Chapter 37. The Esophagus

The esophagus is a muscular tube approximately 25 cm long that extends from the neck down the posterior mediastinum and through the diaphragm to the stomach (Figure 37-1). It is lined by nonkeratinizing stratified squamous epithelium that transforms abruptly to gastric epithelium at the gastroesophageal junction. The junction is usually 37–40 cm from the incisor teeth and may be identified endoscopically by a change in appearance from the white squamous mucosa to the tan glandular mucosa.

The esophagus has physiologic high-pressure zones at either end that act as sphincters. There is no anatomic sphincter at either end. The upper cricopharyngeal sphincter prevents entry of air and pharyngeal contents into the esophagus except during swallowing, and the lower esophageal or “cardiac” sphincter prevents reflux into the esophagus of acidic gastric juice.

Deglutition (swallowing) is a reflex that is initiated when a bolus of food stimulates nerve endings in the mucosa of the posterior pharyngeal wall (Figure 37-1). Efferent impulses from the deglutition center in the brain stem cause pharyngeal muscle contraction and relaxation of the cricopharyngeal sphincter, permitting entry of food into the esophagus and initiating peristalsis.

Peristalsis consists of successive waves of contraction preceded by relaxation of the esophageal muscle, which propels food down the esophagus. Peristaltic action is coordinated by the myenteric plexus of nerves. Three types of peristaltic waves are recognized: (1) primary waves, which originate in the lower pharynx and pass down the entire esophagus; (2) secondary waves, which originate in the mid esophagus and pass down to the stomach; and (3) tertiary waves, which are irregular contractions of segments of the wall. Primary and secondary waves are propulsive; tertiary waves are nonpropulsive. The lower esophageal sphincter relaxes when a propulsive peristaltic wave (either primary or secondary) reaches the lower esophagus, permitting food to enter the stomach (Figure 37-2).

Dysphagia simply means difficulty in swallowing. The patient often complains that food “gets stuck” without passing down normally. The term odynophagia is used when there is pain during deglutition. Most diseases of the esophagus cause dysphagia (Table 37-1).

Retrosternal pain (heartburn) unassociated with deglutition commonly occurs when acidic gastric juice refluxes into the esophagus across an incompetent lower esophageal sphincter.

Hematemesis (vomiting of blood) may be due to acute hemorrhage into the lumen of the esophagus or stomach. Peptic ulcer disease and rupture of esophageal varices are the most common causes of hematemesis (Table 37-2). Slower, more sustained bleeding produces melena (tarry black stools containing blood altered by the action of gastric acid) or iron deficiency anemia with occult blood in the stools. (Occult blood is blood not grossly visible but detectable by chemical testing.)

Clinical Examination

The esophagus is inaccessible for physical examination, with most of its course in the posterior mediastinum.

Radiology

Chest x-ray may in some cases show extreme esophageal dilation. The only condition that commonly produces esophageal enlargement sufficient to be seen on chest x-ray is achalasia of the cardia (megaesophagus).

Swallowing barium permits visualization and videophotography of the passage of dye down the esophagus. This provides information regarding propulsive peristalsis, the presence of any obstructive lesions, and mucosal abnormalities.

Computerized tomography of the chest permits evaluation of lesions in the wall of the esophagus and is a good technique for evaluating spread of esophageal neoplasms.

Esophagoscopy

Passage of a fiberoptic endoscope into the esophagus permits direct visualization and biopsy of mucosal lesions of the esophagus.

Manometry & pH Measurement

The passage of a manometer into the esophagus permits measurement of pressure in different parts of the esophagus at rest and during swallowing (Figure 37-2). Placement of a pH electrode in the lower esophagus over a 24-hour period is the best test for gastroesophageal reflux.

Tracheoesophageal Fistula

Tracheoesophageal fistula is the most common congenital anomaly of the esophagus. Several clinical types exist (Figure 37-3B to 37-3D), some associated with varying degrees of atresia (failure of development) of the esophagus. The most dangerous types of fistula are those in which swallowed material (the first milk meal of the newborn) passes into the trachea, causing severe acute respiratory distress with cyanosis and aspiration pneumonia.

Other Anomalies

Other congenital anomalies are rare. Esophageal atresia (Figure 37-3A) causes narrowing (stricture) of a part of the esophagus. In congenital short esophagus (uncommon), the gastroesophageal junction is above the diaphragm; it must be carefully distinguished from Barrett's esophagus. Also uncommon is the congenital occurrence of ectopic gastric mucosa in the esophagus.

(Table 37-3)

Reflux Esophagitis (Gastroesophageal Reflux Disease; GERD)

Reflux of acidic gastric juice into the lower esophagus occurs several times a day even in normal individuals—without producing symptoms or inflammation. Symptomatic esophagitis is believed to occur when there is prolonged exposure of the mucosa to refluxed gastric contents due to (1) excessive reflux, both in number of episodes and volume, resulting from incompetence of the lower esophageal sphincter; and (2) when the normal mechanisms for clearing the lower esophagus are impaired. The composition of the refluxed gastric juice may also be an important determinant of reflux: The levels of acid and pepsin, as well as the presence of bile and pancreatic enzymes refluxed from the duodenum, all may play a part. When bile reflux is present, esophagitis may occur even when the refluxed gastric juice is alkaline (alkaline reflux).

The relationship of reflux to hiatal hernia is not clear. A hiatal hernia is defined as protrusion of part of the stomach through the diaphragmatic hiatus (Figure 37-4). Reflux occurs most often in sliding type hernias, which are commonly associated with an incompetent lower esophageal sphincter. However, most patients with reflux esophagitis do not have a hiatal hernia, and many patients with hiatal hernias do not have reflux esophagitis.

Pathology

(Figure 37-5)

Reflux esophagitis can be recognized endoscopically as reddening and superficial erosion of the lower esophagus. It may progress to ulceration and fibrous narrowing of the esophagus (stricture).

Histologically, reflux esophagitis is characterized by (1) hyperplasia of the basal cells of the squamous epithelium to more than 15% of mucosal thickness; (2) elongation of lamina propria papillae to more than 70% of mucosal thickness; and (3) the presence of intraepithelial neutrophils and eosinophils. Patients with reflux also show mucosal congestion and inflammation, often severe, in the gastric cardiac mucosa.

Clinical Features

Reflux of acidic gastric juice into an inflamed esophagus causes a low retrosternal sensation of burning pain (heartburn), typically when the patient lies flat. In chronic cases, pain may be constant and dysphagia may occur as a result of fibrous stricture formation. Reflux into the pharynx occurs in severe cases and may cause spasmodic coughing and hoarseness.

Complications

Barrett's Esophagus

(Figure 37-6.) Prolonged reflux esophagitis commonly leads to metaplasia of the esophageal epithelium from squamous to glandular. Barrett's esophagus is defined as the presence of a glandular mucosa showing intestinal metaplasia. The metaplasia is characterized by the presence of globlet cells and acid mucin on Alcian blue stain, which differentiates intestinal (acid) mucin from gastric (neutral) mucin. The finding of gastric cardiac and fundic mucosa in the lower esophagus, while indicating reflux disease, is not now included in the definition of Barrett's esophagus.

Most primary adenocarcinomas of the lower esophagus arise in Barrett's esophagus, which therefore is considered a precancerous lesion. An estimated 5–10% of patients with Barrett's esophagus develop adenocarcinoma. The glandular epithelium passes through progressively increasing dysplastic changes that permit histologic recognition of imminent cancer. Patients with Barrett's esophagus are kept under regular surveillance with endoscopy and biopsy to detect epithelial dysplasia. The finding of high-grade dysplasia (Figure 37-7) is an indication for prophylactic esophageal resection.

Peptic Ulceration and Fibrous Strictures

Severe reflux leads to chronic peptic ulcers in the lower esophagus. Subsequent fibrosis leads to esophageal stricture and dysphagia.

Motility Abnormality

Prolonged reflux leads to abnormal peristalsis in the lower esophagus. This may decrease esophageal clearing and aggravate reflux disease.

Infectious Esophagitis

Infections are rare in the esophagus except in immunocompromised patients, notably those with acquired immunodeficiency disease (AIDS).

Candida Albicans Esophagitis

Esophageal candidiasis is one of the common opportunistic infections in patients receiving cancer chemotherapy and those with AIDS. The yeast infects the superficial layers of the squamous epithelium, forming grossly visible adherent white plaques. The main symptom is odynophagia. The diagnosis is made by identifying the fungus in smears, cultures, or biopsy specimens taken from the lesions.

Viral Esophagitis

Herpes simplex esophagitis is common in AIDS patients. It can be recognized in biopsies by the presence of Cowdry type A intranuclear inclusions, herpetic giant cells, and by the immunologic demonstration of herpes simplex antigen.

Cytomegalovirus is also a common cause of esophagitis in AIDS patients. Cytomegalovirus (CMV) infects submucosal endothelial cells, causing focal ischemia, hemorrhage, inflammation, and ulceration. Typical enlarged cells with large intranuclear inclusions and granular cytoplasmic inclusions are present.

Esophageal involvement may rarely occur in severe attacks of chickenpox, where vesiculation of infected epithelium is followed by ulceration.

Traumatic & Chemical Esophagitis

Prolonged feeding through a nasogastric tube frequently causes mucosal inflammation, often with ulceration.

Ingestion of corrosives such as phenol, strong acids, and mercuric chloride leads to chemical esophagitis. The strongly alkaline chemical known as lye, which is swallowed in suicide attempts and by unwitting children, causes severe esophagitis with mucosal denudation in the acute phase. Marked fibrous scarring in survivors often requires repeated dilation of the esophagus to overcome resulting obstruction. Lye ingestion is associated with a greatly increased risk (1000 times normal) of development of squamous carcinoma of the esophagus.

(Table 37-1)

Plummer-Vinson Syndrome

Plummer-Vinson syndrome consists of severe iron deficiency anemia, koilonychia, atrophic glossitis, and dysphagia. It is common in Scandinavian countries and uncommon in the United States. The disease has a marked female preponderance due to the frequency of negative iron balance resulting from menstrual blood loss.

The dysphagia is corrected when the iron deficiency is treated. Dysphagia results from (1) atrophy of the pharyngeal mucosa caused by iron deficiency, which is believed to interfere with the afferent arc of the deglutition reflex; and (2) web-like mucosal folds present in the upper esophagus in some patients, causing mechanical obstruction.

There is a greater than normal risk of developing squamous carcinoma of the upper esophagus, oropharynx, and posterior tongue.

Progressive Systemic Sclerosis (Scleroderma)

The esophagus is commonly involved in systemic sclerosis, and dysphagia is a common symptom. Involvement takes the form of submucosal and muscular vasculitis with muscle-wall degeneration and fibrosis. Smooth muscle loss leads to failure of peristalsis and dysphagia (Figure 37-2B).

Achalasia of the Cardia

Achalasia (Greek, unrelaxed) of the cardia (lower esophageal sphincter) is a common disease resulting from loss of ganglion cells in the myenteric plexus of the esophagus. Ganglion cell loss is present throughout the body of the esophagus and is not restricted to the cardia. The cause is unknown in most cases; a few cases are caused by Trypanosoma cruzi infection (South American trypanosomiasis; Chagas' disease).

The myenteric plexus abnormality leads to failure of propulsive peristaltic waves without which the cardiac sphincter does not relax, creating a zone of high pressure that obstructs the passage of food into the stomach (Figure 37-2D). The esophagus dilates massively above the cardia and becomes elongated and tortuous (Figure 37-8). The mucosa is usually normal but may show areas of superficial inflammation and ulceration.

Patients present with dysphagia. Nutrition is maintained reasonably well. With collection of food in the esophagus, the hydrostatic pressure therein increases and becomes sufficient to physically overcome the sphincter, permitting the intermittent entry of food into the stomach.

An important complication of achalasia is aspiration of the contents of the dilated esophagus into the trachea, leading to recurrent attacks of aspiration pneumonia.

Treatment by intraluminal dilation or by surgical myotomy is effective, but many patients need repeated dilations. Achalasia is associated with a slightly increased risk of squamous carcinoma.

Diffuse Esophageal Spasm

(Figure 37-2E)

Diffuse esophageal spasm is characterized by high-amplitude, nonpropulsive peristaltic waves occurring simultaneously in different parts of the esophagus. The lower esophageal sphincter is normal. Patients commonly present with chest pain, which can mimic the pain of heart disease. The diagnosis is made by manometry. Radiologic studies may show increased contractions (corkscrew esophagus). Treatment in severe cases may require a longitudinal surgical myotomy.

Esophageal Diverticula

Diverticula (outpouchings of the lumen of a viscus outside the wall of that viscus) are not common, but if large they may cause dysphagia or local inflammation. Pulsion diverticula are believed to occur when internal pressure forces an epithelial sac through a weakened or defective muscle wall. Traction diverticula are due to external inflammatory lesions resulting in fibrosis and traction force that pulls out the full thickness of the esophageal wall as a diverticulum.

Esophageal Varices

Gastroesophageal varices (Figure 37-9) occur in the lower esophagus and gastric fundus at the site of portosystemic venous anastomoses in patients with portal hypertension due to any cause. The dilated, tortuous veins at increased hydrostatic pressure are mainly submucosal, and their rupture causes severe hemorrhage (hematemesis and melena).

Mallory-Weiss Syndrome

Prolonged vomiting is common in alcoholics and pregnant women. Violent retching may produce a longitudinal tear in the mucosa of the lowest part of the esophagus. Severe hemorrhage with hematemesis occurs. Esophageal lacerations are responsible for 5–10% of cases of hematemesis.

Rupture of the Esophagus

Esophageal rupture is rare. It may result from (1) esophagoscopy, particularly during attempts at dilation in patients with strictures and achalasia; (2) increased esophageal luminal pressure associated with forceful vomiting or retching (Boerhaave's syndrome); (3) ingestion of corrosive liquids; (4) external trauma; and, rarely, (5) severe ulcerative reflux esophagitis.

Esophageal rupture causes severe chest pain due to mediastinitis. Air entering the mediastinum may track into the neck (subcutaneous emphysema) or into the pleural cavity (pneumothorax).

Carcinoma of the Esophagus

Incidence

Esophageal carcinoma accounts for over 95% of neoplasms of the esophagus and about 1% of cancers involving the gastrointestinal tract. It is highly lethal and causes about 2% of all cancer deaths in the United States (about 9000 per year). It is a disease of older people (over 50 years) and is more common in males and blacks. Cancer of the esophagus is much more common in the Far East (notably China) and in certain parts of Africa and Iran. In Iran, there is an unusual female preponderance of the disease. In the United States, the incidence of adenocarcinoma of the lower esophagus associated with Barrett's esophagus (metaplasia) is increasing rapidly.

Etiology

In the United States, chronic alcoholism increases the risk of esophageal carcinoma 20- to 30-fold. Cigarette smoking increases the risk 10- to 20-fold. Smoking and alcoholism are less often factors in the epidemiology of esophageal cancer in China, Africa, and Iran. The cause of esophageal cancer in the high-incidence areas of the world is unknown. Hot rice and tea, nitrosamines and aflatoxins in food, contaminants in locally brewed beer, and smoked fish have all been suggested as causative factors—all without proof.

Many premalignant conditions are associated with an increased risk of esophageal carcinoma. These include lye strictures (squamous carcinoma), Plummer-Vinson syndrome (squamous carcinoma), Barrett's esophagus (adenocarcinoma), and achalasia of the cardia (low risk of squamous carcinoma).

Pathology

In the United States, 50% of esophageal cancers arise in the middle third, 30% in the lower third, and 20% in the upper third of the organ. In Scandinavia, where Plummer-Vinson syndrome is common, upper esophageal cancer is more frequent.

The early lesion is a plaque-like thickening of the mucosa (Figure 37-10). From its mucosal origin, carcinoma may extend (1) into the lumen as a polypoid, fungating mass that may break down to form a malignant ulcer with raised everted edges (Figure 37-11); (2) transversely in the submucosa, to involve the whole circumference of the esophagus; or (3) into the wall of the esophagus. A marked desmoplastic (fibrotic) response causes fibrosis with esophageal narrowing (malignant stricture). The exact appearance of the carcinoma depends on which of these growth patterns predominates.

Microscopically, approximately 75% of esophageal carcinomas are squamous carcinomas. Adenocarcinoma (arising in Barrett's esophagus) accounts for the rest and is rapidly increasing in incidence in the United States. Most adenocarcinomas occur in the lower third of the esophagus.

Spread

(Figure 37-12)

Local invasion through the esophageal wall to involve adjacent cervical and mediastinal structures occurs early. Invasion of the bronchial wall may rarely result in tracheoesophageal fistula, commonly complicated by necrotizing pneumonia. Invasion of the aorta may lead to massive hemorrhage. Recurrent laryngeal nerve involvement leads to vocal cord paralysis (hoarseness).

Lymphatic spread occurs early, and lymph node metastases are commonly present at the time of diagnosis. Bloodstream spread with metastases to liver and lung also occurs early.

Clinical Features & Diagnosis

Most patients present with dysphagia and severe weight loss, and most have large unresectable tumors at this stage. Less often, presentation is with anemia, hematemesis, or melena. The diagnosis is best established by endoscopic visualization of the tumor followed by biopsy.

Regular endoscopic surveillance of patients with Barrett's esophagus is effective in detecting high-grade dysplasia and early cancer.

Treatment & Prognosis

Surgery is the primary treatment method. However, many patients with esophageal cancer have unresectable tumors at the time of presentation. The exception is in patients with early cancers detected during surveillance for known Barrett's esophagus. Radiotherapy may cause some regression of tumor but is not curative. Chemotherapy is not very effective, although new regimens are starting to provide a glimmer of hope.

The overall prognosis is very poor, with 70% of patients dead within 1 year after diagnosis and fewer than 10% surviving after 5 years. Patients with early cancers restricted to the esophagus that are detected during surveillance for Barrett's esophagus have an excellent prognosis, with over 80% 5-year survival. Often the aim of treatment is palliation to relieve pain and to permit swallowing.

Other Neoplasms of the Esophagus

Neoplasms other than carcinomas are rare in the esophagus. Leiomyoma is the most common benign neoplasm, but it rarely causes symptoms. Leiomyosarcoma, malignant lymphoma, malignant melanoma, and carcinoid tumors have been reported.