ESOPHAGEAL STRUCTURE AND FUNCTION¶
The esophagus is a hollow, muscular tube coursing through the posterior mediastinum joining the hypopharynx to the stomach with a sphincter at each end. It functions to transport food and fluid between these ends, otherwise remaining empty. The physiology of swallowing, esophageal motility, and oral and pharyngeal dysphagia are described in Chap. 40. Esophageal diseases can be manifested by impaired function or pain. Key functional impairments are swallowing disorders and excessive gastroesophageal reflux. Pain, sometimes indistinguishable from cardiac chest pain, can result from inflammation, infection, dysmotility, or neoplasm. FIGURE 315-61 Crohn’s ileitis. FIGURE 315-62 Internal hemorrhoids with bleeding (arrow) as seen on a retroflexed view of the rectum.
SYMPTOMS OF ESOPHAGEAL DISEASE¶
The clinical history remains central to the evaluation of esophageal symptoms. A thoughtfully obtained history will often expedite management. Important details include weight gain or loss, gastrointestinal bleeding, dietary habits including the timing of meals, smoking, and alcohol consumption. The major esophageal symptoms are heartburn, regurgitation, chest pain, dysphagia, odynophagia, and globus sensation. Heartburn (pyrosis), the most common esophageal symptom, is characterized by a discomfort or burning sensation behind the sternum that arises from the epigastrium and may radiate toward the neck. Heartburn is an intermittent symptom, most commonly experienced after eating, during exercise, and while lying recumbent. The discomfort is relieved with drinking water or antacid but can occur frequently interfering with normal activities including sleep. The association between heartburn and gastroesophageal reflux disease (GERD) is so strong that empirical therapy for GERD has become accepted management. However, the term “heartburn” is often misused and/or referred to with other terms such as “indigestion” or “repeating,” making it important to clarify the intended meaning. Regurgitation is the effortless return of food or fluid into the pharynx without nausea or retching. Patients report a sour or burning fluid in the throat or mouth that may also contain undigested food particles. Bending, belching, or maneuvers that increase intraabdominal pressure can provoke regurgitation. A clinician needs to discriminate
STRUCTURAL DISORDERS ■ HIATAL HERNIA Hiatus hernia is a herniation of viscera, most commonly the stomach, into the mediastinum through the esophageal hiatus of the diaphragm. Four types of hiatus hernia are distinguished with type I, or sliding hiatal hernia, comprising at least 95% of the overall total. A sliding hiatal hernia is one in which the gastroesophageal junction and gastric cardia translocate cephalad as a result of weakening of the phrenoesophageal ligament attaching the gastroesophageal junction to the diaphragm at the hiatus and dilatation of the diaphragmatic hiatus. The incidence of sliding hernia increases with age. True to its name, sliding hernias enlarge with increased intraabdominal pressure, swallowing, and respiration. Conceptually, sliding hernias are the result of wear and tear: increased intraabdominal pressure from abdominal obesity, pregnancy, etc., along with hereditary factors predisposing to the condition. The main significance of sliding hernias is the propensity of affected individuals to have GERD. Type II, III, and IV hiatal hernias are all subtypes of paraesophageal hernia in which the herniation into the mediastinum includes a visceral structure other than the gastric cardia. With type II and III paraesophageal hernias, the gastric fundus also herniates with the distinction being that in type II, the gastroesophageal junction remains fixed at the hiatus, whereas type III is a combined sliding and paraesophageal hernia. With type IV hiatal hernias, viscera other than the stomach herniate into the mediastinum, most commonly the colon. With type II and III paraesophageal hernias, the stomach inverts as it herniates and large paraesophageal hernias can lead to an “upside down stomach,” gastric volvulus, and even strangulation of the stomach. Because of this risk, surgical repair is often advocated for large paraesophageal hernias particularly when they are symptomatic. ■ RINGS AND WEBS A lower esophageal mucosal ring, also called a B ring, is a thin membranous narrowing at the squamocolumnar mucosal junction (Fig. 316-2). Its origin is unknown, but B rings are demonstrable in about 10–15% of the general population and are usually asymptomatic. When the lumen diameter is <13 mm, distal rings are usually associated with episodic solid food dysphagia and are called Schatzki rings. Patients typically present older than 40 years, consistent with an acquired rather than congenital origin. Schatzki ring is one of the most common causes of intermittent food impaction, also known as “steakhouse syndrome” because meat is a typical instigator. Symptomatic rings are readily treated by dilation. Web-like constrictions higher in the esophagus can be of congenital or inflammatory origin. Asymptomatic cervical esophageal webs are demonstrated in about 10% of people and typically originate along the anterior aspect of the esophagus. When circumferential, they can cause intermittent dysphagia to solids similar to Schatzki rings and are similarly treated with dilation. The combination of symptomatic proximal esophageal webs and iron-deficiency anemia in middle-aged women constitutes Plummer-Vinson syndrome. ■ DIVERTICULA Esophageal diverticula are categorized by location with the most common being epiphrenic, hypopharyngeal (Zenker’s), and midesophageal. Epiphrenic and Zenker’s diverticula are false diverticula involving herniation of the mucosa and submucosa through the muscular layer of the esophagus. These lesions result from increased intraluminal pressure associated with distal obstruction. In the case of Zenker’s, the obstruction is a stenotic cricopharyngeus muscle (upper esophageal sphincter), and the hypopharyngeal herniation most commonly occurs in an area of natural weakness proximal to the cricopharyngeus known as Killian’s triangle (Fig. 316-3). Small Zenker’s diverticula are usually asymptomatic, but when they enlarge sufficiently to retain food and saliva they can be associated with dysphagia, halitosis, and aspiration. Treatment is by surgical diverticulectomy and cricopharyngeal
ESOPHAGEAL MOTILITY DISORDERS Esophageal motility disorders are diseases attributable to esophageal neuromuscular dysfunction commonly associated with dysphagia, chest pain, or heartburn. The major entities are achalasia, DES, and GERD. Motility disorders can also be secondary to broader disease processes as is the case with pseudoachalasia, Chagas’ disease, and scleroderma. Not included in this discussion are diseases affecting the pharynx and proximal esophagus, the impairment of which is almost always part of a more global neuromuscular disease process. ■ ACHALASIA Achalasia is a rare disease caused by loss of ganglion cells within the esophageal myenteric plexus with a population incidence estimated to be 1–3 per 100,000 and usually presenting between age 25 and 60. With long-standing disease, aganglionosis is noted. The disease involves both excitatory (cholinergic) and inhibitory (nitric oxide) ganglionic neurons. Functionally, inhibitory neurons mediate deglutitive LES relaxation and the sequential propagation of peristalsis. Their absence leads to impaired deglutitive LES relaxation and absent peristalsis. Increasing evidence suggests that the ultimate cause of ganglion cell degeneration in achalasia is an autoimmune process attributable to a latent infection with human herpes simplex virus 1 combined with genetic susceptibility. Long-standing achalasia is characterized by progressive dilatation and sigmoid deformity of the esophagus with hypertrophy of the LES. Clinical manifestations may include dysphagia, regurgitation, chest pain, and weight loss. Most patients report solid and liquid food dysphagia. Regurgitation occurs when food, fluid, and secretions are retained in the dilated esophagus. Patients with advanced achalasia are at risk for bronchitis, pneumonia, or lung abscess from chronic regurgitation and aspiration. Chest pain is frequent early in the course of achalasia, thought to result from esophageal spasm. Patients describe a squeezing, pressure-like retrosternal pain, sometimes radiating to the neck, arms, jaw, and back. Paradoxically, some patients complain of heartburn that may be a chest pain equivalent. Treatment of achalasia is less effective in relieving chest pain than it is in relieving dysphagia or regurgitation. The differential diagnosis of achalasia includes DES, Chagas’ disease, and pseudoachalasia. Chagas’ disease is endemic in areas of central Brazil, Venezuela, and northern Argentina and spread by the bite of the reduviid (kissing) bug that transmits the protozoan, Trypanosoma cruzi. The chronic phase of the disease develops years after infection and results from destruction of autonomic ganglion cells throughout the body, including the heart, gut, urinary tract, and respiratory tract. Tumor infiltration, most commonly seen with carcinoma in the gastric fundus or distal esophagus, can mimic idiopathic achalasia. The resultant “pseudoachalasia” accounts for up to 5% of suspected cases
DIFFUSE ESOPHAGEAL SPASM DES is manifested by episodes of dysphagia and chest pain attributable to abnormal esophageal contractions with normal deglutitive LES relaxation. Beyond that, there is little consensus. The pathophysiology and natural history of DES are ill defined. Radiographically, DES has been characterized by tertiary contractions or a “corkscrew esophagus” (Fig. 316-7), but in many instances, these abnormalities are actually indicative of achalasia. Manometrically, a variety of defining features have been proposed including uncoordinated (“spastic”) activity in the distal esophagus, spontaneous and repetitive contractions, or highamplitude and prolonged contractions. The current consensus, derived from high-resolution manometry studies, is to define spasm by the occurrence of contractions in the distal esophagus with short latency relative to the time of the pharyngeal contraction, a dysfunction indicative of impairment of inhibitory myenteric plexus neurons. When defined in this restrictive fashion (Fig. 316-8), DES is actually much less common than achalasia. Esophageal chest pain closely mimics angina pectoris. Features suggesting esophageal pain include pain that is nonexertional, prolonged, interrupts sleep, meal-related, relieved with antacids, and accompanied by heartburn, dysphagia, or regurgitation. However, all of these features exhibit overlap with cardiac pain, which still must be the primary consideration. Furthermore, even within the spectrum of esophageal diseases, both chest pain and dysphagia are also characteristic of peptic or infectious esophagitis. Only after these more common entities have been excluded by evaluation and/or treatment should a diagnosis of DES be pursued. Although DES is diagnosed by manometry, endoscopy is useful to identify alternative structural and inflammatory lesions that may cause chest pain. Radiographically, a “corkscrew esophagus,” “rosary bead esophagus,” pseudodiverticula, or curling can be indicative of DES, but these are also found with spastic achalasia. Given these vagaries of defining DES, and the resultant heterogeneity of patients identified for inclusion in therapeutic trials, it is not surprising that trial results have been disappointing. Only small, uncontrolled trials exist, reporting response to nitrates, calcium channel blockers, hydralazine, botulinum toxin, and anxiolytics. The only controlled trial showing efficacy
GASTROESOPHAGEAL REFLUX DISEASE The current conception of GERD is to encompass a family of conditions with the commonality that they are caused by gastroesophageal reflux resulting in either troublesome symptoms or an array of potential esophageal and extraesophageal manifestations. It is estimated that 10–15% of adults in the United States are affected by GERD, although such estimates are based only on population studies of self-reported chronic heartburn. With respect to the esophagus, the spectrum of injury includes esophagitis, stricture, Barrett’s esophagus, and adenocarcinoma (Fig. 316-9). Of particular concern is the rising incidence of esophageal adenocarcinoma, an epidemiologic trend that parallels the increasing incidence of GERD. There were about 8000 incident cases of esophageal adenocarcinoma in the United States in 2013 (half of all esophageal cancers); it is estimated that this disease burden has increased two- to sixfold in the last 20 years. ■ PATHOPHYSIOLOGY The best-defined subset of GERD patients, albeit a minority overall, have esophagitis. Esophagitis occurs when refluxed gastric acid and pepsin cause necrosis of the esophageal mucosa causing erosions and ulcers. Note that some degree of gastroesophageal reflux is normal, physiologically intertwined
With superimposed reflux, fluid retained within a sliding hiatal hernia refluxes back into the esophagus during swallow-related LES relaxation, a phenomenon that does not normally occur. Inherent in the pathophysiologic model of GERD is that gastric juice is harmful to the esophageal epithelium. However, gastric acid hypersecretion is usually not a dominant factor in the development of esophagitis. An obvious exception is with Zollinger-Ellison syndrome, which is associated with severe esophagitis in about 50% of patients. Another caveat is with chronic Helicobacter pylori gastritis, which may have a protective effect by inducing atrophic gastritis with concomitant hypoacidity. Pepsin, bile, and pancreatic enzymes within gastric secretions can also injure the esophageal epithelium, but their noxious properties are either lessened without an acidic environment or dependent on acidity for activation. Bile warrants attention because it persists in refluxate despite acid-suppressing medications. Bile can transverse the cell membrane, imparting severe cellular injury in a weakly acidic environment, and has also been invoked as a cofactor in the pathogenesis of Barrett’s metaplasia and adenocarcinoma. Hence, the causticity of gastric refluxate extends beyond hydrochloric acid. ■ SYMPTOMS Heartburn and regurgitation are the typical symptoms of GERD. Somewhat less common are dysphagia and chest pain. In each case, multiple potential mechanisms for symptom genesis operate that extend beyond the basic concepts of mucosal erosion and activation of afferent sensory nerves. Specifically, hypersensitivity and functional pain are increasingly recognized as cofactors. Nonetheless, the dominant clinical strategy is empirical treatment with acid inhibitors, reserving further evaluation for those who fail to respond. Important exceptions to this are patients with chest pain or persistent dysphagia, each of which may be indicative of more morbid conditions. With chest pain, cardiac disease must be carefully considered. In the case of persistent dysphagia, chronic reflux can lead to the development of a peptic stricture or adenocarcinoma, each of which benefits from early detection and/or specific therapy. Extraesophageal syndromes with an established association to GERD include chronic cough, laryngitis, asthma, and dental erosions. A multitude of other conditions including pharyngitis, chronic bronchitis, pulmonary fibrosis, chronic sinusitis, cardiac arrhythmias, sleep apnea, and recurrent aspiration pneumonia have proposed associations with GERD. However, in both cases, it is important to emphasize the word association as opposed to causation. In many instances, the disorders likely coexist because of shared pathogenetic mechanisms rather than strict causality. Potential mechanisms for extraesophageal GERD manifestations are either regurgitation with direct contact between the refluxate and supraesophageal structures or via a vagovagal reflex wherein reflux activation of esophageal afferent nerves triggers efferent vagal reflexes such as bronchospasm, cough, or arrhythmias.
Treatment¶
Lifestyle modifications are routinely advocated as GERD therapy. Broadly speaking, these fall into three categories: (1) avoidance of foods that reduce LES pressure, making them “refluxogenic” (these commonly include fatty foods, alcohol, spearmint, peppermint, and possibly coffee and tea); (2) avoidance of acidic foods that are inherently irritating (citrus fruits, tomato-based foods); and (3) adoption of behaviors to minimize reflux and/or heartburn. In general, minimal evidence supports the efficacy of these measures. However, clinical experience dictates that subsets of patients are benefitted by specific recommendations, based on their individual history and symptom profile. A patient with sleep disturbance from nighttime heartburn is more likely to benefit from elevation of the head of the bed and avoidance of eating before retiring. The most broadly applicable recommendation is for weight reduction. Even though the benefit with respect to reflux cannot be assured, the strong epidemiologic relationship between body mass index and GERD and the secondary health gains of weight reduction is beyond dispute. The dominant pharmacologic approach to GERD management is with inhibitors of gastric acid secretion, and abundant data support the effectiveness of this approach. Pharmacologically reducing the acidity of gastric juice does not prevent reflux, but it ameliorates reflux symptoms and allows esophagitis to heal. The hierarchy of effectiveness among pharmaceuticals parallels their antisecretory potency. Proton pump inhibitors (PPIs) are more efficacious than histamine2 receptor antagonists (H2 RAs), and both are superior to placebo. No major differences exist among PPIs, and only modest gain is achieved by increased dosage. Paradoxically, the perceived frequency and severity of heartburn correlate poorly with the presence or severity of esophagitis. When GERD treatments are assessed in terms of resolving heartburn, both efficacy and differences among pharmaceuticals are less clear-cut than with the objective of healing esophagitis. Although the same overall hierarchy of effectiveness exists, observed efficacy rates are lower and vary widely, likely reflecting patient heterogeneity. Reflux symptoms tend to be chronic,
ESOPHAGITIS
MECHANICAL TRAUMA AND IATROGENIC INJURY
■ ESOPHAGEAL PERFORATION Most cases of esophageal perforation are from instrumentation of the esophagus or trauma. Alternatively, forceful vomiting or retching can lead to spontaneous rupture at the gastroesophageal junction (Boerhaave’s syndrome). More rarely, corrosive esophagitis or neoplasms lead to perforation. Instrument perforation from endoscopy or nasogastric tube placement typically occurs in the hypopharynx or at the gastroesophageal junction. Perforation may also occur at the site of a stricture in the setting of endoscopic food disimpaction or esophageal dilation. Esophageal perforation causes pleuritic retrosternal pain that can be associated with pneumomediastinum and subcutaneous emphysema. Mediastinitis is a major complication of esophageal perforation, and prompt recognition is key to optimizing outcome. CT of the chest is most sensitive in detecting mediastinal air. Esophageal perforation is confirmed by a contrast swallow, usually Gastrografin followed by thin barium. Treatment includes nasogastric suction and parenteral broad-spectrum antibiotics with prompt surgical drainage and repair in noncontained leaks. Conservative therapy with NPO status and antibiotics without surgery may be appropriate in cases of contained perforation that are detected early. Endoscopic clipping or stent placement may be indicated in nonoperated iatrogenic perforations or nonoperable cases such as perforated tumors.
■ MALLORY-WEISS TEAR Vomiting, retching, or vigorous coughing can cause a nontransmural tear at the gastroesophageal junction that is a common cause of upper gastrointestinal bleeding. Most patients present with hematemesis. Antecedent vomiting is the norm, but not always evident. Bleeding usually abates spontaneously, but protracted bleeding may respond to local epinephrine or cauterization therapy, endoscopic clipping, or angiographic embolization. Surgery is rarely needed.
■ RADIATION ESOPHAGITIS Radiation esophagitis can complicate treatment for thoracic cancers, especially breast and lung, with the risk proportional to radiation dosage. Radiosensitizing drugs such as doxorubicin, bleomycin, cyclophosphamide, and cisplatin also increase the risk. Dysphagia and odynophagia may last weeks to months after therapy. The esophageal mucosa becomes erythematous, edematous, and friable. Submucosal fibrosis and degenerative tissue changes and stricturing may occur years after the radiation exposure. Radiation exposure in excess of 5000 cGy has been associated with increased risk of esophageal stricture. Treatment for acute radiation esophagitis is supportive. Chronic strictures are managed with esophageal dilation.
■ CORROSIVE ESOPHAGITIS Caustic esophageal injury from ingestion of alkali or, less commonly, acid can be accidental or from attempted suicide. Absence of oral injury does not exclude possible esophageal involvement. Thus, early endoscopic evaluation is recommended to assess and grade the injury to the esophageal mucosa. Severe corrosive injury may lead to esophageal perforation, bleeding, stricture, and death. Glucocorticoids have not been shown to improve the clinical outcome of acute corrosive esophagitis and are not recommended. Healing of more severe grades of caustic injury is commonly associated with severe stricture formation and often requires repeated dilation.
■ PILL ESOPHAGITIS Pill-induced esophagitis occurs when a swallowed pill
Peptic ulcer diseaee¶
Disorders of Absorption