TITLE: STRUCTURAL DISORDERS OF THE ESOPHAGUS
AUTHOR: EDGAR ACHKAR, MD -- Department of Gastroenterology and Hepatology
REVIEWED: JANUARY 19, 2005
Print Tables From This Chapter
DYSPHAGIA

Dysphagia, a common symptom in those with esophageal disorders, may arise from a multitude of underlying causes. Dysphagia or difficulty swallowing refers a sensation of impairment of the normal progression of the bolus from the mouth into the stomach. Dysphagia should be distinguished from odynophagia or pain upon swallowing. Recognizing dysphagia and gauging its clinical significance appears simple. There are, however, several important points that may be brought up by the following questions:

  • Is the patient complaining truly of dysphagia? In most cases, patients can express clearly symptoms of difficulty in swallowing. Alternative terms such as "food sticking" or "food moving down slowly into the chest" may assist in identifying those with dysphagia.
  • Is the dysphagia for solids, liquids, or both? Mucosal lesions, benign or malignant, that produce a narrowing of the esophageal lumen will not usually interfere with the passage of liquid substances and dysphagia is limited to solid foods. On the other hand, disorders impairing esophageal peristalsis will cause difficulty with both solids and liquids.
  • Is the dysphagia intermittent or progressive? Structural lesions of the lower esophagus such as rings and strictures, produce intermittent obstruction related to the size of the bolus with often prolonged periods free of symptoms. In motor disorders, on the other hand, dysphagia is insidious and becomes progressively worse.

Proper clinical evaluation of dysphagia requires a detailed history.1 Multiple diagnostic techniques are available and their use depends upon the presenting clinical features. The initial test however is often a barium swallow or an endoscopic examination. The choice between these two techniques, as the most useful and least costly for the evaluation of dysphagia, is the subject of debate. In a patient who presents with intermittent solid dysphagia, suggesting a benign obstructing lesion such as peptic stricture or ring, starting with endoscopy is reasonable as it allows making the diagnosis and simultaneously treating the lesion by dilation. In cases of dysphagia to both solids and liquids and suspicion of a motor disorder, a barium swallow provides more useful information by evaluating esophageal peristalsis. The guidelines of the American Gastroenterological Association (AGA) support the choice of barium swallow in these cases, a recommendation that most clinicians would agree with.2

Various known causes of esophageal disorders may be classified into four different groups:

  • Disorders caused by mucosal injury
  • Neoplastic disorders
  • Anomalies of esophageal lumen
  • Motor disorders
DISORDERS CAUSED BY MUCOSAL INJURY
DEFINITION

Mucosal injury is defined as mucosal damage resulting from an intrinsic or extrinsic agent capable of disrupting the integrity of the mucosa, leading to acute inflammation and potentially chronic inflammation with possible permanent scarring. The most common syndromes of mucosal injuries are:

Gastroesophageal reflux disease is discussed in detail in the chapter on acid peptic disorders.
PREVALENCE

While GERD is very prevalent, causing symptoms in 20% of the population at least once a week, other causes of mucosal injury are less frequent. Infectious esophagitis is rare in normal persons. In an immunocompromised individual, infection occurs today at a lesser rate than in the past because of better diagnostic and therapeutic techniques. Candida is the most frequent organism responsible for causing esophagitis. Radiation esophagitis is reported by some patients during treatment but long term lesions are not frequent. Caustic ingestions has been reduced dramatically since protection laws have been instituted. It is estimated that 5,000 cases occur each year in the U.S. The prevalence of pill induced esophagitis is not known. There are increasing number of cases reported but they constitute a small number compared to the innumerable pills ingested by the public.

PATHOPHYSIOLOGY

Virtually all mucosal injuries are accompanied by inflammation with various degrees of severity including from erythema, frank ulcers with potential scarring and bleeding and strictures.

Infectious esophagitis occurs almost always in immunocompromised patients such as post-transplant patients or patients with cancer or AIDS. Predisposing factors include diabetes, alcoholism, malnutrition and old age as well as treatment with corticosteroids. Diseases leading to stasis such as achalasia may also predispose to some infections. Radiation esophagitis occurs with radiation therapy to the chest and mediastinum. It is dependent upon the total dose administered as well as the time over which treatment is applied. Injury by caustic ingestion is most commonly caused by alkali agents producing burns or acid agents producing necrosis.

Pill esophagitis was first reported with tetracycline. Doxycline and other tetracyclines account for the majority of cases but injuries have been reported with other antibiotics, antiviral agents, nonsteroidal anti-inflammatory drugs, potassium preparations and many other medications.3 There is some evidence that sustained release medications are more commonly associated with injury. The lesion occurs most often between the junction of the proximal and mid-esophagus at the point of impression by the aortic arch or above the esophagogastric junction.
SIGNS AND SYMPTOMS

Mucosal injury may be asymptomatic or may manifest by dysphagia, odynophagia or chest pain. Patients whose nutrition may already be affected by their immunocompromised status and anorexia are further jeopardized by their inability to eat. Candida esophagitis is often asymptomatic and is discovered at endoscopy. Pill injury is accompanied by sudden onset of severe pain over one to three days. Pain is aggravated by eating.
DIAGNOSIS
The diagnosis of mucosal injury is suspected based on patient's background and is established by a barium swallow but more precisely by endoscopy.4 Candida esophagitis shows typical white plaques scattered throughout the esophagus (Figure 1). Viral infections caused either by herpes simplex or CMV will reveal focal or disseminated ulcers and the diagnosis is established by biopsy and special stains. About 40% of ulcers seen in patients with AIDS are not due to a specific infection and are termed idiopathic ulcers. They are typically large and deep. Radiation esophagitis is characterized by erythema and friability during the acute stages and by strictures in the late stages. Caustic ingestion is rare in the adult population and is almost always due to suicidal attempts. Endoscopy is relatively contraindicated in the acute stages. Pill induced esophagitis causes a typical discreet ulcer surrounded by a normal surrounding mucosa (Figure 2).
TREATMENT AND OUTCOMES

The treatment of infectious esophagitis depends upon the isolation of the causative agent. In immunocompromised patients, multiple infections may co-exist. Treatment of candida esophagitis is best carried out with ketaconazole 200-400 mg/day or fluconazole 100 mg/day for 7 -14 days. Nystatin in oral solution may be effective in mild cases and in the absence of immunodeficiency. Viral infections respond in part to antiviral agents. Idiopathic ulcers of AIDS are treated with prednisone 40 mg/day with tapering over 4 weeks by 10 mg/week5 or thalidomide 200-300 mg/day over 4 weeks. The potential risk of birth defects limits the use of thalidomide.

In pill injury the offending medication should be withdrawn and antireflux therapy prescribed to prevent exacerbation of the injury. When odynophagia is pronounced, the use of topical anesthetic agents administered orally may help relieve the pain. In most cases, symptoms disappear within a few days and bleeding and perforation are rare. More importantly, pill injury should be prevented by encouraging patients to drink large amounts of fluid with their pills, to remain upright for 30 minutes after taking the pills and to avoid pills known to cause frequent injury particularly in patients with esophageal strictures or who are bedridden. These preventive measures are very important in elderly patients who tend to take multiple medications particularly at bedtime.

Chronic lesions caused by mucosal injury often lead to strictures. Strictures are managed by periodic dilations and antireflux treatment. In GERD, the use of potent acid suppressing agents has reduced the frequency with which dilation needs to be performed.
NEOPLASTIC DISORDERS
BENIGN TUMORS
Benign esophageal tumors are non-malignant neoplasms arising from the mucosal or muscular layers of the esophagus. Benign tumors of the esophagus are rare. Leiomyoma, the most common, has been described in 5% of autopsy specimens. Benign tumors are classified as mucosal or intramural. Mucosal tumors tend to produce a filling defect in the lumen; they include fibrovascular polyps, granular cell tumors, papillomas and lipomas. Intramural lesions are more common than mucosal tumors. They produce an extrinsic mass projecting from the wall into the lumen. Such tumors include leiomyomas and cysts.
SIGNS AND SYMPTOMS

Most benign tumors of the esophagus are asymptomatic and discovered by chance during an examination obtained for other reasons. When symptomatic, benign tumors cause mostly dysphagia and, in some cases, chest pain and regurgitation. The most important issue is to differentiate them from malignant tumors.

DIAGNOSIS

A barium swallow will often determine if the lesion is intramural or mucosal. Endoscopy is often helpful in determining the tumor's nature (Figure 3). Some polyps appear on a long stalk and may be seen flopping into the lumen. Endoscopic examination will reveal intramural tumors as smooth protrusions covered by normal mucosa. Cysts appear as round and smooth. Mucosal lesions may sometimes ulcerate. Endoscopic ultrasound is helpful in distinguishing a leiomyoma from leiomyosarcoma. Unfortunately, when the tumor is large the differentiation is more difficult.
THERAPY AND OUTCOMES

Small asymptomatic lesions require no treatment. Surgical enucleation is the treatment of choice for symptomatic intramural lesions or when intervention is necessary because malignancy cannot be ruled out with certainty. Polyps are treated by local resection.
MALIGNANT TUMORS
DEFINITION AND CLASSIFICATION

Malignant tumors of the esophagus constitute the majority of esophageal tumors. Different types of tumors have been described and include:

  • Squamous cell carcinoma
  • Adenocarcinoma
  • Sarcoma
  • Lymphoma
  • Primary melanoma
  • Metastatic tumors (breast, lung, melanoma)
Squamous cell carcinoma and adenocarcinoma represent, by far, the largest number of esophageal malignancies.6 About 13,000 cases of esophageal cancer are diagnosed each year in the United States. Squamous cell carcinoma used to account for the majority of malignancies but adenocarcinoma has been rising steadily and now accounts for about 50% of all tumors. Squamous cell carcinoma arises from the squamous epithelium and is encountered most commonly in the mid-esophagus. A smaller number of tumors arise in the distal and upper esophagus. Environmental factors seem to play an important role in the genesis of squamous cell carcinoma with wide geographic variations. Other predisposing factors include alcohol, tobacco, long history of achalasia, previous ingestion of caustic agents, and genetic factors. In the United States, squamous cell carcinoma is more common in African-Americans. Adenocarcinoma of the esophagus is increasing in frequency and is more commonly seen in white men. Most tumors arise in the distal third of the esophagus. Barrett's esophagus is the major predisposing factor for adenocarcinoma of the esophagus. Tylosis or hyperkeratosis of palms and soles is an autosomal dominant disorder strongly associated with gastrointestinal malignancy particularly squamous cell carcinoma of the esophagus.

While there are differences between squamous cell carcinoma and adenocarcinoma in epidemiology, location and patterns of spread, both diseases tend to spread early outside the esophagus and both share a rather poor prognosis unless discovered early. For this reason, efforts are undertaken to detect early signs of cancer or precancer. A guideline of the American Society of Gastrointestinal Endoscopy lists the conditions for which screening is recommended for early detection7:

Screening recommended (every 1-3 years):
  • Barrett's esophagus
  • Caustic ingestion: start 15-20 years after injury
  • Tylosis: Start at age 30
Screening not recommended:
  • Achalasia
SIGNS AND SYMPTOMS
The most common clinical manifestation of esophageal tumors is dysphagia which occurs to solid foods first then progresses to soft foods and, eventually, liquids. Odynophagia is reported in some cases. Chest pain, when present, may represent an ominous sign as it indicates invasion to the mediastinum. Weight loss is frequent as a result of difficulty swallowing and, in late stages, because of anorexia. Bleeding is rare. Physical examination will reveal signs of weight loss. In some cases, supraclavicular nodes may be detected.
DIAGNOSIS

Carcinoma of the esophagus should be suspected in any individual with recent onset dysphagia particularly after the age of 50. A long history of reflux diseases raises the possibility of carcinoma arising in Barrett's esophagus especially in white men. The following diagnostic modalities are used in the evaluation of malignant neoplasms:

  • Barium swallow
  • Endoscopy
  • Computerized tomography (CT)
  • Endoscopic ultrasound (EUS)
  • Bronchoscopy

Barium swallow gives an indication of tumor location and size (Figure 4). Endoscopy determines the size of the esophageal lumen (Figure 5). Biopsy and cytologic brushings establish the tumor's histologic type. The central issue, at that point, is the appropriateness of surgical intervention. The decision to operate is based on tumor staging. Both squamous cell carcinoma and adenocarcinoma are staged according to the TNM system (Tumor invasion, lymph nodes and metastasis). (Table 1) EUS is more sensitive than CT but a combination of both improves staging's accuracy.8
TREATMENT AND OUTCOMES

Curative Treatment:

When full evaluation reveals a favorable stage and the patient's general condition is not a contraindication to surgery, tumor resection represents the most promising treatment. Surgical resection is indicated when the lesion is considered curable. Combined chemo and radiotherapy followed by surgery is offered to patients with local extension. Even in adenocarcinoma which is less sensitive to chemo and radiotherapy, combined treatment improves prognosis. The best chance of significant survival in esophageal cancer resides in a multidisciplinary approach in institutions possessing good experience in gastroenterology, thoracic surgery, chemotherapy and radiation oncology.

The ASGE guideline9 outlines the advantages of and the treatment approach for esophageal cancer with an algorithm (Figure 6).

Palliative Treatment:

When surgery is ruled out because of tumor extension or complications and in cases of tumor recurrence, several palliative methods are available. Esophageal cancer is often diagnosed at an advanced incurable stage and when patients present with dysphagia, 50% of the lumen may already be occluded.

Palliation methods include radiotherapy and the following endoscopic modalities:

  • Periodic dilation
  • Esophageal stenting
  • Photodynamic ablation
  • Laser ablation
  • Endoscopic mucosal resection

Endoscopic techniques have various rates of success and they all carry a risk of complications including perforation, infection and bleeding as well as worsening of the initial symptoms. In late stages and in patients whose dysphagia is insurmountable, insertion of a gastrostomy feeding tube is often necessary.

ANOMALIES OF ESOPHAGEAL LUMEN
RINGS AND WEBS
The definition of webs and rings is confusing because the terms have been used interchangeably. A web is a thin membrane occupying part of the esophageal lumen and is most commonly seen on the anterior aspect of the area just below the cricopharynx.

Rings are concentric narrowings of the lumen usually seen in the lower esophagus. The B-ring or muscular ring occurs at the junction of the tubular portion of the esophagus and the most distal part called the vestibule. The ring is often described by radiologists but is rarely symptomatic. The A or mucosal ring occurs most distally at the esophagogastric junction and usually in association with a hiatal hernia. Also known as Schatzki's ring10, it deserves particular attention because it is often symptomatic (Figure 7).
PREVALENCE
Both webs and rings are frequently seen during radiologic or endoscopic examination. It is estimated that webs are present in 0.5 to 1% of asymptomatic people. Lower esophageal rings are found in 10 to 15% of barium swallow studies. It is now not known how many are symptomatic.
PATHOPHYSIOLOGY
The exact nature of webs is unknown. It is thought that webs result from an anomaly of development in the epithelium of the upper esophagus.

A Schatzki's ring consists of esophageal mucosa and submucosa. This ring is almost always associated with the presence of a hiatal hernia. While it is histologically and probably pathogenetically different from esophageal peptic strictures, the association of a lower esophageal ring with gastroesophageal reflux is frequent. In addition, distinguishing one from the other endoscopically is sometimes difficult. Therefore, many clinicians manage esophageal rings as they do strictures. The PlummerVinson and the Paterson Kelly syndromes refer to the association of webs with iron deficiency anemia and other oropharyngeal abnormalities. These associations are rarely described today and the terms have largely been abandoned.
SIGNS AND SYMPTOMS
When either a cricopharyngeal web or a ring causes difficulty, the patient presents with dysphagia. In the case of a web, the dysphagia is oropharyngeal, associated with solid foods and is rarely severe. The dysphagia associated with a lower esophageal ring is intermittent, occurring with solid foods particularly meat with occasional impaction and is referred, in the old literature, as the "steakhouse syndrome."
DIAGNOSIS
Barium x-ray is the most sensitive method to detect webs and rings. Webs should not be confused with the normal impression of the cricopharynx . On x-ray, a web is seen as an indentation on the anterior aspect of the pharynx (Figure 8). The diagnostic yield for a ring is higher when a solid bolus is given during the test. Endoscopic examination is less sensitive in detecting subtle rings particularly with the use of the new thin endoscopes which may pass through the ring without the endoscopist seeing the luminal narrowing.
TREATMENT AND OUTCOMES
Most webs do not require treatment. When they are symptomatic, however, endoscopic dilation is useful but has to be performed with caution by an experienced operator. Lower esophageal rings are treated easily with dilation by bougies or over a guidewire. The response to treatment is generally good in most patients. There is a small risk of perforation. An acid suppressing agent is usually prescribed.
DIVERTICULA
DEFINITION

An esophageal diverticulum is a sac protruding from the esophageal wall and containing all layers of the esophagus. Esophageal diverticula may be congenital or acquired. The simplest way to classify them is according to anatomy:

  • Zenker's diverticula
  • Mid-esophageal diverticula
  • Epiphrenic diverticula
  • Intramural pseudodiverticulosis
PREVALENCE
Esophageal diverticula have been described in all age groups but they are most commonly seen in adults. They are rare, occurring in less than 1% of upper gastrointestinal X-rays and accounting for less than 5% of dysphagia cases.11
PATHOPHYSIOLOGY

Zenker's diverticulum or pharyngoesophageal diverticulum occurs in a location proximal to the esophagus above the upper esophageal sphincter. The diverticulum bulges posteriorly and its size increases over time. The most widely accepted mechanism for a Zenker's diverticulum is a functional disturbance of the hypopharynx. The most popular explanation is an incoordination between the pharynx and the cricopharyngeus muscle called "cricopharyngeal achalasia." Most recent evidence however suggests that the diverticulum occurs because of reduced compliance of the upper sphincter rather than because of incoordination.12 Mid-esophageal diverticula have been divided into traction and pulsion diverticula. This distinction has no practical value. The exact cause of a mid-esophageal diverticulum is not known but the condition has been associated with scarring and various esophageal motor abnormalities. Epiphrenic diverticula are almost always the result of an esophageal motor abnormality, namely an incoordination between the distal esophagus and the lower esophageal sphincter.13

Esophageal intramural pseudodiverticulosis is characterized by numerous, minute, flask-like outpouchings along the esophageal wall.14 They can be segmental or generalized. They are associated with strictures, carcinoma, candidiasis and motor abnormalities (Figure 9).

SIGNS AND SYMPTOMS
Many esophageal diverticula are discovered by chance during radiologic evaluation. In early stages of Zenker's diverticulum, the patient may complain of vague throat irritation and, when the sac becomes large, more severe symptoms develop particularly dysphagia, regurgitation of food ingested several hours earlier and gurgling sounds upon swallowing. Complications of Zenker's diverticulum such as bleeding, obstruction, or fistulization are rare. Mid-esophageal diverticula are often asymptomatic unless they become so large that food gets trapped in the pouch. For epiphrenic diverticula the severity of symptoms depends upon the associated motor abnormality. The most frequent conditions associated with such diverticula are achalasia and diffuse spasm.
DIAGNOSIS
A barium esophagram with special attention to the oropharyngeal phase of swallowing is the best diagnostic test for Zenker's diverticulum. The diverticulum is seen to protrude posteriorly and the barium tends to fall into the pouch before progressing into the esophagus (Figure 10). Endoscopy adds very little to the evaluation of Zenker's diverticulum. Manometric testing of upper esophageal function is not clinically useful. Both mid-esophageal (Figure 11) and epiphrenic diverticula (Figure 12) are best diagnosed by barium swallow and an associated motor disorder is usually suspected if present.
TREATMENT AND OUTCOMES

Symptomatic Zenker's diverticula can be treated by surgical excision. Newer treatments are applied endoscopically. A transection is made to create a communication between the diverticulum and the esophagus allowing the diverticulum to drain into the esophagus. This technique can be carried out with or without the assistance of laser.15,16 Most surgeons agree that whatever the surgical technique, a myotomy of the cricopharyngeus muscle is necessary to prevent recurrence of the diverticulum. Mid-esophageal diverticula are treated by surgical excision. For an epiphrenic diverticulum the goal of therapy should be to treat the underlying motor disorder with the hope of avoiding further enlargement of the diverticulum. In the absence of achalasia, a long esophagomyotomy is recommended but published results involve a small number of patients. Intramural pseudodiverticulosis requires treatment of the underlying infection or obstruction with dilatation in the case of a distinct obstructing area.

Return to Medicine Index
REFERENCES
  1. AGA technical review on treatment of patients with dysphagia caused by benign disorders of the distal esophagus. Gastroenterology. 1999;117:233-254.

  2. American Gastroenterological Association medical position statement on treatment of patients with dysphagia caused by benign disorders of the distal esophagus. Gastroenterology. 1999;117:229-232.

  3. Kikendall JW. Pill-induced injury in The Esophagus 3rd Edition. Castell DO, Richter JE eds. Lippincott, Williams, and Wilkins, Philadelphia, 1999. Pp527-537.

  4. Wilcox CM, Schwartz DA. Endoscopic pathologic correlates of Candida esophagitis in acquired immunodeficiency syndrome. Dig Dis Sci. 1996;41:1337-1345.

  5. Wilcox CM, Schwartz DA. Comparison of two corticosteroid regimens for the treatment of idiopathic esophageal ulcerations associated with HIV infection. Am J Gastroenterol. 1994;89:2163.

  6. Fleischer DE, Haddad NG. Neoplasms of the esophagus in The Esophagus 3rd Edition. Castell DO, Richter JE eds. Lippincott, Williams, and Wilkins, Philadelphia, 1999. Pp235-257.

  7. The role of endoscopy in the surveillance of premalignant conditions of the upper gastrointestinal tract. Gastrointest Endosc. 1998;48:663-668.

  8. Byrne MF, Jowell PS. Gastrointestinal imaging: Endoscopic ultrasound. Gastroenterology. 2002;122:1631-1648.

  9. The role of endoscopy in the assessment and treatment of esophageal cancer. Gastrointest Endosc. 2003; 57:817-822.

  10. Schatzki R. The lower esophageal ring. Long term follow-up of asymptomatic rings. Am J Roentgenol Radiat Ther Nucl Med.1963;90:805.

  11. Ekberg O, Nylander G. Cineradiography of the pharyngeal phase of deglutition in 250 patients with dysphagia. Br J Radiol. 1982;55:258-262.

  12. Kahrilas PJ, Dodds WF, Dent J, Logemann JA, Shaker R. Upper esophageal sphincter function during deglutition. Gastroenterology. 1988;95:52-62.

  13. Bruggeman LL, Seaman WB. Epiphrenic diverticula. An analysis of 80 cases. Am J Roentgenol. 1973;119:266-276.

  14. Boyd RM, Bogoch A, Grieg JH, et al. Esophageal intramural pseudodiverticulosis. Radiology. 1974;113:267-270.

  15. Scher RL, Richtsmeier WJ. Long-term experience with endoscopic staple-assisted esophagodiverticulostomy for Zenker's diverticulum. Laryngoscope. 1998;108:200-205.

  16. Stoeckli SJ, Schmid S. Endoscopic stapler-assisted diverticuloesophagostomy for Zenker's diverticulum: Patient satisfaction and subjective relief of symptoms. Surgery. 2002;131:158-62.
    17.

This information is provided for general medical education purposes only and is not meant to substitute for the independent medical judgment of a physician relative to diagnostic and treatment options of a specific patient's medical condition.

In no event will The Cleveland Clinic Foundation be liable for any decision made or action taken in reliance upon the information provided through this web site.
Copyright 2003 The Cleveland Clinic Foundation