IDKD 2006

Diseases of the

M.S. Levine Gastrointestinal Radiology, Department of Radiology, University of Pennsylvania Medical Center, Philadelphia, PA, USA

Introduction can also lead to longitudinal shortening of the esophagus and the development of fixed transverse folds, producing a This syllabus reviews the findings on esophagography for ‘stepladder’ appearance due to pooling of barium between a variety of esophageal diseases, including reflux the folds [5]. These folds should be differentiated from the , Barrett’s esophagus, other types of esophagi- thin transverse striations (i.e., ‘feline’ esophagus) often seen tis, benign and malignant esophageal tumors, varices, as a transient finding at fluoroscopy due to contraction of the lower esophageal rings, esophageal intramural pseudodi- longitudinally oriented muscularis mucosae [6]. verticulosis, and esophageal motility disorders. Barrett’s Esophagus Reflux Esophagitis Barrett’s esophagus is a premalignant condition in which Reflux esophagitis is by far the most common inflamma- there is progressive columnar metaplasia of the distal tory disease involving the esophagus. The single most esophagus due to chronic reflux and reflux esophagitis. common sign of reflux esophagitis on double-contrast Barrett’s esophagus is thought to develop in about 10% of esophagrams is a finely nodular or granular appearance all patients with reflux esophagitis. Double-contrast in the distal third of the esophagus, with poorly defined esophagrams can be used to classify patients with reflux radiolucencies that fade peripherally due to edema and symptoms at high, moderate, or low risk for Barrett’s inflammation of the mucosa [1]. In other patients, barium esophagus, based on specific radiologic criteria [7]. Patients studies may reveal shallow ulcers and erosions in the dis- are classified at high risk when double-contrast esopha- tal esophagus contiguous with the gastroesophageal junc- grams reveal a mid- or ulcer, or a retic- tion [2]. Reflux esophagitis may also be manifested by ular mucosal pattern (usually associated with a hiatal her- thickened longitudinal folds due to edema and inflamma- nia and/or gastroesophageal reflux) [7]. In such cases, en- tion that extend into the submucosa. However, thickened doscopy and should be performed for a definitive di- folds should be recognized as a nonspecific finding of agnosis. Patients are classified at moderate risk for Barrett’s esophagitis. Other patients with reflux esophagitis may esophagus when double-contrast studies reveal reflux have a single enlarged, chronically inflamed fold that esophagitis or peptic strictures in the distal esophagus [7]. arises at the gastric cardia and extends into the distal The decision for endoscopy in this group should be based esophagus as a smooth protuberance, also known as an on the severity of symptoms, age, and overall health of the inflammatory esophagogastric [3]. These lesions patients. Finally, patients are classified at low risk for have no malignant potential, so endoscopy is not war- Barrett’s esophagus when double-contrast studies reveal no ranted when barium studies reveal typical findings of an structural abnormalities. The majority of patients are found inflammatory polyp in the distal esophagus. to be in this category, and the prevalence of Barrett’s esoph- Scarring from reflux esophagitis can lead to the develop- agus is so low that they can be treated empirically for their ment of a reflux-induced stricture (i.e., ‘peptic’ stricture) in reflux symptoms, without need for endoscopy [7]. the distal esophagus, almost always above a hiatal . Such strictures typically appear as smooth, tapered segments of concentric narrowing, but asymmetric scarring can lead Infectious Esophagitis to asymmetric narrowing with focal sacculation or balloon- ing of the esophageal wall between areas of fibrosis. Other Esophagitis peptic strictures may be manifested by short, ring-like areas of narrowing that could be mistaken for Schatzki rings in pa- is the most common cause of infec- tients with [4]. Scarring from reflux esophagitis tious esophagitis. It usually occurs as an opportunistic in- 46 M.S.Levine 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 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 Fig. 2. . Double- contrast esophagram shows multi- achalasia or scleroderma may develop a ‘foamy’ esopha- ple small, discrete ulcers with sur- gus with innumerable tiny bubbles layering out in the bar- rounding mounds of edema (ar- ium column; this phenomenon presumably results from rows) in mid-esophagus the form of fungal infection [10]. When typical find- ings of Candida esophagitis are encountered on double- contrast esophagrams, these patients can be treated with clinical setting, small, discrete ulcers without plaques antifungal agents without the need for endoscopy. should be highly suggestive of herpes esophagitis, as ul- ceration in candidiasis almost always occurs on a back- Herpes Esophagitis ground of diffuse plaque formation. As the disease pro- gresses, however, herpes esophagitis may be manifested The herpes simplex virus type 1 is another common by a combination of ulcers and plaques, mimicking cause of infectious esophagitis. Most affected patients are Candida esophagitis [12]. immunocompromised, but herpes esophagitis may occa- sionally develop as an acute, self-limited disease in oth- Cytomegalovirus Esophagitis erwise healthy individuals [11]. Viral infection initially leads to the development of small vesicles that rupture to Cytomegalovirus (CMV) is another cause of infectious form discrete, punched-out ulcers on the mucosa. As a re- esophagitis that occurs in patients with AIDS. CMV sult, herpes esophagitis may be manifested on double- esophagitis may be manifested on double-contrast studies contrast studies by multiple superficial ulcers on a nor- by multiple small ulcers or, even more commonly, by one mal background mucosa (Fig. 2) [12]. In the appropriate 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 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 Fig. 1. Advanced Candida eso- edema, sometimes associated with a cluster of small phagitis in a patient with AIDS. satellite ulcers (Fig. 3) [14]. Occasionally, these individ- Double-contrast esophagram shows uals may have associated palatal ulcers or a characteris- ‘shaggy’ esophagus of fulminant tic rash on the upper body. The diagnosis is established esophageal candidiasis due to innu- merable plaques and pseudomem- by obtaining endoscopic biopsy specimens, brushings, or branes with trapping of barium be- cultures to rule out CMV esophagitis as the cause of the tween lesions ulcers. Unlike CMV ulcers, HIV-related esophageal ul- Diseases of the Esophagus 47

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- Fig. 3. HIV ulcer in a patient with AIDS. Double-contrast esopha- tein-free diets with varying degrees of success. gram shows large, flat ulcer in pro- IEE may be manifested on esophagography by segmen- file (arrows) in distal esophagus. tal strictures in the esophagus. The strictures often contain Although CMV esophagitis could distinctive ring-like indentations, resulting in a so-called produce identical findings, endo- ‘ringed’ esophagus [16]. Other patients with IEE may have scopic brushings and re- vealed no evidence of CMV 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 cers usually heal dramatically on treatment with oral rings indistinguishable from those in IEE (Fig. 4) [17]. steroids [14]. Thus, endoscopy is required in HIV-positive Although congenital esophageal stenosis is usually not as- patients with giant esophageal ulcers to differentiate sociated with an allergic history or peripheral eosinophil- esophagitis caused by HIV and CMV, so appropriate ther- ia, this condition also occurs in young men with long- apy can be instituted in these patients. standing dysphagia, and biopsies from the esophagus may also reveal increased numbers of intra-epithelial Drug-induced Esophagitis eosinophils [17]. Due to the similarities in the clinical, ra- diographic, and pathologic findings of these conditions, Tetracycline and doxycycline are the two most common the symptoms of some of the patients with reported con- causes of drug-induced esophagitis in the United States, genital esophageal stenosis may have been due to IEE. but other offending agents include potassium chloride, quinidine, aspirin or other nonsteroidal antiinflammatory drugs (NSAIDs), and alendronate sodium [15]. Affected Benign Tumors individuals typically ingest the medication with little or no water immediately before going to bed. The capsules or Squamous papillomas are the most common benign mu- pills usually become lodged in the mid-esophagus where cosal tumors in the esophagus, usually appearing on 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 , 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 Fig. 4. Congenital esophageal steno- sis. Double-contrast esophagram Idiopathic eosinophilic esophagitis (IEE) is a chronic shows mild narrowing of mid- esophagus with distinctive ring-like form of esophagitis characterized by an increased number constrictions (arrows), most likely of intraepithelial eosinophils (more than 20 per high pow- due to cartilaginous rings in wall of er field) on endoscopic biopsy specimens [16]. The etiol- esophagus 48 M.S.Levine

double-contrast esophagrams as small, sessile polyps a 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- b 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- Fig. 6. a Giant fibrovascular polyps on CT scan shows expansile lated contour, or by focal irregularity of the esophageal mass (arrow) of fat density in mid-esophagus. This finding is seen wall [20]. Early adenocarcinomas may also be manifest- when a polyp is composed predominantly of adipose tissue. b CT scan in another patient shows expansile, heterogeneous mass (ar- ed by a localized area of wall flattening or irregularity rows) in esophagus. This finding is seen when lesion contains adi- pose and fibrovascular tissue

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 Fig. 5. Giant fibrovascu- studies. Nevertheless, squamous cell carcinomas tend to lar polyp. Double-con- involve the upper or mid-esophagus, whereas adenocarci- trast esophagram shows nomas are located predominantly in the distal esophagus. long, smooth, expansile Unlike squamous carcinomas, adenocarcinomas also mass extending from proximal esophagus dis- have a marked tendency to invade the gastric cardia or tally to near gastroe- fundus, comprising as many as 50% of all malignant tu- sophageal junction mors involving the gastroesophageal junction [20]. Diseases of the Esophagus 49

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 Fig. 7. Adenocarcinoma arising in Barrett’s esophagus. Double- contrast esophagram shows ad- The term is reserved for symptomatic pa- vanced infiltrating carcinoma tients with lower esophageal rings who present with in- (arrows) as an irregular area of termittent dysphagia for solids, especially meat. The luminal narrowing with mucosal rings appear on barium studies as smooth, symmetric nodularity and ulceration in dis- ring-like constrictions at the gastroesophageal junction, tal esophagus above 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. 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 a b

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 Fig. 9. Schatzki ring. a Prone, single-contrast esophagram shows smooth, symmetric, ring-like constriction (white arrow) in distal with hepatofugal flow through dilated esophageal col- esophagus directly above hiatal hernia. b Ring is not seen on up- laterals to the superior vena cava. Uphill varices appear right, double-contrast esophagram from same examination because on barium studies as serpentine longitudinal filling de- of inadequate distention of this region 50 M.S.Levine

Esophageal Intramural Pseudodiverticulosis on barium studies by tapered, beak-like narrowing of the distal esophagus adjacent to the gastroesophageal junc- Esophageal intramural pseudodiverticula consist of dilat- tion. In advanced disease, the esophagus can become ed excretory ducts of deep mucous glands in the esopha- massively dilated and tortuous distally (i.e., a ‘sigmoid’ gus. The pseudodiverticula typically appear on esopha- esophagus). gography as flask-shaped outpouchings in rows parallel Secondary achalasia is also characterized by absent to the long axis of the esophagus (Fig. 10) [24]. When peristalsis in the esophagus and beak-like narrowing near viewed en face on double-contrast esophagrams, the the gastroesophageal junction. In secondary achalasia pseudodiverticula can be mistaken for tiny ulcers. When caused by a tumor at the gastroesophageal junction, how- viewed in profile, however, they often appear to be ‘float- ever, the length of the narrowed segment is often greater ing’ outside the wall of the esophagus without apparent than that in primary achalasia because of spread of tumor communication with the lumen [24]. Barium studies of- into the distal esophagus [25]. The narrowed segment ten reveal an isolated cluster of pseudodiverticula in the may also be asymmetric, nodular, or ulcerated because of distal esophagus in the region of a peptic stricture, so tumor infiltrating this region. In some cases, barium stud- they presumably occur as a sequela of scarring from re- ies may reveal other signs of malignancy at the cardia flux esophagitis [24]. Less frequently, the pseudodiver- with distortion or obliteration of the normal cardiac ticula have a diffuse distribution and are associated with rosette [25]. The clinical history is also important, as pa- high strictures, or they occur as an isolated finding [24]. tients with primary achalasia almost always have long- When strictures are present, these patients may present standing dysphagia, whereas patients with secondary with dysphagia, but the pseudodiverticula themselves achalasia are usually older individuals (over the age of rarely cause symptoms. 60) with recent onset of dysphagia (less than six months) and [25].

Esophageal Motility Disorders

Achalasia Symptomatic diffuse esophageal spasm (DES) may be manifested on barium studies by intermittently weak- Primary achalasia is an idiopathic condition, whereas ened or absent primary peristalsis with repetitive, lu- secondary achalasia is caused by other underlying condi- men-obliterating nonperistaltic contractions, producing tions, most commonly malignant tumors involving the a classic ‘cork-screw’ esophagus [26]. More commonly, gastroesophageal junction (especially carcinoma of the however, these patients have multiple nonperistaltic con- gastric cardia). Primary achalasia is characterized by ab- tractions of mild to moderate severity without a cork- sent primary peristalsis in the esophagus and incomplete screw appearance [26]. The majority of patients with relaxation of the lower esophageal sphincter, manifested 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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