), and sensation of fever (26%).

Enteryx implantation provides an effective and safe alternative for management of gastroesophageal reflux, reducing medication dependency and symptoms and enhancing quality of life.

This aim was to determine whether endoscopic implantation of a biocompatible nonresorbable copolymer (Enteryx; Boston Scientific Corp, Natick, MA) is a more effective therapy for gastroesophageal reflux disease (GERD) than a sham procedure.

In a randomized, single-blind, prospective, multicenter clinical trial, 64 patients with GERD were enrolled whose symptoms were well controlled by proton pump inhibitor (PPI) therapy and rapidly recurred after cessation of PPI therapy. Thirty-two patients were assigned to Enteryx implantation and 32 to a sham procedure consisting of standard upper endoscopy. Patients in both groups with unsatisfactory symptom relief after 3 months were eligible for re-treatment by Enteryx implantation. The primary study end point was > or =50% reduction in PPI use. Secondary end points included > or =50% improvement in GERD score and the proportion of patients not undergoing re-treatment procedure. Follow-up evaluations were performed at 3 and 6 months.

The percentage of Enteryx-treated patients achieving a > or =50% reduction in PPI use (81%) was greater than that of the sham group (53%), with a rate ratio of 1.52 (confidence interval [CI], 1.06-2.28; P=.023). A higher proportion of the Enteryx (68%) than sham group (41%) ceased PPI use completely (rate ratio, 1.67; CI, 1.03-2.80; P=.033). GERD health-related quality of life heartburn score improvement > or =50% was achieved by 67% of the Enteryx group versus 22% of the sham group (rate ratio, 3.05; CI, 1.55-6.33; P <.001). More Enteryx-treated (81%) than sham-treated (19%) patients did not undergo re-treatment (rate ratio, 4.33; CI, 2.23-9.29; P <.001).

Enteryx implantation more effectively reduces PPI dependency and alleviates GERD symptoms than a sham procedure.

Although pharmacologic therapy is safe and effective for gastroesophageal reflux disease (GERD), patients requiring chronic drug treatment often seek alternatives. Surgical alternatives to chronic drug treatment are associated with increased morbidity and long-term failure rates in more than 50% of surgically treated patients. Newer endoluminal therapies using modifications of standard endoscopy techniques are under evaluation as alternatives to chronic drug treatment or surgical intervention for GERD. Appropriate patient selection is KEY. Patients considered for any endoluminal therapy should have well documented GERD and demonstrated appropriate and successful response to medical therapy with a proton pump inhibitor (PPI). The Enteryx implant is an injectable biocompatible polymer approved by the US Food and Drug Administration for the management of GERD symptoms. Clinical trial data indicate that the Enteryx procedure is a safe and effective GERD treatment that manages symptoms of GERD and addresses the underlying anatomic and functional aspects of the disorder. Multicenter clinical trials have shown that the Enteryx procedure safely and effectively eliminates or significantly reduces PPI use in approximately 84% of patients at 1 year and 72% of patients at two years. The risk-benefit profile of this procedure and alternative treatment options should be carefully evaluated for each patient considered a candidate for Enteryx and all endoluminal therapies. Randomized-controlled studies comparing the Enteryx procedure to placebo and cost-effective analyses comparing treatment options will further define the use of the Enteryx implant in patients with GERD.

Guidelines for the diagnosis and treatment of gastroesophageal reflux disease (GERD) were published in 1995 and updated in 1999. These and other guidelines undergo periodic review. Advances continue to be made in the area of GERD, leading us to review and revise previous guideline statements. GERD is defined as symptoms or mucosal damage produced by the abnormal reflux of gastric contents into the esophagus. These guidelines were developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee, and approved by the Board of Trustees. Diagnostic guidelines address empiric therapy and the use of endoscopy, ambulatory reflux monitoring, and esophageal manometry in GERD. Treatment guidelines address the role of lifestyle changes, patient directed (OTC) therapy, acid suppression, promotility therapy, maintenance therapy, antireflux surgery, and endoscopic therapy in GERD. Finally, there is a discussion of the rare patient with refractory GERD and a list of areas in need of additional study.

The Enteryx procedure is an endoscopic injectable treatment for the management of gastroesophageal reflux disease symptoms. Enteryx was approved by the US Food and Drug Administration in April 2003 for patients who respond to, and require daily pharmacologic therapy with proton-pump inhibitors. Although gastroesophageal reflux disease is rarely life threatening, symptoms are often chronic and disabling. Therefore, safe and cost-effective alternative treatments for chronic gastroesophageal reflux disease are sought by patients, physicians and payers. Multicenter clinical trials have demonstrated that the Enteryx procedure safely and effectively eliminates, or significantly reduces, proton-pump inhibitor use in approximately 84% of patients at 1 year, and 72% of patients at 2 years.

Lifetime management goals of gastroesophageal reflux disease (GERD) are to control esophageal as well as extraesophageal symptoms, maintain a stable noninflamed esophageal mucosa, and prevent complications. Large randomized clinical trials and >16 years of worldwide experience have confirmed the high rate of efficacy and excellent safety profile of proton pump inhibitor (PPI) therapy in individuals with all grades of GERD, making these agents the mainstay of treatment. Despite these outcomes, some individuals may desire an alternative to pharmacologic therapy. In such patients, laparoscopic fundoplication may produce symptom relief and healing of esophagitis, but its invasiveness, cost, and inherent surgical risks have created an interest in a variety of endoscopic therapies for reflux disease. Several short-term uncontrolled trials of these endoscopic therapies have reported encouraging preliminary results; however, careful patient selection as well as clinician experience is critical for their success. In addition to clinician expertise with the procedure, success has been observed only in patients with nonerosive GERD and a hiatal hernia <3 cm, abnormal pH monitoring, and normal esophageal motility studies, as well as in those who have experienced at least partial symptom relief with PPI therapy. Endoscopic therapy should not be considered the standard of care in patients with erosive disease or large hiatal hernias.

In the West, gastroesophageal reflux disease (GERD) is a common and well-recognized disease. Lately, it has been described as an emerging problem in the East as well. While it is not a rapidly fatal illness, it causes a myriad of disturbing symptoms that remarkably reduce the patients' quality of life (QOL). The economic impact that results from multiple consultations, diagnostic investigations, and administration of a variety of treatment regimens, including surgery, is enormous. The operative management for GERD is fundoplication, for example Toupet (270 degree wrap of the distal esophagus) and Nissen (360 degree wrap of the distal esophagus). These surgical procedures are aimed at permanently controlling acid reflux by reconstructing the gastroesophageal junction. Currently, the ease, aesthetic advantages, and the comparable outcomes achieved by minimally invasive laparoscopic fundoplication have rekindled interest in the operative alternatives of GERD management. Fundoplication controls or diminishes considerably the severity of the symptoms associated with GERD. However, appearance of new symptoms i.e. dysphagia, 'gas-bloat syndrome', etc. as postoperative events have been reported. Recently, several innovative endoluminal treatment modalities have been introduced, namely; endoscopic plicator/suturing devices, bulking injections, and radiofrequency treatment. They are focused on enhancing the performance of a malfunctioning lower esophageal sphincter. While results of several case series reflect substantial improvements in GERD-HRQL scores, lack of long-term durability data is a major concern when recommending these novel, relatively simple, peroral techniques to a long suffering patient. It is clear that these therapies are still evolving and long-term outcomes of properly designed comparative efficacy trials are awaited.

Enteryx (Boston Scientific) is an injectable solution containing 8% ethylene vinyl alcohol copolymer dissolved in dimethyl sulfoxide that has been approved for the treatment of gastroesophageal reflux disease (GERD). The technique consists of injecting Enteryx into the lower esophageal sphincter where it solidifies into a sponge-like permanent implant and prevents or reduces gastric acid reflux into the esophagus. The procedure appears to be generally safe, even if minor or moderate adverse events have been observed. We present the case of a 52-yr-old female treated by Enteryx injection for GERD who developed subsequently an esophageal parietal abscess.

A debate has been going for decades between surgeons and gastroenterologists about the treatment of choice for gastroesophageal reflux disease (GERD). The lower esophageal sphincter (LES) has been historically far from the reach of gastroenterologists, who adopted the symptomatic treatment as their approach to reflux disease through reduction of gastric acid. As for surgeons, reaching the LES was only possible by invading the thoracic or abdominal cavity. Although their approach was later refined to become "minimally" invasive, it was still deemed too invasive by others to allow it to be the "gold standard." Simple logic should lead one to think about the "natural route" as the easiest way to reach the LES. This concept has opened the door for the new era of GERD treatment through "endoscopic modality." Seven different techniques are currently being used to treat patients with GERD. We review the mechanism of action, potential side effects, efficacy, durability, and results from the most recent or largest experience of each. This review shows that endoscopic treatment has definitely earned its place as a viable option for GERD treatment in selected patients. With the available data from clinical trials, it is not possible to determine the best modality available, and the endoscopic treatment of choice is to be determined with further studies.

Gastroesophageal reflux disease (GERD) is prevalent in 10% of the population. In addition to the established therapy, endoscopic antireflux procedures have been developed to improve the gastroesophageal reflux barrier. This can achieved by endoscopically placed sutures, application of radio frequency energy, or injection of biocompatible materials. These new techniques might be effective in some patients with GERD. To date, there are limited data on the effectiveness and safety of these methods. During a follow-up of 1-2 years, subjective parameters improved in 70-75% of the test patients such that no antisecretory treatment was required. Further, randomized, placebo-controlled studies are needed for objective evaluation of these promising new methods.

Endoscopic esophageal interventions are an exciting topic because indications for the use of both the available devices and the new devices continue to evolve. This article reviews the most notable developments and the results of endoscopic esophageal therapeutic interventions published in 2003.

In 2003, three follow-up series on photodynamic therapy were published. Photodynamic therapy was shown to improve dysphagia from esophageal cancer, but comparative studies with other techniques are needed. Photodynamic therapy was also effective in removing Barrett epithelium. Of concern is that patients with residual Barrett esophagus after ablative treatment are still at an increased risk for esophageal cancer. Endoscopic mucosal resection has become an accepted alternative for surgical resection of early-stage esophageal cancer, with increasing evidence that lesions larger than 20 mm can be safely removed by this technique. Completely covered plastic self-expanding stents have been demonstrated to reduce recurrent dysphagia by the ingrowth or overgrowth of nonmalignant tissue. A new indication for self-expanding metal stents is the treatment of traumatic nonmalignant perforations of the esophagus. Stents are also increasingly used for strictures refractory to repeated dilations and as an alternative to pneumatic dilation in achalasia. Bleeding esophageal varices can safely be treated with vasoactive drugs, which is good news for endoscopists who value a good night's rest. Various follow-up studies of endoscopic antireflux procedures were published that suggested good symptomatic results. However, with respect to the reduction of acid exposure to the esophagus, these data were less impressive.

In 2003, much additional data about current techniques became available. In addition, new indications for existing devices were developed. Finally, for some techniques more information will be needed before their exact role can be established.

Gastroesophageal reflux disease (GERD) is a very common disorder that affects substantially the patient's quality of life. A number of important new developments in the diagnosis, clinical management, and medical, endoscopic, and surgical therapies were described in 2003, and they are summarized here.

Most patients with symptomatic GERD do not have erosive reflux disease. Transient lower esophageal sphincter relaxations and hiatal hernias have emerged as major and interacting factors in GERD. Stretch receptors in the fundus are more relevant than tension receptors in triggering transient lower esophageal sphincter relaxations and subsequent reflux. The wireless Medtronic Bravo pH system has been validated as an alternative to conventional pH monitoring and has better tolerability. The mainstay of medical therapy for GERD is the use of proton pump inhibitors, with as yet no superiority of any one agent over all others. Several endoscopic antireflux therapies aiming at creating an antireflux barrier and reducing or eliminating the need for chronic medical therapy or fundoplication have been introduced and validated as feasible, safe, and effective. It may be possible now to stratify patients with GERD to treatment with either endoscopic therapy or surgery according to the size of hiatal hernia, lower esophageal sphincter pressure, Barrett esophagus, and significant pulmonary symptoms.

Key developments in the recognition and management of GERD in 2003 will have significant implications for clinical practice or research.

Endoscopic radiofrequency energy delivery (Stretta) is effective for managing gastroesophageal reflux disease (GERD) in selected patients. One criticism, however, is a theory that a mechanism of action is partial desensitization of the esophageal body rather than a reduction in esophageal acid exposure. To resolve this question, this study sought to determine if there is a correlation between the improvement in GERD outcomes and esophageal acid exposure after Stretta.

Subgroup analyses were performed between "responder" and "nonresponder" groups from the U.S. Stretta open label trial ( n = 118), on the basis of posttreatment responses for GERD health-related quality of life (HRQL) heartburn, satisfaction, and proton pump inhibitor use. Outcomes were analyzed within and between subgroups. Pearson correlation coefficient analysis was performed comparing distal esophageal acid exposure with each of the continuous outcomes (GERD-HRQL, heartburn, satisfaction).

Responder subgroups had significant improvements in esophageal acid exposure, whereas nonresponders had no change or less improvement in the same. Changes in GERD-HRQL and heartburn severity were correlated with changes in acid exposure ( r = 0.16, p = 0.12 and r = 0.26, p = 0.01, respectively). Changes in satisfaction were negatively correlated with changes in esophageal acid exposure ( r = 0.23, p = 0.02) because satisfaction, as expected, increased as acid exposure decreased.

Responders had significant improvement in esophageal acid exposure, whereas nonresponders had less or no change. There was a positive correlation between esophageal acid exposure and both GERD-HRQL and heartburn. This evidence suggests that symptomatic improvement after Stretta is attributable to a decrease in esophageal acid exposure and not to desensitization of the esophagus.

This report summarizes the conclusions and recommendations of a panel of gastroenterologists practising in the Asia-Pacific region. The group recognized that although gastroesophageal reflux disease (GERD) is less common and milder in endoscopic severity in Asia than in the West, there is nevertheless data to suggest an increasing frequency of the disease. During a 2-day workshop, the evidence for key issues in the diagnosis and clinical strategies for the management of the disease was evaluated, following which the recommendations were made and debated. The consensus report was presented at the Asia-Pacific Digestive Week 2003 in Singapore for ratification. Upper gastrointestinal (GI) endoscopy is the gold standard for the diagnosis of erosive GERD. There is no gold standard for the diagnosis of non-erosive GERD (NERD). Diagnosis therefore relies on symptoms, a positive 24-h pH study or a response to a course of proton pump inhibitor (PPI) treatment. The goals of treatment for GERD are to heal esophagitis, relieve symptoms, maintain the patient free of symptoms, improve quality of life and prevent complications. The PPI are the most effective medical treatment. Following initial treatment, on-demand therapy may be effective in some patients with NERD or mild (GI) erosive esophagitis. Anti-reflux surgery by a competent surgeon could achieve a similar outcome, although there is an operative mortality of 0.1-0.8%. The decision is dependent on the patient's preference and the availability of surgical expertise. Currently, endoscopic treatment should be performed only in the context of a clinical trial. Treatment of patients with typical GERD symptoms without alarm features in primary care could begin with PPI for 2 weeks followed by a further 4 weeks before going to on-demand therapy.

While medical therapy, particularly with proton pump inhibitors, is effective for the large majority of patients with reflux disease, there remains a subset of patients who are dissatisfied, due to cost, side effects of medications, or persistent symptoms such as regurgitation. For this population, surgical fundoplication has been, and remains, an appropriate option. A new class of endoluminal interventions, attempting to create a mechanical antireflux barrier, has emerged recently. Three such devices are currently approved and available, and a number of others are in various stages of evaluation. This article will review the approved technologies, as well as selected promising emerging ones. with particular emphasis on the scientific evidence available to date supporting their efficacy.