Application status of endoscopic anti-reflux mucosal interventions in the treatment of gastroesophageal reflux disease

Abstract

Prevalence of gastroesophageal reflux disease (GERD) has shown an upward trend over the years. Even though patients with GERD have a poor quality of life, the current treatment options are highly limited. In recent years, however, the development of anti-reflux mucosal intervention (ARMI), a novel strategy for treating GERD, has provided hope to such patients. ARMI comprises three main steps: Anti-reflux mucosectomy, anti-reflux mucosal ablation, and peroral endoscopic cardial constriction. ARMI involves the constriction of the pericardial mucosa through endoscopic surgery so as to reduce the damage caused by the reflux of gastric contents. This study compares different ARMI techniques, their therapeutic efficacy in treating GERD, indications and contraindications, endoscopic operational procedures, perioperative management, and adverse events, in an attempt to provide clinical guidance.

Key Words: Gastroesophageal reflux disease; Anti-reflux mucosal intervention; Anti-reflux mucosectomy; Anti-reflux mucosal ablation; Peroral endoscopic cardial constriction; Surgical contraindications; Postoperative adverse reaction

Core Tip: Anti-reflux mucosal intervention is a promising endoscopic treatment for gastroesophageal reflux disease. This article compares three main anti-reflux mucosal intervention techniques - anti-reflux mucosectomy, anti-reflux mucosal ablation, and peroral endoscopic cardial constriction - in terms of efficacy, indications and contraindications, endoscopic operational procedures, perioperative management, and adverse events. It highlights their respective advantages and limitations, emphasizing that treatment selection should be individualized based on patient-specific factors, clinical scenarios, and response to previous interventions.

INTRODUCTION

Gastroesophageal reflux disease (GERD) is a chronic disease caused by the regurgitation of stomach contents into the esophagus, which results in various unpleasant clinical symptoms, including regurgitation, heartburn, retrosternal discomfort, and cough. The prevalence of GERD has significantly increased in recent times owing to changes in lifestyle and dietary structure[1]. GERD severely affects the patients’ quality of life and health[2]. It can even progress to serious conditions such as esophageal ulcers, Barrett’s esophagus (BE), and esophageal carcinoma[3]. Although medical therapy is the most commonly used treatment for GERD, surgical intervention is urgently needed for patients with refractory GERD, especially for those in whom the condition cannot be satisfactorily controlled with medication or those suffering from various complications of the condition. Traditional surgical interventions include multiple forms of fundoplication. However, these surgeries may be accompanied by a series of complications and postoperative discomfort. In addition, the quality of life of patients after surgery cannot be fully improved[4].

Endoscopic anti-reflux mucosal intervention (ARMI), an emerging endoscopic surgical modality, is attracting increasing interest[5]. In ARMI, the structure of the cardia mucosa is endoscopically altered to reduce the possibility of regurgitation of the stomach contents into the esophagus. However, before this new endoscopic procedure is promoted, it is essential to gain a comprehensive understanding of its current application status. In addition, a detailed comparison of its different techniques should be performed by including the indications and contraindications for surgery, the criteria for preoperative evaluations, the key points of intraoperative manipulation, therapeutic effects, and potential complications. This review aims to improve the understanding of ARMI by systematically reviewing its application in treating GERD.

RETRIEVAL STRATEGY

We searched the PubMed and Web of Science databases by combining disease names with surgical procedure names. The following disease names were included: “Gastroesophageal reflux”, “gastroesophageal reflux disease”, and “gastroesophageal and reflux disease”. The names of the surgical procedures were as follows: “Anti-reflux mucosectomy”, “anti-reflux mucosal ablation”, “peroral endoscopic cardial constriction”, “anti-reflux mucosal intervention”, and “anti-reflux mucosal plication”. In addition, we adopted methods such as reference tracing and retrieval of relevant reviews. The included studies were clinical trials that used ARMI techniques for the treatment of GERD, including randomized controlled trials (RCTs), cohort studies, case-control studies, and case series (with ≥ 10 cases). The studies that failed to conclusively validate the therapeutic efficacy of the procedures, including case reports, reviews, conference abstracts (without full text), animal experiments, and basic research, were excluded.

Each literature was manually screened. Finally, 17 studies related to anti-reflux mucosectomy (ARMS), five related to anti-reflux mucosal ablation (ARMA), and eight related to peroral endoscopic cardial constriction (PECC) were selected. A standardized data extraction form was designed. Two researchers independently extracted the data and cross-checked it. Any discrepancies were resolved through discussion or by consulting with a third researcher. The extracted content included the following data: The name of the surgical procedure, number of cases, effective rate, complete proton pump inhibitor (PPI) discontinuation rate, partial PPI discontinuation rate, types of patients with GERD, types of hiatal hernia, Hill score, Los Angeles’s grade, status of BE, circumferential degree of the surgery, whether the surgery involved the lesser curvature or the greater curvature, whether the surgery involved the esophagus or the stomach, the occurrence of stenosis or dysphagia in patients after ARMI and relief after dilatation, and whether patients experienced bleeding or perforation after ARMI.

CURRENT STATUS OF ARMI IN THE TREATMENT OF GERD

ARMI is a class of endoscopic treatments used for refractory GERD. It mainly comprises ARMS, ARMA, and PECC and other methods developed based on these[5].

Current application status of ARMS

ARMS was proposed in 2014 to treat patients with PPI-refractory GERD[6]. Subsequent studies reported improved versions of ARMS procedures, including ligation-assisted ARMS, ARMS using band ligation, and cap-assisted ARMS[7,8]. The range of mucosal resection included 2/3^rd circumferential, 3/4^th circumferential, and 4/5^th circumferential and the butterfly shape[9,10]. ARMS leads to significantly improved symptoms and allows discontinuation of PPI in patients with GERD. However, a comparison of ARMS with other therapeutics, such as Stretta radiofrequency, laparoscopic fundoplication, and magnetic sphincter augmentation, showed that ARMS is not worse than the other interventions in terms of operation time, hospital stay, recovery time, symptom improvement rate, and PPI-discontinuation rate[11-13]. Long-term efficacy evaluations have shown that ARMS significantly improves the symptoms of patients, with a reduced use of PPI and decreased reflux[14,15] Interestingly, in a study by Yoo et al[16], two patients underwent repeated cap-assisted ARMS due to persistent symptoms at 6 months postoperatively. The procedure was performed at scar-free sites, and their symptoms alleviated after the surgery. Wong et al[11] compared laparoscopic Nissen fundoplication with ARMS, and found that the ARMS group had shorter operation time and hospital stay, less blood loss and pain, and an earlier return to daily activities. There was no significant difference in the 30-day complication rate or readmission rate between the two groups. In addition, at 3 weeks, 6 months, 1 year, and 2 years postoperatively, there were no differences between the ARMS group and the laparoscopic Nissen fundoplication group in terms of GERD-specific quality of life scores, reflux symptom index, or dysphagia scores. The ARMS group reported fewer belching and bloating symptoms at all postoperative time points; however, among the 14 patients who maintained the follow-up, pH monitoring showed that most of them had persistent or recurrent reflux symptoms[11]. Additionally, Yang et al[17] reported a study on 180° vs 270° ARMS for treating refractory GERD, involving 39 patients. Among these patients, 18 underwent 180° ARMS and 21 underwent 270° ARMS. At 6 months postoperatively, there was no statistically significant difference in therapeutic efficacy between the 180° and 270° groups[17].

The average overall effective rate of ARMS in treating GERD was approximately 82.60%. The average rate of complete discontinuation of PPI was approximately 63.65%, and that of reduced use of PPI was approximately 23.44% (Table 1). Compared with conventional surgery, ARMS needs a shorter time and presents a faster recovery; in addition, patients who fail to respond to ARMS can be treated with surgery. Therefore, ARMS can be considered as one of the first options for the endoscopic treatment of GERD.

Table 1 Anti-reflux mucosectomy treatment for gastroesophageal reflux disease has shown favorable outcomes, %.

Ref.	Year	Intervention1	Cases	Effective rate	PPI usage
					Discontinuation	Reduction
Inoue et al[6]	2014	ARMS	10	100	100	0
He et al[8]	2022	L-ARMS	69	85.5	55.1	30.4
Gao et al[9]	2023	ARMS	36	75	25	50
Sumi et al[10]	2021	ARMS	88	69.3	40-50	NA
Wong et al[11]	2020	ARMS	33	90.9	90.9	NA
Sui et al[12]	2022	ARMS	39	89.7	71.8	17.9
Sumi et al[14]	2024	ARMS	88	68.3	42	NA
Lee et al[15]	2024	ARMS-C	115	86	37.5	NA
Yoo et al[16]	2020	ARMS-C	33	93.9	63.6	30.3
Yang et al[17]	2021	ARMS	39	85.7	66.7	19
Hedberg et al[18]	2019	ARMS	19	68.4	68.4	NA
Chou et al[22]	2022	ARMS	11	73.9	56.5	NA
Klimczak and Strzelczyk[24]	2023	ARMS	20	86.7	73.33	NA
Monino et al[32]	2020	ARMS-b	21	76.2	57.1	19.0
Patil et al[33]	2020	ARMS	62	88.7	69.4	19.4
Laquière et al[37]	2022	ARMS	13	91	91	NA
Hu et al[38]	2023	ARMS	12	75	50	25
Average				82.60	63.65	23.44

¹Intervention: Nomenclature of the intervention is based on the designation published by the authors rather than the specific surgical approach.

ARMS: Anti-reflux mucosectomy; L-ARMS: Ligation-assisted anti-reflux mucosectomy; ARMS-C: Anti-reflux mucosectomy with cap-assisted; ARMS-b: Anti-reflux mucosectomy using band ligation; PPI: Proton pump inhibitor; NA: Not available.

Current application status of anti-reflux mucosoplasty

In 2023, Inoue et al[18] modified ARMS to anti-reflux mucosoplasty (ARM-P), which involves immediate closure of mucosal defects after mucosectomy. In the present study, 20 patients with GERD underwent ARM-P surgery with 100% technical success and no adverse events. Notably, 55.0% of these patients discontinued PPI usage and 15.0% reduced their PPI dosage after the surgery. Thus, ARM-P demonstrates considerable efficacy in treating GERD. However, not much research has been done on ARM-P. Therefore, additional studies are needed to further assess its immediate and enduring therapeutic effects.

Current application status of ARMA

Inoue et al[19] proposed ARMA in 2020 to treat GERD patients with postoperative scarring after ARMS and found ARMA to be significantly effective for patients with refractory GERD. Hernández Mondragón et al[20] demonstrated anti-reflux ablation therapy, with a therapeutic effect lasting for more than 36 months. A meta-analysis in 2021 revealed that there is no significant difference between ARMA and AMRS and that the clinical success rate of ARMA was around 81%. In addition, approximately 70% of patients who underwent ARMA reduced the PPI usage. The main adverse event of ARMA is dysphagia[21]. In 2022, Chou et al[22] further confirmed the global improvement of reflux symptoms, objective examinations, and discontinuation of PPI after ARMS and ARMA. Shimamura et al[23] showed that patients who did not achieve favorable outcomes with a single ARMA could achieve clinical success through repeated ARMA procedures. A study on ARMI showed that total remission of GERD symptoms was achieved in 86.67% of patients after ARMS/ARMA, while PPI was discontinued in 73.33% of patients[24]. Interestingly, in a study by Shimamura et al[23], nine patients opted to undergo a second ARMA procedure; the follow-up data were available for seven of those patients. The clinical success rate 2-6 months after the second ARMA surgery was 57.1% (4/7). One patient who did not achieve favorable outcomes with the second ARMA intervention underwent a third procedure too, but without any significant clinical improvement. Another patient achieved clinical success after the fifth ARMA intervention[23]. At the same time, some cases of postoperative exacerbation have also been reported. Chou et al[22] reported the worsening of erosive esophagitis and reflux symptoms in one patient.

In general, the average effective rate of ARMA in treating GERD was 84.98%, the average rate of complete discontinuation of medication was approximately 62.86%, and the partial discontinuation average rate was approximately 26.60% (Table 2). Hence, ARMA can be used as a supplement or repeat surgery option for ARMS, providing a new approach to treating GERD.

Table 2 Anti-reflux mucosal ablation or peroral endoscopic cardial constriction treatment for gastroesophageal reflux disease has shown favorable outcomes, %.

Ref.	Year	Intervention	Cases	Effective rate	PPI usage
					Discontinuation	Reduction
Inoue et al[19]	2020	ARMA	8	100	62.5	37.5
Hernández Mondragón et al[20]	2020	ARAT	108	94.3	78.6	15.7
Chou et al[22]	2023	ARMA	12	73.9	56.5	NA
Shimamura et al[23]	2024	ARMA	68	70	43.4	NA
Klimczak et al[24]	2023	ARMA	10	86.7	73.3	NA
Average				84.98	62.86	26.60
Li et al[25]	2017	PECC	47	73.7	NA	NA
Liu et al[26]	2020	C-BLART	60	43	43	NA
Seleem et al[27]	2018	EBL	75	65	65	NA
Li et al[28]	2021	PECC-b	68	77.9	77.9	NA
Jiang et al[29]	2022	PECC-b	16	62.5	NA	NA
Deshmukh et al[30]	2022	ARBM	4	100	100	NA
Hu et al[34]	2018	PECC	13	69	NA	NA
Wang et al[39]	2020	PECC	15	100	93.3	6.7
Average				73.89	75.84	6.70

ARMA: Anti-reflux mucosal ablation; ARAT: Anti-reflux ablation therapy; PECC: Peroral endoscopic cardial constriction; EBL: Endoscopic band ligation; C-BLART: Clip band ligation anti-reflux therapy; PECC-b: Peroral endoscopic cardial constriction with band ligation; ARBM: Anti-reflux band mucosectomy; PPI: Proton pump inhibitor; NA: Not available.

Current application status of PECC

PECC mainly uses mucosal ligation rather than resection to change the mucosal structure around the cardia. Several studies have shown that patients’ symptoms and quality of life significantly improved after PECC, with an overall effective rate of 73.7%[25]. Subsequently, new treatment methods such as endoscopic band ligation and clip band ligation anti-reflux therapy were developed, which afforded significantly improved outcomes[26,27]. The PECC with band ligation (PECC-b) method of ligating the near-circumferential mucosa of the cardia effectively treats refractory GERD, presenting improved symptoms. Most patients were able to discontinue PPI with PECC-b[28,29]. Deshmukh et al[30] used anti-reflux band mucosectomy, a procedure similar to PECC-b, to treat GERD, and reported a low DeMeester score and a high PPI discontinuation rate. A meta-analysis reported improvement in multiple GERD indicators after endoscopic cardia peripheral tissue scar formation (comprising PECC, ARMS, ARMA, and radiofrequency ablation), with a high rate of discontinuation of PPI and satisfactory treatment outcomes[31]. In a study on clip band ligation anti-reflux therapy, Liu et al[26] demonstrated that the endoscopic treatment group showed greater improvements in lower esophageal sphincter pressure and GERD self-assessment scale scores compared to those reported by the medication treatment group. However, there was no significant difference in the reduction of esophagitis postoperatively when compared to that present preoperatively. In addition, between 6 months and 12 months, 10% of patients in the endoscopic treatment group underwent laparoscopic fundoplication[26].

In general, the overall average efficacy of PECC in treating GERD was approximately 73.89%, the average rate of complete discontinuation of PPI was approximately 75.84%, and that of partial discontinuation of PPI was approximately 6.70% (Table 2). Although the overall efficacy of PECC was less than that of AMRS and ARMA, it afforded a slightly higher rate of complete discontinuation of PPI. However, the rate of medication reduction was lower with PECC. Notably, PECC can be applied alone or used as a supplement to other surgical procedures.

INDICATIONS AND CONTRAINDICATIONS OF ARMI

Indications and contraindications of ARMS

In recent years, many studies on ARMS selected patients based on whether they have hiatal hernia and esophagitis, pregnancy and age are other deciding factors in selecting appropriate patients[6,32,33]. Most studies included patients with PPI-dependent or refractory GERD, setting specific criteria such as the mucosal flap valve grade, hiatal hernia length, and degree of esophagitis and whether to include BE[6,32,33]. In general, the indications for ARMS are mainly patients with confirmed diagnosis of refractory/PPI-dependent GERD. Contraindications include hiatal hernia longer than 2-3 cm, achalasia or other primary esophageal motility disorders, previous history of esophageal and gastric surgery, eosinophilic esophagitis, esophageal varices, esophageal stenosis, other severe systemic diseases that are intolerant of surgery, and contraindications to endoscopic examinations. Some studies excluded patients with specific esophagitis grades and BE, although no significant difference in the overall efficacy was observed. Theoretically, ARMS can remove metaplastic mucosa by endoscopic submucosal dissection. However, attention should be paid to the possible stenosis caused by circumcision (Table 3).

Table 3 Concise inclusion criteria for anti-reflux mucosectomy in gastroesophageal reflux disease patients.

Ref.	Year	Intervention	Inclusion criteria1
			GERD diagnosis	Hiatal hernia	Hill score	Los Angeles’s grade	Barrett’s esophagus
Inoue et al[6]	2014	ARMS	Refractory GERD	Without	NA	NA	Included
Inoue et al[6]	2014	ARMS-C	Refractory GERD	≤ 3 cm	NA	NA	Included
He et al[8]	2022	ARMS	Refractory GERD	≤ 3 cm	NA	NA	NA
Sumi et al[10]	2021	ARMS	Refractory/PPI-depended GERD	≤ 2 cm	2-4	NA	NA
Wong et al[11]	2020	ARMS	Refractory GERD	≤ 2 cm	NA	A-B	NA
Sui et al[12]	2022	ARMS	PPI-depended GERD	≤ 2 cm	NA	A-B	Excluded
Sumi et al[14]	2024	ARMS-C	Refractory/PPI-depended GERD	≤ 3 cm	NA	NA	NA
Yang et al[17]	2021	L-ARMS	Refractory/PPI-depended GERD	≤ 2 cm	NA	A-C	NA
Chou et al[22]	2022	ARMS	GERD	3-5 cm	NA	NA	NA
Monino et al[32]	2020	ARMS-b	Refractory GERD	≤ 2 cm	≤ 2	A-B	Included
Monino et al[32]	2020	ARMS	Refractory GERD	≤ 2 cm	≤ 3	A-C	NA
Patil et al[33]	2020	ARMS	Refractory GERD	≤ 3 cm	NA	NA	NA
Patil et al[33]	2020	ARMS	Refractory/PPI-depended GERD	≤ 3 cm	≤ 3	A-C	Included
Hedberg et al[35]	2019	ARMS	GERD	≤ 2 cm	NA	NA	NA
Hedberg et al[35]	2019	ARMS	GERD	≤ 2 cm	NA	NA	NA
Laquière et al[37]	2022	ARMS	PPI-depended GERD	≤ 3 cm	NA	NA	NA
Hu et al[38]	2023	ARMS	Refractory GERD	NA	NA	NA	NA

¹Inclusion criteria: The patient inclusion criteria as defined in the study.

ARMS: Anti-reflux mucosectomy; ARMS-C: Anti-reflux mucosectomy with cap-assisted; L-ARMS: Ligation-assisted anti-reflux mucosectomy; ARMS-b: Anti-reflux mucosectomy using band ligation; GERD: Gastroesophageal reflux disease; PPI: Proton pump inhibitor; NA: Not available.

Indications and contraindications of ARM-P

Inoue studied ARM-P by including patients experiencing typical reflux symptoms more than twice a week with double-dose PPI treatment[18]. Patients with primary esophageal motility disorders were identified with barium esophagography, while high-resolution esophageal manometry (HREM) and gastroscopy were excluded. Further research is needed on ARM-P, as very few relevant studies are available on the topic.

Indications and contraindications of ARMA

Inoue et al[19] included patients with refractory GERD. However, they excluded pregnant patients, patients under 20 years of age, as well as those with esophageal motility disorders, hiatal hernia longer than 3 cm, grade 4 Hill valve, and esophagitis. Hernández Mondragón et al[20] included patients with refractory GERD without hiatal hernia but excluded those with esophageal motility disorders, BE, Hill valve grade 4, and so on. Chou et al[22] included patients with PPI-dependent GERD but excluded those with hiatal hernia longer than 3 cm, Hill valve grade 4, and so on. Shimamura et al[23] included patients with refractory/PPI-dependent GERD but excluded those with hiatal hernia longer than 3 cm. The indications for ARMA are similar to those for ARMS; however, the hiatal hernia is generally shorter than 3 cm and there are no restrictions on Los Angeles esophagitis classification. Only one study excluded BE (Table 4).

Table 4 Concise inclusion criteria for anti-reflux mucosal ablation and peroral endoscopic cardial constriction in gastroesophageal reflux disease patients.

Ref.	Year	Intervention	Inclusion criteria
			GERD diagnosis	Hiatal hernia	Hill score	Los Angeles’s grade	Barrett’s esophagus
Inoue et al[19]	2020	ARMA	Refractory GERD	≤ 3 cm	≤ 3	NA	NA
Hernández Mondragón et al[20]	2020	ARAT	Refractory GERD	Without	≤ 3	NA	Excluded
Chou et al[22]	2023	ARMA	PPI-depended GERD	≤ 3 cm	2-3	NA	NA
Shimamura et al[23]	2024	ARMA	Refractory/PPI-depended GERD	≤ 3 cm	NA	NA	NA
Klimczak et al[24]	2023	ARMA	Refractory GERD	NA	NA	NA	NA
Li et al[25]	2017	PECC	GERD	NA	NA	NA	NA
Liu et al[26]	2020	C-BLART	Refractory GERD	≤ 2 cm	NA	A-C	Excluded
Seleem et al[27]	2018	EBL	Refractory GERD	≤ 2 cm	NA	A-B	NA
Li et al[28]	2021	PECC-b	GERD	≤ 2 cm	NA	NA	NA
Jiang et al[29]	2022	PECC-b	Refractory/PPI-depended GERD	≤ 2 cm	NA	NA	Excluded
Deshmukh et al[30]	2022	ARBM	Refractory GERD	≤ 2 cm	NA	NA	NA
Hu et al[34]	2018	PECC	GERD	≤ 3 cm	NA	NA	Excluded
Wang et al[39]	2020	PECC	Refractory/PPI-depended GERD	≤ 3 cm	NA	NA	Excluded

ARMA: Anti-reflux mucosal ablation; ARAT: Anti-reflux ablation therapy; PECC: Peroral endoscopic cardial constriction; EBL: Endoscopic band ligation; C-BLART: Clip band ligation anti-reflux therapy; PECC-b: Peroral endoscopic cardial constriction with band ligation; ARBM: Anti-reflux band mucosectomy; GERD: Gastroesophageal reflux disease; PPI: Proton pump inhibitor; NA: Not available.

Indications and contraindications of PECC

Seleem et al[27] and Hu et al[34] investigated the application of PECC and endoscopic band ligation for treating GERD. They excluded patients with lower esophageal ulcers, esophageal and gastric varices, hiatal hernias longer than 2 cm, para-esophageal hernias, eosinophilic esophagitis, BE, early esophageal cancer, previous endoscopic or surgical anti-reflux surgery history, and other esophageal motility disorders[27,34]. The indications for PECC are generally similar to those of ARMS, including patients with hiatal hernias shorter than 2-3 cm but without restrictions on Hill valve grading (Table 4). Several studies also excluded patients with BE. Two studies excluded patients with grade D esophagitis because the ligation may involve the esophageal lesion and aggravate the original disease (Table 4).

Procedure details and perioperative management of ARMI

Endoscopic procedures under the ARMI umbrella do not have any established standardized protocols and hence demonstrate significant heterogeneity. For this study, we categorized mainstream techniques and their derivatives into three main groups: ARMS, ARMA, and PECC. Further subclassification can be made based on the operative extent, including horseshoe- or butterfly-shaped resection patterns involving the esophagus or the stomach, respectively (Figure 1).

Figure 1 Schematic diagrams of anti-reflux mucosectomy, anti-reflux mucosal ablation, and peroral endoscopic cardial constriction techniques. A: Anti-reflux mucosectomy: Horseshoe configuration - longitudinal and cross-sectional views, predominantly performed using snare resection; B: Anti-reflux mucosectomy: Butterfly configuration - longitudinal and cross-sectional views, snare resection primarily employed; C: Anti-reflux mucosal ablation: Horseshoe configuration - longitudinal and cross-sectional views, argon plasma coagulation predominantly applied; D: Anti-reflux mucosal ablation: Butterfly configuration - longitudinal and cross-sectional views, argon plasma coagulation based technique primarily used; E: Peroral endoscopic cardial constriction: Esophageal component - longitudinal and cross-sectional views, snare resection technique; F: Peroral endoscopic cardial constriction: Gastric component - longitudinal and cross-sectional views, snare resection technique.

Procedure details and perioperative management of ARMS

Inoue et al[6] evaluated GERD through specific examinations and removed the esophageal mucosa using EMR and endoscopic submucosal dissection. The patients resumed a regular diet and PPI treatment after surgery. Other interventions removed different ranges of the gastric and/or esophageal mucosa. The main difference between the studies was whether the esophageal mucosa was removed and whether part of the mucosa on the lesser curvature was retained, which is considered to be closely related to postoperative dysphagia[10,11]. Postoperative management includes fasting, PPI treatment, and follow-up. Some studies conducted specific surgical methods, such as transparent cap-assisted mucosal resection[16,32]. The preoperative examination is essential for diagnosing GERD, postoperative management and follow-up are equally critical. Preoperative examinations before ARMS mainly include gastroscopy, HREM, and impedance-pH monitoring, which can be supplemented by esophagography and questionnaire evaluation. The surgery mainly resected gastric mucosa. The mucosa on the lesser curvature can be selectively retained (Table 5). The patient generally fasts for 24 hours after surgery and then gradually resumes a regular diet. PPI is used for 4-8 weeks with an adjustable dosage. Follow-up is mainly based on a 6-month review; a 1-3-month review can also be conducted if necessary, and the follow-up interval can be extended.

Table 5 Technical specifications and subtypes of anti-reflux mucosectomy.

Ref.	Year	Intervention	Excision range1
			Circumferential degree	Lesser curvature	Greater curvature	Esophagus	Stomach
Inoue et al[6]	2014	ARMS	240°-360°	Resected	Remained	1 cm	2 cm
He et al[8]	2022	L-ARMS	240°	Resected + ligated	Remained	Resected	Resected
Gao et al[9]	2023	ARMS	240°-270°	Resected	Remained	1 cm	1 cm
Sumi et al[10]	2021	ARMS	240°-290°	Remained	Remained	0	Resected
Wong et al[11]	2020	ARMS	240°-270°	Remained	Remained	0	Resected
Sui et al[12]	2022	ARMS	240°-270°	Resected	Remained	1 cm	2 cm
Sumi et al[14]	2024	ARMS	240°-290°	Resected	Remained	0	Resected
Lee et al[15]	2024	ARMS-C	210°-290°	Resected	Remained	0	Resected
Yang et al[17]	2021	ARMS	180°-270°	Resected	Remained	1 cm	2 cm
Chou et al[22]	2022	ARMS	240°-290°	Remained	Remained	0	Resected
Klimczak and Strzelczyk[24]	2023	ARMS	2-3 cm remained	Remained/resected	Remained	0	1 cm
Monino et al[32]	2020	ARMS-b	270°	Resected	Remained	1 cm	2 cm
Patil et al[33]	2020	ARMS-C	210°-290°	Resected	Remained	0	Resected
Patil et al[33]	2020	ARMS	240°	Resected	Remained	1 cm	2 cm
Hedberg et al[35]	2019	ARMS	240°-270°	Resected	Remained	0	3 cm
Laquière et al[37]	2022	ARMS	Esophagus 180°; stomach 240°	Resected	Remained	1 cm	2 cm
Hu et al[38]	2023	ARMS	240°-290°	Resected	Remained	1 cm	2 cm

¹Excision range: The surgical scope as described in the study.

ARMS: Anti-reflux mucosectomy; ARMS-b: Anti-reflux mucosectomy using band ligation; ARMS-C: Anti-reflux mucosectomy with cap-assisted; L-ARMS: Ligation-assisted anti-reflux mucosectomy.

Procedure details and perioperative management of ARM-P

Inoue et al[18] conducted a study on ARM-P in 2024, and performed preoperative HREM, gastroscopy, esophagography, and 24-hour impedance-pH monitoring. The patients were required to stop taking acid-suppressing drugs for at least 7 days before the test. In cases where esophageal edema, exudate, furrowing, concentric rings, or strictures were observed, an esophageal biopsy was performed to rule out the presence of eosinophilic esophagitis. The surgery removed approximately 1/3^rd of the circumference of the mucosa along the lesser curvature of the gastric cardia by endoscopic mucosal resection with transparent cap. Then, the mucosal defect was closed using the Loop-9, Loop-10, and Loop-11 closure techniques[18]. Blood tests and endoscopic examinations were conducted on the first day after surgery. Patients showing no abnormalities in post-operation examinations were allowed to consume a liquid diet. The second endoscopic examination was conducted on the fourth or fifth day after surgery before discharge if patients claimed to be asymptomatic after diet. Further follow-up was performed twice: One between the first and the second-month post-surgery and the other between the third and fourth-month post-surgery.

Procedure details and perioperative management of ARMA

In 2020, Inoue et al[19] performed a pre-operative thorough evaluation of GERD using GERD-Health Related Quality of Life and Frequency Scale for Symptoms of GERD questionnaires and examinations, including gastroscopy, barium esophagography, HREM and pH monitoring. Patients underwent mucosal ablation around the cardia with a median operation time of 40.3 minutes and received single-dose PPI for 1 month. The median postoperative stay was 4 days. Follow-up evaluations were conducted at 2 months post-surgery. Hernández Mondragón et al[20] presented a median 300° circumference ablation of cardia with a median operation time of 35.5 minutes. PPI was administered at a double dose for 8 weeks, and follow-up evaluations were performed at 3 months, 6 months, 12 months, 24 months, and 36 months post-surgery. Chou et al[22] declared a median operation time of 50 minutes and a median postoperative stay of 2 days. Shimamura et al[23] reported the clinical application of the horseshoe or butterfly-shaped mucosal ablation technique; patients were fasted for 24 hours after the surgery and received a single dose of PPI or PCAB for 1 month[23]. The median hospital stay was 4 days. The preoperative examinations of ARMA were generally the same as those of ARMS, although barium esophagography was less frequently used. The butterfly-shaped mucosal ablation was the most frequently adopted technique in ARMA, with two contralateral areas of normal cardia mucosa, each about one scope diameter, spared to avoid stenosis (Table 6). The postoperative management and follow-up of ARMA are similar to those of ARMS. Regarding PPI usage, a single dose or double dose for 4 weeks was mainly prescribed.

Table 6 Technical specifications and subtypes of anti-reflux mucosal ablation and peroral endoscopic cardial constriction.

Ref.	Year	Intervention	Excision range
			Circumferential degree	Lesser curvature	Greater curvature	Esophagus	Stomach
Inoue et al[19]	2020	ARMA	2-3 cm remained	Remained	Remained	0	2 cm
Hernández Mondragón et al[20]	2020	ARAT	270°-320°	Remained	Remained	0	3 cm
Chou et al[22]	2023	ARMA	2-3 cm remained	Remained	Remained	0	2 cm
Shimamura et al[23]	2024	ARMA	2-3 cm remained	Remained/ablated	Remained	0	2 cm
Klimczak et al[24]	2023	ARMA	2-3 cm remained	Remained	Remained	0	> 1 cm
Li et al[25]	2017	PECC	2	Ligation	Ligation	1 cm	0
Liu et al[26]	2020	C-BLART	2	The anterior wall of the cardia	The posterior walls of the cardia	Ligated	0
Seleem et al[27]	2018	EBL	3-4	Ligation	Ligation	Ligated	0
Li et al[28]	2021	PECC-b	Esophagus 1-3; stomach 4-10	Ligation	Stomach remained Esophagus ligated	1 cm	3 cm
Jiang et al[29]	2022	PECC-b	240°	Ligation	Remained	1 cm	2 cm
Deshmukh et al[30]	2022	ARBM	4	Ligation	Remained	0	Ligated
Hu et al[34]	2018	PECC	2	Ligation	Ligation	1 cm	0
Wang et al[39]	2020	PECC	3	Ligated (trisection)	Ligated (trisection)	Ligated	0

ARMA: Anti-reflux mucosal ablation; ARAT: Anti-reflux ablation therapy; PECC: Peroral endoscopic cardial constriction; EBL: Endoscopic band ligation; C-BLART: Clip band ligation anti-reflux therapy; PECC-b: Peroral endoscopic cardial constriction with band ligation; ARBM: Anti-reflux band mucosectomy.

Procedure details and perioperative management of PECC

Before the PECC procedure, examinations including gastroscopy, esophageal pH monitoring, and motility evaluations were conducted. The surgery was performed by ligation at both the lesser curvature and greater curvature, approximately 1 cm proximal to the gastroesophageal junction. After surgery, patients were required to fast for 1-3 days and received PPI treatment for more than 2 weeks[25]. The operation strategies differed between ARMS and PECC, although both had similar postoperative management. In addition, the studies had different procedural details and post-operation recovery, such as fasting time and PPI usage. Preoperative examinations for PECC are almost the same as those for ARMA. The scope of surgery gradually develops from ligation of the lesser and greater curvatures of the esophagus to peri circumferential ligation involving the esophageal or gastric mucosa circumference (Table 6). A faster recovery was observed in patients treated with PECC than in those treated with ARMA and ARMS. Regarding post-surgery PPI usage, a single dose or double dose for 2 weeks was mainly chosen.

POST-OPERATIVE ADVERSE EVENTS OF ARMI

Post-operative adverse events of ARMS

Multiple adverse events after the ARMS procedure were reported, including dysphagia, bleeding, perforation, effusion, and pneumonia[33,35]. Some of the patients suffering from dysphagia needed dilation to relieve the symptoms. Some patients consuming anticoagulants reported bleeding as an adverse event. Despite these complications, most patients recovered well after surgery; very few patients required continuous endoscopic dilation. Patil et al[33] managed complications such as perforation, paraesophageal fluid accumulation, and mediastinitis with thoracoscopy, drainage, and nasojejunal nutrition for 4 weeks. They also reported postoperative aspiration pneumonia in three patients, who then received antibiotic therapy[33]. In a 2021 study by Sumi et al[10], two patients experienced postoperative bleeding and one had a minor perforation. Among 88 patients, 13 cases of dysphagia required more than three dilatations. However, after switching to the butterfly resection technique, only one patient (1/21) needed dilatation[10]. In another subsequent study, Sumi et al[10] reported that 23% of patients received additional treatments. Among these, 11 underwent surgical intervention and three received further endoscopic therapy. The median duration until additional treatment was 518.5 days. Among the 11 patients who underwent additional surgical treatment, eight showed significant symptom improvement. Of the three patients who continued to receive ARMA treatment, one reported improved condition, another remained in the follow-up, and the last patient withdrew due to other diseases[14]. In a study by He et al[8], 45 patients reported mild dysphagia, which resolved spontaneously within 4 weeks. Interestingly, compared with patients without dysphagia, those who reported postoperative dysphagia experienced better clinical benefits.

Although the proportion of patients with dysphagia and the treatment methods vary slightly in different studies, the overall average rate of stenosis or dysphagia of ARMS was approximately 14.69%, the average bleeding rate was approximately 2.09%, and the average perforation rate was approximately 0.27% (Table 7). It is important to note that postoperative dysphagia and stenosis are considered to be related to the extent of resection, whether the esophageal mucosa is resected, and whether the butterfly resection is performed.

Table 7 Incidence of postoperative dysphagia and related complications following anti-reflux mucosal ablation.

Ref.	Year	Intervention	Cases	Incidence of adverse events (%)
				Stenosis or dysphagia	Relief after dilatation	Bleeding	Perforation
Inoue et al[6]	2014	ARMS	10	20.0	Yes	0.0	0.0
He et al[8]	2022	L-ARMS	69	65.2	No	0.0	0.0
Gao et al[9]	2023	ARMS	20	0.0	NA	0.0	0.0
Sumi et al[10]	2021	ARMS	88	15.9	Yes	2.3	1.1
Wong et al[11]	2020	ARMS	33	9.1	Yes	3.0	0.0
Sui et al[12]	2022	ARMS	39	2.6	Yes	0.0	0.0
Sumi et al[14]	2024	ARMS	36	22.2	Yes	0.0	0.0
Yang et al[17]	2021	ARMS	39	23.1	Yes	2.6	0.0
Chou et al[22]	2022	ARMS	11	0.0	NA	0.0	0.0
Klimczak and Strzelczyk[24]	2023	ARMS-C	115	0.0	NA	0.0	0.0
Monino et al[32]	2020	ARMS-b	21	14.3	Yes	4.8	0.0
Patil et al[33]	2020	ARMS-C	33	6.1	Yes	0.0	0.0
Patil et al[33]	2020	ARMS	62	8.1	Yes	0.0	3.2
Hedberg et al[35]	2019	ARMS-b	19	15.8	Yes	5.3	0.0
Laquière et al[37]	2022	ARMS	13	7.7	Yes	15.4	0.0
Hu et al[38]	2023	ARMS	12	25.0	No	0.0	0.0
Average				14.69		2.09	0.27

ARMS: Anti-reflux mucosectomy; L-ARMS: Ligation-assisted anti-reflux mucosectomy; ARMS-b: Anti-reflux mucosectomy using band ligation; ARMS-C: Anti-reflux mucosectomy with cap-assisted; NA: Not available.

Postoperative adverse events of ARM-P

In his study on ARM-P, Inoue et al[18] did not observe any adverse events, such as bleeding, perforation, readmission, or dysphagia requiring balloon dilatation after discharge. The current evidence is not sufficient to determine the definite therapeutic effect of ARM-P. However, regarding the extent of surgery and wound closure technique, ARM-P should have relatively fewer postoperative adverse events.

Postoperative adverse events of ARMA

When Inoue et al[19] proposed ARMA in 2020, he did not report any other adverse events except for one patient who declared dysphagia and recovered from dilation twice. In Hernández Mondragón et al’s study[20] on anti-reflux ablation therapy, 13 patients reported chest pain, nine claimed dysphagia, and six endured mild abdominal pain. Stenosis occurred in 14 out of 108 patients. However, all of them responded to balloon dilatation, and no severe adverse events were found. Chou et al[22] reported a case of self-limited postoperative bleeding, as well as dysphagia and fever. According to Shimamura et al[23], 30.9% of patients reported post-operative pain, which could be effectively alleviated with medication. Nine patients experienced transient stenosis that required balloon dilatation. All patients reported improvement, although one patient needed repeated dilatation treatments. Six patients experienced delayed bleeding nearly 10 days after surgery.

In general, the average incidences of stenosis or dysphagia, bleeding, and perforation after ARMA surgery were 9.40%, 3.42%, and 0% (Table 8). Stenosis after the ARMA surgery can usually be relieved by balloon dilatation. The post-ARMA incidence of stenosis was lower than that of post-ARMS, probably due to the avoidance of the esophageal mucosal damage and preservation of the lesser curvature mucosa. Bleeding was more frequent after ARMA than it was after ARMS. No perforation was reported after ARMA. Postoperative chest pain or painful swallowing was common, and some required drug treatment.

Table 8 Incidence of postoperative dysphagia and related complications following anti-reflux ablation therapy and peroral endoscopic cardial constriction.

Ref.	Year	Intervention	Cases	Incidence of adverse events (%)
				Stenosis or dysphagia	Relief after dilatation	Bleeding	Perforation
Inoue et al[19]	2020	ARMA	8	12.5	Yes	0.0	0.0
Hernández Mondragón et al[20]	2020	ARAT	108	13.0	Yes	0.0	0.0
Chou et al[22]	2023	ARMA	12	8.3	Yes	8.3	0.0
Shimamura et al[23]	2024	ARMA	68	13.2	Yes	8.8	0.0
Klimczak et al[24]	2023	ARMA	10	0.0	NA	0.0	0.0
Average				9.40		3.42	0.0
Li et al[25]	2017	PECC	47	4.3	No	4.3	0.0
Liu et al[26]	2020	C-BLART	60	5.0	No	0.0	0.0
Seleem et al[27]	2018	EBL	75	25.3	No	0.0	0.0
Li et al[28]	2021	PECC-b	68	41.2	No	2.9	0.0
Jiang et al[29]	2022	PECC-b	16	12.5	No	12.5	0.0
Deshmukh et al[30]	2022	ARBM	4	0.0	NA	0.0	0.0
Hu et al[34]	2018	PECC	13	0.0	NA	0.0	0.0
Wang et al[39]	2020	PECC	15	40.0	No	0.0	0.0
Average				16.04		2.46	0.0

ARMA: Anti-reflux mucosal ablation; ARAT: Anti-reflux ablation therapy; PECC: Peroral endoscopic cardial constriction; EBL: Endoscopic band ligation; C-BLART: Clip band ligation anti-reflux therapy; PECC-b: Peroral endoscopic cardial constriction with band ligation; ARBM: Anti-reflux band mucosectomy; NA: Not available.

Postoperative adverse events of PECC

Several studies have shown that patients may experience retrosternal pain or dysphagia after surgery. Thankfully, such pain can be alleviated spontaneously within days or weeks in most of the patients, and no serious adverse events or deaths were reported[25,26,34]. Hematemesis has also been reported in some patients, but without any severe adverse events or deaths[28]. The average incidences of stenosis or dysphagia, bleeding, and perforation after PECC were 16.04%, 2.46%, and 0% (Table 8). The stenosis rate after PECC is comparable to that after ARMS and higher than that after ARMA, probably owing to the procedural details mainly involving the esophagus. Notably, most patients with stenosis or dysphagia can be relieved without balloon dilatation, indicating a mild and transient symptom. The bleeding rate after PECC was slightly higher than that after ARMS but lower than that after ARMA, which may be caused by tissue necrosis and detachment; however, no special treatment was required. No perforation was reported to occur after PECC. Although chest pain after PECC had a relatively higher incidence, it is generally a milder symptom.

COMPARISON AND APPLICATION OF DIFFERENT ARMI TECHNOLOGIES

All ARMI procedures (ARMS, ARMA, and PECC) are safe and highly efficient, and afford the advantages of being minimally invasive, avoiding artificial implants, requiring short operative time durations, enabling rapid recovery, and preserving the possibility of subsequent surgical interventions[11]. Specifically, ARMS provides the additional benefit of allowing tissue specimen collection for pathological evaluation, while ARMA shows a lower stenosis rate compared to that achieved with ARMS. Hence, ARMA can be used as a complementary treatment following ARMS, as it permits the repetition of procedures[19]. PECC stands out for its technical simplicity and simpler instrumentation requirement, which reduces the cost and shortens the procedure duration[31]. All ARMI modalities can modulate stenosis risk by adjusting the extent of mucosal interventions. In contrast, ARMS is associated with a relatively higher incidence of postoperative stenosis and perforation. In addition, it is not very suitable for repeated procedures[21,36]. The main limitations of ARMA include the inability to obtain tissue specimens for pathological examination and a slightly elevated bleeding risk relative to ARMS. PECC, while advantageous in several aspects, cannot provide specimens for analysis, and may aggravate lesions of the esophagus and exacerbate dysphagia and bloating (Table 9)[27].

Table 9 Advantages and limitations of anti-reflux mucosal intervention in clinical practice (anti-reflux mucosectomy, anti-reflux mucosal ablation, and peroral endoscopic cardial constriction).

Intervention		Advantages	Limitations
ARMS	ARMS-horseshoe	(1) No artificial device implantation required; (2) Short procedure time, hospital stay, and fast recovery than surgery; (3) Does not preclude future laparoscopic surgery; (4) Low bleeding rate; and (5) Available tissue specimens for pathology	Relative higher stenosis rate than ARMA
	ARMS-butterfly	(1) The same as ARMS-horseshoe; and (2) Reduced stenosis rate	Relative higher stenosis rate than ARMA
ARMA	ARMA-horseshoe	(1) No artificial device implantation required; (2) Short procedure time, hospital stay, and fast recovery than surgery; (3) Does not preclude future laparoscopic surgery; (4) Lower stenosis rate than ARMS; (5) Low perforation rate; (6) Adjunctive therapy for post-ARMS; and (7) Can be safely re-administered	(1) Tissue specimens for pathological analysis unavailable; and (2) Relative higher bleeding rate than ARMS
	ARMA-butterfly	(1) The same as ARMA-horseshoe; and (2) Further reduced stenosis rate	(1) Tissue specimens for pathological analysis unavailable; and (2) Higher bleeding rate than ARMS
PECC	PECC-esophagus	(1) Does not preclude future laparoscopic surgery; (2) Short hospital stays, and fast recovery; (3) Easier to conduct than ARMS; (4) Shorter procedure time; (5) Simpler instrumentation required; (6) Lower dysphagia rate than ARMS; and (7) Improves extra-esophageal symptoms	(1) Slight lower therapeutic effective rate; (2) Tissue specimens for pathological analysis unavailable; and (3) Risk of esophageal lesion aggravation
	PECC-stomach	The same as PECC-esophagus	(1) The same as PECC-esophagus; and (2) May exacerbate dysphagia and bloating
	PECC-esophagus & stomach	The same as PECC-esophagus	The same as PECC-stomach

ARMS: Anti-reflux mucosectomy; ARMA: Anti-reflux mucosal ablation; PECC: Peroral endoscopic cardial constriction; NA: Not available.

ARMS demonstrates the broadest clinical applicability. It is suitable for patients without hernia or with mild-to-moderate hernia, patients across all Hill grades, those without BE or with short-segment BE, those with mild-to-moderate esophagitis (Los Angeles’s grades A-C), younger patients refusing surgery, elderly patients or those with complex comorbidities who cannot tolerate surgical procedures, patients with or without any history of previous upper gastrointestinal surgery, and those requiring tissue specimens for pathological evaluation. However, ARMS has limited utility in patients with severe hernia (> 5 cm), long-segment BE, or severe esophagitis (Los Angeles’s grade D). While ARMA shares most contraindications with ARMS, it carries additional limitations for moderate herniation (3-5 cm), high Hill grade (IV), short-segment BE, moderate esophagitis (grade-C Los Angeles), and cases necessitating tissue specimens for pathological assessment. PECC demonstrates similar applicability to ARMA, though with marginally broader inclusion criteria for esophagitis (grade A-C Los Angeles) but stricter exclusion parameters regarding hernia (≤ 2 cm). Table 10 outlines the applicability of different ARMI (ARMS, ARMA, and PECC) for refractory GERD under varying clinical conditions, providing suggestion for selecting optimal interventions in patients with refractory GERD and different comorbidities.

Table 10 Options of anti-reflux mucosal intervention for refractory gastroesophageal reflux disease patients with different comorbidities.

Patient population			Intervention options
			ARMS	ARMA	PECC
Hiatal hernia	No	NA	Recommended	Recommended	Recommended
	Yes	≤ 2 cm	Recommended	Recommended	Recommended
		2-3 cm	Recommended	Recommended	Optional
		3-5 cm	Optional	Not recommended	Not recommended
Hill grade	I-II	NA	Recommended	Recommended	Recommended
	III	NA	Recommended	Recommended	Not recommended
	IV	NA	Recommended	Not recommended	Not recommended
Barrett’s esophagus	No	NA	Recommended	Recommended	Recommended
	Yes	Short BE	Recommended	Not recommended	Not recommended
		Long BE	Not recommended	Not recommended	Not recommended
Esophagitis (Los Angeles’s grade)	LA-A - LA-B	NA	Recommended	Recommended	Recommended
	LA-C	NA	Optional	Not recommended	Optional
	LA-D	NA	Not recommended	Not recommended	Not recommended
Age	Young (refusal of surgical procedures)	NA	Recommended	Recommended	Recommended
	Old (inability to tolerate surgical procedures)	NA	Recommended	Recommended	Recommended
Previous history of upper gastrointestinal surgery1	No	NA	Recommended	Recommended	Recommended
	Yes	NA	Recommended	Optional	Optional
Presence of mucosal abnormalities2	No	NA	Recommended	Recommended	Recommended
	Yes	NA	Recommended	Not recommended	Not recommended

¹Previous history of upper gastrointestinal surgery: Any prior upper gastrointestinal operation involving the lower esophagus, gastric cardia, or stomach, which may compromise surgical access and complicate surgical anti-reflux procedures.

²Presence of mucosal abnormalities: Confirmed or suspected mucosal abnormalities (e.g., Barrett’s esophagus) in the esophagogastric junction region requiring histopathological confirmation.

BE: Barrett’s esophagus; ARMS: Anti-reflux mucosectomy; ARMA: Anti-reflux mucosal ablation; PECC: Peroral endoscopic cardial constriction; NA: Not available.

LIMITATIONS

This review may be subject to publication bias, as studies with positive results (demonstrating the efficacy and safety of ARMI) are more likely to be published than those with negative or neutral results. Despite our extensive literature search, there may still be unpublished or unreported studies that have been missed, leading to an overly optimistic assessment of efficacy and safety. There is a lack of high-quality RCTs. Most studies on ARMI for treating GERD are observational studies (cohort studies and case series) or small-sample RCTs. The limited number of high-quality, large-sample, long-term follow-up RCTs restricts our ability to reliably compare the efficacy and safety of different ARMI techniques and may introduce selection bias and confounding bias. In addition, the surgical techniques display large-scale heterogeneity. ARMI encompasses a variety of techniques (such as ARMS, ARMA, and PECC). Even when same techniques are used (e.g., ARMS), there may be significant differences regarding operational details (such as resection range, depth, and instruments used) among different studies/centers. This poor standardization of techniques complicates the interpretation of pooled analysis results and may affect the comparability of efficacy and safety. Study quality and reporting also exhibit heterogeneity. The included studies vary in methodological quality (such as control of bias risk and completeness of follow-up) and the reporting of outcome indicators (such as the definition of effective rate and standards for recording adverse events), which increases the difficulty and uncertainty of result integration.

CONCLUSION

In general, the therapeutic effect of ARMI in treating GERD is relatively definite, with short operation time, fast postoperative recovery, and an acceptable incidence of adverse events. Thus, it can be considered one of the main surgical options for refractory or PPI-dependent GERD. The overall effectiveness of ARMS and ARMA is equivalent, and the effectiveness of PECC is slight less. The technical difficulty of surgery decreases in turn. ARMA and PECC procedures can be repeated if necessary. ARMS brings about a high rate of stenosis and a possibility of perforation, but a low rate of bleeding; ARMA results in a high rate of bleeding and pain, but a low rate of stenosis; PECC presents a high rate of stenosis and pain, but no specific interventions are required. In addition, the butterfly-shaped surgical range in ARMS and ARMA may help prevent stenosis. The selection of a suitable technique should be guided by individual patient characteristics and the specific clinical scenario. Given its demonstrated efficacy, technical simplicity, and cost-effectiveness, PECC is recommended as the initial treatment for younger patients with GERD who meet ARMI criteria. For cases showing suboptimal response to PECC, escalation to ARMA or ARMS may be considered, with ARMA offering the additional advantage of being repeatable when clinically needed. For those with unsatisfactory outcomes, as well as for surgical-naïve patients presenting with severe hernia (> 5 cm), long-segment BE, or severe esophagitis (grade D Los Angeles), laparoscopic anti-reflux surgery remains a viable therapeutic option. Furthermore, following endoscopic intervention, the necessity of additional surgical procedures may be determined based on the extent of GERD symptom alleviation and the informed preference of the patient.