Jiang WJ, Liu J, Liu YL, Tang MD, Sheng Y, Wang YT. Anti-reflux mucosectomy is associated with better short-term symptoms than double-dose proton pump inhibitor in reflux esophagitis patients. World J Gastrointest Surg 2026; 18(6): 119941 [DOI: 10.4240/wjgs.119941]
Corresponding Author of This Article
Ye-Tao Wang, MD, Chief Physician, Department of Gastroenterology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, No. 17 Lujiang Road, Hefei 230001, Anhui Province, China. wangyt96@163.com
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Jiang WJ, Liu J, Liu YL, Tang MD, Sheng Y, Wang YT. Anti-reflux mucosectomy is associated with better short-term symptoms than double-dose proton pump inhibitor in reflux esophagitis patients. World J Gastrointest Surg 2026; 18(6): 119941 [DOI: 10.4240/wjgs.119941]
Wen-Jun Jiang, Jie Liu, Ying-Ling Liu, Meng-Die Tang, Yuan Sheng, Ye-Tao Wang, Department of Gastroenterology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
Author contributions: Jiang WJ and Liu J drafted the original manuscript; Liu YL conducted and Tang MD conducted the gastroscopy; Sheng Y and Wang YT supervised the study and made critical revisions; Wang YT conceptualized, designed, supervised the study and made critical revisions; Jiang WJ and Liu J contributed equally for the study completion and manuscript writing, they were listed as co-first authors; all authors prepared the final draft and approved the final version.
Supported by the Scientific Research Plan Project of Universities in Anhui Province, No. 2024AH052045.
Institutional review board statement: This study received approval from the Ethics Committee of Anhui Provincial Hospital, No. XJS2022-2-18(NK).
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.
Data sharing statement: Data, analytic methods, and study materials are available to other researchers upon request to the corresponding author.
Corresponding author: Ye-Tao Wang, MD, Chief Physician, Department of Gastroenterology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, No. 17 Lujiang Road, Hefei 230001, Anhui Province, China. wangyt96@163.com
Received: February 11, 2026 Revised: March 11, 2026 Accepted: April 3, 2026 Published online: June 27, 2026 Processing time: 134 Days and 2.2 Hours
Abstract
BACKGROUND
Anti-reflux mucosectomy (ARMS) has been introduced as a therapeutic approach for patients with gastroesophageal reflux disease (GERD) refractory to proton pump inhibitor (PPI) therapy.
AIM
To assess the safety, feasibility, and efficacy of ARMS in comparison to double-dose PPI treatment.
METHODS
A retrospective cohort study was conducted at Anhui Provincial Hospital utilizing collected data from March 2023 to January 2026. The study population comprised patients with refractory reflux esophagitis who had previously received single-dose PPI therapy. Participants were categorized into two groups based on the treatment modality: The ARMS group and the double-dose PPI group. Therapeutic efficacy was evaluated by comparing differences in clinical outcomes, including scores from the GERD health-related quality of life (GERD-HRQL) questionnaire, the GERD questionnaire (GERDQ), the reflux disease questionnaire (RDQ), and the reflux symptom index (RSI) between the two groups.
RESULTS
A total of 28 patients with reflux esophagitis were allocated to either the ARMS or double-dose PPI group according to their treatment. Regarding quality of life outcomes, patients undergoing ARMS showed statistically significant improvements in RSI, GERDQ, RDQ, and GERD-HRQL scores at both 3 weeks and 3 months post-treatment compared to those receiving double-dose PPI therapy (all P values < 0.010). The ARMS group demonstrated an operative time of 31.71 ± 6.94 minutes, slight blood loss, short length of hospital stays, and low pain scores at discharge. Additionally, this group exhibited a 0% complication rate within 3 months post-procedure.
CONCLUSION
This pilot study provides preliminary evidence that ARMS may represent a promising endoscopic option for selected patients with refractory reflux esophagitis, though larger prospective studies are needed to confirm its efficacy and safety.
Core Tip: Anti-reflux mucosectomy (ARMS) is an innovative endoscopic technique developed for the management of refractory gastroesophageal reflux disease. The procedure aims to induce submucosal fibrosis following mucosectomy at the esophagogastric junction, offering the advantage of a minimally invasive endoscopic approach. Since its inception, multiple prospective and retrospective studies have been conducted to evaluate the clinical outcomes associated with ARMS. In this context, we present the findings of a retrospective cohort study comparing the efficacy of ARMS to twice-daily proton pump inhibitor (PPI) therapy in a well-defined population of patients exhibiting moderate-to-severe regurgitation despite once-daily PPI treatment.
Citation: Jiang WJ, Liu J, Liu YL, Tang MD, Sheng Y, Wang YT. Anti-reflux mucosectomy is associated with better short-term symptoms than double-dose proton pump inhibitor in reflux esophagitis patients. World J Gastrointest Surg 2026; 18(6): 119941
Gastroesophageal reflux disease (GERD) is among the most prevalent disorders affecting the foregut, impacting approximately 20%-30% of the population in the United States and imposing considerable economic burdens[1]. The pathophysiology of GERD is generally regarded as multifactorial, involving factors such as elevated intra-abdominal pressure, alterations in the crural diaphragm aperture and lower esophageal sphincter (LES) dysfunction, with transient LES relaxation identified as a critical mechanism[2]. Although GERD is commonly managed through lifestyle interventions and pharmacological therapies. Moreover, prolonged proton pump inhibitors (PPIs) use has been associated with adverse effects[3,4].
Current standard medical guidelines, as endorsed by leading gastroenterology organizations, recommend PPIs as the first-line treatment for problematic symptoms associated with GERD and erosive esophagitis[5,6]. PPIs function by suppressing gastric acid secretion, which frequently results in the alleviation of heartburn and promotes healing of esophageal mucosal injury. Nonetheless, PPIs do not exert a direct effect on LES function and are limited in their ability to prevent the reflux of gastric contents into the esophagus[7]. Consequently, PPI therapy often fails to adequately control regurgitation, demonstrating only a modest therapeutic benefit of approximately 17% compared to placebo[8]. Despite this, the clinical practice of escalating PPI dosages to manage persistent regurgitation remains prevalent, even among patients who do not respond to standard once-daily PPI regimens[9]. In contrast, surgical intervention for GERD addresses the underlying sphincter dysfunction and substantially decreases the frequency of reflux episodes, rather than solely reducing the acidity of the refluxate[10]. Therefore, surgical treatment is highly effective in managing regurgitative symptoms.
Anti-reflux mucosectomy (ARMS) is an innovative endoscopic technique developed for the management of refractory GERD, initially described by Inoue et al[11]. The procedure aims to induce submucosal fibrosis following mucosectomy at the esophagogastric junction, offering the advantage of a minimally invasive endoscopic approach. Since its inception, multiple prospective and retrospective studies have been conducted to evaluate the clinical outcomes associated with ARMS. In this context, we present the findings of a retrospective cohort study comparing the efficacy of ARMS to twice-daily PPI therapy in a well-defined population of patients exhibiting moderate-to-severe regurgitation despite once-daily PPI treatment.
MATERIALS AND METHODS
Study design
A retrospective cohort study was conducted from March 2023 to January 2026. Patients were consecutively enrolled and were allocated based on shared decision-making between patient preference and physician recommendation after discussion of risks and benefits. The study enrolled 28 patients (16 females and 12 males) diagnosed with refractory reflux esophagitis (RE). All participants had previously undergone conservative treatment with single-dose PPI therapy, which failed to alleviate GERD-related symptoms. Prior to inclusion, all patients completed gastroscopic examinations confirming RE graded A to D. Symptom assessment was conducted at baseline and upon treatment completion or discontinuation using validated instruments: The GERD health-related quality of life (GERD-HRQL), reflux symptom index (RSI), reflux disease questionnaire (RDQ), and GERD questionnaire (GERDQ).
Upon enrollment, patients were allocated to one of two treatment groups: A double-dose PPI regimen administered for three months, or ARMS therapy, as illustrated in Figure 1. The treatment allocation was based on shared decision-making between patients and physicians, reflecting real-world clinical practice. Participants in the double-dose PPI group received esomeprazole at a dosage of 20 mg twice daily over a three-month period[12]. Conversely, in ARMS group, patients were administered PPIs for 3 weeks after surgery: Esomeprazole at a dosage of 20 mg one time per day. After 3 weeks the PPI were discontinued. Patients were reassessed using the same symptom scoring tools (RSI, GERD-HRQL, GERDQ, RDQ) at three weeks and three months. Meanwhile, three months post-treatment, patients underwent follow-up gastroscopy.
Figure 1 Study flow diagram illustrating patient enrollment and group allocation.
Patients with reflux esophagitis were allocated into two groups: The anti-reflux mucosectomy group and the double-dose proton pump inhibitor group. Follow-up assessments were conducted at 3 weeks and 3 months post-treatment, including the collection of baseline information such as gastroesophageal reflux disease questionnaire scores, LA classification, quality of life, and mental health status. RE: Reflux esophagitis; PPI: Proton pump inhibitor; ARMS: Anti-reflux mucosectomy; GERDQ: Gastroesophageal reflux disease questionnaire; QoL: Quality of life.
ARMS procedure
The ARMS procedure employed at our institution has been previously detailed[13]. Initially, the cardia was examined endoscopically from within the stomach, revealing a mild dilation in this region. Subsequently, the oral margin of the resection area was identified, using the point at which the esophageal lumen begins to open as a reference. The resection area was then delineated by marking half of the circumference on the lesser curvature side. Following this, submucosal dissection was performed from the oral side employing the standard technique utilized in conventional endoscopic submucosal dissection. Upon reaching the angle of his during submucosal detachment, mucosal desquamation was observed. Ultimately, a semi-circumferential mucosal defect was established along the lesser curvature of the esophagogastric junction (Figure 2)[14]. Before undergoing the ARMS procedure, all patients underwent a thorough preoperative assessment.
Figure 2 Endoscopic views of the anti-reflux mucosectomy procedure.
A: Endoscopic view of the esophagogastric junction showing mild dilation of the cardia; B: Marking of the resection margin along the lesser curvature, covering half the circumference; C: Submucosal injection to lift the mucosa; D: Mucosal incision using endoscopic submucosal dissection technique; E: Submucosal dissection progressing toward the gastric side; F: Completion of semicircular mucosectomy along the lesser curvature; G: Final view of the mucosal defect after resection, expected to result in scar-induced tightening of the esophagogastric junction.
Evaluation questionnaires
Following approval from the institutional review board, a retrospective analysis was conducted utilizing a prospectively maintained database of patients with RE. Written informed consent was obtained from all participants. This database comprises patient demographic data, as well as clinical information obtained preoperatively, intraoperatively, and postoperatively from electronic medical records, in addition to responses from GERD-related questionnaires. The administered surveys include the GERD-HRQL, RSI, GERDQ, and RDQ. The GERD-HRQL is a validated instrument designed to assess typical reflux symptoms and their severity using a 5-point Likert scale. Notably, item 9 of the GERD-HRQL, which pertains to symptoms of gas bloat, was analyzed independently[15].
The RSI questionnaire emphasizes atypical reflux manifestations, such as cough and hoarseness, with a score exceeding 13 indicative of clinically significant reflux[16]. Additionally, dysphagia severity was evaluated using a 5-point scale, where a score of 1 corresponds to the ability to consume a normal diet, and a score of 5 denotes an inability to swallow any substances.
Reflux symptoms were quantitatively assessed using both the RDQ and GERDQ instruments. The RDQ measures the frequency and severity of heartburn, non-cardiac chest pain, acid regurgitation, and the sensation of stomach contents rising, with a diagnostic cutoff score of 12[17]. The GERDQ evaluates the frequency and severity of heartburn, acid regurgitation, sleep disturbances, use of over-the-counter medications, abdominal pain, and nausea, employing a diagnostic threshold of 8. These assessments were conducted at baseline and three months following treatment[18].
Statistical analysis
Statistical analysis were performed utilizing the Statistical Package for the Social Sciences version 22.0 and GraphPad Prism version 8.0. The Shapiro-Wilk test was employed to assess the normality of the data, confirming that all variables conformed to a normal distribution. Continuous variables were analyzed using Student’s t-test, whereas categorical variables were expressed as proportions and examined using the χ2 test. In instances where expected frequencies were less than five within a category, the Fisher’s exact test was applied. No adjustments were made for multiple comparisons.
RESULTS
Demographics
Among the 28 RE patients, the average age was 55.86 ± 12.49 years old, which included 5 males and 9 females in ARMS group, among the 14 RE patients in double-dose PPI group, the average age was 53.79 ± 12.75 years old, which include 5 males and 9 females. There are 4 smoker, 3 patients with hypertension, and 2 patients with diabetes in ARMS group, while 6 smoker, 4 patients with hypertension, and 2 patients with diabetes in double-dose PPI group. According to potential of hydrogen study, the acid exposure time (AET) in the two groups were 9.09 ± 1.44, 8.33 ± 1.65, respectively, which indicated pathological acid reflux. No significant differences in age, sex, and body mass index were detected between the two groups, see Table 1.
Table 1 Patient demographics and characteristics between the two groups, mean ± SD/n (%).
Similar reflux symptoms were detected in the two groups. With regard to ARMS group, reflux (n = 12), nocturnal symptoms (n = 9), heartburn (n = 9), regurgitation (n = 9), laryngitis (n = 8), epigastric/chest pain (n = 7), and globus sensation (n = 7) were the commen symptoms in ARMS group, while reflux (n = 11), heartburn (n = 10), nocturnal symptoms (n = 10), regurgitation (n = 8), globus sensation (n = 8), laryngitis (n = 7) were the commen symptoms in double-dose PPI group. No significant differences in GERD-related symptoms were detected between the two groups, see Table 2.
Table 2 Patient reported preoperative symptom between the two groups, n (%).
As presented in Table 3, the ARMS cohort demonstrated an operative time of 31.71 ± 6.94 minutes, minimal estimated blood loss (EBL), a brief length of hospital stay, and low pain scores at the time of discharge. Additionally, the ARMS group exhibited a 0% complication rate at the three-month follow-up. These findings are detailed in Table 3.
Table 3 Patient perioperative outcomes in anti-reflux mucosectomy groups, mean ± SD/n (%).
No significant differences in GERD-related symptoms and endoscopic findings (LA grade C-D) were detected between the two groups preoperatively. Regarding quality of life outcomes, patients who received ARMS demonstrated a significant reduction in RSI, GERDQ, RDQ, and GERD-HRQL scores compared with double-dose PPI group postoperative scores at 3 weeks, 3 months (all P values < 0.010). While no statistically significant difference was observed in endoscopic findings (LA grade C-D) between the two groups following treatment, the surgery group exhibited a lower number of patients classified with LA grade C-D compared to the medication group (2 vs 6, P = 0.209). See Table 4 and Figure 3. Meanwhile, the typical gastroscopy findings three months after ARMS was shown in Figure 4.
Figure 4 Gastroscopic findings three months post-anti-reflux mucosectomy.
Follow-up endoscopy revealed fibrotic changes and narrowing at the esophagogastric junction, consistent with the intended anti-reflux effect of mucosal scarring. The image shows typical post-anti-reflux mucosectomy appearance with reduced patency of the cardia, contributing to mechanical prevention of reflux.
Table 4 Patient pre- and post-operative symptoms outcomes between the two groups, mean ± SD.
Prior investigations have established that ARMS constitutes a safe and viable endoscopic procedure for the treatment of RE[11,19]. Nevertheless, no prior studies have directly compared the clinical outcomes of ARMS with those of double-dose PPI therapy in patients with RE. In the present study, we demonstrate that ARMS yields superior postoperative outcomes relative to double-dose PPI treatment, as evidenced by significant improvements in both short-term and long-term reflux-related symptomatology, including measures such as the RSI, RDQ, GERDQ, and GERD-HRQL scores.
Previous literature has reported that a majority of patients undergoing ARMS were able to discontinue PPI therapy, with rates ranging from 63% to 86%[19-21]. Consistent with these findings, our study observed that the ARMS cohort exhibited an operative time averaging 31.71 ± 6.94 minutes, minimal EBL, brief hospital stays, and low pain scores at discharge. Furthermore, the ARMS group demonstrated a 0% complication rate within 3-month post-procedure. Notably, patients treated with ARMS experienced statistically significant reductions in RSI, GERDQ, RDQ, and GERD-HRQL scores compared to those receiving double-dose PPI therapy at both 3-week and 3-month postoperative intervals (all P < 0.010). These findings align with recent reports indicating minimal EBL in ARMS procedures, with values comparable to those observed in our cohort[22].
More recently, Inoue et al[23] introduced anti-reflux mucosal ablation (ARMA), an endoscopic technique predicated on the same fundamental principle as ARMS, wherein mucosal scarring is induced; however, ARMA purportedly reduces the risks of perforation and bleeding[23]. While ARMA achieves a comparable tightening effect at the gastroesophageal (GE) junction, it addresses only a single mechanistic pathway implicated in GERD pathophysiology. Given the well-established role of transient LES relaxations as a principal contributor to pathological reflux, it is hypothesized that the resection of gastric cardia mucosa in ARMS may disrupt the transient LES relaxation pathway in addition to mechanically reinforcing the GE junction[24].
All primary outcomes are symptom-based (RSI, GERD-HRQL, GERDQ, RDQ). No objective endpoints (AET normalization, impedance metrics, PPI cessation rates) are incorporated into comparative analysis, despite available follow-up endoscopy. In this study, although no statistically significant difference was observed in endoscopic findings (LA grade C-D) between the two groups following treatment, the surgery group exhibited a lower number of patients classified with LA grade C-D compared to the medication group (2 vs 6, P = 0.209). During the follow-up period, no adverse events, including bleeding, perforation, or hospital readmission were reported, nor were there any instances of dysphagia necessitating balloon dilation after discharge. The EBL associated with ARMS is estimated to be approximately 5 mL, with an elevated risk observed in patients receiving antiplatelet therapy[25,26]. The 0% complication rate is now presented as preliminary and descriptive, not as a definitive safety claim. There is a need for larger studies to confirm safety.
Anti-reflux surgical procedures, such as laparoscopic fundoplication, have demonstrated efficacy in patients with refractory GERD; however, approximately 25% of patients experience postoperative complications including dysphagia, gas bloat syndrome, diarrhea, and increased flatulence[27]. Furthermore, between 25% and 62% of patients require ongoing acid-suppressive medication 5 to 15 years following anti-reflux surgery[28]. Consequently, several novel surgical techniques that preserve the anatomical integrity of the cardia have been developed, though these approaches also present procedural limitations[29]. Additionally, various endoscopic treatments for GERD, such as transoral incisionless fundoplication and magnetic sphincter augmentation, have not demonstrated sustained long-term efficacy[30]. Accordingly, the American Gastroenterological Association Institute, in its technical review concerning endoscopic therapies for GERD, concluded that there are currently no definitive indications for the use of endoscopic treatment in GERD management[31].
A limitation of this study is the absence of a formal sample size calculation and power analysis. Given the pilot nature of this investigation and the relatively small sample size (n = 14 per group), the study may not have been adequately powered to detect clinically meaningful differences between treatment groups, particularly for secondary outcomes or subgroup analyses. While this study represents one of the limited clinical investigations comparing the efficacy of ARMS and double PPI therapy, its small sample size constrains the generalizability of the findings. We acknowledge the small sample size and the absence of a priori sample size calculation. This was a pilot study intended to generate preliminary data for future prospective trials. Additionally, the procedural execution of ARMS exhibits variability across different practitioners. We also acknowledge the lack of randomization and adjustment as a key limitation, which may lead to selection bias. Currently, we are undertaking a prospective study with the aim of generating results that can be more readily translated into clinical practice.
CONCLUSION
In summary, ARMS represents a safe and effective minimally invasive endoscopic intervention for refractory esophagitis, yielding superior perioperative outcomes in terms of postoperative symptom control and quality of life when compared to double-dose PPI therapy. Overall, ARMS may represent a promising endoscopic option for selected patients with refractory RE, though larger prospective studies are needed to confirm its efficacy and safety.
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