Endoscopic Mucosal Techniques for GERD: Dawn of New Era in Endoscopic GERD Management

Abstract

Gastroesophageal reflux disease is commonly managed with proton pump inhibitors (PPIs) or antireflux surgery (e.g., fundoplication). However, a subset of patients remains PPI-refractory or PPI-dependent, prompting the development of less invasive endoscopic therapies. In the last decade, several endoscopic mucosal-directed techniques have emerged to augment the gastroesophageal junction barrier by inducing mucosal remodeling. These include antireflux mucosectomy, antireflux mucosal ablation, antireflux mucosal valvuloplasty, and antireflux mucoplasty with flap valve formation. Each technique involves altering the distal esophageal or gastric cardia mucosa to enhance the reflux barrier, but they differ in approach (resection, ablation, or creation of a flap valve) and clinical experience. This narrative review describes each procedure and summarizes human clinical data focusing on symptom relief, esophageal acid exposure, durability of effect, and safety.

Keywords

ARMA - ARMS - ARMV - GERD

Introduction

Gastroesophageal reflux disease (GERD) is commonly managed with proton pump inhibitors (PPIs) or antireflux surgery (e.g., fundoplication). However, a subset of patients remains PPI-refractory or PPI-dependent, prompting the development of less invasive endoscopic therapies. In the last decade, several endoscopic mucosal-directed techniques have emerged to augment the gastroesophageal junction (GEJ) barrier by inducing mucosal remodeling. These include antireflux mucosectomy (ARMS), antireflux mucosal ablation (ARMA), antireflux mucosal valvuloplasty (ARMV), and antireflux mucoplasty with flap valve formation (ARM-P/V). Each technique involves altering the distal esophageal or gastric cardia mucosa to enhance the reflux barrier, but they differ in approach (resection, ablation, or creation of a flap valve) and clinical experience. This narrative review describes each procedure and summarizes human clinical data focusing on symptom relief, esophageal acid exposure, durability of effect, and safety.

Antireflux Mucosectomy and Antireflux Mucosectomy with Banding

Technique

ARMS involves endoscopic resection of a portion of the mucosa around the GEJ to induce scarring and tighten the valve. Typically, mucosal markings are placed to outline a crescent-shaped area (∼270 degrees of the circumference) along the lesser curvature side of the cardia, spanning ∼3 cm in length (roughly 1 cm above the Z-line into the distal esophagus and 2 cm onto the gastric cardia). This was initially described by Inoue et al[1] in their pilot study. The marked mucosa is then removed using endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR) techniques, while preserving an intact strip of mucosa on the opposite (greater curvature) side. This was demonstrated in the initial 10 patients by Inoue et al. In the first two cases, a circumferential mucosal resection was done, but subsequently, a small area was left intact. By leaving the mucosa intact along the greater curvature (the location of the natural flap valve), the subsequent scar contraction of the resected area pulls the GEJ taut and enhances the flap valve on the intact side. In essence, ARMS creates an artificial ulcer that heals over several weeks, resulting in a tighter, more robust antireflux valve at the esophagogastric junction (EGJ). Another method of performing ARMS includes banding, followed by resection. It is also called as ARMS with banding. This technique involves banding the mucosa around the lesser curvature after an initial injection, followed by resection of the banded site. The technical and clinical success of the two techniques are comparable in the meta-analysis by Garg et al.[2]

Clinical Outcomes and Efficacy

ARMS has been evaluated in numerous human studies over the past decade, including pilot trials, large case series, and comparative studies. Key findings include:

• Symptom Relief: ARMS produces significant improvement in GERD symptoms. In the initial pilot (10 patients), heartburn and regurgitation scores dropped dramatically (e.g., DeMeester score from 5.2 to 0.67).[1] A large single-center series of 109 PPI-refractory GERD patients reported significant improvement in symptom scores post-ARMS (p < 0.01).[3] This large series was also conducted by Inoue et al. Pooled data confirm marked symptom relief: a 2022 meta-analysis found GERD-health-related quality of life (HRQL) scores improved by an average 15 points after ARMS[2] and GERD-Questionnaire scores improved by 4.9 points. This meta-analysis by Garg et al confirmed the usefulness of ARMS in managing patients with refractory GERD. These improvements translate clinically to reduced heartburn/regurgitation frequency and better quality of life (QOL). In an Indian study by Patil et al,[4] 62 patients underwent successful ARMS. GERD-Q score reduced from 10.6 to 3.4. For troublesome laryngopharyngeal reflux disease (LPRD), ARMA has been shown to be effective. In 183 patients who had proven LPRD and underwent ARMA, 72% were found to have benefited. Significantly, Short Form-36 scores were higher, and there was symptomatic improvement.[5] In a recent meta-analysis by Angeramo et al, ARMA was compared with radiofrequency (RF) ablation, the weighted pooled patient satisfaction rate was 65% for ARMA and 77% for RF ablation. Both the procedures significantly reduced PPI use as well as improved GERD-HRQL scores.[6]

• PPI Dependency: ARMS often allows reduction or cessation of acid suppressants. In the 109-patient series, 40 to 50% of patients were able to discontinue PPIs after ARMS.[3] Across studies, the rate of clinical success (complete PPI cessation or dose reduction) averages ∼80%.[2] Meta-analyses report ∼65% of patients can completely come off PPIs post-ARMS, with an additional 15 to 20% able to reduce their dose. A randomized controlled trial (RCT) by Wang et al[7] comparing ARMS to RF (Stretta) found that at a 2-year follow-up, 61% of ARMS-treated patients had completely stopped PPIs, which was comparable to the Stretta group (69%).

• Esophageal Acid Exposure: Objective pH studies show ARMS yields a modest but significant reduction in acid reflux parameters. Pooled results indicate the mean 24-hour acid exposure time (AET) decreases by ∼2.4% of time pH <4 after ARMS (e.g., from 8.6 to 6.2%).[2] Some studies demonstrate a trend toward lower composite DeMeester scores, though meta-analysis of early data did not reach significance (likely due to heterogeneity).[2] In practice, a substantial subset achieves normalized pH: for example, in the original pilot series, five of eight patients had normalized DeMeester scores after ARMS.[1] The larger 109-patient series showed significant improvement in AET and DeMeester score post-ARMS (p < 0.01), confirming that ARMS can objectively reduce acid exposure.[3] Endoscopically, ARMS also improves the anatomy of the EGJ; the mean Hill flap valve grade often shifts from a lax Grade III toward a tighter Grades I and II, indicating restoration of a competent valve. The Indian study as well by Patil et al[4] did not mention the percentage drop in AET but did mention that the DeMeester score normalized in all the patients postintervention.

• Durability: The therapeutic effects of ARMS appear to be fairly durable. Follow-up data up to 2 to 3 years are now available. In Inoue et al's large series, those followed for up to 3 years showed sustained improvement in subjective symptoms without significant relapse. Similarly, a 2-year RCT outcome demonstrated that symptom scores remained significantly improved from baseline, and patient satisfaction was high.[7] Overall, ∼68 to 81% of patients maintain long-term benefit from ARMS at 2 to 3 years. There is some drop-off over time (as with any reflux intervention), but the majority continue to enjoy symptom relief and reduced medication dependence in the longer term.

Safety Profile

ARMS creates a mucosal defect that must heal, so there are recognized adverse events related to the postprocedure ulcer. Transient dysphagia due to stricture formation is the most common complication. The pooled analysis of around 300 patients found stricture (requiring endoscopic dilation) in 11.4% of cases.[2] These typically present as dysphagia 2 to 4 weeks after ARMS (during ulcer healing) and are managed with 1 to 2 dilations; importantly, such strictures are transient and resolved by later follow-up or with one or two sessions of dilation, in essentially all patients. In the Indian patient series by Patil et al,[4] stricture formation was seen in 8% of patients. Bleeding is the next most frequent risk—postprocedural bleeding occurred in 5% of patients on average. Immediate bleeding during procedures is seen in almost all the cases and can be controlled by endoscopic means in almost all cases. Some of the bleeds are delayed (within 1–2 weeks) and can be managed endoscopically; risk may be higher in those on anticoagulation. Rarely, perforation has been reported (in meta-analysis,[2] 3 cases among hundreds, <1%, there is one case of perforation at the level of cricopharynx due to the EMR cap also), likely related to deep submucosal dissection; with refined technique, this risk is likely to be low. Overall, ARMS is considered safe and well-tolerated—the technical success rate is 98 to 100%, and its side effects (pain, transient chest discomfort) are usually mild. In direct comparison, ARMS had a higher early dysphagia rate than Stretta RF (due to post-ESD scar formation), but no long-term swallowing issues. To mitigate risks, some centers temporarily use sucralfate slurries or short-term PPIs to promote ulcer healing. In summary, ARMS has an acceptable safety profile, with no permanent adverse effects in the vast majority of patients, and the trade-off is a period of ulcer healing that can cause mild-stricture or bleeding in a minority of cases.

Antireflux Mucosal Ablation

Procedural Technique

ARMA was developed by Inoue et al, as a less invasive variant of ARMS, aiming to induce similar scar contraction without excising the mucosa.[8] Instead of resection, ARMA uses controlled cautery ablation, usually using argon plasma coagulation (APC), of the EGJ mucosa to create superficial “burns” that heal with fibrosis. In practice, it requires a “butterfly-shaped” ablation around the gastric cardia, often in retroflex view.[9] For example, one technique ablates roughly three-fourths of the circumference on the gastric side of the GEJ, while deliberately leaving two small opposing areas of normal mucosa intact (each about one endoscope diameter wide) to reduce stricture risk.[9] Another technique involves using saline with dye, usually indigo carmine or methylene blue, which is injected into the submucosa to create a cushion and mark the proper depth. Then, using an electrocautery knife or APC probe in coagulation mode, the targeted mucosa is ablated down to the submucosal layer (confirmed by the appearance of the submucosal dye).[9] The result is a “butterfly” pattern ulcer (an open area with two intact “wings” of mucosa) at the EGJ.[9] This ulcer heals over ∼2 to 4 weeks, much like in ARMS, contracting and tightening the GEJ. Importantly, ARMA is considered to have lower risk for perforation as compared with ARMS, as there is no resection, it is predominantly ablation. It is also repeatable if needed, and multiple sessions can be utilized for adequate tightening of the GEJ.

Clinical Outcomes and Efficacy

Although ARMA is a newer modality (first reported in 2018), emerging clinical studies—including a pilot trial and a multicentric series—suggest that it produces meaningful symptom and pH improvement in GERD:

• Symptom Improvement: ARMA can significantly ameliorate GERD symptoms. In the first pilot trial by Inoue et al,[9] ARMA trial (12 PPI-refractory patients), median GERD-HRQL scores improved from 30.5 at baseline to 12.0 at 2 months (p = 0.002). Similarly, the Japanese GERD symptom score (frequency scale for the symptoms of GERD) fell from 25 to 10.5 (p = 0.002). Many patients report marked relief of heartburn and regurgitation within 1 to 2 months as the ablated area scars in. An international two-center study (Showa University in Japan and a center in Spain) on ARMA (published 2024) confirmed significant symptomatic benefit, echoing that GERD symptom scores drop substantially after ARMA.[10] These improvements are comparable in magnitude to those seen with ARMS.

• PPI Use: Early evidence indicates ARMA can reduce dependence on acid suppressants. In the pilot cohort, patients' median GERD-QOL scores improved and the majority were able to discontinue or halve PPI therapy. A recent bi-institutional study reported that ∼70 to 75% of patients could stop or reduce PPIs post-ARMA. While exact percentages vary, ARMA's effect on reducing medication use appears on par with ARMS. It is notable that some ARMA candidates have already failed maximal PPIs, so even partial PPI reduction is clinically meaningful. In a larger series, almost 65% reported discontinuation of PPIs post-ARMA.[11]

• Acid Exposure, pH Metrics, and Motility Changes: ARMA has shown the ability to normalize esophageal acid exposure in a significant subset of patients. In the single-center pilot, the median 24-hour DeMeester score plummeted from 33.5 preprocedure to 2.8 post-ARMA (p = 0.049)[9] essentially into the normal range. Likewise, median AET dropped from 9.0 to 0.5% (though with a strong trend, p = 0.068). In that study, five of eight patients who underwent impedance-pH monitoring achieved a normalized DeMeester score after one ARMA session. This magnitude of acid reduction is striking and suggests ARMA can restore near-normal EGJ barrier function in many cases. A larger series reported improvement in Hill flap valve grade and reflux parameters in 80% of patients after ARMA.[11] That study also looked into changes in esophageal motility after ARMA, Improved EGJ barrier function, increased lower esophageal sphincter resting pressures, and increased EGJ contractile integral. Esophageal body contractility also improved, possibly as a change due to higher esophageal sphincter pressures. Taken together, ARMA reliably reduces pathological acid exposure, though results can vary by patient; those with less severe baseline reflux (e.g., reflux hypersensitivity) may normalize pH more readily than those with large hiatal hernias or very high baseline AET.

• Follow-up and Durability: Follow-up data for ARMA are still limited but encouraging. In the pilot trial, patients were followed for a median of 9 months (up to 14 months), during which their symptom improvement persisted.[9] The international study (2024) tracked patients out to 12 months, finding sustained symptom control and PPI reduction in the majority. There is at least one report of patients remaining symptomatically well at 18 months post-ARMA. Given ARMA's relative recency, longer-term durability (2–5 years) is under investigation. One theoretical advantage is repeatability—because ARMA does not remove tissue, it could be repeated if GERD recurs or is undertreated initially.[9] In practice, some patients who only partially responded to ARMA have undergone a second ablation session with further improvement. This “touch-up” capability could enhance long-term efficacy, but more data on repeated ARMA are needed.

Safety Profile

By avoiding full-thickness mucosal resection, ARMA was designed to improve safety relative to ARMS. The early results support a favorable safety profile:

• Immediate Procedure Risk: ARMA is typically performed with a diathermy knife in spray coagulation mode or APC, which results in a controlled superficial burn. No perforations or deep muscle injuries were reported in the initial series.[9] Operators note that as no cutting of the muscle layer is done, the risk of transmural injury is very low.[9] In the pilot trial, there were no immediate complications observed during or after the ablation procedure.[9] Procedure times (usually 30–60 minutes) and hospital stays (often outpatient or 1 day) are similar to ARMS.

• Ulcer Healing and Stricture: ARMA still creates an ulcer that must heal, so strictures can occur, though possibly at a lower frequency. In the 12-patient study, 1 patient (8%) developed an EGJ stricture causing dysphagia at 2 weeks.[9] This was successfully treated with two balloon dilations, after which the patient was symptom-free. Other series have also noted occasional short-segment strictures requiring dilation (rates roughly 5–10%, similar to ARMS).[11] Importantly, ARMA protocols intentionally leave islands of intact mucosa (the “butterfly wings”) to mitigate circumferential scarring. This likely explains why stricture rates are not higher despite the large ablation area.

• Bleeding: The thermal ablation causes coagulation, so bleeding risk appears low. In published ARMA studies, no significant postprocedure bleeding was reported.[9] Minor oozing during the procedure is controlled with the coagulation itself. Even patients on antithrombotic drugs have been treated (with appropriate periprocedure holds) without major hemorrhage noted. ARMA's avoidance of a large open ulcer might reduce delayed bleeding risk compared with ARMS, although patients are still advised to remain on acid suppression for a few weeks to promote healing. In our own experience (unpublished data), bleeding is usually mild and controlled during the procedure itself.

• Pain and Other Effects: Patients experience some retrosternal discomfort post-ARMA, but it tends to be mild to moderate and resolves within days. In the pilot trial, no one had severe pain requiring anything beyond standard analgesics. Unlike ARMS, which physically removes tissue and can cause a “tight” sensation, ARMA's effect is gradual as scars form, possibly leading to a slower onset of symptom relief but also a gentler healing period. One consideration is that ARMA's full effect may take a few weeks (until the ablated mucosa fibroses), whereas ARMS sometimes has an earlier mechanical effect. This slight delay is not a safety issue per se, but patients should be counseled that maximal relief might be felt a month after the procedure. Overall, ARMA appears safe and well-tolerated, with complication rates comparable to ARMS but with a theoretical margin of safety (lower perforation risk and easier repeatability).

Antireflux Mucosal Valvuloplasty

Procedural Technique

ARMV is an innovative endoscopic procedure that aims to create a new antireflux flap valve by reconstructing the cardia mucosa, rather than removing or ablating it. It was inspired by observations of the natural antireflux mechanism in animals and surgical valve reconstruction. In ARMV, the endoscopist performs a modified ESD at the EGJ to mobilize a broad flap of mucosa and then fix it in a double-layer configuration, thereby augmenting the GEJ valve. In practice, approximately three-fourths of the circumference of the gastric cardia mucosa (lesser curvature side) is incised and released from the underlying submucosa.[8] [12] Crucially, the mucosal segment is not discarded; instead, it is folded back on itself or against the remaining wall to form a “double-layer” mucosal flap valve. This is achieved by placing endoscopic clips or sutures: after the submucosal dissection creates a semidetached flap, reopenable clips are used to anchor the free edge of the mucosa onto the underlying esophageal or gastric wall.[8]

The result is a reconstructed valve at the GEJ—essentially, the loose mucosa is turned into an additional fold that bolsters the native valve. The remaining one-fourth circumference (usually along the greater curvature) is left unincised, serving as a hinge for the flap and preserving blood supply. The combination of the new mucosal fold and subsequent scarring of the submucosal dissection site creates a robust barrier that resists reflux.[8] [12] ARMV does involve a large mucosal incision (similar in extent to ARMS), but by conserving and repurposing the mucosa as a valve, it aims to reduce the mucosal defect that must heal on its own. In essence, ARMV is an endoscopic valvuloplasty that mimics a partial fundoplication, using the patient's own mucosa to form the flap.

Clinical Outcomes and Efficacy

Though ARMV is a very new technique (pioneered in the last 3–4 years), early clinical series are extremely promising—in some cases showing results approaching surgical fundoplication in efficacy:

• Symptom Relief: Patients undergoing ARMV have reported profound improvement in GERD symptoms. In the first reported human series (30 patients, 2019–2021), typical reflux symptoms markedly resolved in most patients. Standardized questionnaires showed significant drops in symptom scores: mean GERD-Q score fell from 14.0 at baseline to 7.7 at 12 months post-ARMV (p < 0.0001)[12]—a change of more than 6 points, which is clinically dramatic. Likewise, the GERD-HRQL score plummeted from a severe 48.7 (baseline) to 10.2 at 1 year (p < 0.0001)[12] indicating resolution of most daily reflux symptoms. Patients report elimination of heartburn and regurgitation in the majority of cases after ARMV. These improvements were not only statistically significant but also far exceeded the typical response seen with medication, highlighting the robust effect of the newly created valve.

• PPI Discontinuation: The vast majority of patients are able to wean off acid-suppressive therapy after ARMV. In the 30-patient pilot study, 83% had reduced or stopped PPIs by 3 months, and by 1 year, nearly 89% of patients had either discontinued PPIs or at least reduced the dose (23 of 26 patients followed at 12 months).[12] Most notably, many were completely off medication. This high rate of PPI cessation reflects the significant symptom relief and restoration of reflux control that ARMV provides. For context, nearly all these patients had been refractory or dependent on PPIs prior to the procedure. By 1 year post-ARMV, their need for daily PPIs was largely obviated by the anatomical fix. This durability of PPI independence (roughly 9 in 10 patients off or on minimal therapy at 1 year) appears to be maintained into the second year as well (mean follow-up ∼29 months).[12]

• Esophageal Acid Exposure: ARMV has demonstrated striking improvements in objective reflux measures. In the 30-patient series, a subset of 11 patients underwent 24-hour pH monitoring before and after the procedure—the results were akin to surgical outcomes. Mean AET dropped from 56.9% before ARMV to 5.5% after (p < 0.0001).[12] In other words, many patients went from extremely high acid exposure (over half the day with pH <4) to essentially normal levels (<6% of time). The mean DeMeester score fell from 167.1 pre-ARMV to 18.6 post-ARMV (p < 0.0001),[12] which is an enormous reduction bringing the composite score well into the normal range (<14.7 is normal). Such results indicate that ARMV can almost completely correct pathologic reflux in properly selected patients. Endoscopically, a recreated flap valve is observed; follow-up endoscopy shows the cardia tightly hugging the endoscope with a newly formed valve ridge, correlating with the absence of reflux on pH testing.[8] [12] These objective outcomes are among the most impressive reported for endoscopic therapy, suggesting ARMV effectively restores the barrier function of the GEJ in a manner similar to a partial fundoplication. That said, these are early results from high-volume expert centers; ongoing studies (including an RCT comparing ARMV vs. medical therapy) will further clarify the pH outcomes in broader populations.

• Durability: The initial ARMV cases have been followed on average 2 to 2.5 years, and the results appear durable to date. In the pilot study, mean follow-up was 28.9 ± 13.9 months.[12] Symptomatic benefits persisted throughout follow-up, with only a minority of patients requiring any resumption of daily PPI (none of the followed patients returned to baseline symptom levels). Objective improvements in those who had repeat pH testing also persisted at 1 year. While detailed 2-year pH data were not reported in the pilot abstract, the sustained symptom control and medication independence out to 2+ years suggest the anatomical valve remains competent. It is expected that, much like antireflux surgery, ARMV will have a lasting effect given it produces permanent fibrosis and a structural valve; of course, very long-term data (5+ years) are not yet available. An important point is that ARMV intentionally preserves mucosa (no large resection), which might promote more durable tissue integrity of the valve. Additionally, any minor loosening over time could theoretically be touched-up endoscopically, though this has not yet been described. In summary, early data indicate ARMV's efficacy is maintained at least into the mid-term (2–3 years) with high rates of continued symptom remission.

Safety Profile

Given the extensive mucosal dissection involved, one might expect ARMV to carry risks similar to ARMS (bleeding, stricture). However, an advantage of ARMV is that the mucosa is not removed but rather repositioned, potentially reducing the exposed ulcer area. The clinical series to date suggests that ARMV is feasible and has an acceptable safety profile, though experience is still limited to specialized centers:

• Procedure Tolerance: All 30 patients in the pilot trial had the ARMV completed successfully (100% technical success) with an average procedure time of ∼72 minutes.[12] There were no intraprocedural perforations or conversions. The method does require advanced ESD skills and extensive clipping, but in experienced hands, it was achieved without major incident. Patients generally stayed one to two nights for observation.

• Bleeding: Only one patient (3.3%) experienced significant bleeding after ARMV in the first series.[12] That case involved postprocedural hemorrhage requiring endoscopic hemostasis, but the patient recovered fully. No patients required transfusions or surgery for bleeding. The low bleed rate is notable given the large incision—it is likely attributable to meticulous endoscopic hemostasis during the procedure and possibly the effect of reapproximating tissue (when the flap is clipped in place, less raw surface is exposed to bleed). Patients are typically kept on PPI for a few weeks after the procedure to promote healing of any minor oozing.

• Stricture: Impressively, no strictures were reported in the initial 30 ARMV patients. By conserving the mucosa and securing it as a flap, ARMV avoids leaving a circumferential open ulcer; thus, the scarring that occurs is distributed, and the lumen remains lined. The creation of a double-layer flap inherently reduces the risk of a circumferential scar contracture. Follow-up endoscopies showed a patent esophagus with the new valve but no narrowing in the treated segment. This is a major advantage over ARMS—despite a similar area of intervention, ARMV's design appears to minimize postprocedure stenosis. Of course, vigilance is warranted as more cases are done, but so far, the need for dilation after ARMV seems rare.

• Other Adverse Events: No cases of perforation were seen in the pilot trial, even though an ESD was performed on three-fourths of the EGJ circumference. The preservation of a one-fourth segment likely maintains some anchoring and blood supply that help healing. There were no reported cases of aspiration, infection, or anesthesia-related issues beyond standard. Patients did experience transient mild odynophagia and chest discomfort during the first 1 to 2 weeks as the clipped flap healed in place, but this was managed with dietary modifications and analgesics. By 1 month, patients generally felt normal aside from their improved reflux status. One consideration is that as clips are left in situ (they typically fall out in a few weeks), there is a small risk of a clip becoming displaced; however, no adverse events from the clips were noted in published cases. In summary, ARMV has shown a favorable safety profile in the hands of experts, with a low incidence of complications (one bleed in 30 cases, no strictures). It represents a more complex intervention, but when executed properly, it avoids many of the pitfalls of an open ulcer seen in ARMS/ARMA.

Antireflux Mucoplasty with Flap Valve Formation

Procedural Technique

Antireflux mucoplasty with valve (sometimes called ARM-P/V) is the latest evolution, essentially combining the principles of ARMS, ARMA, and ARMV to maximize efficacy and safety. Pioneered by Inoue et al in 2024, ARM-P/V involves performing a limited mucosal resection or incision and then immediately closing the defect to create a flap valve without leaving an open ulcer.[8] The procedure can be thought of in two phases: (1) creation of a mucosal flap (as in ARMV) and (2) mucosal closure (as in a mucoplasty). First, a partial circumferential mucosal incision is made (e.g., ∼one-third to half of the circumference along the lesser curve) and a submucosal dissection is done to raise a semiattached flap of mucosa. This flap is analogous to the ARMV flap, except in ARM-P/V the incision can be somewhat smaller because the intention is to physically close it. Through the submucosal dissection, a “double flap” of mucosa is created (one layer being the lifted flap, and the second layer being the remaining attached mucosa). Next, instead of relying on eventual scarring to fix the flap, the operator uses endoscopic clips to immediately secure the flap and close the mucosal defect. In Inoue et al's description, after creating the flap, a series of “anchor prong” clips (e.g., OverStitch or Mantis clips) is placed in a zig-zag fashion to pull the edges of the mucosal incision together, eliminating any open gap (no submucosal gap technique). This effectively sandwiches the raised flap in place, forming an instant new valve, and eliminates the large ulcer bed that would otherwise be exposed.[8]

The end result is a tightened EGJ with a reinforced flap valve, achieved without leaving a significant raw area. By promptly closing the resected area (hence the term mucoplasty), this technique prevents the issues of postprocedure bleeding or stenosis that were seen with ARMS, ARM-P/V thus attempts to harness ARMV's mucosa-sparing valvuloplasty while also addressing ARMV's concern of a large ESD incision (by immediately closing it). In summary, ARM-P/V creates a flap valve and repairs the defect in one session, offering a potential “best of both worlds” approach.

Clinical Data and Outcomes

Because ARM-P/V is very new, published human data are currently limited to case reports and a small pilot study. Nonetheless, the feasibility and initial outcomes are encouraging:

• Feasibility and Acute Outcomes: In the first reported ARM-P/V case (VideoGIE, 2023), the procedure was completed in ∼60 minutes using five endoscopic clips.[8] The immediate postprocedure endoscopy confirmed a nicely closed incision and an augmented flap valve. At 2-month follow-up, that patient's Hill grade improved to I (from III), the hiatal hernia tightening was evident endoscopically, and 24-hour pH monitoring showed AET of 0% and DeMeester 0.8—essentially complete normalization. The patient was able to discontinue all acid-suppressive medications. This dramatic result in a single case exemplified the potential of ARM-P/V to immediately and effectively treat GERD. A subsequent pilot series of ARM-P/V (Inoue et al, 2024) included a small number of patients and similarly reported successful creation of a flap valve in all cases, with significant symptom improvement on follow-up (exact figures pending publication).[8] Although robust efficacy data are not yet available, it is expected that ARM-P/V will mirror ARMV in reducing reflux, with the added benefit of faster symptom resolution since the flap is secured at the time of procedure (the “slow onset” of effect seen in ARMS/ARMA due to waiting for scar contraction may be bypassed).

• Durability: By virtue of addressing the limitations of earlier techniques, ARM-P/V is hypothesized to have good durability, but follow-up is currently short term (months). The pilot report noted that at a few months, patients maintained improved symptom scores and had not required return to PPIs. The created flap is permanent unless disrupted, and the rapid healing from complete closure likely means a strong fibrous union forms. More time and larger cohorts are needed to determine long-term durability; ongoing cases will shed light on whether ARM-P/V can match the multiyear efficacy of ARMV.

Safety Profile

The primary motivation for ARM-P/V was to enhance safety by avoiding an open mucosal defect. Initial experiences confirm that this approach can virtually eliminate certain complications:

• Bleeding and Stricture: In the early ARM-P/V cases, there have been no reports of delayed bleeding or strictures. By closing the mucosal incision immediately, the risk of delayed hemorrhage is minimized (the tissue edges are approximated and heal primarily, rather than leaving an ulcer base that could bleed). Inoue et al noted that after adopting mucosal closure, postprocedure bleeding was 0% and no stenoses occurred, as opposed to 5 and 13% rates previously seen with ARMS.[8] This is a major safety gain. The pilot ARM-P/V study explicitly reported no incidents of postprocedural bleeding or narrowing.[8] Thus, ARM-P/V appears to successfully address the two most common ARMS/ARMA complications.

• Other Risks: The trade-off for improved healing is the added technical complexity of closure. The use of multiple clips in the GEJ area could, in inexperienced hands, carry a small risk of causing a laceration or ischemia if placed improperly. However, no such issues have been documented in the initial cases. There is also a theoretical risk that if the closure is not complete (leaving a small gap), a partial ulcer could still form and cause a focal stricture—careful technique mitigates this. The initial patients did not experience any adverse events like perforation or significant pain beyond what is expected for a mucosal resection. Postprocedural discomfort was mild, likely less than ARMS since the wound is closed. Overall, while data are early, ARM-P/V has demonstrated excellent safety in its first applications, with the closure step effectively preventing the ulcer-related complications seen before. This suggests that as the technique is refined and adopted, it could make endoscopic GERD therapy safer and more accessible to more patients.

It is important to note that ARM-P/V is still under evaluation. The current data are from high-volume endoscopists with advanced skill in ESD and endoscopic closure. Wider adoption will require training to ensure the technique's safety and efficacy translate universally. Moreover, comparative studies are needed—for example, to see if ARM-P/V provides equal reflux control as ARMV (which might involve a larger dissection) and whether the extra steps are justified in all cases. Nonetheless, this approach represents an exciting advancement by potentially delivering surgical-level outcomes with minimal complications in endoscopic GERD treatment.

Comparative Analysis of Endoscopic Mucosal Techniques

Each of the four endoscopic techniques (ARMS, ARMA, ARMV, ARM-P/V) shares the common goal of enhancing the antireflux barrier via mucosal modification, but they differ in method and clinical profile. [Table 1] provides a side-by-side comparison of these techniques, highlighting differences in their approach, outcomes, safety, and follow-up from the available human studies.

Table 1 Comparison of endoscopic mucosal techniques for GERD management, including mechanism of action, clinical outcomes, durability, and safety profile

Technique	Mechanism (endoscopic approach)	Symptom relief and PPI reduction	Acid exposure improvement	Durability (follow-up)	Complications
ARMS	Partial mucosal resection (ESD/EMR) of 270 deg of EGJ mucosa along lesser curvature, inducing scar contraction; intact mucosa on greater curvature forms enhanced flap	Significant symptom improvement in most patients (GERD-HRQL scores improve by 15 points); 65% can completely discontinue PPIs, and additional 15–20% reduce dose	Modest but significant reduction in 24 h acid exposure (AET ↓ 2–4%); 50% achieve normalized pH on follow-up pH test	Sustained benefits in ∼70% of patients at 2–3 y. Symptom control and low PPI use maintained at 2-y RCT follow-up	Stricture: 10–13% (usually transient, dilated successfully). Bleeding: 5% (delayed bleeding controllable endoscopically). Rare perforation (<1%)
ARMA	Mucosal ablation (e.g., with cautery knife or APC) of 270 deg around gastric cardia in a “butterfly” pattern; no tissue removed, two small opposing mucosal areas left intact to prevent full ring scar	Marked symptom relief similar to ARMS (GERD-Q and HRQL scores significantly improved). Majority (70% in studies) able to come off or reduce PPIs (many completely off)	Can substantially lower acid exposure: DeMeester scores often normalize in responders. Median AET reductions of 5–9% observed (e.g., 9%→0.5% in pilot)	Medium-term (6–12 mo) efficacy demonstrated; improvements sustained at 9–12 mo follow-up. Early data up to 1–1.5 y show maintained symptom control; repeatable if relapse occurs	Stricture: 5–10% (one case in 12 patients in pilot study). Bleeding: uncommon (no significant bleeds in initial series). Very low perforation risk (no resection/cutting into wall)
ARMV	Mucosal flap valvuloplasty via ESD: 75% circumference of cardia mucosa is incised and mobilized, then clipped to form a double-layer flap valve (mucosa conserved). Effectively creates a new mucosal valve at the EGJ	Dramatic symptom resolution in most patients (GERD-Q from 14 to 8); 83–89% able to stop or reduce PPIs by 1 year (majority off entirely)	Major acid reduction: AET often normalizes (e.g., 57%→5.5% in 30-patient series). DeMeester scores drop ∼90% into normal range. Essentially restores physiological pH in many cases	Durable up to 2–3 y (mean ∼29 mo follow-up in first series) with sustained symptom relief and minimal need for PPIs. Further follow-up ongoing; expected long-term efficacy high given robust structural change	Bleeding: 3% (1 case in 30, treated endoscopically). Stricture: negligible so far (mucosa not removed; no strictures seen in initial 30). No perforations reported in initial series
ARM-P/V	Hybrid mucosectomy + closure: A partial mucosal resection/incision (like a limited ARMS) is performed to create a flap, then the mucosal defect is immediately closed with clips (mucosal “mucoplasty”). Results in an instant flap valve with no open ulcer	Early cases show significant symptom improvement even by 2 mo (Hill grade normalized, symptoms resolved). Initial pilot study reports patients off PPIs with good relief at short-term follow-up (data from small N)	Very promising initial pH outcome in case reports (AET 0% postprocedure). Expected to mirror ARMV's profound acid reduction, but larger data pending	Only short-term follow-up available so far (mo). Anticipated to have durable effect akin to ARMV, without the healing lag time (flap is secured immediately). Longer-term studies are underway	Bleeding: so far 0% in initial series (defect closed = no ulcer bleed). Stricture: 0% to date (immediate closure prevents scar ring). No significant complications reported, though procedure is technically demanding (requires advanced clipping)

Abbreviations: AET, acid exposure time; APC, argon plasma coagulation; ARMA, antireflux mucosal ablation; ARM-P/V, antireflux mucoplasty with flap valve formation; ARMS, antireflux mucosectomy; ARMV, antireflux mucosal valvuloplasty; EGJ, esophagogastric junction; EMR, endoscopic mucosal resection; ESD, endoscopic submucosal dissection; GERD, gastroesophageal reflux disease; HRQL, health-related quality of life; PPI, proton pump inhibitor.

Conclusion

Endoscopic mucosal therapies have rapidly evolved as viable treatments for GERD in patients seeking alternatives to life-long PPIs or surgery. Over the past decade, evidence from case series, meta-analyses, and early trials indicates that these techniques—ARMS, ARMA, ARMV, and ARM-P/V—can achieve significant symptom relief and meaningful reduction in esophageal acid exposure in carefully selected patients. ARMS, the first introduced, has demonstrated lasting benefits in the majority of refractory GERD cases, albeit with some risk of postprocedure stricture and bleeding. ARMA provides a less invasive variant with comparable efficacy and potentially fewer deep injuries, making repeat treatments feasible. ARMV represents a major step change in efficacy—by constructing a new flap valve, it has yielded near-normalization of pH and symptom resolution for many, with minimal complications in initial studies. The newest innovation, ARM-P/V, seeks to further refine safety by eliminating the open ulcer; early experience shows it can prevent strictures/bleeding while still restoring the antireflux barrier.

In terms of outcomes, all techniques show improvement in GERD symptom scores and HRQL.

1. Symptomatic success rates (freedom from troublesome heartburn/regurgitation) generally range from roughly 70% (ARMS/ARMA) to 90% (ARMV) at 1 to 2 years. Many patients can discontinue PPIs entirely after these procedures, particularly with ARMV and advanced mucoplasty approaches.

2. Objective acid reflux control is achieved to varying degrees: ARMS and ARMA tend to reduce (though not always fully normalize) acid exposure, whereas ARMV can normalize pH in a high proportion. Follow-up durability appears good for all, with ARMS and ARMA having documented benefits through 2 to 3 years, and ARMV showing maintenance at 2 years in initial reports. As these procedures continue to be refined, ongoing trials (e.g., a randomized trial of ARMV vs. PPIs and longer-term cohort studies will clarify their exact place in GERD management).

3. Safety profiles have incrementally improved with each innovation. ARMS taught us that leaving an extensive mucosal defect can cause stricturing in about 1 in 10 patients a manageable issue but one that spurred the development of the later techniques. ARMA showed that one can achieve similar effects by ablating the mucosa—avoiding a full cut may slightly lessen stricture risk and makes the procedure more approachable for endoscopists already skilled in ablative techniques. ARMV demonstrated that by preserving mucosa and creating a valve, it is possible to dramatically improve efficacy and simultaneously observe a low complication rate (no strictures in 30 patients). Finally, ARM-P/V underscores that even in ARMV there was room to remove the healing period ulcer—by closing the flap defect immediately, it promises to virtually eliminate ulcer-related complications. The trade-off is increased technical complexity, meaning proper training and careful case selection are critical.

In summary, endoscopic mucosal therapies for GERD have matured from experimental ideas to clinically applicable treatments supported by human data. ARMS and ARMA are already in use at specialized centers, with meta-analyses confirming their efficacy for PPI-refractory GERD. ARMV is at the forefront of innovation, achieving outcomes approaching those of surgical fundoplication in early series. The concept of antireflux mucoplasty with valve (ARM-P/V) further pushes the envelope by enhancing safety, though it is currently in early stages. As experience grows, patient selection will be important—for instance, those with small hiatal hernias and no severe motility disorder appear to benefit most, whereas very large hernias may still require surgical repair. Combination with other therapies (like minor hiatal hernia repair or complementary techniques) might expand applicability.

The available clinical data from the last decade provide optimism that these endoscopic techniques can effectively fill a therapeutic gap: offering durable GERD symptom relief and acid control without external incisions or implants. For patients who are young or reluctant to commit to life-long PPIs, or those who are poor surgical candidates, procedures such as ARMS, ARMA, and ARMV present valuable options. Ongoing trials and longer follow-up will continue to define their role relative to traditional fundoplication and newer interventions (such as magnetic sphincter augmentation).

Nonetheless, the current evidence supports that endoscopic mucosal interventions can achieve significant reflux control with a favorable safety profile, marking an important advancement in the endoscopic management of GERD.

Conflict of Interest

None declared.

Authors' Contributions

Z.S. conceptualized and prepared the manuscript and reviewed the final draft and approval. S.S., N.C., and R.B. prepared the manuscript and edited the draft and final approval. G.C. reviewed the manuscript and edited the draft and approval.

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Publication History

Article published online:
22 May 2025