Zenker's diverticulum is a posterolateral pulsion diverticulum arising at Killian's triangle secondary to impaired relaxation of the cricopharyngeal muscle (CPM). Although its prevalence in the general population is estimated at 0.01-0.11 %, it predominantly affects elderly, comorbid patients in whom dysphagia, regurgitation, and aspiration risk translate into a disproportionate burden on quality of life.

Horner's syndrome is a clinical entity encountered by head and neck surgeons in patients with penetrating neck injury, post-neck dissections, and cervical sympathetic chain schwannomas. However, Horner's syndrome after transcervical resection of Zenker's diverticulum has not been previously described in the published literature. A patient who had failed two previous attempts at endoscopic repair of a large Zenker's diverticulum underwent transcervical diverticulectomy with cricopharyngeal myotomy. A previous history of anterior cervical fusion at C5 and C6 was also present. Postoperatively, he developed pupillary asymmetry, left upper eyelid ptosis, and ipsilateral anhydrosis. Ophthalmology consultation was initiated, and cocaine 10% solution drops applied to both eyes confirmed the diagnosis. His symptoms persisted at 2 years postsurgery. Horner's syndrome is a potential complication of Zenker's diverticulectomy due to the close proximity of the pouch base to the sympathetic chain. The likelihood of injury to the cervical sympathetic chain is also increased in the setting of previous neck surgery.

Third-space endoscopy refers to a set of endoscopic techniques that allow access to the submucosal space or "third space" between the mucosa and muscularis propria, enabling therapeutic intervention while preserving mucosal integrity. The unifying concept across all third-space endoscopy procedures is the creation of a submucosal tunnel with a mucosal flap acting as a safety valve, allowing separation of access from therapy. This principle is the key factor underlying its rapid adoption across diverse indications. The evolution of third-space endoscopy began with the submucosal endoscopy with mucosal flap technique, followed by the first porcine per-oral endoscopic myotomy and its clinical application in humans nearly two decades ago. Per-oral endoscopic myotomy has not only transformed the management of achalasia but also established a platform that has since been extended to multiple gastrointestinal disorders, including per-oral endoscopic myotomy for refractory gastroparesis, submucosal tunneling endoscopic resection for sub-epithelial tumors, Zenker's per-oral endoscopic myotomy, and per-oral endoscopic myotomy for epiphrenic diverticula. Although some procedures, such as per-oral endoscopic myotomy and tunneling resection for subepithelial tumors, have matured with well-defined roles in clinical algorithms, others, including per-oral endoscopic myotomy in refractory gastroparesis and Zenker's per-oral endoscopic myotomy, demonstrate promising safety and efficacy but continue to face unresolved questions regarding patient selection, durability, and comparative effectiveness. Despite these limitations, third-space endoscopy has emerged as a minimally invasive alternative for several conditions traditionally managed surgically. Its standardized core principles allow broad adaptability across disease phenotypes. This narrative review discusses the evolution, technical framework, clinical outcomes, and current limitations of key third-space endoscopy procedures.

Endoscopic management of Zenker's diverticulum has rapidly evolved with the emergence of innovative therapeutic endoscopic approaches and the integration of novel devices. These techniques offer unprecedented precision and safety, although rare, adverse events can become catastrophic if not promptly recognized and managed. This narrative review explores recent innovations in third-space techniques and novel devices, with a focused, detailed discussion on recognizing and effectively managing adverse events.