Introduction
In 1877, Friedrich Albert von Zenker reported the pulsion diverticulum, which was
termed Zenker’s diverticulum [1 ]. It is an acquired prolapse of the mucosal and submucosal layers located dorsally
at the pharyngoesophageal junction through Killian’s triangle [2 ]. It is the most common type of esophageal diverticula with a reported prevalence
ranging between 0.01 % and 0.11 %, and typically occurs in middle-aged and elderly
patients [3 ]
[4 ]. Its pathophysiology in detail remains unknown but it could result from discoordination
between pharyngeal contraction and upper esophageal sphincter relaxation [5 ]. A significant portion of patients with Zenker’s diverticulum are asymptomatic [6 ]
[7 ] and in most cases, the condition is diagnosed during a routine evaluation. The most
severe complication is the aspiration of food, especially during the night, which
can promote pneumonia. Other rare complications are cancer, bleeding, and perforation
[4 ].
Treatment is indicated for the majority of cases, especially when the patient is symptomatic,
regardless of the size of the diverticulum, and consists basically of the myotomy
of the cricopharyngeal muscle. Endoscopic treatment was initially proposed in 1917
[8 ], and developed over time [9 ]
[10 ]
[11 ]
[12 ]
[13 ]. However, potential complications such as perforation, bleeding, and infection have
curtailed its use. In 1993, an endoscopic stapling technique using an endosurgical
stapler was presented that, at the same time, cut the septum of the pouch and stapled
the wound edges closed [14 ]. The techniques in the surgical approach were cricopharyngeal myotomy and suspension
of pouch; cricopharyngeal myotomy and inversion of pouch; cricopharyngeal myotomy
and excision of pouch; cricopharyngeal myotomy only; Dolman’s procedure and pouch
excision only [15 ].
The aims of this systematic review were to identify all published studies that compared
endoscopic versus surgical treatment of Zenker’s diverticulum and assess outcomes
in terms of length of procedure, length of hospitalization, time of diet introduction,
rates of complication, and rates of recurrence.
Methods
The review was registered on the PROSPERO international database (www.crd.york.ac.uk/prospero/ ), number CRD42014014675.
Data search
A systematic review of articles reporting endoscopic versus surgical treatment of
Zenker’s diverticulum was conducted in accordance with the Preferred Reporting Items
for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Studies have been selected by searching electronic databases and scanning reference
lists of articles. This search was applied for Medline (considering all years) and
Embase (considering all years). Cochrane and LILACS (via BVS), Scopus and CINAHL (via
EBSCO) databases were also reviewed. The last search was run on 18 September 2014
and no limits were applied for language.
The following search strategy was used for Medline database, named #1 for abbreviation
purposes and stratified by Population (P), Intervention (I), and Comparison (C):
P: Zenker (MeSH) AND
I: [Endoscopy (MeSH) OR Endoscopy, Digestive System (MeSH) OR Endoscopy, Gastrointestinal
(MeSH)] AND
C: [Surgical Procedures, Operative (MeSH) OR Digestive System Surgical Procedures
(MeSH) OR Surgery (Subheading)].
Aiming to select high quality studies, the search strategy mentioned above (#1) was
filtered twice, as follows: (a) “(#1 AND random *)”, called #2; and (b) ((clinical[Title/Abstract]
AND trial[Title/Abstract]) OR clinical trials as topic [MeSH Terms] OR clinical trial[Publication
Type] OR random*[Title/Abstract] OR random allocation[MeSH Terms] OR therapeutic use
[MeSH Subheading]), called #3. The totality of articles was obtained by mixing the
investigation in the PubMed Advanced Search Builder as follows: “(#2 OR #3)”. As part
of the process, the Medline search strategies were peer reviewed.
For Embase, Cochrane, LILACS, Scopus, and CINAHL databases, the search was: “(Zenker’s
diverticulum AND endoscopy AND surgery)”.
Selection criteria
Clinical trials and/or observational studies were initially identified and targeted
to the selection process. No limits on language or publication data were initially
imposed. The titles and abstracts of all potentially relevant studies were reviewed
independently by two authors for eligibility. Disagreements between the reviewers
were resolved by consensus. The references in the included studies were then selected
for any relevant articles.
Studies that compared endoscopic versus surgical treatment of Zenker’s diverticulum
were included. There were no restrictions with regard to different modalities of treatment
in each arm. Studies were excluded if they did not compare both techniques or if different
techniques were combined in the same patient. We also excluded studies that were written
in languages different from English, Portuguese or Spanish, as well as reviews and
case reports. There were no exclusions based on patient numbers or length of follow-up.
The main outcome measures were length of procedure, length of hospitalization, time
until diet introduction, rate of complications, and rate of recurrences. To summarize
the study selection process, an adapted PRISMA Flow Diagram was used [16 ].
Data extraction
Details, such as number of patients, age, gender, method of treatment, size of the
diverticulum, and study design were recorded from all included articles when available.
The modality of intervention was also assessed. Any disagreements in the process of
study selection and data extraction were resolved by discussion and consensus.
Risk of bias in individual studies
The articles were analyzed for selection bias, quality bias, publication bias, and
sensitivity analysis. To avoid selection bias, studies were selected after extensive
searching in electronic databases and scanning reference lists of articles that applied
to the inclusion criteria. This search was applied for Medline, Embase, LILACS, Scopus,
and CINAHL databases. To prevent quality bias, the Newcastle-Ottawa Scale [17 ] was applied. The studies selected were all assessed if the risk of bias was acceptable,
i. e., critical evaluation of the included trials should reveal a score ≥ 6, with
a total of 9 being the highest possible score.
Summary measures and synthesis of results
Heterogeneity between studies was assessed using the I2 index introduced by Higgins
and Thompson [27 ]
[28 ]. For computations of confidence intervals, estimates of mean and standard deviation
(mean ± SD) were required. However, some of the published articles did not describe
the mean and standard deviation, and did not show data that would enable calculation,
so they were not included in the meta-analysis. Funnel plots were produced to identify
the presence of publication bias in the meta-analysis. Both total sample size and
precision (1/standard error) were plotted against the treatment effects (absolute
risk, absolute risk increase, and absolute risk reduction for binary variables and
standardized mean difference (SMD) for continuous variables) [29 ]. The outcome was considered to be statistically significant if the confidence interval
of 95 % was achieved.
The I2 statistic is appealing because it may be expressed as a percentage, and this
percentage has an intuitive meaning. It represents the percentage of variation in
the data that is due to between-study variability. Thus, a perfectly homogeneous study
will have an I2 value of 0. Conversely, a perfectly heterogeneous set of studies would
have an I2 value approaching 100 % [30 ].
The statistical method used for the meta-analysis was the fixed effects model. A fixed-effects
model makes the presupposition that each of the studies in the meta-analysis was studying
the same overall population of patients. Therefore, it only takes into account the
variation within studies.
Depending on heterogeneity, as measured by I2, data were calculated by the fixed effects
model using the Mantel-Haenszel method [31 ]. When the heterogeneity was higher than 50 %, sensitivity analysis was performed,
generating a new analysis. Subgroup analyses and meta-regression were performed to
identify the origin of heterogeneity. All analyses were performed using Review Manager
5.3 Software (Cochrane Informatics & Knowledge Management Department) [32 ].
Results
Study selection
The process of study selection is summarized in [Fig. 1 ]. During the systematic review, 357 articles were identified through MEDLINE searching.
Another 671 were screened in EMBASE, CINAHL, LILACS, and BVS databases. One additional
study was not identified in MEDLINE, giving a total of 358 articles. Of those, 345
were excluded for different reasons (did not meet the inclusion criteria, language,
systematic reviews, and case reports). After the abstracts had been carefully analyzed,
13 articles were assessed for eligibility. Among them, only 11 studies met the inclusion
criteria. All studies were retrospective cohorts. There were no randomized trials.
In total, 596 patients were included in the final analysis.
Fig. 1 PRISMA flow diagram providing information on the selection of studies.
Study characteristics
The study characteristics of those who were included are summarized in [Table 1 ]. All 11 studies were retrospective cohorts. The total number of patients, age, gender,
and how many were submitted to the endoscopy or surgery groups were observed.
Table 1
Summary of the characteristics of the studies that met the inclusion criteria.
Study
No. of patients
Measures
Outcomes
Total
Endoscopy
Surgery
Method
Age
Size
Seth et al., 2014 [18 ]
55
24
31
Stapler
Y
Y
LP, M, COMP, REC, IS, CR, LOSS
Henry et al., 2013 [2 ]
36
12
24
Stapler
Y
Y
M, COMP, REC, IS, CR
Koch et al., 2011 [19 ]
155
101
54
Laser
Y
N
LP, LH, COMP, IS, CR, LOSS
Brace et al., 2010 [20 ]
18
10
8
Stapler
Y
Y
LP, LH, COMP, LOSS
Porcuna et al., 2009 [21 ]
16
6
10
Combined
Y
Y
LP, DI, M, COMP, REC, CR
Wirth et al., 2006 [22 ]
47
23
24
Stapler
Y
N
LP, LH, M, COMP, LOSS
Safdar et al., 2004 [23 ]
19
10
9
Stapler
Y
N
LP, LH, DI, COMP, REC
Smith et al., 2002 [24 ]
16
8
8
Stapler
N
N
LP, LH, DI, COST
Gutschow et al., 2002 [25 ]
184
86
98
Both singly
Y
Y
LH, DI, COMP
Sydow et al, 2001 [26 ]
16
3
13
Both singly
Y
Y
COMP, REC
van Eeden et al., 1999 [15 ]
34
17
17
Stapler
Y
N
LP, LH, DI, COMP, REC, IS, LOSS
Y: information present; N: missing information; LP: length of procedure; LH: length
of hospitalization; DI: time to diet introduction; M: mortality; COMP: complications;
REC: recurrence; IS: improvement in symptoms; CR: conversion rates; LOSS: loss on
follow-up; COST: costs.
Regarding the treatment approach, the method used in both groups, and the initial
size of diverticulum were evaluated. Endoscopic treatment of Zenker’s diverticulum
includes endoscopic stapling diverticulotomy, CO2 laser, and harmonic scalpel as the most common techniques [12 ]
[14 ]. The surgical approach includes cricopharyngeal myotomy and suspension of pouch;
cricopharyngeal myotomy and inversion of pouch; cricopharyngeal myotomy and excision
of pouch; cricopharyngeal myotomy only; Dolman’s procedure and pouch excision only
[13 ].
In terms of outcomes, the data considered were: length of procedure, length of hospitalization,
time to diet introduction, complication rates, recurrence rates, improvement in symptoms,
conversion rates, costs, and loss to follow-up.
Risk of bias within studies
All 11 studies that were selected were retrospective and controlled trials (Level
of evidence IIB from Oxford Centre for Evidence-based Medicine). The Newcastle – Ottawa
Scale was used for quality assessment. The studies selected were all assessed as “acceptable”
for the risk of bias, and the detailed information is shown in [Table 2 ]. As mentioned earlier, the included trials should have a score ≥ 6, with a total
of 9 being the highest possible score (each asterisk symbol in [Table 2 ] represents one point).
Table 2
Newcastle-Ottawa Scale; all studies had acceptable risk of bias.
Study
Selection
Comparability
Exposure
Total score
Seth et al., 2014 [18 ]
*
*
*
*
*
*
*
*
8
Henry et al., 2012 [2 ]
*
*
*
*
*
*
*
*
8
Koch et al., 2011 [19 ]
*
*
*
*
*
*
*
*
8
Brace et al., 2010 [20 ]
*
*
*
*
*
*
*
*
8
Porcuna et al., 2009 [21 ]
*
*
*
*
*
*
*
*
*
9
Wirth et al., 2006 [22 ]
*
*
*
*
*
*
*
*
8
Safdar et al., 2004 [23 ]
*
*
*
*
*
*
*
*
*
9
Smith et al., 2002 [24 ]
*
*
*
*
*
*
*
*
*
9
Gutschow et al., 2002 [25 ]
*
*
*
*
*
*
*
*
*
9
Sydow et al., 2001 [26 ]
*
*
*
*
*
*
*
*
8
van Eeden et al., 1999 [15 ]
*
*
*
*
*
*
*
*
*
9
Included trials should have a score ≥ 6, with a total of 9 being the highest possible
score (each asterisk symbol represents one point).
Results of individual studies
The most relevant variables that could be extracted from each study are summarized
in [Table 3 ] and include the total number of patients, age, method used in both groups, length
of procedure, length of hospitalization, time to introduction of diet, complication
rates, recurrence rates, and costs. [Table 3 ] compares the outcomes of the endoscopic versus surgical approach to Zenker’s diverticulum.
Table 3
Results of all 11 studies summarized.
Study
Total, n
Endoscopy, n
Surgery, n
Length of procedure, min
Length of hospitalization, days
Time to diet introduction, days
Complication
Recurrence
Seth et al., 2014 [18 ]
55
24
31
48.3/131.1
IU
IU
7/2
8/3
Henry et al., 2012 [2 ]
36
12
24
IU
IU
IU
0/4
4/0
Koch et al., 2011 [19 ]
155
101
54
51/146
8.7/10.4
IU
9/14
12/1
Brace et al., 2010 [20 ]
18
10
8
19.5/110.88
2.3/4.71
1.1/2
1/0
0/0
Porcuna et al., 2009 [21 ]
16
6
10
45/90
2/3.8
1/1.5
0/2
0/2
Wirth et al., 2006 [22 ]
47
23
24
32/106
5.5/12.3
IU
3/4
1/1
Safdar et al., 2004 [23 ]
19
10
9
20 – 30/90 – 120
3.9/10
1/6
1/3
1/2
Smith et al., 2002 [24 ]
16
8
8
25.5/87.6
1.3/5.2
0.8/5.1
1/0
0/0
Gutschow et al., 2002 [25 ]
184
86
98
IU
4/6.12
2/4
3/3
11/8
Sydow et al., 2001 [26 ]
16
3
13
IU
IU
IU
0/3
2/2
van Eeden et al., 1999 [15 ]
34
17
17
IU
2.26/4
3/3.6
3/7
0/0
IU: information unavailable.
Synthesis of results
All 11 studies were reviewed. It was possible to develop a meta-analysis of five outcomes.
The other outcomes were not suitable for meta-analysis because of the absence of essential
data such as mean and standard deviation or standard error. The outcomes that could
be assessed were length of procedure, length of hospitalization, time to diet introduction,
rate of complications, and rate of recurrences.
Length of procedure
The outcome length of procedure was described and contained data that allowed meta-analysis
(mean and standard deviation) in three studies, with acceptable heterogeneity (I2 = 16 %).
A statistically significant reduction of operating time was noted favoring endoscopic
treatment (standardized mean difference (SMD) – 78.06, 95 %CI – 90.63, – 65.48). Note
that “minutes” was used as the unit for the analysis ([Figs. 2, 3 ]).
Fig. 2 Length of procedure: endoscopic and surgical treatment of Zenker’s diverticulum-forest
plot.
Fig. 3 Length of procedure: endoscopic and surgical treatment of Zenker’s diverticulum-funnel
plot.
Length of hospitalization
The outcome length of hospitalization was suitable for meta-analysis in two studies
and they demonstrated homogeneity (I2 = 34 %) in the funnel plot. A statistically
significant reduction in length of hospitalization was observed favoring endoscopic
treatment (SMD – 3.72, 95 %CI – 4.49, – 2.95). Note that “days” was used as the unit
for this analysis ([Figs. 4, 5 ]).
Fig. 4 Length of hospitalization: endoscopic and surgical treatment of Zenker’s diverticulum-forest
plot.
Fig. 5 Length of hospitalization: endoscopic and surgical treatment of Zenker’s diverticulum-funnel
plot.
Recurrence rates
All 11 articles had data that were suitable for meta-analysis and had low and acceptable
heterogeneity (I2 = 45 %). Meta-analysis showed a statistically significant reduction
in the risk of recurrence of symptoms when treatment of Zenker’s diverticulum was
performed through the surgical approach compared with endoscopic treatment (SMD 0.08,
95 %CI 0.03, 0.13) ([Figs. 6, 7 ]).
Fig. 6 Recurrence of Zenker’s diverticulum: endoscopic and surgical treatment-forest plot.
Fig. 7 Recurrence of Zenker’s diverticulum: endoscopic and surgical treatment-funnel plot.
Diet introduction
The time to diet introduction after the procedure was found to be suitable for meta-analysis
in two studies. Due to a high level of heterogeneity between both articles (I2 = 94 %),
the study that had the lowest weight and produced a publication bias was excluded
[20 ]. It was observed that there was a statistically significant reduction in the fasting
period for patients who were submitted to endoscopic treatment for Zenker’s diverticulum
(SMD – 4.30, 95 %CI – 5.18, – 3.42). “Day” was used as the unit during this analysis
([Figs. 8 – 10 ]).
Fig. 8 Time to diet introduction after endoscopic and surgical treatment of Zenker’s diverticulum-forest
plot.
Fig. 9 Time to diet introduction after endoscopic and surgical treatment of Zenker’s diverticulum-funnel
plot.
Fig. 10 Time to diet introduction after endoscopic and surgical treatment of Zenker’s diverticulum – forest
plot (after outlier exclusion).
Complication rates
All 11 articles had data that allowed meta-analysis of this outcome. The main complications
that were described were cervical leak, hoarseness, aspiration pneumonia, chest pain,
and perforation of the esophagus. Due to heterogeneity (I2 = 53 %) promoted by one
specific article [18 ] and identified through the funnel plot, it has been removed from the meta-analysis.
After that, the heterogeneity became acceptable (I2 = 43 %). Meta-analysis of complication
rates showed a statistically significant reduction in the risk of complications when
patients were submitted to endoscopic treatment (SMD – 0.09, 95 %CI 0.03, 0.43) in
comparison with the surgical approach ([Figs. 11 – 13 ]).
Fig. 11 Rates of complications after endoscopic and surgical treatment-forest plot.
Fig. 12 Rates of complications after endoscopic and surgical treatment-funnel plot.
Fig. 13 Rates of complications after endoscopic and surgical treatment-forest plot (after
outlier exclusion).
Risk of bias across the studies
All 11 studies presented low indices of heterogeneity detected for the five outcomes
that were analyzed (time of operation, length of hospitalization, time to diet introduction,
rate of complications, and rate of recurrences).
Time of operation, length of hospitalization, and recurrence rate demonstrated low
rates of heterogeneity (I2 = 16 %, I2 = 34 %, and I2 = 45 %, respectively) ([Figs. 3, 5, 7 ]).
Meta-analysis of time to introduction of diet presented a high level of heterogeneity
between two articles (I2 = 94 %) [20 ]
[24 ]. One was excluded [20 ] because of its lowest weight. After that, the concept of heterogeneity became inapplicable
for this meta-analysis ([Fig. 9 ]).
Considering complication rates, all 11 articles were suitable for meta-analysis, but
the funnel plot demonstrated asymmetry of one of them in comparison with the other
10 studies (I2 = 53 %). That one [18 ] was removed from the meta-analysis, and then the analysis had an acceptable heterogeneity
(I2 = 43 %) ([Fig. 11 ]).
Discussion
Summary of evidence
The treatment of choice for Zenker’s diverticulum has historically been surgical.
Both open transcervical and endoscopic approaches are associated with complications
and potential risks. Nowadays, endoscopic surgery is the first approach [33 ], but surgery still has its utility in the treatment of Zenker’s diverticulum [34 ]. An incomplete myotomy is associated with a higher degree of symptomatic recurrence
[35 ]
[36 ]
[37 ]
[38 ]
[39 ]. Usually, the surgical approach allows diverticulum resection and a complete myotomy,
decreasing recurrence. In addition, individual anatomic or disease-related factors,
such as upper teeth protrusion or insufficient neck motility hinders endoscopic treatment.
So, although not considered in this review, some points are important for general
consideration. The introduction of the diverticuloscope in the correct position, enabling
sufficient and safe exposure of the surgical field is often, in fact, the most difficult
and time consuming part of the endoscopic procedure [40 ]. Exposure of the diverticulum sac, which can be based on clinical conditions (upper
teeth protrusion, recessed mandible, narrow mouth opening, cervical spine mobility,
position of the larynx, depth of the fundus of the diverticulum sac) and the results
of the barium esophagogram (size and anatomy of the pouch, protection by the dorsal
esophageal wall) are some adopted criteria for treatment choice [19 ]. If any major adversity is found, the surgical approach may be considered.
Regarding the size of Zenker’s diverticulum, there is no consensus considering different
studies [21 ]
[22 ]. A disadvantage of the stapling technique seems to be the incomplete section of
the diverticular septum, leaving a remanent sac due to the stapler tip, not reachable
by the knife.
In this review, considering all 11 articles, the decision concerning the method to
be applied to each patient was variable. Usually, elderly patients tended to be treated
with an endoscopic approach, as it has lower rates of complications and a shorter
hospital stay [2 ]. Considering that patients with Zenker’s diverticulum usually have many comorbidities,
their clinical condition is essential to define the best treatment. Also, physician
preferences, training, and standards of practice were important aspects in the final
decision [18 ]
[20 ]. Seth et al. [18 ] reported that the patient’s wishes should be taken into account. Some authors reported
no clinical criteria in choosing the treatment modality [15 ]
[23 ].
Through the systematic review, certain outcomes were found that were not present in
all articles and were not suitable for meta-analysis,. The improvement in symptoms
was assessed through multiple different questionnaires, usually subjective, which
prevented the meta-analysis of this specific outcome.
In summary, patients for open or endoscopic procedures should be selected according
to several criteria. Regarding all the nuances of patients with Zenker’s diverticulum,
the endoscopic approach seems to have better results than surgical management.
Limitations
In this systematic review, all 11 articles included were retrospective cohorts. In
the literature, there were no prospective cohorts or randomized trials comparing both
techniques that met the inclusion criteria.
Zenker’s diverticulum is a rare disease and typical of an elderly population, which
may confound cases of complications or even death due to other health problems.
The decision to allocate patients to the groups could be biased by the age of the
patient, diverticulum size, and anatomic variation that induces the patient to be
allocated to one specific group.
Analysis of symptom improvement was evaluated in a variable manner in each article
and was associated with a large loss at follow-up, which constrained the statistical
analysis.
Conclusions
Compared with a surgical approach, endoscopic treatment appears to result in a shorter
length of procedure and hospitalization, earlier diet introduction, and lower rates
of complications, but in higher rates of symptom recurrence.
