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

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.