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scalpel, thulium laser, etc., have been introduced to assist the FES with satisfactory outcomes. Additionally,
the use of CO insufflation and routine mucosal closure have consistently been recommended to minimize
2
the risk of perforation. Regardless of the device used, FES has proven feasible and effective during
short-term follow-up, with a recurrence rate of 29% [22-25] . However, FES is repeatable, and multiple
treatments can be done to complete septum division. A systematic review and network meta-analysis
including nine cohort studies with a total of 903 patients and comparing endoscopic laser-assisted
diverticulotomy, endoscopic stapler-assisted diverticulotomy, and transcervical diverticulectomy concluded
that the open surgical approach has a decreased likelihood of persistent or recurrent symptoms compared
with the endoscopic techniques .
[26]

[27]
Experience with the use of POEM for esophageal achalasia helped translate the principles of third-space
endoscopy to the pharyngoesophageal area, thereby pushing the boundaries of FES. The Z-POEM
technique has quickly gained popularity and will be accepted as the gold standard flexible endoscopic
technique. Z-POEM is an innovative technique that allows cricopharyngeal myotomy through submucosal
tunneling. The majority of reports now differentiate between two different tunneling techniques based on
the site of mucosal incision. In the conventional technique, originally described by Li et al., the
hypopharyngeal mucosa is opened 1.5-2 cm proximal to the septum and the submucosal tunneling is
[28]
created to reach and divide the cricopharyngeal muscle . The mucosal entry site is then closed using
endoscopic clips. Performing the incision proximal to the septum makes the procedure safer, given its
distance from the mediastinum, but care must be taken to avoid tearing the thin hypopharyngeal mucosa
during clip closure. A limitation of Z-POEM is that only the cricopharyngeal muscle is divided, not the
proximal esophageal muscle, and that the defunctionalized remnant pouch may be responsible for residual
symptoms.

An alternative third-space approach, called Zenker peroral endoscopic septotomy (Z-POES), was described
by Mavrogenis et al. to overcome the technical challenges of the Z-POEM technique and to improve
outcomes . Z-POES is a modified tunneling technique that consists in opening the mucosa alongside the
[29]
long axis of the septum, directly on top of it, to gain direct access to the muscle. Then, the submucosal
tunnel ahead and behind the cricopharyngeal muscle is created, and the proximal esophageal muscle fibers
are also divided [Figure 2]. At the end of the myotomy, a remodeling V-shaped mucosal septal incision can
be performed to widen the communication between the residual pouch and the esophagus, making this
procedure particularly suitable for larger diverticula .
[30]
[31]
A recent pilot study by Repici et al. on 20 patients advocated the use of Z-POES for ZD > 20 mm in size .
The average procedural time was 13.8 min, and the technique was successful in 100% of patients. No
symptomatic adverse events occurred, and the one-year clinical success rate was 95%. In a recent systematic
review by Spadaccini et al., which included nine studies with a total of 196 patients undergoing Z-POEM or
Z-POES, the pooled rate of clinical success and the pooled rate of adverse events were 93.4% and 4.9%,
[32]
respectively . No significant differences in terms of efficacy and safety were found between the two
tunneling techniques. A recent meta-analysis of 11 studies that included a total of 357 patients
[33]
undergoing Z-POEM showed a pooled technical success of 96.3% (95%CI: 93.6%-97.9%), a pooled incidence
of adverse events of 12.4% (95%CI: 9.1%-16.7%), and a clinical success rate of 93% (95%CI: 89.4%-95.4%).
The pooled clinical recurrence rate was 11.2% (95%CI: 7.6%-16.2%).

CLINICAL RESULTS OF Z-POEM AND Z-POES
A summary of the outcomes of Z-POEM and Z-POES reported in the literature, including our personal
experience, is presented in Table 3.