Endoscopic anti-reflux therapy for gastroesophageal reflux disease

Table 1 Comparison of current endoscopic therapies for gastroesophageal reflux disease

	TIF	MUSE	Stretta®	GERDx™	ARMS/ARMA	Band ligation
Efficacy	++	+	+ -	+	+	+
Safety	+	+	++	+	+	+
Technical difficulty	++	++	+	++	+	+
Add-on device	+	+	+	+	-	-
RCT available	+	-	+	-	-	-
Maximum follow-up (yr)	10	5	10	0.25	3	1
Cost	++	++	++	++	+	+

++: Indicates the highest score; +: Indicates a moderate score or yes; -: Indicates uncertainty; TIF: Transoral incisionless fundoplication; MUSE: Medigus ultrasonic surgical endostapler; GERDx™: Endoscopic full-thickness plication device; ARMS: Anti-reflux mucosectomy; ARMA: Anti-reflux mucosal ablation; RCT: Randomized controlled trial.

Table 2 Summary of guidelines and consensus recommendations and invasive gastroesophageal reflux disease therapies

Society guidelines and year of publication	Indication for surgery	Strength of recommendation, level of evidence, and grade of consensus	Endoscopic anti-reflux therapy addressed	Guideline recommendation on endoscopic anti-reflux therapy	Strength of recommendation and level of evidence
ACG guidelines for diagnosis and management of GERD, 2013[2]	Option for long-term treatment	Quality: High. Strength: Strong	Radiofrequency, bulking agents, endoscopic suturing	Not recommended	Quality: Moderate. Strength: Conditional
	Generally not recommended in PPI-unresponsive patients	Quality: High. Strength: Strong
	Refractory patients with objective evidence of ongoing reflux as the cause of symptoms	Quality: Low. Strength: Conditional
EAES recommendations, 2014[22]	Good response but dependent on long-term PPI therapy, after optimal risk-benefit discussion	Grade: C. Consensus: 100%	Radiofrequency (Stretta®), bulking agent injection (Enteryx®), plication (EndoCinch®, full-thickness plication, EsophyX®	Not enough evidence available to recommend any as an alternative option to surgery	Grade of recommendation: B. Expert consensus: 100%
	Total or partial refractoriness despite adequate PPI therapy in terms of dosage and intake	Grade: A. Consensus: 100%
	Well-selected NERD patients and those with hypersensitive esophagus	Grade: C. Consensus: 100%
American Society of Gastrointestinal Endoscopy: The role of endoscopy in the management of GERD, 2015[95]	Not provided	Not provided	Radiofrequency (Stretta®) and transoral incisionless fundoplication	Consider in highly selected patients. No details on selection criteria	Low quality
Asia-Pacific consensus on refractory GERD management, 2016[23]	Refractory symptoms with objectively documented GERD	Quality: Moderate. Strength: Strong. Consensus: 100%	None	Not applicable	Not applicable
World Gastroenterology Organisation Global Guidelines, 2017[24]	Large hiatal hernia with volume-related reflux symptoms. Refractory esophagitis. Refractory symptoms documented as caused by GERD. Medication adverse effects	Not specified	Endoscopic therapies in general	Only in the context of clinical trials	Not specified
SAGES Guidelines on GERD surgical treatment, 2010, and on endoluminal anti-reflux treatments, 2017[21,34]	Appropriately selected GERD patients	Grade A	Transoral incisionless fundoplication	Control of symptoms in appropriately selected patients in the short term; appears to lose effectiveness	Quality: Moderate. Strength: Strong
			Radiofrequency	Control of symptoms in appropriately selected patients; long-term effect in appropriately selected patients	Quality: Moderate. Strength: Strong
USA expert panel (surgeons and advanced therapeutic endoscopists) recommendations on GERD management, 2020[25]	PPI responders (complete or partial)	Appropriate. Consensus: 87%-100%	Transoral incisionless fundoplication	PPI responders (complete or partial), no hernia, any other scenario	Appropriate. Consensus: 93%
				PPI responders (complete or partial) or nonresponders, significant hernia, any other scenario	Not appropriate
				PPI nonresponder, no hernia and acid breakthrough, hypersensitivity or negative pH-impedance study for heartburn	Appropriate. Consensus: 80%–93%
	PPI nonresponder, no hernia, heartburn-hypersensitivity, or negative pH-impedance study	Appropriateness uncertain
				PPI nonresponder, regurgitation, negative pH-impedance study	Appropriateness uncertain
	PPI nonresponder, any other scenario	Appropriate. Consensus: 80%-100%
			Radiofrequency	PPI responders (complete or partial) or nonresponders, no hernia, any scenario	Appropriateness uncertain
				PPI responders (complete or partial) or nonresponders, significant hernia	Not appropriate
ESGE guidelines on endoscopic management of gastrointestinal motility disorders, 2020[35]	Not applicable	Not applicable	Transoral incisionless fundoplication	Possible role in mild GERD patients who are unwilling to take PPIs or undergo surgery. Against widespread use	Quality: Moderate. Strength: Strong. Consensus: 92.8%
			Medigus Ultrasonic Surgical Endostapler	Insufficient data. Use only in clinical trials	Quality: Low. Strength: Strong. Consensus: 100%
			Radiofrequency	Can be considered in selected patients only, without erosive esophagitis and hiatal hernia	Quality: Moderate. Strength: Weak. Consensus: 92.9%
			Anti-reflux mucosectomy	Against routine use in clinical practice	Quality: Low. Strength: Strong. Consensus: 100%
ESNM/ASNM consensus paper on management of refractory GERD, 2020[26]	Refractory GERD symptoms in patients with proven GERD	Consensus: 100%	Transoral incisionless fundoplication	Short-term benefit in improving regurgitation in carefully selected patients	Consensus: 100%
			Radiofrequency	Variable symptom improvement, limited objective improvement in acid burden or manometric esophagogastric junction features	Consensus: 100%

ACG: American College of Gastroenterology; EAES: European Association of Endoscopic Surgery; SAGES: Society of the Americans Gastrointestinal and Endoscopic Surgeons; GERD: Gastroesophageal reflux disease; ESGE: European Society of Gastrointestinal Endoscopy; ESNM: European Society of Neurogastroenterology and Motility; ASNM: American Society of Neurogastroenterology and Motility; PPIs: Proton pump inhibitors; NERD: Nonerosive reflux disease.

Table 3 Clinical success and safety of endoscopic therapies

Technique	Study design and population	Clinical success, range	Major adverse events, range
Transoral incisionless fundoplication	No. of RCTs: 5; n = 343	50%–92%	0%–4.4%
	No. of nonrandomized case series: 9; n = 543
Medigus ultrasonic surgical endostapler	No. of RCTs: 0	69%–92%	0%–9%
	No. of nonrandomized case series: 5; n = 199
Nonablative radiofrequency (Stretta®)	No. of RCTs: 5; n = 173	15%–100%	0%–1%
	No. of nonrandomized case series: 29; n = 2571
Endoscopic plication device (GERDx™)	No. of RCTs: 0	19 out of 40 patients were off PPIs	10%
	No. of nonrandomized case series: 1; n = 40
Band ligation techniques	No. of RCTs: 1; n = 150	43%–54%1	0%
	No. of nonrandomized case series: 2; n = 73
Anti-reflux mucosectomy	No. of RCTs: 0	58%–100%	0%–17%
	No. of nonrandomized case series: 12; n = 331
Anti-reflux mucosal ablation	No. of RCTs: 0	58%–89%	0%–13%
	No. of nonrandomized case series: 3; n = 130

¹Clinical success not defined in the randomized controlled trial. There was a significant reduction in gastroesophageal reflux disease health-related quality of life score and 24-h pH-metry outcomes. RCT: Randomized controlled trial; PPIs: Proton pump inhibitors.