FULL PAPER

Internal Medicine

Clinical features and prognosis of canine

megaesophagus in Japan
Taisuke NAKAGAWA1), Akihiro DOI1), Koichi OHNO1)*, Nozomu YOKOYAMA1)
and Hajime TSUJIMOTO1)
1)Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences,
The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan

ABSTRACT. Megaesophagus (ME) is a common esophageal disease in dogs and the prognosis
is generally poor, especially with aspiration pneumonia (AP). We retrospectively investigated
J. Vet. Med. Sci. the clinical features and prognosis of canine ME in Japan. Twenty-eight dogs were included in
81(3): 348–352, 2019 this study, with the Miniature Dachshund breed being significantly overrepresented (odds ratio:
4.33). Most cases (21 of 28) were diagnosed as idiopathic ME and Myasthenia gravis was the most
doi: 10.1292/jvms.18-0493
common cause of secondary ME. The overall median survival time (MST) was not reached and the
3-month survival rate was 85.7%. Ten dogs were diagnosed with AP, at least once during the study
period, and the MST of ME dogs with AP was 114 days. The survival time overall and even with AP,
Received: 18 August 2018
was notably more prolonged compared to the previous studies. We hypothesized that treatment
Accepted: 26 December 2018 for canine ME could prolong the survival time, even in those with both ME and AP.
Published online in J-STAGE:
10 January 2019
KEY WORDS: aspiration pneumonia, megaesophagus, miniature dachshund

Megaesophagus (ME) is a common cause of regurgitation in dogs and it is characterized by diffuse esophageal dilation and
concurrent esophageal dysmotility. ME is categorized into congenital and acquired forms [14]. Congenital ME is attributed to vagal
afferent dysfunction [9, 10]. Acquired ME is either idiopathic, or secondary to another disease, such as myasthenia gravis (MG)
[8, 15, 20], hypoadrenocorticisim [2, 24], dysautonomia [5, 16], polyradiculoneuritis [3], hypothyroidism [7], polymyopathies [6],
and esophageal cancer [1, 12]. MG is the most common cause of the secondary ME and it has been reported that positive anti-
acetylcholine receptor antibody titers were found in 26% of ME dogs without generalized muscle weakness. [15, 20]. Most cases,
however, of canine ME are of unknown cause and are therefore considered to be idiopathic [15].
Although there have been few reports about the prognosis of canine ME, the prognosis is generally considered guarded.
Boudrieau et al. reported that the 3-month survival rate of canine ME, after the onset of clinical signs was 38% [3]. Secondary ME
may recover with successful treatment of the underlying disease [2, 20, 24]. Meanwhile, the idiopathic form is difficult to treat, and
the prognosis is generally considered poor [3, 14, 15]. Mcbreaty et al. reported that 76% of ME had no underlying disease and the
median survival time (MST) was 90 days [15]. Aspiration pneumonia (AP) is one of the most common causes of death in canine
ME and related to a significantly shorter survival time [3, 15]. In one study [15], the MST of ME dogs with and without AP was
16 days and 589 days, respectively. In the study, however, 80% of the ME cases that died were euthanatized, therefore the actual
prognosis and the effect of treatments remain unknown.
Elevated feeding, which involves feeding from a high position, or keeping dogs in a standing posture after feeding, is a common
palliative treatment of canine ME [14]. Elevated feeding is not easy to perform with large breed dogs, therefore the population of
affected breeds may resultantly skewed, in relation to the treatment and survival times in canine ME. Clinical features of canine
ME in the Japanese population of dogs have not been previously reported. The purpose of this study is to clarify the clinical
features and the prognosis of canine ME in Japan.

MATERIALS AND METHODS

Case records from dogs with ME, diagnosed at the Veterinary Medical Center at the University of Tokyo (VMC-UT) from
January 2012 to August 2017, were included in this study. Clinical data were collected from the clinical database and investigated
retrospectively. The following clinical data parameters were collected: breed; age; sex; body weight; clinical signs; treatments
undertaken; and case outcome. All dogs were diagnosed with ME by plane or contrast thoracic radiography, as they had evidence
of generalized esophageal dilation. Cases were excluded from the study if they had no evidence of apparent esophageal dilation on

*Correspondence to: Ohno, K.: [email protected]

©2019 The Japanese Society of Veterinary Science
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd)
License. (CC-BY-NC-ND 4.0: https://creativecommons.org/licenses/by-nc-nd/4.0/)

348
 CANINE MEGAESOPHAGUS IN JAPAN

radiography. Anti-acetylcholine receptor titer was measured to diagnose ME caused by MG and cases without measurement of anti-
acetylcholine receptor antibody titer were excluded. All dogs included in the study were categorized as having idiopathic (primary)
or secondary ME based on the clinical findings and laboratory data. Idiopathic ME is defined as having no evidence of diseases
that are associated with secondary ME. Dogs who neither underwent ACTH stimulation test nor measurement of total thyroxine
concentration were included in this study. AP was defined as evidence of clinical signs relating to pneumonia (cough, dyspnea, and
fever) and/or thoracic radiographic abnormalities (pulmonary alveolar pattern or lung consolidation) during the study period.
Clinical response was described as either complete response (CR: complete resolution of regurgitation), partial response (PR:
improvement but not complete resolution of regurgitation), and uncontrolled (UC: no improvement or worsening of regurgitation).
Overall survival was calculated from the time of diagnosis to the time of death. Clinical data, if not available from medical records,
was collected from owners and referring veterinarians by telephone interviews or questionnaire. Dogs still alive at the time of
statistical analysis were censored from analysis. Kaplan-Meier method was used to estimate the overall survival. Wilcoxon test was
used to compare survival between two groups classified by the categories. The Fisher’s exact test was used to compare the 3-month
survival. A P value of less than 0.05 was considered statistically significant.
To evaluate the predisposition of ME in each breed, all cases presenting to VMC-UT during the study period were used as
the reference population. The odds ratio and 95% confidence interval (CI) were calculated. A lower limit of the 95% CI was >1
was considered to represent a significantly higher risk of ME in the breed (P<0.05). All statistical analyses were performed using
commercially available software (JMP Pro version 13.0.0, SAS Institute, Cary, NC, U.S.A.).

RESULTS
A diagnosis of ME was made in 37 dogs during the study period. Of these dogs, 9 dogs were excluded from the study because 6
of these dogs were not examined anti-acetylcholine receptor antibody titers and the other 3 dogs did not exhibit esophageal dilation
by thoracic radiography, at the time of diagnosis. A total of 28 dogs met the inclusion criteria. Of the 28 dogs, 12 were male (6
castrated) and 16 were female (9 spayed). The median age of the dogs was 98.5 months (range: 7–170). Median body weight was
5.5 kg (range: 1.8–36) and 20 were small (body weight <10 kg) breed dogs. In total, 13 breeds were represented, and one dog
was crossbreed. The most common breed was Miniature Dachshund (n=13). Other breeds included the American Cocker Spaniel
(n=2), Chihuahua (n=2), Yorkshire Terrier (n=2). One case presented in each of the French Bulldog, Standard Poodle, Shih Tzu,
Border Collie, Welsh Corgi Pembroke, Doberman, Wire Fox Terrier, and Labrador Retriever breed. Miniature Dachshund was
overrepresented, and the odds ratio was 4.33 (95% CI: 2.06–9.13). Clinical signs at the time of diagnosis were regurgitation (n=28),
body weight loss (n=14), coughing (n=8), anorexia (n=6) and fever (n=1).
Secondary ME was diagnosed in 7 dogs, of which 5 dogs were diagnosed with MG, shown by an elevation of anti-acetylcholine
receptor antibody titers. Other diseases diagnosed included atypical hypoadrenocorticism (n=1) and esophagitis (n=1). The cause
of ME was not recognized in 21 cases, which were then given a diagnosis of idiopathic ME. AP was diagnosed in 10 dogs, at least
one time during the study period. Of 10 dogs with AP, 4 dogs were diagnosed with AP at the first examination and 6 dogs were
diagnosed further into the study period. Of the 10 dogs with AP, 7 dogs were idiopathic ME and 2 dogs were MG, and a dog was
esophagitis.
In cases of secondary ME, the underlying disease process was treated. Pyridostigmine bromide was used for MG (n=4) and
idiopathic ME (n=1). Other treatments for MG were azathioprine (n=3), prednisolone (n=2). An atypical hypoadrenocorticism dog
was treated with hydrocortisone initially. Three months after the diagnosis of atypical hypoadrenocorticism, the dog developed
hyperkalemia and hyponatremia, and prednisolone and fludrocortisone acetate were substituted for hydrocortisone. Elevated
feeding was indicated for all idiopathic ME dogs, to prevent regurgitation and AP. Other therapies administered to cases of
idiopathic ME were mosapride citrate (n=9), bethanechol (n=1), gastrostomy tube placement (n=1), and esophagostomy tube and
esophagogastric tube placement (n=1). Nine dogs were treated solely with elevated feeding.
Clinical response was evaluated in all dogs. Three dogs were CR: idiopathic ME (n=1); MG (n=1); atypical hypoadrenocorticism
(n=1). PR was recognized in 10 dogs: idiopathic ME (n=7); and MG (n=3). The remaining 15 dogs were UC: idiopathic ME
(n=13); MG (n=1); esophagitis (n=1).
During the study period, 12 dogs died while 16 dogs were alive at the study conclusion. The MST was not reached (NR) and
the mean survival time for all dogs was 648 days (Fig. 1). The cause of death included AP (n=4), gastric ulcer induced by contact
of the esophagogastric tube to the stomach (n=1), renal carcinoma (n=1), oral melanoma (n=1), mammary gland carcinoma (n=1)
and chronic kidney disease (n=1). In three dogs, the cause of death was not apparent. Four dogs had died within three months of
diagnosis, and the overall 3-month survival rate was 85.7%.
The relationship between variables and survival dates is shown in Table 1. The survival time of ME dogs, with or without AP,
was significantly different between the two groups with the MST being 114 days and NR, respectively (Fig. 2). Three months after
diagnosis, four dogs with AP died, while all dogs without AP were alive, showing that the 3-month survival rate was significantly
different between dogs with or without AP (P=0.03, Table 2). Other variables including age, sex, breed, body weight, prokinetics
administration and diagnosis (idiopathic or secondary) were not of significance to the overall survival time or 3-month survival rate
(Table 2).
In the group of idiopathic ME, nine dogs were treated exclusively with elevated feeding, while another 12 dogs were given
combination therapy (elevated feeding with other medications). The difference in survival time between dogs treated exclusively
with elevated feeding or with combination therapy, was not significant. The MST was NR and 951 days, respectively (P=0.49).

doi: 10.1292/jvms.18-0493 349

 T. NAKAGAWA ET AL.

Fig. 1. Kaplan-Meier survival curve for 28 dogs with ME. Vertical marks represent censored data.

Table 1. Relationship between survival time and clinical variables

Median Survival
Variable Level n P value
Time (days)
Age <24 month 4 NR 0.10
>24 month 24 852
Sex Male 12 NR 0.43
Female 16 536
Breed MD 14 NR 0.84
Other breed 14 951
Body weight <10 kg 20 NR 0.94
>10 kg 8 951
Prokinetic administration Absent 10 NR 0.74
Present 18 536
Aspiration Pneumonia Absent 18 NR 0.03
Present 10 114
Diagnosis Idiopathic 21 951 0.79
Secondary 7 NR
NR: Not Reached, MD: Miniature Dachshund.

Fig. 2. Kaplan-Meier survival curve for ME dogs with AP (dashed line) and those without AP (solid line).
Vertical marks represent censored data.

doi: 10.1292/jvms.18-0493 350

 CANINE MEGAESOPHAGUS IN JAPAN

Table 2. Relationship between the three-month survival rate and clinical variables
3-month survival
Variable Level n P value
rate
Age <24 month 4 4/4 (100.0%) 1.00
>24 month 24 20/24 (83.3%)
Sex Male 12 11/12 (91.6%) 0.61
Female 16 13/16 (81.2%)
Breed MD 14 12/14 (85.7%) 1.00
Other breed 14 12/14 (85.7%)
Body weight <10 kg 20 17/20 (85.0%) 1.00
>10 kg 8 7/8 (87.5%)
Mosapride administration Absent 10 10/10 (100.0%) 0.26
Present 18 14/18 (77.7%)
Aspiration Pneumonia Absent 18 18/18 (100.0%) 0.01
Present 10 6/10 (60.0%)
Diagnosis Idiopathic 21 18/21 (85.7%) 1.00
Secondary 7 6/7 (85.7%)
MD: Miniature Dachshund.

DISCUSSION
Previous studies have shown that cases of canine ME had only short survival times [3, 15]. However, the present study suggests
that canine ME can have a more favorable prognosis. The MST of ME was NR and the 3-month survival rate was 85.7%. The
result is substantially better than the previous studies, in which MST was 90 days [15] and the 3-month survival rate was 38%
[3]. One of the possible explanations for the discrepancy is the rate of euthanasia. In the previous study [15], 37% of dogs died
within 1 month of diagnosis, 79% of these patients were euthanized because of factors related to either ME or AP [15]. In this
study, in contrast, no dogs were euthanized. From the high euthanasia rate, it was inferred that many dogs died without treatment
in the previous study [15]. Meanwhile, many dogs in our study were performed several treatments and nine dogs were treated with
elevated feeding only. The efficacy of elevated feeding alone is unknown, however, the dogs treated with elevated feeding only had
a good prognosis, comparable to the combination therapy in the present study. Therefore, treatment involving elevated feeding and
medications, resulted in a better prognosis in the present study.
Regarding AP, the prevalence was 35.7% in this study, and dogs with AP had significantly shorter survival times, with a lower
3-month survival rate than dogs without AP. This result was similar to the previous report that the prevalence of AP was 45% and
that AP was a negative prognostic factor for canine ME [15]. In the present study, however, the MST of ME with AP was 114 days,
substantially longer than the previous study, which reported the MST of canine ME with AP as 16 days [15]. As mentioned above,
euthanasia of cases without treatment, in the previous study is likely to alter the study outcome. Several studies reported that the
prognosis for AP was favorable and the presence of ME did not adversely impact the survival rate [13, 21]. This suggests that
appropriate treatment for concurrent AP would likely prolong the survival time of ME. In our study, patients diagnosed with AP
at least once during the study period were included. In the previous study, in contrast, AP was diagnosed at the initial presentation
[15]. Therefore, the prevalence and survival time of the dogs with AP may be overestimated in the present study.
We hypothesized that it is difficult to keep a large breed dog in an elevated position appropriately, resulting in a negative effect
on the prognosis of canine ME. However, body weight (>10 kg vs <10 kg) was found to have no significant influence on the
survival time in this study. The previous study showed that higher body weight dogs (>25 kg) were prone to worse prognosis [15].
In this study, only four dogs were of a bodyweight more than 25 kg, and further investigation is therefore needed to clarify the
effect of elevated feeding and body weight on the prognosis of canine ME.
Some dogs in our study were prescribed prokinetics, of which mosapride citrate is most frequently used. Although Mosapride
citrate is 5-HT4 receptor agonist, serotonin does not have prominent effect on canine esophageal contraction and 5-HT4
receptor agonist are not considered to be effective to the canine ME [4, 14]. Moreover, prokinetics may prolong the esophageal
transportation time, due to an increase in the tone of the lower esophageal sphincter, and are therefore not proven to be beneficial
in the management of idiopathic megaesophagus in dogs [4, 11, 14, 22]. In the present study, there was no significant difference in
survival between groups with or without mosapride citrate administration. Therefore, the efficacy of prokinetics remains unclear.
In the present study, the Miniature Dachshund was at a significantly higher risk of developing acquired ME. A predisposition of
congenital ME has been reported in some dog breeds such as the Irish Setter, Great Dane, German Shepherd, Labrador Retriever,
Newfoundland, and Chinese Shar-Pei. Autosomal dominant inheritance has been demonstrated in the Miniature Schnauzer and Fox
Terrier breeds [23]. Conversely, no predisposition has been reported in canine acquired ME. The underlying causes of acquired
idiopathic ME can be challenging. Vagal afferent dysfunction has been demonstrated to relate with the congenital idiopathic form
of ME [9, 10], while the cause of acquired idiopathic ME is unknown. Previous studies suggested that the Miniature Dachshund

doi: 10.1292/jvms.18-0493 351

 T. NAKAGAWA ET AL.

in Japan was predisposed to some immunological diseases, such as inflammatory colorectal polyps, idiopathic polyarthritis,
and sterile panniculitis [17–19, 25]. Immunological dysfunction against the esophagus may play a role in the development of
acquired idiopathic ME in the Miniature Dachshund, but this remains unclear as cases of idiopathic ME dogs were not treated
with immunosuppressive drugs in this study. Further examination is warranted regarding the pathogenesis of ME in the Miniature
Dachshund.
A limitation of this study is its retrospective nature and therefore, the diagnostic approach and treatment are naturally
inconsistent. Idiopathic ME is a diagnosis of exclusion; however, the panel of diagnostic tests was incomplete in some dogs and
therefore, secondary ME may be underestimated in this study. Furthermore, the treatment was not standardized and the detail of the
elevated feeding procedure was unclear. Therefore, inconsistency in the treatment regime may affect the clinical response and the
prognosis in the present study.
In conclusion, the present study revealed the clinical features and prognosis of canine ME in Japan. Small breed dogs are
predominantly affected with the Miniature Dachshund having a high odds ratio, therefore being considered a predisposition to
acquired ME. The prognosis overall, and even with AP, was notably improved compared to the previous studies. Therefore, we
hypothesized that treatment for canine ME could prolong the survival time, even in those with both ME and AP.

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