Keywords
zenker diverticulum - pharyngeal pouch - esophageal diverticulum - dysphagia - dysphonia
Introduction
Zenker diverticulum (ZD) or pharyngeal pouch is a rare disorder affecting 2 in every
100,000 people. The incidence is male predominant (ratio 1:5) and usually occurs in
middle-aged adults and older adults in the 7th or 8th decades of life. The etiology of ZD remains controversial; however, the presence
of a structural or functional abnormality of the cricopharyngeus muscle plays an important
role.[1]
[2]
[3] Patients presenting to the otolaryngology clinic with ZD often have multiple complaints.
The co-occurrence of pathologies such as gastroesophageal reflux disease (GERD) or
hiatal hernia makes the clinical evaluation of these patients a clinical challenge
to decipher which swallowing complaints are related to the ZD.[4]
Common clinical presentations include dysphagia, regurgitation, choking, chronic cough,
aspiration pneumonitis, globus, weight loss and, less commonly, dysphonia.[5] Clear clinical history and physical examination, associated with positive findings
on radiologic swallow evaluation – modified barium swallow study (MBSS) and barium
esophagram – are crucial for the diagnosis and size classification of ZD.[6] According to Van Overbeek the ZD size can be classified using a radiological scale
into a small pouch when it is shorter than one vertebra, and into a large pouch when
it is longer than three vertebrae.[7] This classification provides a better understanding of the correlation of the symptoms
of the patient with diverticulum size to improve clinical insight in diagnosis, treatment
planning, and preoperative counseling.
Treatment for ZD is indicated for all symptomatic patients, but some patients prefer
to defer surgical treatment until symptoms get more persistent and decrease their
quality of life.[8] Some studies have evaluated the relation of some clinical symptoms, such as globus
and regurgitation, with diverticulum size in patients with ZD who underwent surgical
procedures. However, studies that assessed the preoperative clinical presentations
with diverticulum size in ZD patients are currently lacking. The present study aims
to evaluate the association of the preoperative symptoms in ZD patients with the diverticulum
size.
Methods
A retrospective study design approved by the Institutional Review Board (IRB 20–003440)
was conducted. Electronic medical records (EMR) were used to identify patients diagnosed
with ZD (ICD-10: K22.5 diverticulum of the esophagus, acquired) from January 2009 through April 2020.
A total of 165 patients were identified and enrolled after the inclusion and exclusion
criteria were applied. A chart review of clinical data, including the first visit
to the otolaryngology clinic, previous medical history, and findings on the radiologic
swallow evaluation with MBSS or a barium esophagram, was completed. The initial medical
evaluation included the assessment of the presenting complaint and symptoms, including
dysphagia, odynophagia, dysphonia, cough, choking, regurgitation, aspiration, globus,
and weight loss. The intraoperative reports were also examined to evaluate the ZD
size and the method of treatment. The ZD size was stratified into 3 groups: small
(< 1 cm), moderate (1–3 cm), and large (> 3 cm). Surgical treatment included open
diverticulectomy with or without cricopharyngeal myotomy, endoscopic CO2 laser or
staple diverticulectomy, and cricopharyngeal myotomy. All the data were collected
from the medical record and stored in a RedCap database.
Statistical analyses were performed using IBM SPSS Statistics for Windows, version
25 (IBM Corp., Armonk, NY, USA). Standard descriptive statistics were obtained and
presented as percentages, mean ± standard deviations (SDs). A parametric statistical
analysis (student t-test) was used to compare demographics and comorbidities between the groups of patients.
Additionally, a Pearson correlation and a logistic regression analysis were also performed
to evaluate the association of presenting symptoms (independent variables) and the
ZD size (dependent variable). A p-value < 0.05 was considered statistically significant.
Results
The mean age of the patients among the overall cohort was 73 years old (range 39–96
years old) with a 1.2:1 male/female ratio. Pre-existing GERD diagnosis was present
in 65.5% of the patients, and 43.5% of the patients reported a history of tobacco
consumption. Thirty-eight patients had a diagnosis of hiatal hernia (23%). There was
no difference in age, gender distribution, body mass index (BMI), frequency of hiatal
hernia, and comorbidities between groups (p > 0.05). The demographic summary of ZD patients is shown in [Table 1].
Table 1
Demographic Summary and Clinical characteristics, overall cohort
|
Characteristics
|
n = 165
|
|
Gender, No. (%), male
|
92 (55.8)
|
|
Mean age, y (range, SD)
|
73 (39–96, 11)
|
|
BMI kg/m2, mean (SD)
|
26.9 (5.6)
|
|
Tobacco consumption, No. (%)
|
71 (43.5)
|
|
EtOH consumption, No. (%)
|
56 (34.3)
|
|
Radiologic evaluation
|
|
|
MBSS, No. (%)
|
108 (67.5)
|
|
Esophagram, No. (%)
|
146 (90.6)
|
|
Comorbidities
|
|
|
Hypertension, No. (%)
|
86 (52.1)
|
|
Diabetes Mellitus, No. (%)
|
19 (11.5)
|
|
Dyslipidemia, No. (%)
|
75 (45.5)
|
|
GERD, No. (%)
|
108 (65.5)
|
|
OSA, No. (%)
|
18 (11)
|
|
Hiatal Hernia, No. (%)
|
38 (23)
|
Abbreviations: BMI, Body Mass Index; EtOH, Ethanol; GERD, Gastroesophageal reflux disease; MBSS,
Modified barium swallow study; OSA, Obstructive sleep apnea; SD, standard deviation.
Small ZD size (< 1 cm) was found in 48 patients, medium size (1–3 cm) in 67 patients,
and large size (> 3 cm) in 50 patients. The prevalence of symptoms per ZD size is
shown in [Table 2]. Dysphagia was the most prevalent symptom among all patients (89.1%), followed by
cough (65.5%) and regurgitation (58.8%). Dysphonia was a more frequent symptom among
patients with a small ZD (22%) than in those with a medium and large diverticulum
(9 and 4%, respectively).
Table 2
Prevalence of symptoms according to Zenker Diverticulum size
|
All
|
Small
|
Medium
|
Large
|
|
n
|
%
|
n
|
%
|
n
|
%
|
n
|
%
|
|
Dysphagia
|
147
|
89.1%
|
37
|
77.1%
|
64
|
95.5%
|
46
|
92%
|
|
Cough
|
108
|
65.5%
|
30
|
62.5%
|
44
|
65.7%
|
34
|
68%
|
|
Regurgitation
|
97
|
58.8%
|
23
|
47.9%
|
44
|
65.7%
|
30
|
60%
|
|
Globus
|
80
|
48.5%
|
20
|
41.7%
|
31
|
46.3%
|
29
|
58%
|
|
Choking
|
61
|
37%
|
8
|
16.7%
|
27
|
40.3%
|
26
|
52%
|
|
Aspiration
|
31
|
18.8%
|
7
|
14.6%
|
16
|
23.9%
|
8
|
16%
|
|
Dysmotility
|
23
|
13.9%
|
6
|
12.5%
|
8
|
11.9%
|
9
|
18%
|
|
Weight loss
|
20
|
12.1%
|
2
|
4.2%
|
9
|
13.4%
|
9
|
18%
|
|
Dysphonia
|
19
|
11.5%
|
11
|
22.9%
|
6
|
9%
|
2
|
4%
|
|
Odynophagia
|
11
|
6.7%
|
3
|
6.3%
|
4
|
6%
|
4
|
8%
|
Correlation Coefficients
Pearson correlation between presenting symptoms and ZD size was performed and is shown
in [Table 3]. A small but statistically significant positive correlation was found between ZD
size and choking (r = 0.28; p = 0.001), dysphagia (r = 0.18; p = 0.019), and weight loss (r = 0.16; p = 0.037). Also, a statistically significant negative correlation between ZD size and dysphonia
(r = −0.22; p = 0.003) was noted.
Table 3
Pearson correlation between presenting symptoms and Zenker Diverticulum size
|
r
|
p-value
|
|
Dysphagia
|
0.18
|
0.019
|
|
Choking
|
0.28
|
0.001
|
|
Weight loss
|
0.16
|
0.037
|
|
Dysphonia
|
−0.22
|
0.003
|
Logistic Regression
Our logistic regression model showed a statistically significant relationship between
the presence of dysphagia and choking with the presence of a medium-sized and large-sized
ZD when compared with small-sized diverticula (p < 0.05). The odds ratio (OR) of dysphagia to be associated with a medium diverticula was
9.7 (95% confidence interval (CI): 2.0–46.1; p = 0.004) and the OR associated with a large-sized diverticula was 6.0 (95%CI: 1.3–27.0;
p = 0.018). The OR of choking associated with a medium diverticula was 4.8 (95%CI:
1.5–15.2; p = 0.008), and with large diverticula it was 5.6 (95%CI: 1.8–17.5; p = 0.003). Although dysphonia was the least frequent symptom among the three groups of
patients, its presence was significantly associated with the presence of a small-sized
ZD when compared with a bigger ZD (p < 0.04). The full details of our logistic regression analysis are presented in [Table 4].
Table 4
Logistic regression model between clinical symptoms and Zenker Diverticulum size
|
β-value
|
Standard Error
|
OR (95%CI)
|
p-value
|
|
Dysphagia
|
|
|
|
|
|
Small (> 1 cm)
|
Reference
|
|
|
|
|
Medium (1–3 cm)
|
2.27
|
0.79
|
9.75 (2.06–46.16)
|
0.004*
|
|
Large (> 3 cm)
|
1.80
|
0.76
|
6.06 (1.36–27.04)
|
0.018*
|
|
Choking
|
|
|
|
|
|
Small (> 1 cm)
|
Reference
|
|
|
|
|
Medium (1–3 cm)
|
1.57
|
0.58
|
4.81 (1.51–15.28)
|
0.008*
|
|
Large (> 3 cm)
|
1.72
|
0.58
|
5.63 (1.8–17.56)
|
0.003*
|
|
Dysphonia
|
|
|
|
|
|
Small (> 1 cm)
|
Reference
|
|
|
|
|
Medium (1–3 cm)
|
−1.34
|
0.64
|
0.26 (0.74–0.91)
|
0.036*
|
|
Large (> 3 cm)
|
−1.99
|
0.84
|
0.13 (0.02–0.75)
|
0.023*
|
|
Regurgitation
|
|
|
|
|
|
Small (> 1 cm)
|
Reference
|
|
|
|
|
Medium (1–3 cm)
|
0.27
|
0.49
|
1.31 (0.5–3.46)
|
0.576
|
|
Large (> 3 cm)
|
0.04
|
0.52
|
1.04 (0.37–2.91)
|
0.939
|
|
Globus
|
|
|
|
|
|
Small (> 1 cm)
|
Reference
|
|
|
|
|
Medium (1–3 cm)
|
−0.41
|
0.49
|
0.65 (0.24–1.73)
|
0.398
|
|
Large (> 3 cm)
|
0.11
|
0.53
|
1.11 (0.39–3.17)
|
0.833
|
Discussion
The present study evaluated the presence of preoperative symptoms among a large cohort
of patients with a diagnosis of ZD and its association with the documented diverticulum
size. Our population showed an elderly male predominance, agreeing with the data found
in several cohort studies.[9]
[10]
[11]
[12]
[13] The coprevalence of GERD and hiatal hernia was also evident in our sample. These
two pathologies have been commonly reported as co-occurring conditions in individuals
with ZD, making their symptoms easily confused with the presence or recurrence of
a pharyngeal pouch.[10]
[14]
[15] This finding confirms the importance of early treatment, as the presence of ZD could
lead to a nutritional compromise and to a potential escalating comorbidity over time.[16] Our results showed that dysphagia, cough, regurgitation, and globus are the most
prevalent symptom among all groups.
Interestingly, a global incidence of dysphonia of 11.5% was also found among our patients.
This is consistent with other studies (Palmer et al., 2007; Bergeron et al., 2013;
Greene et al., 2015).[9]
[10]
[12] For example, Greene et al. reported dysphagia caused by outflow resistance in the
esophagus as the primary preoperative symptom in their cohort of 77 patients, followed
by regurgitation and cough.[12] Palmer et al. surveyed symptoms before and after the endoscopic repair of the ZD
among a group of 72 patients, finding that food avoidance, regurgitation, choking,
and cough were the most prevalent clinical manifestations.[10] A difference in the study design (i.e., both pre- and postsurgical repair were included
relative to our study) could explain the difference in the results.
Our data also indicates that dysphagia and choking are significantly associated with
the presence of a medium-sized or large-sized pharyngeal pouch. Bergeron et al. evaluated
the characteristics of dysphagia and its correlation with the ZD size within a cohort
of 46 patients. Their findings were similar to our data, suggesting the relationship
between dysphagia and regurgitation with a medium or large ZD size, and highlighting
the importance of a radiologic swallow evaluation if patients with a history of ZD
removal persist with dysphagia.[9] However, our study benefited from having a larger sample size and not previously
analyzed symptoms such as dysmotility, dysphonia, weight loss, and other medical history
variables.
Only one study, by Schoeff et al., has identified dysphonia as a disease feature among
patients with ZD. Although they found dysphonia as an unrecognized preoperative complaint,
a significant improvement in the voice handicap index-10 (VHI-10) before and after
surgery was noted.[17] Our results correlate with this study, as the incidence of dysphonia within the
groups of patients with a medium-sized and large-sized diverticulum was also low.
We hypothesize that the misperception and underestimation of voice handicap among
individuals with ZD can explain this finding. We also hypothesize that the presence
of dysphonia among patients with a small pouch could have caused an early endoscopic
evaluation and diagnosis during the study of more prevalent causes of dysphonia, including
GERD, more than the ZD per se. It is noteworthy that radiologic swallow evaluation
with MBSS or a barium esophagram has been widely recommended for patients with suspected
structural abnormalities, including ZD.[6]
[18] Our results contribute to the literature and can be the starting point to consider
a fluoroscopic swallowing evaluation among those patients in whom no other apparent
cause of dysphonia is documented.
Limitations
As a retrospective study, there are several intrinsic limitations to consider. For
example, cointerventions and confounders could not be controlled due to the nature
of our study. In some medical records, limited data were available, including notes
regarding the improvement of symptoms after the surgical repair of the ZD and voice-related
questionnaires. We consider that further prospective studies with larger sample sizes
and a complete preoperative and postoperative evaluation of symptoms will increase
the statistical power. Additionally, to confirm our findings, studies involving the
preoperative and postoperative assessment of patient-reported outcome measures, including
the VHI-10, Glottal Function Index (GFI), Reflux Symptoms Index (RSI), and the Voice-Related
Quality of Life score (VRQOL), are needed.
Conclusions
Our study suggests that upper gastrointestinal symptoms such as dysphagia and choking
may be associated with a ZD > 1 cm and should always be evaluated. Additionally, the
presence of dysphonia was found to correlate with a ZD < 1 cm, suggesting that a prompt
and appropriate fluoroscopic evaluation must be considered in those patients in whom
no other clear cause of dysphonia is evident.
