Diseases of the EsophagusM.S.Levine

Introduction

This syllabus reviews the findings on esophagography for a variety of esophageal diseases, including reflux esophagitis, Barrett’s esophagus, other types of esophagi- tis, benign and malignant esophageal tumors, varices, lower esophageal rings, esophageal intramural pseudodi- verticulosis, and esophageal motility disorders.

Reflux Esophagitis

Reflux esophagitis is by far the most common inflamma- tory disease involving the esophagus. The single most common sign of reflux esophagitis on double-contrast esophagrams is a finely nodular or granular appearance in the distal third of the esophagus, with poorly defined radiolucencies that fade peripherally due to edema and inflammation of the mucosa [1]. In other patients, barium studies may reveal shallow ulcers and erosions in the dis- tal esophagus contiguous with the gastroesophageal junc- tion [2]. Reflux esophagitis may also be manifested by thickened longitudinal folds due to edema and inflamma- tion that extend into the submucosa. However, thickened folds should be recognized as a nonspecific finding of esophagitis. Other patients with reflux esophagitis may have a single enlarged, chronically inflamed fold that arises at the gastric cardia and extends into the distal esophagus as a smooth protuberance, also known as an inflammatory esophagogastric polyp [3]. These lesions have no malignant potential, so endoscopy is not war- ranted when barium studies reveal typical findings of an inflammatory polyp in the distal esophagus.

Scarring from reflux esophagitis can lead to the develop- ment of a reflux-induced stricture (i.e., ‘peptic’ stricture) in the distal esophagus, almost always above a hiatal hernia.

Such strictures typically appear as smooth, tapered segments of concentric narrowing, but asymmetric scarring can lead to asymmetric narrowing with focal sacculation or balloon- ing of the esophageal wall between areas of fibrosis. Other peptic strictures may be manifested by short, ring-like areas of narrowing that could be mistaken for Schatzki rings in pa- tients with dysphagia [4]. Scarring from reflux esophagitis

can also lead to longitudinal shortening of the esophagus and the development of fixed transverse folds, producing a

‘stepladder’ appearance due to pooling of barium between the folds [5]. These folds should be differentiated from the thin transverse striations (i.e., ‘feline’ esophagus) often seen as a transient finding at fluoroscopy due to contraction of the longitudinally oriented muscularis mucosae [6].

Barrett’s Esophagus

Barrett’s esophagus is a premalignant condition in which there is progressive columnar metaplasia of the distal esophagus due to chronic reflux and reflux esophagitis.

Barrett’s esophagus is thought to develop in about 10% of all patients with reflux esophagitis. Double-contrast esophagrams can be used to classify patients with reflux symptoms at high, moderate, or low risk for Barrett’s esophagus, based on specific radiologic criteria [7]. Patients are classified at high risk when double-contrast esopha- grams reveal a mid-esophageal stricture or ulcer, or a retic- ular mucosal pattern (usually associated with a hiatal her- nia and/or gastroesophageal reflux) [7]. In such cases, en- doscopy and biopsy should be performed for a definitive di- agnosis. Patients are classified at moderate risk for Barrett’s esophagus when double-contrast studies reveal reflux esophagitis or peptic strictures in the distal esophagus [7].

The decision for endoscopy in this group should be based on the severity of symptoms, age, and overall health of the patients. Finally, patients are classified at low risk for Barrett’s esophagus when double-contrast studies reveal no structural abnormalities. The majority of patients are found to be in this category, and the prevalence of Barrett’s esoph- agus is so low that they can be treated empirically for their reflux symptoms, without need for endoscopy [7].

Infectious Esophagitis Candida Esophagitis

Candida albicans is the most common cause of infec-

tious esophagitis. It usually occurs as an opportunistic in-

Diseases of the Esophagus

M.S. Levine

Gastrointestinal Radiology, Department of Radiology, University of Pennsylvania Medical Center, Philadelphia, PA, USA

fection in immunocompromised patients, particularly AIDS patients. Only about 50% of patients with Candida esophagitis are found to have thrush, so the absence of oropharyngeal disease in no way excludes this diagnosis.

Candida esophagitis is usually manifested on double-

contrast studies by multiple discrete plaque-like lesions that tend to be oriented longitudinally and are separated by normal mucosa [8]. Double-contrast esophagrams have a sensitivity of 90% in detecting Candida esophagitis [8], primarily because of their ability to demonstrate these mu- cosal plaques. During the past two decades, a much more fulminant form of candidiasis has been encountered in pa- tients with AIDS, who may present with a grossly irregu- lar or ‘shaggy’ esophagus caused by innumerable coales- cent pseudomembranes and plaques with trapping of bar- ium between these lesions (Fig. 1) [9]. Other patients with achalasia or scleroderma may develop a ‘foamy’ esopha- gus with innumerable tiny bubbles layering out in the bar- ium column; this phenomenon presumably results from the yeast form of fungal infection [10]. When typical find- ings of Candida esophagitis are encountered on double- contrast esophagrams, these patients can be treated with antifungal agents without the need for endoscopy.

Herpes Esophagitis

The herpes simplex virus type 1 is another common cause of infectious esophagitis. Most affected patients are immunocompromised, but herpes esophagitis may occa- sionally develop as an acute, self-limited disease in oth- erwise healthy individuals [11]. Viral infection initially leads to the development of small vesicles that rupture to form discrete, punched-out ulcers on the mucosa. As a re- sult, herpes esophagitis may be manifested on double- contrast studies by multiple superficial ulcers on a nor- mal background mucosa (Fig. 2) [12]. In the appropriate

clinical setting, small, discrete ulcers without plaques should be highly suggestive of herpes esophagitis, as ul- ceration in candidiasis almost always occurs on a back- ground of diffuse plaque formation. As the disease pro- gresses, however, herpes esophagitis may be manifested by a combination of ulcers and plaques, mimicking

Cytomegalovirus Esophagitis

Cytomegalovirus (CMV) is another cause of infectious esophagitis that occurs in patients with AIDS. CMV esophagitis may be manifested on double-contrast studies by multiple small ulcers or, even more commonly, by one or more giant, flat ulcers that are several centimeters or more in length [13]. Herpetic ulcers rarely become this large, so the presence of one or more giant ulcers should suggest CMV esophagitis in patients with AIDS. However, the differential diagnosis also includes giant human im- munodeficiency virus (HIV) ulcers in the esophagus (see next section). Because CMV is treated with toxic antiviral agents such as ganciclovir, endoscopy is required to con- firm the presence of CMV before treating these patients.

Human Immunodeficiency Virus Esophagitis

HIV infection can lead to the development of giant esophageal ulcers indistinguishable from those caused by CMV. Double-contrast esophagrams typically reveal one or more giant ulcers surrounded by a radiolucent rim of edema, sometimes associated with a cluster of small satellite ulcers (Fig. 3) [14]. Occasionally, these individ- uals may have associated palatal ulcers or a characteris- tic rash on the upper body. The diagnosis is established by obtaining endoscopic biopsy specimens, brushings, or cultures to rule out CMV esophagitis as the cause of the ulcers. Unlike CMV ulcers, HIV-related esophageal ul-

phagitis in a patient with AIDS.

Double-contrast esophagram shows

‘shaggy’ esophagus of fulminant esophageal candidiasis due to innu- merable plaques and pseudomem- branes with trapping of barium be- tween lesions

Fig. 2. Herpes esophagitis. Double- contrast esophagram shows multi- ple small, discrete ulcers with sur- rounding mounds of edema (ar- rows) in mid-esophagus

cers usually heal dramatically on treatment with oral steroids [14]. Thus, endoscopy is required in HIV-positive patients with giant esophageal ulcers to differentiate esophagitis caused by HIV and CMV, so appropriate ther- apy can be instituted in these patients.

Drug-induced Esophagitis

Tetracycline and doxycycline are the two most common causes of drug-induced esophagitis in the United States, but other offending agents include potassium chloride, quinidine, aspirin or other nonsteroidal antiinflammatory drugs (NSAIDs), and alendronate sodium [15]. Affected individuals typically ingest the medication with little or no water immediately before going to bed. The capsules or pills usually become lodged in the mid-esophagus where it is compressed by the adjacent aortic arch or left main bronchus. Prolonged contact of the esophageal mucosa with these medications presumably causes an irritant con- tact esophagitis. Affected individuals may present with se- vere odynophagia, but marked clinical improvement usu- ally occurs after withdrawal of the offending agent.

The radiographic findings depend on the offending medication. Tetracycline and doxycycline are associated with the development of small, shallow ulcers in the up- per or mid-esophagus indistinguishable from those in her- pes esophagitis [15]. These ulcers almost always heal without scarring because of their superficial nature. In contrast, potassium chloride, quinidine, NSAIDs, and al- endronate sodium may cause more severe esophageal in- jury, sometimes leading to the development of larger ul- cers and strictures [15].

Idiopathic Eosinophilic Esophagitis

Idiopathic eosinophilic esophagitis (IEE) is a chronic form of esophagitis characterized by an increased number of intraepithelial eosinophils (more than 20 per high pow- er field) on endoscopic biopsy specimens [16]. The etiol-

ogy is uncertain, but this condition most likely develops as a result of an inflammatory response to ingested food allergens. Most adults with IEE are young men with long- standing dysphagia and recurrent food impactions [16].

They classically have an atopic history (e.g., asthma, al- lergic rhinitis) and peripheral eosinophilia, but IEE fre- quently occurs as an isolated condition [16]. Affected in- dividuals are treated with topical steroids (swallowing me- tered doses of aerosolized steroid preparations) and pro- tein-free diets with varying degrees of success.

IEE may be manifested on esophagography by segmen- tal strictures in the esophagus. The strictures often contain distinctive ring-like indentations, resulting in a so-called

‘ringed’ esophagus [16]. Other patients with IEE may have diffuse esophageal narrowing, resulting in a ‘small-cal- iber’ esophagus [16]. A ringed esophagus has also been described in congenital esophageal stenosis. Affected in- dividuals may develop strictures with multiple concentric rings indistinguishable from those in IEE (Fig. 4) [17].

Although congenital esophageal stenosis is usually not as- sociated with an allergic history or peripheral eosinophil- ia, this condition also occurs in young men with long- standing dysphagia, and biopsies from the esophagus may also reveal increased numbers of intra-epithelial eosinophils [17]. Due to the similarities in the clinical, ra- diographic, and pathologic findings of these conditions, the symptoms of some of the patients with reported con- genital esophageal stenosis may have been due to IEE.

Benign Tumors

Squamous papillomas are the most common benign mu- cosal tumors in the esophagus, usually appearing on

AIDS. Double-contrast esopha- gram shows large, flat ulcer in pro- file (arrows) in distal esophagus.

Although CMV esophagitis could produce identical findings, endo- scopic brushings and biopsies re- vealed no evidence of CMV

Fig. 4. Congenital esophageal steno- sis. Double-contrast esophagram shows mild narrowing of mid- esophagus with distinctive ring-like constrictions (arrows), most likely due to cartilaginous rings in wall of esophagus

double-contrast esophagrams as small, sessile polyps with a smooth or slightly lobulated contour. In contrast, leiomyomas are the most common benign submucosal tumors in the esophagus, appearing on esophagography as intramural masses with the typical features of the submucosal lesions found elsewhere in the gastroin- testinal tract.

Fibrovascular polyps are rare, benign tumors consisting of fibrovascular and adipose tissue covered by squamous epithelium [18]. Fibrovascular polyps usually arise near the cricopharyngeus, gradually elongating over a period of years as they are dragged inferiorly by esophageal peri- stalsis. Rarely, these patients may have a spectacular clin- ical presentation with regurgitation of a fleshy mass into the mouth or even asphyxia and sudden death if the re- gurgitated polyp occludes the larynx [18]. Fibrovascular polyps typically appear on barium studies as smooth, ex- pansile, sausage-shaped masses in the esophagus (Fig. 5) [18]. Polyps composed predominantly of adipose tissue may appear as fat-density lesions on CT (Fig. 6a), where- as polyps containing adipose and fibrovascular tissue may have a more heterogeneous appearance with areas of fat juxtaposed with areas of soft-tissue density (Fig. 6b) [18].

Esophageal Carcinoma

Double-contrast esophagography has a sensitivity of greater than 95% for the detection of esophageal cancer [19]. Early esophageal cancers are usually small, pro- truded lesions less than 3.5 cm in size. These tumors may be manifested on double-contrast studies by plaque-like lesions, by sessile polyps with a smooth or slightly lobu- lated contour, or by focal irregularity of the esophageal wall [20]. Early adenocarcinomas may also be manifest- ed by a localized area of wall flattening or irregularity

within a pre-existing peptic stricture [20]. Superficial spreading carcinoma is another form of early esophageal cancer characterized by poorly defined nodules or plaques that merge with one another, producing a conflu- ent area of disease [20].

Advanced esophageal carcinomas usually appear on barium studies as infiltrating (Fig. 7), polypoid, ulcera- tive (Fig. 8), or varicoid lesions that mimic the appear- ance of varices due to submucosal spread of tumor [20].

Squamous cell carcinomas and adenocarcinomas of the esophagus cannot be reliably differentiated on barium studies. Nevertheless, squamous cell carcinomas tend to involve the upper or mid-esophagus, whereas adenocarci- nomas are located predominantly in the distal esophagus.

Unlike squamous carcinomas, adenocarcinomas also have a marked tendency to invade the gastric cardia or fundus, comprising as many as 50% of all malignant tu- mors involving the gastroesophageal junction [20].

Fig. 5. Giant fibrovascu- lar polyp. Double-con- trast esophagram shows long, smooth, expansile mass extending from proximal esophagus dis- tally to near gastroe- sophageal junction

b a

Fig. 6. a Giant fibrovascular polyps on CT scan shows expansile mass (arrow) of fat density in mid-esophagus. This finding is seen when a polyp is composed predominantly of adipose tissue. b CT scan in another patient shows expansile, heterogeneous mass (ar- rows) in esophagus. This finding is seen when lesion contains adi- pose and fibrovascular tissue

Other Malignant Tumors

Esophageal lymphoma may be manifested on barium studies by submucosal masses, polypoid lesions, enlarged folds, or strictures. Spindle cell carcinoma (formerly known as carcinosarcoma) is another rare malignant tu- mor characterized by bulky, polypoid intraluminal mass- es that expand the lumen of the esophagus without caus- ing obstruction. Other rare malignant tumors involving the esophagus include leiomyosarcoma and malignant melanoma.

Varices

Uphill varices are usually caused by portal hypertension with hepatofugal flow through dilated esophageal col- laterals to the superior vena cava. Uphill varices appear on barium studies as serpentine longitudinal filling de-

fects in the distal thoracic esophagus. They are best seen on mucosal relief views of the collapsed esophagus us- ing a barium paste or high-density barium suspension.

In contrast, downhill varices are caused by superior ve- na cava obstruction with downward flow via dilated esophageal collaterals to the portal venous system. Most patients with downhill varices present clinically with the superior vena cava syndrome. Downhill varices also ap- pear as serpentine longitudinal filling defects, but these varices are almost always confined to the upper or mid- esophagus.

Lower Esophageal Rings

The term Schatzki ring is reserved for symptomatic pa- tients with lower esophageal rings who present with in- termittent dysphagia for solids, especially meat. The rings appear on barium studies as smooth, symmetric ring-like constrictions at the gastroesophageal junction, almost always located above a hiatal hernia (Fig. 9a) [21]. The rings can be missed if the distal esophagus is not adequately distended at fluoroscopy (Fig. 9b), so it is important to obtain prone views of the esophagus during continuous drinking of a low-density barium suspension [21]. Conversely, rings can also be missed if the hiatal hernia is over-distended, resulting in overlap of the dis- tal esophagus and hernia that obscures the ring [22].

Rings with a maximal luminal diameter of more than 20 mm rarely cause dysphagia, whereas rings with a maxi- mal diameter of less than 13 mm almost always cause dysphagia [23].

Fig. 7. Adenocarcinoma arising in Barrett’s esophagus. Double- contrast esophagram shows ad- vanced infiltrating carcinoma (arrows) as an irregular area of luminal narrowing with mucosal nodularity and ulceration in dis- tal esophagus above hiatal hernia

Fig. 8. Squamous cell carcinoma of esoph- agus. Double-contrast esophagram shows polypoid mass (black arrows) with central area of ulceration (white arrow) in mid- esophagus

Fig. 9. Schatzki ring. a Prone, single-contrast esophagram shows smooth, symmetric, ring-like constriction (white arrow) in distal esophagus directly above hiatal hernia. b Ring is not seen on up- right, double-contrast esophagram from same examination because of inadequate distention of this region

a b

Esophageal Intramural Pseudodiverticulosis

Esophageal intramural pseudodiverticula consist of dilat- ed excretory ducts of deep mucous glands in the esopha- gus. The pseudodiverticula typically appear on esopha- gography as flask-shaped outpouchings in rows parallel to the long axis of the esophagus (Fig. 10) [24]. When viewed en face on double-contrast esophagrams, the pseudodiverticula can be mistaken for tiny ulcers. When viewed in profile, however, they often appear to be ‘float- ing’ outside the wall of the esophagus without apparent communication with the lumen [24]. Barium studies of- ten reveal an isolated cluster of pseudodiverticula in the distal esophagus in the region of a peptic stricture, so they presumably occur as a sequela of scarring from re- flux esophagitis [24]. Less frequently, the pseudodiver- ticula have a diffuse distribution and are associated with high strictures, or they occur as an isolated finding [24].

When strictures are present, these patients may present with dysphagia, but the pseudodiverticula themselves rarely cause symptoms.

Esophageal Motility Disorders Achalasia

Primary achalasia is an idiopathic condition, whereas secondary achalasia is caused by other underlying condi- tions, most commonly malignant tumors involving the gastroesophageal junction (especially carcinoma of the gastric cardia). Primary achalasia is characterized by ab- sent primary peristalsis in the esophagus and incomplete relaxation of the lower esophageal sphincter, manifested

on barium studies by tapered, beak-like narrowing of the distal esophagus adjacent to the gastroesophageal junc- tion. In advanced disease, the esophagus can become massively dilated and tortuous distally (i.e., a ‘sigmoid’

esophagus).

Secondary achalasia is also characterized by absent peristalsis in the esophagus and beak-like narrowing near the gastroesophageal junction. In secondary achalasia caused by a tumor at the gastroesophageal junction, how- ever, the length of the narrowed segment is often greater than that in primary achalasia because of spread of tumor into the distal esophagus [25]. The narrowed segment may also be asymmetric, nodular, or ulcerated because of tumor infiltrating this region. In some cases, barium stud- ies may reveal other signs of malignancy at the cardia with distortion or obliteration of the normal cardiac rosette [25]. The clinical history is also important, as pa- tients with primary achalasia almost always have long- standing dysphagia, whereas patients with secondary achalasia are usually older individuals (over the age of 60) with recent onset of dysphagia (less than six months) and weight loss [25].

Diffuse Esophageal Spasm

Symptomatic diffuse esophageal spasm (DES) may be manifested on barium studies by intermittently weak- ened or absent primary peristalsis with repetitive, lu- men-obliterating nonperistaltic contractions, producing a classic ‘cork-screw’ esophagus [26]. More commonly, however, these patients have multiple nonperistaltic con- tractions of mild to moderate severity without a cork- screw appearance [26]. The majority of patients with DES have also been found to have impaired opening of the lower esophageal sphincter on barium studies, with beak-like narrowing of the distal esophagus similar to that seen in achalasia [26]. It should therefore be recog- nized that DES is characterized radiographically by fre- quent LES dysfunction with nonperistaltic contractions of varying severity, rather than a classic corkscrew ap- pearance.

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