Flexible endoscopic septotomy (FES) is the gold standard for the endoscopic treatment of Zenker’s diverticulum (ZD), although limitations of the technique remain. We report the first experience with a novel FES-based approach, termed Submucosal INjection-Guided septotomy (SING) technique.

In this retrospective analysis of prospectively collected data, all consecutive patients with ZD referred to three Italian centers between October 2019 and August 2024 were treated by the SING technique and included. SING procedure includes a classic septotomy, a mucosal incision with a Hook-Knife along the midline of the septum, and a cricopharyngeal myotomy extending along the entire length of the diverticulum and at least 10mm into the esophageal muscular layer. During septotomy, a submucosal injection is performed on both the esophageal and diverticular sides, enhancing visualization of the muscular layer and guiding a complete myotomy.  This represents the innovative aspect of the technique and an improvement over the traditional septotomy. The primary outcome was clinical success (CS), defined as a Kothari-Haber Scoring system score (KHSS) <2 at 3 months. Secondary outcomes included technical success (TS), procedural time, and adverse events (AEs). Time to recurrence was estimated using the Kaplan–Meier method.

A total of 102 patients underwent the SING procedure (median age 74 years [IQR 68–81]; 69.7% male). Median diverticulum depth was 30 mm (IQR 25–40), and median baseline KHS score was 4 (IQR 3–6).  CS was achieved in 98% (100/102) of patients, and, after a median follow-up of 370 days (IQR, 297–747), the recurrence of symptoms was 7%. The probability of remaining recurrence-free was 93.5% at 6 months, 92.0% at 12 months, and 92.0% at 24 months. TS was obtained in all cases, with a median procedural time of 30 minutes (IQR, 25–45 minutes). AEs occurred in 3 patients (2.9%) and were all managed endoscopically. Sixty-three patients (61.8%) underwent the conventional SING technique (C-SING), while 39 patients (38.2%) were treated with the diverticuloscope-assisted variant (D-SING). AEs occurred more frequently in the D-SING group (7.7% vs 0%, p=0.04), including the only case of perforation, which was attributed to mechanical trauma from the distal end of the diverticuloscope. Recurrence was more frequent in the D-SING group compared to the C-SING group, although this difference did not reach statistical significance (12.8% vs 3.3%, p = 0.06. Seventy-eight patients (76.5%) had large diverticula (>25 mm), while 24 patients (23.5%) had small diverticula (<25 mm). was similarly high (L-SING 97.4% vs S-SING 100%, p=0.43). No significant differences in AEs (3.8% vs 0%, p=0.62) and recurrence rates (7.9% vs 4.2%, p=0.53) were observed.  TS was 100% in both groups (p=1.00).

SING appears to be a safe and effective technique for the endoscopic treatment of ZD, potentially offering technical advantages and improved outcomes over conventional FES.