Persistent Regurgitation in Four Dogs with Caudal Esophageal Neoplasia

Introduction

Esophageal neoplasia accounts for < 5% of all tumors in domestic dogs and cats.¹ The most common tumor types include squamous cell carcinoma, leiomyosarcoma, fibrosarcoma, and osteosarcoma. Sarcomas can also develop secondary to Spirocerca lupi (S. lupi) in indigenous areas. Other paraesophageal tumors involving the heart base, thymus, or thyroid glands may invade the esophagus. Esophageal metastasis can rarely occur as well. Esophageal neoplasia is also uncommon in humans and is believed to be due to a variety of causes, including certain environmental influences, chronic esophagitis, and gastroesophageal reflux. Advanced disease is common in humans where surgery, radiation therapy, chemotherapy, or multimodality therapy results in a survival time of 5 yr in < 20% of patients.² Those palliative therapies are often used to improve quality of life and increase survival times.

Affected animals typically present for signs consistent with either partial or complete esophageal obstruction, including progressive dysphagia, pain when swallowing, regurgitation, weight loss, dehydration, and/or respiratory signs secondary to aspiration pneumonia.³ Esophageal neoplasia can be either diffusely invasive or a well-defined mass and may metastasize to the gastric wall, trachea, lungs, or local lymph nodes. Esophageal neoplasia can be diagnosed using survey thoracic radiography, contrast radiographic studies (with or without fluoroscopy), thoracic computed tomography (CT), or esophagoscopy. A definitive diagnosis requires histopathology. Treatment options include local tumor debulking, definitive surgical excision, radiation therapy, chemotherapy, neoplastic stricture dilation, palliative esophageal stents, and photodynamic therapy.

This case series describes the presentation, diagnostic evaluation, and therapy of four dogs presenting with regurgitation and caudal esophageal neoplasia. Three of the four dogs were also diagnosed with megaesophagus.

Case Report

Case 1

An 11 yr old castrated male Labrador retriever presented with a 6 wk history of coughing and regurgitation. Physical examination revealed minimal stridor and increased bronchovesicular sounds in all lung fields. A complete blood count (CBC), serum biochemical panel, total thyroxine level, and an acetylcholine receptor antibody titer were all normal. Thoracic radiographs revealed moderate, diffuse esophageal dilation and a mild, diffuse pulmonary interstitial pattern. Barium contrast esophagram with fluoroscopy revealed diffuse esophageal hypomotility and a suspected intermittent sliding hiatal hernia. The owner declined further diagnostics at that time, and the patient was treated with famotidine^a (0.5 mg/kg per os [PO] q 12 hr for 14 days), amoxicillin trihydrate/clavulanate potassium^b (12.75 mg/kg PO q 12 hr for 14 days), tramadol^c (1.6 mg/kg PO q 8–12 hr pro re nata), and elevated feedings.

The patient was re-examined 1 mo after the initial examination due to persistent coughing and regurgitation. Thoracic radiographs showed progressive esophageal dilation, a soft-tissue opacity within the caudal esophagus, and a diffuse interstitial pulmonary pattern (Figure 1). Esophagoscopy revealed a 3–4 cm sessile, lobulated, smooth, pink, and vascular mass in the caudoventral esophagus immediately cranial to the lower esophageal sphincter. The esophageal mass was endoscopically debulked by approximately 50% using loop electrocautery. Histopathology revealed a well-differentiated leiomyoma. Bronchoscopy was also performed showing gross changes consistent with chronic bronchitis and partial collapse of the left caudal lobar bronchus. Cytology of the bronchoalveolar lavage samples showed neutrophilic inflammation, and an aerobic culture of the bronchial brush samples yielded light growth of Escherichia coli. Based on sensitivity testing, the patient was prescribed amoxicillin trihydrate/clavulanate potassium (12.75 mg/kg PO q 12 hr for 14 days).

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Surgical excision of the residual esophageal leiomyoma was recommended, and preoperative thoracic and abdominal CT scans revealed a caudal esophageal mass involving the distal 3 cm of the esophagus that was suspected to involve the lower esophageal sphincter and cardia. Concurrent obstructive megaesophagus was also noted. A ventral midline celiotomy was performed to excise the distal esophageal mass, and the defect was closed via cranial gastric advancement. Histopathology confirmed the diagnosis of a completely excised, well-differentiated esophageal leiomyoma, with complete excision defined as at least 0.5 cm for the lateral and deep margins. The patient developed aspiration pneumonia in the postoperative period, which was treated with ticarcillin disodium/clavulanate potassium^d (50 mg/kg IV q 8 hr) and enrofloxacin^e (10 mg/kg IV q 24 hr). The dog was discharged 6 days postsurgically with marbofloxacin^f (5 mg/kg PO q 24 hr for 5 days) and azithromycin^g (6.4 mg/kg PO q 24 hr for 14 days).

Thoracic radiographs taken 12 days postoperatively revealed persistence of the megaesophagus, near complete resolution of the aspiration pneumonia, and no evidence of pulmonary metastasis. Over the following 13 mo, the regurgitation and coughing became less frequent. Follow-up thoracic radiographs 13 mo postoperatively revealed persistent megaesophagus and recurrence of the caudal esophageal mass.

Repeat esophagogastroscopy 15 mo postoperatively revealed a 1.9 cm esophageal mass in the same caudal esophageal location as the original tumor. Recurrence of the previous leiomyoma was suspected, but the owner elected not to schedule a second surgery. The patient was re-examined 3 mo after the second tumor was diagnosed due to an increased frequency of regurgitation. Thoracic radiographs at that time revealed persistent megaesophagus with a persistent soft-tissue density in the region of the caudal esophagus at the level of the diaphragm. Repeat esophagoscopy for tumor debulking was discussed but was declined. The patient’s diet was changed to a gruel consistency, which markedly reduced the frequency of regurgitation. At the time this manuscript was prepared, this patient was doing well (37 mo after the initial diagnosis).

Case 2

An 11 yr old castrated male German shepherd dog was referred to the authors’ hospital for evaluation of acute regurgitation. The patient had a history of a left anal sacculectomy performed 6 days prior to referral to remove an anal sac apocrine gland adenocarcinoma. Preoperative abdominal and thoracic CT scans revealed a left anal sac mass, pelvic and sublumbar lymphadenopathy, a right adrenal mass, a right caudal pulmonary nodule, and dilation of the caudal esophagus with fluid but no visible mass.

At the time of referral, the patient’s physical examination, CBC, serum biochemical panel, and specific canine pancreatic lipase immunoreactivity tests were all within normal limits. Thoracic radiographs revealed mild air accumulation within the thoracic esophagus and a caudal right lung nodule. Abdominal radiographs revealed ventral deviation of the colon, which was consistent with iliac lymphadenopathy. An esophagram with fluoroscopy revealed intrathoracic esophageal dilation and a mucosal irregularity within the caudal esophagus that was not persistent throughout the entire study. The patient was hospitalized and treated for suspected reflux esophagitis with metoclopramide^h (3 mg/kg/day on a continuous rate infusion), maropitant citrateⁱ (2.1 mg/kg PO q 24 hr), famotidine (0.5 mg/kg PO q 12 hr), and sucralfate^j (26.7 mg/kg PO q 8 hr). The patient’s clinical signs improved, and he was discharged from the hospital the following day with omeprazole^k (0.5 mg/kg PO q 24 hr), sucralfate (26.7 mg/kg PO q 8 hr), cisapride^l (0.4 mg/kg PO q 8 hr), and elevated feedings.

The following day the patient was re-examined for persistent regurgitation. Thoracic radiographs revealed persistent, mild air accumulation in the thoracic esophagus and persistence of the caudodorsal lung mass, but no evidence of pneumonia. Inpatient treatment of suspected reflux esophagitis was continued for 2 days. The patient was then discharged for outpatient care. The patient was re-examined 5 days later for persistent regurgitation. Thoracic radiographs at that time revealed a progressive, diffuse megaesophagus. Esophagoscopy revealed a dilated esophagus and partially obstructive friable mass located within 5 cm of the lower esophageal sphincter (Figure 2). Biopsies of the mass were obtained, and a percutaneous endoscopic gastrotomy tube was placed. Histopathology of the esophageal mass showed an esophageal adenocarcinoma. Due to progressive poor quality of life over the next 1 wk, the patient was ultimately euthanized.

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Discussion

All four dogs described in this case series presented with either acute or chronic regurgitation and were confirmed to have caudal esophageal neoplasia. Additionally, three of the four cases either presented with or developed megaesophagus radiographically. For those three cases, the most likely mechanism for the regurgitation and development of megaesophagus was either partial or complete distal esophageal obstruction due to the esophageal mass. Decreased lower esophageal sphincter tone resulting in gastroesophageal reflux, reflux esophagitis, and dysmotility, as well as either idiopathic acquired megaesophagus or megaesophagus secondary to other causes were possible, but were considered less likely.

The caudal esophageal neoplasms in two of the four cases were carcinomas and the other two were leiomyomas. Benign leiomyomas are rare and tend to occur in either the caudal esophagus or gastric cardia.^4,5 In humans, endoscopic biopsies are contraindicated when sampling leiomyomas because biopsies can disrupt the mucosal layer and risk secondary infection, hemorrhage, and perforation.⁶ Three of the four cases described herein (one leiomyoma and two carcinomas) had large biopsy samples obtained by wire loop electrocautery with no complications.

In humans, esophageal cancer accounts for 2% of all cancer deaths (7,000 deaths per year in the United States).^7,8 Potential causes include environmental influences (e.g., thermal irritation from hot food, excessive alcohol consumption), chronic esophagitis, gastroesophageal reflux, esophageal strictures, pharyngoesophageal diverticulum, and esophageal achalasia.⁹ Barrett’s esophagus in humans is a complication of chronic gastroesophageal reflux, which involves the replacement of normal squamous epithelium of the distal esophagus with metaplastic columnar epithelium.¹⁰ A similar syndrome has been described in a case series of three cats that had lower esophageal sphincter incompetence, hiatal hernia (or a combination of the two), and secondary chronic gastroesophageal reflux.¹⁰ Histopathology revealed lesions characterized by metaplastic, intestinal-like, columnar epithelium, defined by the presence of goblet and columnar cells lining the distal third of the esophagus that stained with periodic acid-Schiff.¹⁰ In dogs, a strong correlation has been established between S. lupi infection and esophageal sarcoma development. S. lupi, an esophageal parasite indigenous to the southeast United States and Kenya, can lead to scarring and aneurysm of the thoracic aorta, spondylosis deformans of the posterior thoracic vertebrae, and reactive granuloma formation.¹¹ Those inflammatory lesions can contain metaplastic fibroblasts that can transform the lesions into sarcomas.

The diagnosis of an esophageal tumor is typically based on clinical signs, diagnostic imaging, esophagoscopy, or a combination of those modalities. Ultimately, the diagnosis is confirmed histologically. Symptoms are generally directly related to esophageal dysfunction and include dysphagia, pain when swallowing, regurgitation, and/or respiratory signs secondary to aspiration pneumonia.³

According to one study, the most important criteria for a radiographic diagnosis of an esophageal tumor include the retention of air in the esophagus (either with or without esophageal displacement) and motor dysfunction.¹ Air is classically retained within the esophageal lumen cranial to the neoplasm, and both segmental and complete dilation of the esophagus are possible sequelae.² Three of the four cases describe in this report had diffuse esophageal hypomotility, and two of the three cases had generalized megaesophagus radiographically. Other thoracic radiographic findings include a mass effect, pulmonary metastases, and aspiration pneumonia. Case two had a persistent, pulmonary soft-tissue mass that may have been a metastatic lesion from the esophageal carcinoma, and the esophageal carcinoma could have been a metastatic lesion from the anal sac apocrine gland adenocarcinoma; however, this theory could not be proven.

A barium esophagram can highlight the presence of either an intraluminal mass or obstructive lesion. CT is an increasingly available imaging modality that is useful for imaging mass lesions, identifying metastatic disease, and surgical planning. The value of CT is limited by its ability to detect masses < 1 cm and a low sensitivity for detecting nodal spread. Also, inflammation can have a similar appearance as a tumor on CT, and depth of tumor infiltration into the esophageal wall can be difficult to determine. Two of the cases described in this report underwent a CT and only one case had the mass identified, which demonstrates the limitations of even advanced diagnostic imaging. Esophagogastroscopy allows for visualization of esophageal and gastric masses, allows for the collection of samples, and palliative debulking. Two of the patients in this case series had 50% of their masses debulked using wire loop electrocautery, which not only provided a large sample for histopathology but also provided short-term relief from a potentially obstructing mass lesion.

Treatment options for esophageal tumors are limited given the challenging anatomic location. Treatment modalities include surgical resection, radiation therapy, chemotherapy, neoplastic stricture dilation, palliative esophageal stent placement, and photodynamic therapy. Primary surgical esophageal resection and anastomosis is only an option if < 5 cm length is affected because removing > 5 cm length of the esophagus significantly increases the risk of dehiscence.¹² An intrathoracic approach typically provides poor exposure, and intrathoracic surgical resection can result in a lengthy procedure, tension on the anastomosis, and tissue healing issues.¹² If tumors are located more distally within either the caudal esophagus or gastric cardia, gastric advancement via the diaphragm is feasible via an abdominal approach.¹³ Increased tension increases the risk of dehiscence, and without an esophageal serosal layer to produce a fibrin clot, meticulous apposition is necessary to prevent leakage.¹² Several methods have been attempted to help limit tension on surgical sites and improve outcomes, including using jejunal or colonic grafts and striated muscle to replace sections of affected esophagus.¹⁴

Radiation therapy is a potential treatment option for esophageal tumors; however, the location of esophageal tumors often limits this modality. Chemotherapy has been used primarily for the adjunctive treatment of esophageal sarcomas. In one study, three dogs were prescribed four treatments of doxorubicin at a dose of 30 mg/m², and there was no significant correlation between survival and chemotherapy.¹⁵ One dog also received a single dose of carboplatin at a dose of 300 mg/m².¹⁵ In a study involving five dogs with spirocercosis-associated esophageal sarcomas that underwent partial esophagectomy and chemotherapy with doxorubicin (30 mg/m² q 3 wk for a total of 4–6 treatments), the average survival time was 267 days.¹⁶ Two of those dogs had endoscopic follow-up examinations at 3 mo and 3.5 mo after surgery with no signs of either tumor recurrence or stricture formation at the resection site.¹⁶

Other adjunctive therapies include stricture dilation, esophageal stent placement, and photodynamic therapy. Esophageal balloon dilation can be used to treat neoplastic strictures. Esophageal stent placement can also be considered a palliative therapy for malignant esophageal masses. Both covered and uncovered self-expanding laser cut or mesh stents can be used, and stents can be placed either via fluoroscopy, endoscopy, or a combination of the two methods.¹⁷ Additionally, self-expandable covered metallic esophageal stents impregnated with a β-emitting radionuclide have been used experimentally.¹⁸ Those stents can be used for either palliation without further treatment or an adjunctive therapy following radiation therapy. Debulking an esophageal mass prior to stent placement does not improve survival and is typically not performed.¹⁷ In one case, an esophageal stent was placed in a dog with esophageal squamous cell carcinoma and subsequent esophageal obstruction. The dog did well following stent placement and lived an additional 10 wk with a liquid gruel diet, but was ultimately euthanized for progressive weakness.¹⁷ Photodynamic therapy involves the systemic administration of a photosensitizing dye that preferentially binds to tumor cells and then exposing the tumor to a specific wavelength of light administered via a laser. The combination of the dye and light in the presence of oxygen creates tissue necrosis.¹⁹ Photodynamic therapy is limited by tumor depth because the light used can only penetrate a certain distance. Thus, that technique is limited to tumors confined to the mucosal layer of the esophagus.¹⁹

There are few studies evaluating the outcome in dogs with esophageal neoplasia and varying treatment modalities. One study described four dogs with grade 1 (well-differentiated) leiomyosarcoma following marginal surgical excision. Two of those dogs died due to unrelated conditions, one dog had a persistent megaesophagus and was lost to follow-up 388 days postsurgery, and the remaining dog was still alive 405 days postsurgery.²⁰ Another study of dogs with esophageal sarcomas reported a survival rate of 60–610 days, with a median survival rate of 278 days.¹⁵ In the same study, there was no correlation between survival and signalment, duration of clinical signs, tumor type, tumor grade, or chemotherapy.¹⁵ In the report described herein, case 1 had an esophageal leiomyoma that was treated with definitive surgery. Recurrence was identified 13 mo postoperatively, and the patient was still alive and doing well 37 mo postdiagnosis.

Conclusion

Although occurring infrequently, esophageal neoplasia should be considered in the differential diagnoses for either acute or chronic regurgitation as well as megaesophagus in dogs. With early detection and appropriate therapy, long-term survival is possible.