Natural orifice transluminal endoscopic surgery: The true frontier of gastrointestinal endoscopy

Table 1 Evolution and key milestones in natural orifice transluminal endoscopic surgery

Ref.	Date	Model or setting	Access route	Procedure/innovation	Key contribution/outcomes
Kalloo et al[1]	2000	Porcine model	Trans-gastric	Diagnostic peritoneoscopy	First proof-of-concept of transluminal endoscopic access to the peritoneal cavity
Rao et al[2]	2008	Human	Trans-gastric	Appendectomy	First human NOTES procedure
Rattner et al[3]	2006	Consensus group	-	Established safety framework	Laid research and training foundations for clinical NOTES
Jamshidi et al[10]	2009	Human	Trans-gastric	Human magnetic compression gastroenterostomy	First human magnetic-assisted transluminal anastomosis
Liu et al[7]	2013-2014	Human	Trans-gastric	Ovarian cystectomy	First pure transgastric human NOTES
Liu et al[5]	2015	Human	Trans-rectal	Gallbladder preserving cholecystolithotomy	First pure organ-preserving NOTES procedure
Liu et al[6], Liu et al[7], Liu et al[8], Wang et al[9]	2018-2020	Clinical	Trans-rectal, trans-gastric, trans-vaginal	Appendectomy, gastroenterostomy	Expansion to transluminal therapeutic applications
Zhao et al[16]	2021-2023	Human	Trans-rectal	Balloon-assisted access and closure	Development of detachable balloon system reducing peritoneal contamination risk
Jamshidi et al[10], Ryou et al[11], Ryou et al[12], Thigpen et al[13], Simsek et al[15]	2023-2025	Clinical and Experimental	Trans-rectal, trans-gastric, trans-vaginal	Gallbladder, liver, pancreas, mediastinal interventions	Integration of robotics, magnetic platforms, and AI-assisted navigation into NOTES

NOTES: Natural orifice transluminal endoscopic surgery; AI: Artificial intelligence.

Table 2 Current and emerging clinical and experimental applications of natural orifice transluminal endoscopic surgery across organ systems

Ref.	Organ system/application area	Representative procedures	Preferred access route	Stage of development	Key technical features	Outcomes/technical success
Liu et al[5], Hao et al[14], Dubcenco et al[20], Shang et al[43]	Gallbladder	Gallbladder-preserving cholecystolithotomy; cholecystectomy	Transrectal, transgastric	Early clinical to selected clinical application	Transparent cap assistance; transrectal or transgastric access; endoscopic gallstone retrieval; endoscopic closure using clips or OTSC when needed	Reported as feasible in selected patients; long-term recurrence, gallbladder function, and comparative outcomes require further study
Steele et al[45], Hazey et al[46], Chen et al[47], Liu et al[48], Chen et al[49]	Liver	Transgastric peritoneoscopy and liver biopsy; hepatic cyst deroofing or sclerotherapy	Transgastric, trans-sigmoid	Experimental to early clinical	Transluminal access to the peritoneal cavity; biopsy forceps or cyst intervention; electrocautery or endoscopic hemostasis when needed	Liver biopsy and hepatic cyst interventions have been reported as feasible in early human experience and selected cases; evidence remains limited
Wang et al[51], Matthes et al[52]	Pancreas	Pancreatic tail resection; pancreatic tumor enucleation	Transgastric	Experimental, animal models	Transgastric access; endoscopic dissection; clip closure; endoscopic management of minor bleeding or injury	Demonstrated technical feasibility in porcine models; pancreatic leak and adjacent organ injury remain important safety concerns
Liu et al[8]	Appendix/cecum	Transcecal appendectomy for appendiceal polyps	Transcecal	Limited clinical experience	Direct cecal access; flexible endoscopic resection; endoscopic closure of the cecal defect	Reported as feasible in selected clinical cases; broader safety and reproducibility require further evaluation
Liu et al[6], Pham et al[21], Ge and Thompson[22], Jin et al[23]	Stomach/small bowel	Pure NOTES gastroenterostomy; endoscopic suturing or defect closure related to transluminal intervention	Transgastric	Early clinical and device-development stage	Submucosal tunneling or transluminal access; endoscopic suturing; OTSC or clip-assisted closure	Early reports support feasibility, but outcomes vary by indication, technique, and available closure platform
Inoue et al[32], Liu et al[33], Inoue et al[37], Vespa et al[38], Nabi et al[39], Draganov et al[40], Harlow et al[41], Grimaldi et al[42]	Third-space endoscopy/esophagus	POEM; modified POEM; POEM-F; ESD and traction-assisted ESD	Transoral	Established for selected indications; evolving for expanded applications	Submucosal tunneling; selective or full-thickness myotomy; endoscopic fundoplication; traction-assisted submucosal dissection	Established for selected luminal and third-space indications such as achalasia and early gastrointestinal neoplasia; reflux and long-term outcomes remain procedure-dependent

NOTES: Natural orifice transluminal endoscopic surgery; OTSC: Over-the-scope clip; POEM: Peroral endoscopic myotomy; POEM-F: Peroral endoscopic myotomy with fundoplication; ESD: Endoscopic submucosal dissection.