Introduction
Per-oral endoscopic myotomy (POEM) has emerged as a safe and efficacious treatment
for the management of various esophageal motility disorders [1]
[2]
[3]. The technical success of POEM is high and reported in upto 90–100 % cases. However,
severe submucosal fibrosis (SMF) may pose special challenges during submucosal tunneling
procedures like POEM [4]
[5]. SMF has been shown to correlate with a prolonged operation, longer hospital stay,
and higher perioperative adverse events [5]
[6]
[7]. There is limited data regarding the outcomes of POEM in cases with SMF as well
as techniques to improve technical success in these cases.
In this study, we evaluated the impact of double tunnel technique (DT POEM) on the
technical success of POEM in cases with SMF.
Patients and methods
The data of patients with achalasia who underwent POEM during the study period (Jan
2013 to Jan 2020) were analysed, retrospectively. The cases with SMF were included
in the final analysis. SMF was defined as either difficulty in lifting mucosa or sparse
submucosal fibers resulting in poor separation between mucosa and muscle layer during
tunneling. SMF was further classified as severe if mucosa and muscle were completely
adherent and did not separate with repeated injections resulting in either termination
of the POEM procedure or requiring a second tunnel for completion of POEM ([Fig. 1]) [8]. The decision to abort POEM via first tunnel and create a new tunnel was made after
agreement among at least two of the three POEM experts (ZA, MR, DNR).
Fig. 1 Submucosal tunneling in cases with varying severity of submucosal fibrosis (SMF).
a Submucosal tunnelling in a case with no SMF. b, c, d SMF with loose adherence of mucosa and muscle layer. Note that POEM could be completed
using the same tunnel. e, f Severe SMF with complete adherence of mucosa and muscle layer. double tunnel POEM
was performed in these cases.
POEM technique
POEM was performed using single or DT technique in cases with SMF. Single tunnel POEM
was performed using standard technique as described previously [4]
[9]. In cases with a poor mucosal lift with initial injection, several attempts were
made at different sites. The procedure was abandoned in cases with complete adherence
of mucosa and muscle layer during submucosal tunneling in the single tunnel group.
Whereas, a second tunnel was created along different orientation in esophagus in the
DT technique group.
The technique of DT-POEM is as follows ([Video 1]). Initially the submucosal lifting injection was performed anteriorly (2 O’clock)
or posteriorly (5 O’clock). Mucosal incision and submucosal tunneling were performed
in the standard fashion. In cases with severe SMF not allowing continuation of tunneling,
a second tunnel was created along the anterior or posterior esophageal wall depending
on the initial site of tunneling ([Fig. 2]). The site of second submucosal injection was selected at least 1 to 2 cm below
the initial incision along the alternate route (anterior or posterior). Subsequent
procedure was accomplished using the standard technique of POEM. Finally, mucosal
incisions of both the tunnels were closed using endoscopic clips.
Video 1 Double tunnel per-oral endoscopic myotomy in a patient with severe submucosal fibrosis.
Fig. 2 Technique of double tunnel per-oral endoscopic myotomy. a Submucosal injection along posterior esophageal wall (note the reflection of water
jet indicative of severe submucosal fibrosis). b Poor lifting of mucosa after submucosal injection. c Adequate lifting of mucosa after injection along anterior esophageal wall. d Severe submucosal fibrosis after tunnelling for a few centimeters. e Third submucosal injection along the posterior esophageal wall about 2 cm below the
first injection. f Adequate expansion of the submucosal space allowing for successful submucosal tunnelling.
g Endoscopic myotomy performed after completion of tunnelling. h Closure of the mucosal incision using multiple endoclips.
Primary outcome
The primary outcome of the study was to evaluate the impact of DT-POEM on technical
success in cases with severe SMF. The technical success of POEM procedure in cases
with SMF was compared before and after the utilization of double tunnel technique.
Adverse events
Events requiring an additional procedure, such as needle drainage for capno-peritoneum,
temporary cessation of procedure due to accumulation of retroperitoneal CO2, mucosal injuries requiring closure with endoclips, intra-procedural or post-procedural
events leading to prolongation of hospital stay were considered as adverse events
(AEs) [10]
[11]. Major AEs were defined as those associated with hemodynamic instability, blood
transfusion, mucosal injuries requiring special closure techniques, and major leaks
[11].
Statistical analysis
The continuous data were expressed as mean (SD) or median (range) and the categorical
data as frequencies unless otherwise specified. Comparison of categorical data between
groups was performed using chi-square test with Yates correction. All the tests of
significance were two tailed and a P < 0.05 was considered to indicate statistical significance.
Results
A total of 1,150 POEM procedures were performed during the study period. Of these,
POEM was performed using single tunnel technique in the initial cohort (n = 479) irrespective
of the presence of SMF. Whereas, double tunnel technique was utilized as required
in the latter cohort (n = 671). Overall, SMF of any severity was detected in 104 (9 %)
patients (males 67, 51.82 ± 10.57 years) including 41 (8.5 %) and 63 (9.4 %) cases
in the initial and latter cohort, respectively. The median disease duration was 48
(range 6–144) months ([Table 1]).
Table 1
Procedure details in cases with SMF before and after utilization of the double tunnel
technique
|
Cohort 1
n = 479
|
Cohort 2
n = 671
|
P
|
|
SMF (Overall)
|
41 (8.5 %)
|
63 (9.4 %)
|
0.677
|
|
Severe SMF
|
10 (2.1 %)
|
11 (1.6 %)
|
0.457
|
|
Technical success (SMF)
|
28 (68.3 %)
|
62 (98.4 %)
|
0.0001
|
|
Technical failure
|
Severe SMF (10)
Extension of incision (3)
|
Leiomyomatosis (1)
|
|
|
Orientation of POEM
|
Anterior 31 (75.6 %)
|
Anterior 27 (42.8 %)
|
0.001
|
|
DT-POEM
|
0
|
11 (17.5 %)
|
|
|
Mucosal edema
|
|
|
13 (56.5 %)[1]
|
25 (65.8 %)[2]
|
0.478
|
|
|
7 (70 %)
|
10 (90.9 %)
|
|
|
Disease duration months, mean (SD)
|
49.27 ± 32.04
(range, 9–120)
|
53.70 ± 33.96
(range, 6–144)
|
0.508
|
|
Length of myotomy, cm
|
n = 28
|
n = 62
|
|
|
|
9.18 ± 3.02
|
7.36 ± 2.18
|
0.002
|
|
|
2.90 ± 0.54
|
2.85 ± 0.34
|
|
|
Procedure duration in minutes, mean (SD)
|
79.44 ± 27.92
|
71.65 ± 29.67
|
0.184
|
|
Adverse events
|
0.605
|
|
|
4
|
5
|
|
|
|
2
|
7
|
|
|
|
–
|
1
|
|
SMF, submucosal fibrosis; POEM, per-oral endoscopic myotomy; DT-POEM, double tunnel
per-oral endoscopic myotomy
1 Data not available for eight patients
2 Data not available for 13 patients
Severe SMF was encountered in 21 patients (1.8 %) (males 18, 52.48 ± 9.49 years).
The subtypes of achalasia in cases with severe SMF were type II (2), type I (17) and
unknown (2). Prior treatment history and sigmoidization of esophagus were noted in
nine (42.8 %) and five patients (23.8 %), respectively. POEM could not be completed
in 14 patients (1.2 %) due to severe SMF in 10, inadvertent extension of mucosal incision
in three, and circumferential leiomyoma leading to sigmoid achalasia in one. Mucosal
edema or changes of stasis esophagitis were evident in 17 patients (94.4 %) ([Table 2], [Fig. 3]).
Table 2
Characteristics of patients with severe submucosal fibrosis.
|
Patient characteristics
|
N = 21
|
|
Severe submucosal fibrosis
|
21 (1.2 %)
|
|
Mean age in years (SD)
|
52.48 (9.49)
|
|
Disease duration in months, median (range)
|
66 (18–144)
|
|
Type I/II/III/unknown
|
17/2/0/2
|
|
Sigmoid achalasia
|
5
|
|
Technical failures
|
14 (1.2 %)
|
|
Severe submucosal fibrosis
|
10
|
|
Others
|
4
|
|
Double tunnel technique
|
11
|
|
Length of myotomy, cm
|
|
|
4.64 (1.36)
|
|
|
3 (0.67)
|
|
Procedure duration in minutes, median (range)
|
150 (85–210)
|
|
Mucosal injury
|
3
|
Fig. 3 Mucosal changes in cases with severe SMF. a Mucosal inflammation obscuring the normal vascular pattern. b Severe inflammation and nodularity of the esophageal mucosa. c Mucosal inflammation with ulceration giving a cobblestone appearance to the mucosa.
Primary outcome
Of 104 cases with SMF, POEM was successfully completed using single tunnel and double
tunnel in 83 (79.8 %) and 11 patients (10.6 %), respectively. POEM could not be completed
in 10 cases (9.6 %) due to severe SMF in the single tunnel group. DT-POEM technique
was utilized in 11 patients (10.6 %) with severe SMF. The second tunnel was created
along the posterior route (5 O’clock) in the majority of patients (9, 81.8 %) after
failure to complete the initial tunnel via anterior route (2 O’clock). DT-POEM was
successful in all the cases where utilized ([Table 2]).
Double tunnel versus single tunnel POEM
In cases with SMF, the technical success was achieved in 28 (68.3 %) in the initial
cohort. The technical success of POEM procedure was significantly better after the
adoption of the double tunnel technique in the latter cases with SMF (98.4 % vs 68.3 %,
P = 0.0001). There was no technical failure due to severe SMF after adoption of the
DT-POEM technique as compared to 10 failures in cases where the technique was not
utilized ([Fig. 4])
Fig. 4 Graphic summary of the results of the study.
Outcomes in technical failure cases
Of the 14 cases with technical failures, four underwent POEM after a median of 3 months,
six underwent pneumatic dilatation, two patients received botulinum toxin injection
and two patients underwent esophagectomy for advanced achalasia and leiomyomatosis
in one patient each.
Adverse events
There were no major AEs in patients with SMF who underwent POEM with or without DT-POEM
technique. Minor AEs were encountered in 17 (16.3 %), including capno-peritoneum (n = 9),
mucosal injury (n = 9), and submucosal hematoma (n = 1). The cases with capno-peritoneum
were managed using needle decompression. Whereas, mucosal injuries were successfully
closed using standard endoclips after the completion of procedure. Submucosal hematoma
was noticed within the index tunnel in one patient who underwent POEM via the double
tunnel technique. No intervention was required in this case as there were no signs
of active bleeding ([Table 2]).
Discussion
In this study, we found that severe SMF is rare but the most common reason for technical
failure during POEM. DT-POEM is a safe and effective technique and reduces technical
failure in patients with severe SMF.
SMF is one of the major reasons for technical failure during POEM [5]
[8]. The severity of SMF is relative and has not been well defined in the literature.
Feng et al categorized SMF into three grades of severity – mild, moderate, and severe
– based on the distribution or density of fibers and lifting effect of submucosal
injection [8]. In their study, SMF was detected in all the cases, including mild in 73 % and moderate
to severe in 27 % [8]. However, mild SMF usually does not pose special challenges to the POEM procedure
as mucosa can be lifted easily. Moreover, it may be difficult to differentiate mild
SMF from no SMF based on distribution and density of fibers. In our study, we utilized
an objective and clinically relevant definition of SMF. Severe SMF was classified
only if it precluded continuation of the POEM procedure, resulting in either abortion
or requirement of a second tunnel to complete the procedure. With this definition,
SMF and severe SMF were found in 9 % and 1.8 % of patients, respectively, who underwent
POEM at our center.
The technical success in the entire cohort was 98.8 %. Overall, severe SMF accounted
for technical failure in 0.9 % of all cases. The majority (71.4 %) of the technical
failures could be attributed to severe SMF. Our results are in concordance with previous
studies where SMF resulted in technical failures in 0.7 % to 2.6 % of cases and responsible
for most (> 90 %) of the technical failures [5]
[8]
[12]
[13].
The risk factors for SMF include long disease duration ( ≥ 6 years), sigmoid esophagus,
mucosal edema, and prior interventions [5]. In our study, the median disease duration in patients with severe SMF was more
than 5 years, the majority had type I achalasia and sigmoidization of esophagus apparent
in nearly one-fourth of these cases suggestive of advanced achalasia. The presence
of mucosal inflammation has been shown to correlate with the degree of SMF [8]. Although we did not grade the degree of mucosal edema, the changes of stasis esophagitis
and mucosal inflammation were evident in most of the patients with severe SMF ([Fig. 3]). Besides mucosal inflammation, the water jet sign, slow and uneven mucosal lift,
and rapid dissipation of the bulge are other potential indicators of SMF ([Fig. 2]).
The management options in patients with severe SMF include performing simultaneous
tunneling and myotomy and open POEM and POEM via double tunnel technique [14]
[15]. The risk of mucosal injury may be higher with the former technique. Similarly,
the safety concerns with open POEM preclude its widespread utilization [16]. DT-POEM is similar to the conventional POEM technique, and therefore, may not be
technically difficult to perform. Sanaka et al reported the utility of creating a
second submucosal tunnel in a patient with severe SMF [14]. Besides this report, there are no studies evaluating the role of DT-POEM in patients
with severe SMF. Because the endoscopist has access to the entire esophagus, a second
tunnel can be attempted at several different locations without much difficulty. In
our study, the DT-POEM technique was successful in all the cases where utilized. Importantly,
there were no technical failures due to severe SMF after the adoption of the DT-POEM
technique.
Our results suggest that SMF is usually focal and a second tunnel along the opposite
route allows for successful POEM in the majority of the cases [17]. On the other hand, one potential drawback of the technique is that the final length
of the myotomy may be shorter than the initially intended length as the second tunnel
is initiated 1 to 2 cm distal to the site of the initial tunnel. Nevertheless, a short
esophageal myotomy has been shown to be adequate at least in type I and II achalasia
[10]
[18]
[19]
[20]
[21]. The other drawback of the DT-POEM technique is the requirement for adequate expertise
in performing POEM via both orientations (anterior and posterior).
There are several implications of our study. First, severe SMF is rare but the most
important reason for technical failure during POEM. SMF is usually focal, and therefore,
provides the opportunity of performing POEM by creating a second tunnel at a different
site or orientation. In the present study, although mucosal changes were evident along
both the anterior and posterior esophageal walls, a second submucosal tunnel could
be created successfully. This finding suggests that mucosal changes may not correlate
perfectly with the presence of SMF and the degree of SMF may vary along the esophagus,
even with a similar grade of mucosal changes.
Our study has several strengths. To the best of our knowledge, this is the first study
describing the utility of DT-POEM in patients with severe SMF. We acknowledge a few
noteworthy limitations of our study. Technical success is dependent on operator’s
experience and improvisation in devices (e. g. water jet-equipped knives). Therefore,
improvement in technical success in the latter period may not be attributed solely
to the DT-POEM technique. We used a stringent definition for defining SMF. Therefore,
we may have underestimated the true incidence of SMF in the current study.
Conclusions
In conclusion, severe SMF is the major reason for technical failures during POEM.
DT-POEM is safe and reduces technical failures in these cases.
