INTRODUCTION — Standard therapy for gastroesophageal reflux disease (GERD) involves behavioral modifications and treatment with medications that reduce acid production or improve esophageal motility. Open or laparoscopic Nissen fundoplication may be chosen for those patients who do not wish to remain on an antisecretory medication, have an inadequate response to antisecretory medication, have a large hiatal hernia, or have persistence of esophagitis on medication. Esophagitis and GERD symptoms are improved or resolved after fundoplication in 76 to 98 percent of patients, while esophageal acid exposure time is normalized in approximately 90 percent of patients. (See "Surgical management of gastroesophageal reflux in adults".)
Minimally invasive alternatives to standard antireflux surgery have been developed, including the application of controlled radiofrequency (RF) energy to the lower esophageal sphincter region (Stretta procedure) [1]. An advantage of RF treatment is that it can be used in patients with challenging anatomy [2]. The Stretta system was approved by the United States Food and Drug Administration in 2000.
This topic review will provide an overview of radiofrequency treatment for GERD. Medical and surgical treatments for GERD are discussed separately. (See "Medical management of gastroesophageal reflux disease in adults" and "Surgical management of gastroesophageal reflux in adults".)
RATIONALE — Radiofrequency (RF) energy induces collagen contraction and has been shown to have therapeutic benefits in patients with cardiac arrhythmias, joint laxity, benign prostatic hyperplasia, and sleep-disordered breathing. Although the precise mechanisms of benefit in gastroesophageal reflux disease (GERD) are unclear, RF treatment appears to reduce postprandial transient lower esophageal sphincter relaxations and decrease compliance of the gastroesophageal junction, may decrease esophageal acid sensitivity by inducing healing of esophageal erosive disease, and may improve gastroparesis [2-4]. (See "Pathophysiology of reflux esophagitis", section on 'Transient lower esophageal sphincter relaxations'.)
One theory is that RF treatment improves symptoms of GERD through radiofrequency ablation of sensory neurons of the distal esophagus, leading to hyposensitization without an effect on pH. In a study of 13 patients undergoing pH monitoring and Bernstein acid perfusion testing, esophageal acid sensitivity was decreased six months after RF treatment [3]. However, this hypothesis was not supported in a report of 118 patients examining the relationship between symptom improvement (GERD-health-related quality of life [HRQL] and heartburn scores, general satisfaction, daily proton pump inhibitor [PPI] use) and intraesophageal acid exposure (percent proximal and distal esophageal time with pH <4.0) six months after RF treatment [5]. Responders to RF treatment had significant improvements in both proximal and distal acid exposure times. By contrast, non-responders had either no improvement or less improvement in proximal and distal acid exposure times. Changes in GERD-HRQL and heartburn severity positively correlated with changes in acid exposure.
In a sham-controlled study, RF treatment improved GERD symptoms and decreased gastroesophageal junction (GEJ) compliance three months after the initial procedure. In this trial, the administration of sildenafil, an esophageal smooth muscle relaxant, normalized GEJ compliance again to pre-procedure levels, arguing against GEJ fibrosis as the underlying mechanism. Decreased GEJ compliance, which reflects altered lower esophageal sphincter neuromuscular function, may contribute to the symptomatic benefit of RF treatment by decreasing refluxate volume. The study was limited because it did not include impedance monitoring [4].
Delayed gastric emptying (gastroparesis) may be associated with severe reflux. In a small cohort study, RF treatment was shown to correct gastroparesis and improve symptoms. Of 31 patients treated, 23 patients (74 percent) normalized gastric emptying, while all patients had significant improvements in GERD-HRQL at one-year symptom assessment. The mechanism of action remains unknown [6].
PATIENT SELECTION
Good candidates — Ideal candidates for radiofrequency (RF) treatment are those who:
●Suffer from frequent heartburn, regurgitation, or both.
●Have adequate esophageal peristalsis and normal relaxation of the lower esophageal sphincter (ie, patients with features of achalasia are not candidates for RF treatment) (see "Achalasia: Pathogenesis, clinical manifestations, and diagnosis").
●Have a 24-hour pH study demonstrating pathologic acid reflux (total acid exposure time greater than 4 percent, or a DeMeester composite score >14.7).
●Have nonerosive reflux disease, have grade I or II esophagitis by Savary-Miller criteria (or LA Grade A or B), or have higher grades of esophagitis healed by drug therapy (see "Clinical manifestations and diagnosis of gastroesophageal reflux in adults", section on 'Endoscopic findings').
●Have unsatisfactory control of GERD despite high dose proton pump inhibitor (PPI) therapy (ie, typically, twice daily dosing).
In addition, patients may be offered RF therapy if they do not wish to be on long-term medical treatment for GERD. The Society of American Gastrointestinal and Endoscopic Surgeons considers RF treatment an appropriate therapy for patients being treated for GERD who are 18 years of age or older; who have had symptoms of heartburn, regurgitation, or both for six months or more; and who have been partially or completely responsive to antisecretory pharmacologic therapy [7].
Contraindications — Patients are not good candidates for RF therapy if they have any of the following:
●More than 3 cm long hiatal hernia detected endoscopically or radiographically
●Significant dysphagia
●Grade III or IV esophagitis by Savary-Miller criteria that has not been healed after two months of medical therapy
●Inadequate esophageal peristalsis and incomplete lower esophageal sphincter relaxation in response to a swallow
TECHNIQUE — Radiofrequency (RF) treatment for GERD is performed endoscopically (picture 1). The four-channel radiofrequency generator and catheter system delivers pure sine-wave energy (465 kHz, 2 to 5 watts per channel, 80 volts maximum at 100 to 800 ohms). Each needle tip incorporates a thermocouple that automatically modulates power output to maintain a desired target (muscle) tissue temperature. Maintaining lesion temperatures below 100°C minimizes the collateral tissue damage due to vaporization and high impedance values. Temperature is similarly monitored with a thermocouple at each needle base, and power delivery ceases if the mucosal temperature exceeds 47°C.
Patients are prepared in a manner similar to that for standard esophagogastroduodenoscopy (EGD). Intravenous access is obtained, and heart rate, blood pressure, and oxygen saturation are monitored. Patients typically require high doses of midazolam (5 to 7 mg) and either fentanyl (100 to 150 mcg) or meperidine (100 to 125 mg) during treatment. There is mild discomfort due to catheter passage in 25 percent of cases; mild-to-moderate discomfort is also experienced with RF delivery in 50 to 70 percent of cases. In those cases, additional medication is generally provided. Alternatively, intravenous propofol may be used. (See "Anesthesia for gastrointestinal endoscopy in adults".)
An esophagogastroduodenoscopy (EGD) is then performed, and the distance from the incisors to the squamocolumnar junction (z-line) is measured. The endoscope is removed, and the RF catheter is passed transorally and positioned 2 cm above the z-line according to the distance measured during EGD (figure 1 and figure 2). The four needle electrodes are deployed to a preset length of 5.5 mm, and RF delivery is commenced. Each electrode delivers RF energy for 90 seconds to achieve a target temperature of 85°C. Additional lesion sets are created by rotating and changing the linear position of the catheter to create several rings of lesions 2 cm above and below cardia. The catheter is then removed and the EGD repeated. Patients receive 56 lesions placed over a period of 35 minutes (figure 3 and figure 4).
EFFICACY
Overall results — Multiple studies have examined the efficacy of radiofrequency (RF) treatment for gastroesophageal reflux disease (GERD). Overall, 55 to 83 percent patients have reported satisfactory symptom control or cessation of proton pump inhibitor (PPI) use in studies with follow-up intervals ranging from approximately 6 to 33 months [8-14].
In a systematic review and meta-analysis of 28 studies of over 2400 patients with GERD, scores for health-related quality of life and heartburn were improved in patients who underwent radiofrequency treatment (Stretta) compared with patients in a sham treatment group [15]. The rate of PPI use was lower in patients who underwent radiofrequency treatment compared with rate of preprocedure PPI use (49 versus 97 percent). Radiofrequency treatment reduced esophageal acid exposure, but it did not significantly improve LES basal pressure.
The efficacy of RF treatment was also examined in a meta-analysis of 18 randomized trials, cohort studies, and reviews with 1441 patients performed over a 10-year span [16]. RF treatment improved heartburn scores (decrease in mean heartburn score in the pooled analysis from 3.55 to 1.19) and quality of life. Esophageal acid exposure was lower following the procedure compared with baseline (DeMeester score of 28.5 versus 44.4) but did not normalize. There was also a trend toward improved lower esophageal sphincter pressure. In a subsequent meta-analysis of 10 trials including 516 patients with GERD, radiofrequency treatment resulted in greater improvement in health-related quality of life (HRQL) and heartburn scores compared with PPI [17]. Compared with transoral incisionless fundoplication (TIF), radiofrequency treatment resulted in greater reduction in esophageal acid exposure but was less effective at increasing LES pressure.
Long-term studies — Studies with long-term follow-up have found radiofrequency treatment to be effective [18-21]. The durability of radiofrequency treatment was assessed in 26 patients who were followed for eight years [18]. At eight years, 77 percent of patients were completely off PPIs [18]. In a study with 217 patients with refractory GERD who underwent RF treatment, normalization of GERD health-related quality of life (the primary outcome) was seen in 72 percent of patients at 10 years [19]. Secondary outcomes were 50 percent reduction or elimination of PPIs, and 60 percent or greater improvement in satisfaction at 10 years. A 50 percent or greater reduction in PPI use occurred in 64 percent of patients (41 percent eliminating PPIs entirely), and a 60 percent or greater increase in satisfaction occurred in 54 percent of patients [19]. A prospective study evaluated the outcomes of 138 patients with refractory GERD who were followed for five years after RF treatment [20]. At the end of the five-year follow-up, all symptom scores (heartburn, regurgitation, chest pain, cough, and asthma) had decreased. In addition, 59 patients (43 percent) achieved complete PPI therapy independence, and 104 patients (75 percent) were completely or partially satisfied with their GERD symptom control [20]. In a case series including 50 patients who were followed for a median of 771 days, radiofrequency treatment was associated with improvement in post-procedure GERD-HRQL scores [21].
Comparison with surgical treatment — Studies have compared RF treatment with fundoplication for the treatment of GERD with variable results:
●One group stratified patients to either endoscopic therapy or laparoscopic fundoplication [9,22,23]. Patients were offered RF treatment if they did not have a hiatal hernia greater than 2 cm, had a lower esophageal pressure of at least 8 mmHg, and did not have Barrett's esophagus. At six months, the quality of life scores were similar in both groups, and both groups were satisfied with their procedures (89 percent of RF treated patients and 96 percent of fundoplication patients). Fifty-eight percent of RF patients and 97 percent of fundoplication patients were off of proton pump inhibitors (PPI) and an additional 31 percent of RF patients had reduced their PPI dose significantly. The mean hospital cost for RF treatment was $1808, whereas it was $5715 for fundoplication.
●In a non-randomized cohort of 32 patients referred to a surgical practice who underwent RF treatment with an average follow-up of 53 months, 19 patients (59 percent) subsequently required anti-reflux surgery [24]. Those not undergoing surgery showed a significant improvement in their GERD satisfaction scores from 3.1 to 1.5, but had significantly lower pre-procedure heartburn scores (2.4) than those who proceeded to surgery. The RF treatment was effective in reducing symptoms in 40 percent of patients.
●A non-randomized study prospectively evaluated outcomes of 215 patients with refractory GERD five years after laparoscopic Nissen fundoplication (LNF) or RF treatment [25]. At the end of the five-year follow-up, the post-treatment symptoms scores for regurgitation, heartburn, chest pain, belching, hiccup, cough, and asthma were lower compared with the pre-treatment scores in both groups. However, the symptom improvements after RF treatment were lower than those after LNF. After LNF, 81 patients (91 percent) achieved complete PPI therapy independence, compared with 47 patients (51 percent) after RF treatment.
●In an observational study including 226 patients with GERD, there were no significant differences in acid exposure time at one year following radiofrequency treatment (Stretta) compared with Toupet fundoplication [26]. However, radiofrequency treatment was associated with higher post-procedure DeMeester score and lower LES pressure compared with fundoplication.
Patients with elevated body mass index — Patients with obesity (ie, body mass index [BMI] >30 kg/m2) are often not ideal candidates for fundoplication and are at increased risk of failure after antireflux surgery [27,28]. RF treatment has been effective in improving GERD in selected patients with elevated BMI [29]. Following RF treatment, 6 of 10 patients reported having no or very mild symptoms. Since obesity is a preoperative predictor of failure after antireflux surgery, RF treatment can provide a safe means of improving GERD symptoms for some patients with GERD refractory to medical therapy. In a retrospective study of 12 consecutive patients with mean BMI 38.6 and GERD who were undergoing RF treatment with a mean follow-up of 1.5 years, there were fewer patients on PPI medications after the procedure than before (45 versus 81 percent, p = 0.1) [12].
Patients with gastric surgery — Limited data suggest that radiofrequency treatment (Stretta) may benefit patients with GERD and a history of gastric surgery. In a database study, 11 patients with GERD and previous gastric surgery who had radiofrequency treatment were identified. After a median follow-up of 23 months, radiofrequency treatment was associated with improved GERD-HRQL scores in nine patients (82 percent) [30].
Patients with reflux after fundoplication — Patients with refractory GERD after laparoscopic fundoplication may undergo radiofrequency treatment (Stretta) to ameliorate symptoms and reduce medication requirements. In a study of 18 patients with refractory symptoms after Nissen fundoplication, radiofrequency treatment improved GERD-health related quality of life, patient satisfaction, and reduced medication use during follow-up of up to 10 years [31].
Limited data have suggested that performing radiofrequency treatment after transoral incisionless fundoplication was feasible, safe, and associated with symptomatic improvement [32].
Patients after lung transplantation — For patients who had lung transplantation, limited data suggested that radiofrequency treatment was not associated with improvements in acid reflux parameters or LES pressure [33]. (See "Physiologic changes following lung transplantation", section on 'Oropharyngeal dysphagia, gastroesophageal reflux, and gastroparesis'.)
COMPLICATIONS — Radiofrequency (RF) treatment has a track record of successful clinical outcomes, and post-marketing experience has supported a generally good safety profile. However, serious complications have been described, including esophageal perforation in four patients and two deaths due to aspiration pneumonia [34]. The perforations were attributed to either poor patient selection or operator error.
In a meta-analysis of 26 studies of over 2400 patients with GERD, the rate of adverse events associated with the radiofrequency procedure was 0.9 percent, and the most common adverse events were small erosions and mucosal lacerations, which both occurred in less than one percent of patients [15].
In a literature review of endoscopic therapies for gastroesophageal reflux disease, the most common complications were transient epigastric pain (66 percent), chest pain (15 percent), esophageal ulceration (4 percent), and dysphagia or odynophagia (3 percent) [35].
COST-EFFECTIVENESS — Long-term follow-up with radiofrequency (RF) treatment in large groups of patients with gastroesophageal reflux disease (GERD) suggests that RF treatment has favorable characteristics in terms of ease of use, efficacy, and cost [36].
To evaluate the cost-effectiveness of RF treatment compared with competing strategies in the long-term management of GERD in Canada, a Markov model was designed to estimate health outcomes and costs from a Ministry of Health perspective over five years [37]. Strategies included the use of a daily proton pump inhibitor (PPI), laparoscopic Nissen fundoplication (LNF), and RF treatment using the RF treatment procedure. If symptom-free months were used as the measure of effectiveness, PPIs dominated both RF treatment and LNF strategies. If quality-of-life years were used, PPIs still presented the lowest cost, but LNF had the highest efficacy.
A second study sought to estimate the cost-effectiveness of PPI therapy, transoral incisionless fundoplication, RF treatment, and LNF for patients with GERD using a Markov model generated from the payer's perspective using a six-month cycle and 30-year time horizon [38]. Low-cost PPIs, RF treatment, and LNF were all cost-effective treatment strategies.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Gastroesophageal reflux in adults".)
SUMMARY AND RECOMMENDATIONS
●Radiofrequency (RF) treatment of the gastroesophageal junction may act by reducing postprandial transient lower esophageal sphincter relaxations, decreasing compliance of the gastroesophageal junction, decreasing esophageal acid sensitivity, and improving gastroparesis. (See 'Rationale' above.)
●Patients who are candidates for RF treatment include those with daily heartburn or regurgitation who exhibit inadequate or partial symptom response to antisecretory therapy. This treatment can also be an option for those who wish to discontinue the long-term use of drugs, for those who cannot tolerate drug therapy, and for those patients who are considering fundoplication. However, RF treatment has only been evaluated in patients without large (>3 cm) hiatal hernias or Barrett esophagus and who have normal esophageal peristalsis and lower esophageal sphincter relaxation. (See 'Patient selection' above.)
●Overall, 55 to 83 percent patients who had radiofrequency treatment have reported satisfactory symptom control or cessation of proton pump inhibitor use in studies with average follow-up periods of 6 to 33 months. (See 'Efficacy' above.)
●The rate of adverse events associated with radiofrequency treatment is 0.9 percent, and the most common adverse events are small erosions and mucosal lacerations. However, rare serious complications have also been described including esophageal perforation and death due to aspiration pneumonia. (See 'Complications' above.)
