The comparative study of Stretta radiofrequency and anti-reflux mucosectomy in the management of intractable gastroesophageal reflux disease: a single-center retrospective study from South Korea
Article information
Abstract
Background/Aims
Chronic gastroesophageal reflux disease (GERD) requires symptom relief and treatment of associated conditions. In this study, we aimed to compare anti-reflux mucosectomy (ARMS) and Stretta radiofrequency (SRF) for treating patients with chronic GERD who are unresponsive to proton pump inhibitors (PPIs) and to identify the indications for each procedure.
Methods
Data of patients who underwent ARMS or SRF between March 2021 and April 2023 were analyzed. Changes in GERD questionnaire (GERDQ) scores, endoscopic Los Angeles (LA) grade, flap valve grade (FVG) based on Hill’s type, EndoFLIP distensibility index (DI), endoscopic Barrett’s epithelium (BE) resolution rate, and PPI withdrawal rate were compared between the two groups.
Results
Improvements in the GERDQ scores and PPI withdrawal rates were similar between the groups. The ARMS group showed significantly better changes in endoscopic LA grade, FVG, and EndoFLIP DI than the SRF group. The complications were more prevalent in the ARMS group than in the SRF group.
Conclusions
The change in endoscopic LA grade before and after the procedure was significantly higher in the ARMS group than in the SRF group. Significant improvements in endoscopic FVG, BE resolution, and EndoFLIP DI were observed only with the ARMS group.
INTRODUCTION
Gastroesophageal reflux disease (GERD) is characterized by the reflux of stomach contents, leading to troublesome symptoms and potential complications, such as reflux esophagitis, esophageal strictures, and esophageal adenocarcinomas, which significantly impair patients’ quality of life.1,2 Proton pump inhibitors (PPIs) are commonly used to treat GERD and are considered the cornerstone of therapy.3 However, relapse of symptoms occurs in 75% to 90% of patients after PPI discontinuation, and several patients require lifelong treatment, resulting in a substantial financial burden.4 Furthermore, long-term PPI use is associated with an increased risk of enteric infections, such as those caused by Clostridium difficile and Campylobacter, and community-acquired pneumonia.5,6
Considering these concerns, alternative treatments have been explored, including surgical fundoplication.7 However, this approach has several side effects.8 Although numerous procedures have been implemented, the response rates have been inconsistent and an optimal technique has not yet been established.7,9 Endoscopic anti-reflux mucosectomy (ARMS) and Stretta radiofrequency (SRF) are two such alternatives. ARMS, introduced in the mid-2000s, utilizes the endoscopic mucosal resection (EMR) technique to increase lower esophageal sphincter (LES) tone and alter the structure of the esophagogastric junction (EGJ), thereby possibly reducing transient LES relaxation (TLESRs) and esophageal acid exposure. By contrast, SRF, introduced in the late 1990s, applies radiofrequency (RF) to the muscularis propria of the EGJ, relieving its compliance and reducing LES relaxation, ultimately decreasing esophageal acid exposure.10-12
Previous studies comparing these two procedures have failed to provide clear indications and implications for each intervention in specific clinical settings.13 In this study, we aimed to provide a comprehensive comparison between ARMS and SRF, including changes in EndoFLIP (Medtronic) and resolution of endoscopic Barrett’s epithelium (BE), to distinguish between indications and facilitate their application in clinical settings.
METHODS
Study design
This single-center, retrospective observational study was conducted at the Gangnam CHA Medical Center, Seoul, Republic of Korea, between March 2021 and April 2023. The study included patients with refractory GERD who had previously responded to PPIs14 but later underwent SRF or ARMS. We collected data from electronic medical records, including patient demographics and clinical data before, during, and after the procedures. We also obtained patient responses through validated symptom surveys such as the GERD questionnaire (GERDQ).
Patients and eligibility criteria
Patients aged 19 to 75 years with a history of daily PPI use for at least six months and persistent GERD symptoms, with or without endoscopically confirmed reflux esophagitis, were included. Functional cases were excluded by comprehensively evaluating the EndoFLIP distensibility index (DI), past PPI responses, and endoscopic findings. Additionally, patients were excluded if they had untreated motility disorders, significant medical conditions (e.g., ischemic heart disease, chronic kidney disease, and cirrhosis), respiratory illnesses, substance abuse, pregnancy, psychiatric conditions, or contraindications to endoscopy.
Stretta radiofrequency
We followed the well-established procedure for SRF, as previously described.15 The procedure involves an initial endoscopy to gauge the distance from the bite block to the Z-line, followed by insertion of a coated guidewire into the stomach. The Stretta catheter was introduced transorally and guided by a wire and positioned 1.5> cm below the Z-line. Upon inflating the balloon to 17.2 kPa, the catheter’s needle electrodes are deployed into the gastroesophageal junction muscle and RF energy is applied for 60 seconds at 85 °C. This process is repeated by strategically repositioning the catheter to create a circumferential lesion. Then, “pull-back” lesions are created in a stepwise manner with the catheter moved in 0.5-cm increments, from 1.5 cm distal to 1 cm proximal to the EGJ. Finally, the catheter was pulled back, and RF energy was delivered to complete the treatment (Fig. 1).
(A) The procedure for anti-reflux mucosectomy. (B) The procedure for Stretta radiofrequency therapy.
Anti-reflux mucosectomy
ARMS begins with argon plasma coagulation (APC) to mark the intended area of mucosal reduction along the lesser curve of the gastric cardia. For resection, the cap-EMR method was employed, using a large hard cap and a thin-diameter crescent snare. Saline solution mixed with indigo carmine was injected into the submucosa for mucosal elevation. The mucosal area was removed piecemeal using the EndoCUT Q mode of the Erbe system (Erbe Elektromedizin GmbH). Any bleeding that occurred during the procedure was managed using APC (Fig. 1).
Pre- and post-assessment
GERD symptoms were assessed using the GERDQ score before and six months after the procedure. Comprehensive assessments, including EndoFLIP DI, endoscopic flap valve grade (FVG) based on Hill’s type, Barrett’s esophagus, and the Los Angeles (LA) classification, were performed before and six months post-procedure. FVG was graded from 1 to 4, corresponding to scores of 1 to 4 points, respectively. Similarly, the esophagogastroduodenoscopy (EGD) LA classification ranged from “normal” (score 0) to grade “D” (score 5). The GERDQ uses a 0 to 3 Likert scale to evaluate major GERD symptoms such as regurgitation, heartburn, and the use of over-the-counter medications. Conversely, it employs a reverse Likert scale (3–0) for symptoms such as nausea and epigastric pain, which may indicate the absence of GERD. EGD was performed the day after the procedure to assess potential complications or signs of bleeding.
Outcome measures
The primary outcome was improvement in the GERDQ score. Secondary outcomes included the rate of PPI discontinuation, differences in the GERDQ score, changes in the FVG, complications, resolution of endoscopic Barrett’s esophagus shifts in the LA classification, and differences in EndoFLIP DI.
Statistical analyses
Continuous data, given their skewed distribution, are presented as medians with interquartile ranges (IQRs). Group comparisons were performed using the Mann-Whitney U-test. Categorical data are expressed in percentages, and group differences were analyzed using either the χ2 or Fisher exact test. A p-value <0.05 was considered statistically significant.
Ethical statement
All procedures were conducted in accordance with the ethical standards of the Hospital Ethics Committee and Institutional Review Board of CHA University (approval number: GCI 2023-06-003). Given the retrospective study design, written informed consent was not required.
RESULTS
Patients’ demographic and clinical features
We retrospectively analyzed the data of 140 patients who underwent ARMS or SRF between March 2021 and April 2023. Of the 39 patients who underwent ARMS and 101 patients who underwent SRF, three and five, respectively, either did not undergo follow-up endoscopy or declined to complete the GERDQ, leaving 132 patients for analysis (Fig. 2). The median ages were 43.5 (IQR, 34.0–57.0) years in ARMS and 52.0 (IQR, 39.0–63.0) years in SRF, with SRF trending older than ARMS, although not statistically significant (p=0.08). Sex distribution significantly differed between the groups, with 25.0% female in the ARMS group and 56.3% female in the SRF group (p=0.001).
Patient screening. GERD, gastroesophageal reflux disease; ARMS, anti-reflux mucosectomy; GERDQ, gastroesophageal reflux disease questionnaire; SRF, Stretta radiofrequency.
In the objective tests for GERD, the two groups showed a significant difference in endoscopic reflux esophagitis (p=0.009), with the ARMS group having more severe symptoms than the RFS group. In the ARMS group, 0.0%, 50.0%, 25.0%, 22.2%, 0.0%, and 2.8% of the patients had normal, minimal, grades A, B, C, and D endoscopic reflux esophagitis, respectively. In the SRF group, 5.2%, 65.6%, 24.0%, 4.2%, 1.0%, and 0.0% of the patients had normal, minimal, grades A, B, C, and D endoscopic reflux esophagitis, respectively. Additionally, a significant difference was observed in basal Hill’s FVG, with 2.8% normal, 19.4% grade I, 30.6% grade II, 27.8% grade III, and 19.4% grade IV FVGs in the ARMS group and 1.0% normal, 66.7% grade I, 30.2% grade II, 2.1% grade III, and 1.0% grade IV FVGs in the SRF group (p<0.001). However, no significant differences were noted in other parameters, such as the GERDQ score (p=0.20), basal integrated relaxation pressure (p=0.35), basal LES (p=0.44), EndoFLIP DI (p=0.29), DeMeester score (p=0.28), basal number of reflux (p=0.52), basal number of acid reflux (p=0.25), and Barrett’s esophagus (p=0.28) (Table 1).
Patient demographics and peri-procedure characteristics
Clinical outcomes
Both the ARMS and SRF demonstrated a 100% technical success rate. Symptomatic improvement was observed in 34 (94.4%) and 92 (95.8%) patients undergoing ARMS and SRF, respectively (p=0.73) (Table 2). The change in the GERDQ scores before and after the procedure showed significant improvement in both groups. In the ARMS group, the median GERDQ score improved from 10.0 (IQR, 8.0–10.5) pre-procedure to 4.5 (IQR, 3.0–6.0) points post-procedure (p<0.001). In the SRF group, the score improved from 10.0 (IQR, 8.0–11.0) pre-procedure to 6.0 (IQR, 4.0–7.0) points post-procedure (p=0.001). The changes in GERDQ score pre- and post-procedure were 4.0 (IQR, 3.0–6.0) in the ARMS group and 4.0 (IQR 2.0–6.0) points in the SRF group (p=0.238), showing no clear difference between the two groups (Fig. 3).
Technical and clinical outcomes in ARMS and SRF
Comparison of the Gastroesophageal Reflux Disease questionnaire (GERDQ) scores before and after treatment using two procedures: anti-reflux mucosectomy (ARMS) and Stretta radiofrequency (SRF). Both the ARMS and SRF groups showed significant improvements in GERDQ scores post-treatment (ARMS, p<0.001; SRF, p=0.001), and no significant difference was observed in the degree of improvement between the two groups (p=0.238).
ARMS was significantly more effective than SRF in im proving endoscopic esophagitis, with 22 (61.1%) patients in the ARMS group showing improvement compared to 34 (35.4%) patients in the SRF group (p=0.008). Reflux esophagitis was effectively treated in both groups, with the median LA grade scores improving from 1.5 (IQR, 1–2.8) to 1 (IQR, 0–1) (p=0.001) in the ARMS group and from 1 (IQR, 1–2) to 1 (IQR, 1–1) (p=0.001) in the SRF group. However, the median change in the LA grade scores was significantly greater in the ARMS group (1 [IQR, 0–1]) than in the SRF group (0 [IQR, 0–1]) (p=0.019). Regarding endoscopic FVG, 27 (75.0%) patients undergoing ARMS showed improvement compared to 16 (16.7%) patients undergoing SRF (p<0.001). The median pre- and post-procedure FVG scores in the ARMS group improved from 2 (IQR, 2–3) to 1 (IQR, 1–2) (p<0.001), whereas those in the SRF group remained the same at 1 (IQR, 1–2) (p=0.544). The median change in FVG scores was also significantly greater in the ARMS group (1 [IQR, 0.25–2]) compared with the SRF group (0 [IQR, 0–0]) (p<0.001). For the EndoFLIP DI, the median pre- and post-procedure values in the SRF group improved from 4.2 (IQR, 3.5–4.9) to 3.4 (IQR, 2.9–4.6) (p=0.243), whereas in the ARMS group, they improved from 6.9 (IQR, 5.1–7.9) to 3.8 (IQR, 3.3–4.8) (p=0.025). However, the number of patients who showed improvement was not significantly different between the two groups: 11 (30.6%) in the ARMS group and 10 (10.4%) in the SRF group (p=0.45). The median change in EndoFLIP DI was also greater in the ARMS group (3.4 [IQR, 2.7–3.7]) compared with the SRF group (0.8 [IQR, –0.6 to 2.4]), although the difference was not significant (p=0.184) (Table 2, Fig. 4).
Comparative analysis of anti-reflux mucosectomy (ARMS) and Stretta radiofrequency (SRF). (A) Comparison in improving endoscopic esophagitis (p=0.019). (B) Differences in improving flap valve grade (FVG) (p<0.001). (C) A significant improvement in the EndoFLIP distensibility index (DI) pre- and post-procedure was observed in the ARMS group (p=0.025).
Additionally, a subgroup analysis based on the endoscopic LA grade and FVG was performed. In the subgroup with a lower endoscopic LA grade (normal, minimal, A), ARMS showed a significantly higher rate of endoscopic FVG improvement than SRF (44.4% vs. 3.3%, p<0.001). Although the rate of improvement in endoscopic esophagitis was higher in the ARMS group, this difference was not statistically significant (48.1% vs. 31.9%, p=0.12). Similarly, in the subgroup with a higher endoscopic LA grade (B, C), the ARMS group exhibited a higher rate of FVG improvement (88.9% vs. 40.0%, p=0.05).
Within the lower FVG group (FVG=0, 1, 2), the ARMS group demonstrated significantly greater endoscopic FVG improvement than the SRF group (52.6% vs. 14.0%, p<0.001), with a trend toward higher endoscopic esophagitis improvement in the ARMS group (57.9% vs. 34.4%, p=0.06). In the higher FVG group (FVG=3, 4), both the ARMS and SRF groups showed 100% improvement in endoscopic FVG, with a higher rate of endoscopic esophagitis improvement observed in the ARMS group (64.7% vs. 33.3%, p=0.31) (Table 3).
Subgroup analysis of clinical outcomes in ARMS and SRF groups based on higher vs. lower grades of LA and FVG
Moreover, ARMS led to a significant improvement in BE, as observed in endoscopic examinations, with six out of 36 (16.7%) patients in the ARMS group showing improvement compared to two out of 95 (2.1%) patients in the SRF group (p=0.006). More specifically, in the ARMS group, all six patients experienced resolution of BE on endoscopy, whereas in the SRF group, two out of five patients showed resolution. PPI withdrawal rates were comparable between the two groups, with 60.0% of patients in the ARMS group and 58.9% of patients in the SRF group successfully discontinuing PPIs (p=0.91) (Table 2, Fig. 4).
Regarding adverse effects, bleeding was reported in 25.0% of patients in the ARMS group, whereas no cases were reported in the SRF group (p<0.001). Strictures were observed in 2.8% of the patients in the ARMS group and in 0.0% of the patients in the SRF group (p=0.10) (Table 2).
DISCUSSION
This retrospective cohort study comprehensively evaluated objective measures, including the EndoFLIP DI. To date, no study has been assessing the EndoFLIP DI in the evaluation of GERD treatments. In the baseline evaluation, the GERDQ scores were not significantly different between the two groups. However, the ARMS group included patients with statistically more severe conditions, as indicated by objective measurements, such as the endoscopic LA grade, Hill’s type FVG, and EndoFLIP DI. Nonetheless, no significant difference was observed in the severity between the two groups based on the basal 24-hour pH impedance test (p=0.28). Regarding clinical outcomes, the proportion of patients experiencing symptomatic improvement as measured by the GERDQ score and the extent of this improvement were similar between the two groups. PPI withdrawal rates were also comparable. However, complications such as bleeding and strictures were significantly more frequent in the ARMS group than in the SRF group. Bleeding was effectively controlled on the next day with APC, with no post-discharge issues. A single case of stricture caused by the broad extent of the procedure was successfully treated with two balloon dilations, as reported in previous studies,16,17 and was not considered clinically significant.
Consequently, for patients with clear symptoms of GERD but no evident deterioration observed through endoscopy or EndoFLIP, particularly in cases of non-erosive reflux disease (NERD) that might not be accurately captured by the GERDQ score—and especially for elderly patients taking medications with a risk of bleeding—SRF should be considered over ARMS.
Significant differences in the endoscopic LA classification and basal Hill’s FVG were observed between the ARMS and SRF groups. Post-procedure, both groups showed improvement in the endoscopic LA grade, with greater improvement in the ARMS group (p=0.02). However, the subgroup analysis revealed only trends rather than significant differences. Although significant FVG improvements were observed in the ARMS group, the differences between the groups were not significant in the higher-grade LA and FVG subgroups.
In treating GERD, the objective is not only to achieve symptomatic relief, but also to prevent progression to dysplasia, which can result from the chronic effects of GERD.18,19 BE is a premalignant condition that arises secondary to severe chronic GERD20 and has the potential for cancer progression. Although ARMS can directly resolve BE, as observed through endoscopy, significantly reducing Hill’s FVG is crucial for preventing future risk factors associated with BE.21 Our study found no significant difference between SRF and ARMS in symptomatic improvement, but ARMS resulted in substantial improvements in BE, the extent of reflux esophagitis, which can lead to dysplasia if prolonged, and FVG compared with SRF. In particular, ARMS is the preferred option for patients presenting with high-grade endoscopic LA, hiatal hernia, or Barrett’s esophagus.
Understanding the pathophysiology of GERD is essential to determine the optimal treatment for these patients. Constantly low LES pressure,22 increased number of TLESRs by interrupting the vagal neural pathway, acid pocket, hiatal hernia, and mitigated hypersensitivity caused by dilated intercellular spaces may be responsible23; however, each mechanism is not clearly associated with symptoms and objective examination, including endoscopic findings. SRF reduces TLESRs through neural pathway damage, LES scarring, mechanical alteration of the EGJ, and normalization of delayed gastric emptying.11 ARMS reduces hiatal hernia through LES tone-scarring fibrosis. However, it is likely that other mechanisms are also at play; otherwise, ARMS would not have achieved comparable results to SRF in alleviating GERD symptoms. Further studies are necessary to fully understand these pathophysiological mechanisms and guide the choice of treatment, as the complex nature of GERD often requires individualized therapy.
From a technical standpoint, SRF requires specific equipment and is expensive; however, the protocol for SRF is well established, making it accessible without a significant learning curve. Nevertheless, the range of ARMS procedures, along with their associated side effects and outcomes, have not been fully established, and the procedure requires a degree of proficiency. Both SRF and ARMS have limitations in terms of cost and potential adverse events owing to scarring and fibrosis. Further studies are required to investigate the efficacy of secondary procedures after SRF and ARMS.
The implication of the findings of this study is that by comparing the effects of anti-reflux ablation therapy and ARMS, we can better identify the primary applications of each procedure. Although no significant difference was reported between the two groups in terms of symptoms, ARMS was superior in improving reflux esophagitis and FVG. Thus, ARMS may be considered the preferred treatment option for patients with NERD who have poor endoscopic findings in preference to SRF.
A limitation of this study was the smaller number of patients in the ARMS group than in the SRF group. However, the sample size was statistically sufficient for a comparison between the two groups. In some patients, baseline high-resolution manometry and 24-hour pH impedance data, and post-procedure results were limited. Nevertheless, we believe that data on symptoms and objective endoscopic indicators, which are crucial for GERD, are sufficient for comprehensive evaluation. Despite baseline differences in the endoscopic LA grade and FVG between the groups, a subgroup analysis was conducted. However, larger cohort studies are required to better balance the number of patients in each subgroup.
In conclusion, both SRF and ARMS led to similar improvements in the GERDQ scores and PPI withdrawal rates. However, ARMS is associated with a higher incidence of complications such as bleeding than SRF. Moreover, ARMS demonstrates significant improvements in endoscopic LA grade, FVG, Barrett’s esophagus resolution, and EndoFLIP DI.
Notes
Conflicts of Interest
The authors have no potential conflicts of interest.
Funding
None.
Author Contributions
Conceptualization: JoYC; Formal analysis: AYL; Methodology: JWC, JHH, JuYC; Writing–original draft: AYL; Writing–review & editing: all authors.