Restrepo-Rodas G, Rodriguez J. Mastering the third space: Innovations in intramural endoscopic surgery for gastrointestinal disorders. World J Gastrointest Endosc 2025; 17(12): 111206 [DOI: 10.4253/wjge.v17.i12.111206]
Corresponding Author of This Article
John Rodriguez, MD, FACS, General Surgery, Cleveland Clinic Abu Dhabi, 59 Hamouda Bin Ali Al Dhaheri St, Abu Dhabi 00000, United Arab Emirates. rodrigj2@ccad.ae
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Surgery
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Minireviews
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Dec 16, 2025 (publication date) through Dec 19, 2025
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Publication Name
World Journal of Gastrointestinal Endoscopy
ISSN
1948-5190
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Restrepo-Rodas G, Rodriguez J. Mastering the third space: Innovations in intramural endoscopic surgery for gastrointestinal disorders. World J Gastrointest Endosc 2025; 17(12): 111206 [DOI: 10.4253/wjge.v17.i12.111206]
World J Gastrointest Endosc. Dec 16, 2025; 17(12): 111206 Published online Dec 16, 2025. doi: 10.4253/wjge.v17.i12.111206
Mastering the third space: Innovations in intramural endoscopic surgery for gastrointestinal disorders
Gabriela Restrepo-Rodas, John Rodriguez
Gabriela Restrepo-Rodas, John Rodriguez, General Surgery, Cleveland Clinic Abu Dhabi, Abu Dhabi 00000, United Arab Emirates
Gabriela Restrepo-Rodas, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi 00000, United Arab Emirates
John Rodriguez, College of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, United States
Author contributions: All authors wrote the original draft, investigation, review-editing, and final approval.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: John Rodriguez, MD, FACS, General Surgery, Cleveland Clinic Abu Dhabi, 59 Hamouda Bin Ali Al Dhaheri St, Abu Dhabi 00000, United Arab Emirates. rodrigj2@ccad.ae
Received: June 25, 2025 Revised: August 17, 2025 Accepted: November 11, 2025 Published online: December 16, 2025 Processing time: 174 Days and 5.2 Hours
Abstract
Third-space endoscopy, also known as intramural surgery, represents a major evolution in minimally invasive gastrointestinal interventions. While natural orifice transluminal endoscopic surgery provided early conceptual groundwork, third-space endoscopy builds upon it by maintaining interventions within the submucosal layer, offering improved precision and reduced risk. The creation of a controlled submucosal working space enables precise therapeutic interventions while potentially reducing the morbidity associated with traditional surgical approaches. Among its most impactful applications are the peroral endoscopic myotomy techniques, including cricopharyngeal, esophageal, gastric, and Zenker’s myotomies. These procedures have redefined the management of cricopharyngeal bar, achalasia, gastroparesis, and Zenker’s diverticulum, respectively. These techniques offer durable symptom relief with reduced recovery times. Over the past five years, refinements in technique, advancements in instrumentation, technology, and improved patient selection have expanded indications and enhanced safety. However, challenges remain, including the limited standardization and accessibility to specialized training. This review provides a comprehensive analysis of the evolution, technical refinements, and clinical outcomes of third-space endoscopy, with a focus on its expanding role in foregut surgery. By consolidating current evidence and highlighting future directions, we aim to provide a critical perspective on the impact of intramural surgery and its potential to further transform the management of complex gastrointestinal disorders.
Core Tip: Third-space endoscopy has redefined the management of complex foregut disorders through techniques such as cricopharyngeal, esophageal, gastric, and Zenker’s myotomies. These procedures offer effective, less invasive alternatives to traditional surgery, with growing evidence of durable outcomes. This review outlines key technical refinements and clinical milestones that have expanded their indications and safety. Emerging innovations such as artificial intelligence models and precision-based techniques signal the next frontier. These advancements are expanding the scope and safety of third-space endoscopy, moving it closer to broader clinical adoption and personalized surgical care.
