Chapter 36. Benign & Malignant Disorders of the Esophagus

The esophagus is a muscular tube that extends from the level of the sixth cervical vertebra to the 11th thoracic vertebra, spanning three anatomic regions. The cervical esophagus lies left of the midline and posterior to the larynx and trachea. This portion receives its blood supply from branches of the inferior thyroid arteries and drains into the inferior thyroid veins. The upper portion of the thoracic esophagus passes behind the tracheal bifurcation and the left mainstem bronchus. The lower portion of the thoracic esophagus passes behind the left atrium and then enters the abdomen through the esophageal hiatus of the diaphragm.

The thoracic esophagus is supplied by the bronchial arteries (upper portion) and the branches of the thoracic aorta (midportion) and drains into the hemiazygos and azygos veins. The abdominal esophagus ends at the level of the junction with the stomach. The lowermost thoracic esophagus and the abdominal esophagus are nourished by the branches of the left gastric and inferior phrenic arteries and drain into the left gastric veins. Abundant lymphatics form a dense submucosal plexus. Lymph from the upper esophagus drains mostly in the cervical and paratracheal lymph nodes, whereas the lower thoracic and abdominal esophagus drains preferentially into the retrocardiac and celiac nodes.

The architecture of the esophageal wall consists of three layers. The mucosa is made of squamous epithelium overlying a lamina propria and a muscularis mucosa. The submucosa is made of elastic and fibrous tissue and is the strongest layer of the esophageal wall. The esophageal muscle is composed of an inner circular and outer longitudinal layer. The upper third of the esophageal musculature consists of skeletal muscle and the lower two thirds consist of smooth muscle. The upper esophageal sphincter (UES) is formed by the cricopharyngeus muscle along with the inferior constrictors of the pharynx and fibers of the esophageal wall. The lower esophageal sphincter (LES) is not a distinct anatomic structure. Unlike the remainder of the gastrointestinal tract, the esophagus does not have a serosal layer.

The coordinated activity of the UES, the esophageal body, and the LES is responsible for the motor function of the esophagus.

Upper Esophageal Sphincter

The UES receives motor innervation directly from the brain (ie, the nucleus ambiguus). Contributions from the inferior pharyngeal constrictor, cricopharyngeus, and cervical esophageal form this muscular sphincter, with the primary contributor being the cricopharyngeus. The sphincter is continuously in a state of tonic contraction, with a resting pressure of approximately 60–100 mm Hg. The sphincter prevents both the passage of air from the pharynx into the esophagus and the reflux of esophageal contents into the pharynx. During swallowing, a food bolus is moved by the tongue into the pharynx, which contracts while the UES relaxes. Supra- and infrahyoid musculature contribute to pulling the laryngotracheal apparatus away from the spinal column and further dilating the UES. After the food bolus has reached the esophagus, the UES regains its resting tone (Figure 36–1).

Esophageal Body

When food passes through the UES, a contraction is initiated in the upper esophagus, which progresses distally toward the stomach. The wave initiated by swallowing is referred to as primary peristalsis. It travels at a speed of 3–4 cm/s and reaches peak amplitudes of 60–140 mm Hg in the distal esophagus.

Lower Esophageal Sphincter

The LES measures 3–4 cm in length and is tonic, with resting pressure ranges between 15 and 24 mm Hg. At the time of swallowing, the LES relaxes for 5–10 s to allow the food bolus to enter the stomach, and then it regains its resting tone (see Figure 36–1). The LES relaxation is mediated by vasoactive intestinal polypeptide and nitric oxide, both nonadrenergic and noncholinergic neurotransmitters. The resting tone depends mainly on intrinsic myogenic activity. The LES has a tendency to relax periodically at times, independent from swallowing. These periodic relaxations are called transient LES relaxations to distinguish them from relaxations triggered by swallows. The cause of these transient relaxations is not known, but gastric distention probably plays a role.

Transient LES relaxations account for the small amount of physiologic gastroesophageal reflux present in any individual and are also the most common cause of reflux in patients with gastroesophageal reflux disease (GERD). A decrease in the length or the pressure (or both) of the LES is responsible for abnormal reflux in the remaining patients. Overall, it is thought that although transient LES relaxation is the most common mechanism of reflux in patients with either absent or mild esophagitis, the prevalence of a mechanically defective sphincter (ie, hypotensive, short, or both) increases in patients with more severe esophagitis. The crus of the esophageal hiatus of the diaphragm contributes to the resting pressure of the LES. The pinchcock action of the diaphragm is particularly important because it protects against reflux caused by sudden increases of intraabdominal pressure, such as with coughing or bending. This synergistic action of the diaphragm is lost when a sliding hiatal hernia is present, since the gastroesophageal junction is displaced above the diaphragm (Figure 36–2).

Achalasia

Essentials of Diagnosis

• Dysphagia
• Regurgitation
• Radiologic evidence of distal esophageal narrowing
• Absence of esophageal peristalsis on manometry.

General Considerations

Esophageal achalasia is a primary esophageal motility disorder characterized by the absence of esophageal peristalsis and increased pressure of the LES, which fails to relax completely in response to swallowing. The disease is rare, with an incidence of about 1 in 100,000 individuals. It affects men more than women, and it can occur at any age.

Pathogenesis

The cause of esophageal achalasia is unknown. A degeneration of the myenteric plexus of Auerbach has been documented, with loss of the postganglionic inhibitory neurons. These neurons contain nitric oxide and vasoactive intestinal polypeptide, which mediate LES relaxation. Because the postganglionic cholinergic neurons are spared, there is unopposed cholinergic stimulation that can result in increased LES resting pressure and insufficient relaxation. However, it is primarily decreased esophageal motility and incomplete relaxation that characterizes achalasia, as not all patients have a hypertensive LES.

Clinical Findings

Symptoms and Signs

Dysphagia, for solids and liquids, is the most common symptom, occurring in over 90% of patients. Most patients adapt to this symptom by changing their diet and are able to maintain a stable weight, whereas others experience a progressive increase in dysphagia that eventually leads to weight loss. Regurgitation is the second most common symptom and it is present in about 75% of patients. It occurs more often in the supine position and may lead to the aspiration of undigested food. Heartburn is present in about 50% of patients, and it is caused by stasis and fermentation of undigested food in the distal esophagus. Chest pain also occurs in 40% of patients. The symptoms of heartburn and chest pain can erroneously be attributed to GRED if proper studies are not performed.

Imaging Studies

In evaluating a patient with dysphagia, a barium swallow should be the first test performed. It usually shows a narrowing at the level of the gastroesophageal junction (Figure 36–3A). A dilated, sigmoid esophagus may be present in patients with long-standing achalasia (Figure 36–3B). An endoscopy should be performed to rule out a tumor of the esophagogastric junction and gastroduodenal pathology.

Special Tests

Esophageal Manometry

Esophageal manometry is the key test for establishing the diagnosis of esophageal achalasia. The classic manometric findings are (1) absence of esophageal peristalsis and (2) a hypertensive LES that relaxes only partially in response to swallowing.

Ambulatory pH Monitoring

In patients who have undergone pneumatic dilatation or a myotomy, ambulatory pH monitoring should always be performed to rule out abnormal gastroesophageal reflux; if present, it should be treated with acid-reducing medications.

Differential Diagnosis

Benign strictures caused by gastroesophageal reflux, eosinophilic esophagitis, and esophageal carcinoma may mimic the clinical presentation of achalasia. Sometimes an infiltrating tumor of the cardia can mimic not only the clinical and radiologic presentation of achalasia, but also the manometric profile. This condition is known as secondary achalasia or pseudoachalasia and should be suspected in patients older than 60 years of age who present with a recent onset of dysphagia and excessive weight loss. An endoscopic ultrasound or a computed tomography (CT) scan can help to establish the diagnosis.

Complications

The aspiration of retained and undigested food can cause repeated episodes of pneumonia. Achalasia is also a risk factor for esophageal cancer. Squamous cell carcinoma is probably due to the continuous irritation of the mucosa by the retained and fermenting food. However, adenocarcinoma can occur in patients who develop gastroesophageal reflux after either pneumatic dilatation or myotomy.

Treatment

Therapy is palliative and is directed toward relieving symptoms by decreasing the outflow resistance caused by the dysfunctional LES. Because peristalsis is absent, gravity becomes the key factor that allows the emptying of food from the esophagus into the stomach. Several treatment modalities are available to achieve this goal.

Nonsurgical Measures

Calcium Channel Blockers

Calcium channel blockers are used to decrease LES pressure. However, only 10% of patients benefit from this treatment. It should be used primarily in elderly patients who have contraindications to either pneumatic dilatation or surgery.

Endoscopy

An intrasphincteric injection of botulinum toxin is used to block the release of acetylcholine at the level of the LES, therefore restoring the balance between excitatory and inhibitory neurotransmitters. This treatment, however, is of limited value since only 30% of treated patients still experience a relief of dysphagia 2.5 years later. It should be used primarily in elderly patients who are poor candidates for dilatation or surgery.

Pneumatic Dilatation

Pneumatic dilatation has been the main form of treatment for many years. The initial success rate is between 70% and 80%, but it decreases to 50% 10 years later, even after multiple dilatations. The perforation rate is approximately 5%. If a perforation occurs, patients are taken emergently to the operating room, where closure of the perforation and a myotomy are performed through a left thoracotomy. The incidence of abnormal gastroesophageal reflux is about 25%. Patients who fail pneumatic dilatation are usually treated by a Heller myotomy.

Surgical Measures

A laparoscopic Heller myotomy and partial fundoplication is the procedure of choice for esophageal achalasia. The operation consists of a controlled division of the muscle fibers (ie, a myotomy) of the lower esophagus (5 cm) and proximal stomach (2 cm), followed by a partial fundoplication to prevent reflux (Figure 36–4). Patients remain in the hospital for 24–48 h, and return to regular activities in about 2 weeks. The operation effectively relieves symptoms in 85–95% of patients, and the incidence of postoperative reflux is between 10% and 15%. Because of the excellent results, short hospital stay, and fast recovery time, a laparoscopic Heller myotomy and partial fundoplication is considered today to be the primary treatment modality for esophageal achalasia.

Prognosis

A laparoscopic Heller myotomy allows for the excellent relief of symptoms in the majority of patients and should be preferred to pneumatic dilatation whenever surgical expertise is available. Botulinum toxin and medications should be used only in patients who are not candidates for pneumatic dilatation or laparoscopic Heller myotomy. Periodic follow-up by endoscopy is recommended to rule out the development of esophageal cancer.

Esophageal Diverticula

Diverticula of the esophagus are mainly located above the LES (epiphrenic diverticulum) or the UES (pharyngoesophageal—or Zenker—diverticulum). They are both caused by abnormalities involving the LES or the UES, which result in protrusion of the mucosa and submucosa through the muscular layers.

Essentials of Diagnosis

• Dysphagia
• Regurgitation of undigested food (with risk of aspiration)
• Gurgling sounds in the neck
• Halitosis.

General Considerations

Zenker diverticulum originates from the posterior wall of the esophagus in a triangular area of weakness, limited inferiorly by the cricopharyngeus muscle and superiorly by the inferior constrictor muscles (ie, the Killian triangle). As the diverticulum enlarges, it tends to deviate from the midline, mostly to the left (Figure 36–5).

Pathogenesis

Zenker diverticulum results from either a lack of coordination between the pharyngeal contraction and the opening of the UES or a hypertensive UES (including cricopharyngeal spasm). Because of the increased intraluminal pressure, there is progressive herniation of mucosa and submucosa through the Killian triangle.

Clinical Findings

Symptoms and Signs

Dysphagia is the most common symptom. The regurgitation of undigested food from the diverticulum often occurs and can lead to aspiration both into the tracheobronchial tree and pneumonia. Patients frequently have halitosis and can hear gurgling sounds in the neck. About 30–50% of patients have associated GERD.

Imaging Studies

A barium swallow can clearly show the position and size of the diverticulum. It can also show a hiatal hernia.

Special Tests

Esophageal manometry can demonstrate a lack of coordination between the pharynx and the cricopharyngeus muscle, as well as a hypertensive UES. In addition, it can show a hypotensive LES and abnormal esophageal peristalsis. Ambulatory pH monitoring can determine whether abnormal esophageal acid exposure is present.

Differential Diagnosis

The differential diagnosis of Zenker diverticulum includes esophageal stricture, achalasia, esophageal cancer, and pneumonia. A sudden increase in pain and dysphagia symptoms or hematemesis in a patient with an existing Zenker diverticulum should raise suspicion for a squamous cell carcinoma arising within the diverticulum, which is a rare but reported event. Other diverticula can occur in the pharyngeal (pharyngeal pouch) and upper esophageal (Killiam–Jamieson diverticulum) areas and should be distinguished because the treatment is different.

Treatment

The classic treatment consists of excision of the diverticulum and myotomy of the cricopharyngeus muscle, including the upper 3 cm of the posterior esophageal wall through a cervical incision. For small diverticula (ie, <2 cm), myotomy alone is sufficient.

In more recent years, transoral endoscopic management has gained popularity, using either rigid or flexible endoscopy. The wall of the diverticulum and the cricopharyngeus muscle is divided with a stapling device, electrocautery, or laser. Use of a stapling device has been preferred for diverticula between 3 and 6 cm because it effectively seals the cut edges of the wound as it divides the sac. The stapling device is mechanically limited in short segment (<3 cm) diverticula due to inability to advance the staple line to the end of the sac and thus incomplete division of the party wall, and this can also result in recurrence in patients with longer sacs. Division of short- and long-segment diverticula can be performed with CO2 laser or electrocautery, with some authors advocating mucosal closure with an endoscopic suturing device following division. Endoscopic injection of botulinum toxin into the cricopharyngeus has also been used with some success for small diverticula.

If GERD is present, it should be treated aggressively with either proton pump inhibitors or fundoplication in order to avoid aspiration into the tracheobronchial tree.

Prognosis

The prognosis is excellent in about 90% of cases.

Epiphrenic Diverticulum

Essentials of Diagnosis

• Dysphagia
• Regurgitation
• Diverticulum evident on barium swallow
• Esophageal motility disorder shown by esophageal manometry.

General Considerations

Epiphrenic diverticula are located just above the diaphragm (Figure 36–6). The diverticulum is not a primary anatomic abnormality but rather the consequence of an underlying motility disorder of the esophagus; achalasia is the most common, followed by diffuse esophageal spasm. The disorder causes an outflow obstruction at the level of the gastroesophageal junction, with a consequent increase in intraluminal pressure as well as progressive herniation of mucosa and submucosa through the esophageal muscle wall.

Clinical Findings

Symptoms and Signs

The symptoms experienced by patients with epiphrenic diverticulum are in part due to the underlying motility disorder (eg, dysphagia or chest pain) and in part due to the diverticulum per se (ie, regurgitation with the risk of aspiration). Some diverticula, however, can be asymptomatic.

Imaging Studies

A chest radiograph can show an air-fluid level in the posterior mediastinum. A barium swallow clearly shows the position and size of the diverticulum (see Figure 36–6).

Special Tests

In most cases, esophageal manometry identifies the underlying motility disorder.

Differential Diagnosis

A paraesophageal hernia can be confused with an epiphrenic diverticulum. Barium swallow and endoscopy help in establishing the diagnosis.

Treatment

The treatment is surgical and the laparoscopic approach is currently preferred. This procedure consists of (1) resection of the diverticulum, (2) a long myotomy, and (3) a partial fundoplication to prevent gastroesophageal reflux. The myotomy is performed on the side of the esophagus opposite to where the diverticulum is located. It should extend proximally to the upper border of the neck of the diverticulum and distally for 2 cm onto the gastric wall; a partial fundoplication is then performed.

Prognosis

A laparoscopic diverticulectomy, with myotomy and fundoplication, is successful in 80–90% of cases.

Eosinophilic Esophagitis

Essentials of Diagnosis

• Dysphagia
• Recurrent food impactions
• Heartburn
• Esophagitis on endoscopy with absence of reflux on pH monitoring
• Eosinophilic infiltration on biopsy.

General Considerations

Eosinophilic esophagitis (EE) is an uncommon but increasingly recognized and reported disease entity involving esophagitis in the setting of absent or controlled reflux. These patients tend to have a history of atopy and can present with dysphagia and recurrent food impactions. Currently it is a diagnosis of exclusion but diagnostic criteria are being developed.

Pathogenesis

This disease is not yet well understood. However, a strong association with hypersensitivity reactions to airborn alloantigens and particularly food has been found, suggesting a role for antigen-driven eosinophilic infiltration of the esophagus. This is supported by reports of success with food elimination strategies in reducing symptoms. Eosinophilic infiltration is thought to lead to smooth muscle dysfunction and resulting motor disturbances.

Clinical Findings

Symptoms and Signs

Dysphagia is the most common presenting sign, occurring in >90% of patients with EE. Patients can also present with recurrent food impaction, and in the setting of unimpressive endoscopy this should raise suspicion for EE. Heartburn is present in approximately a quarter of patients. Due to the association with atopy, a personal and family history of atopic diseases and reactions should be sought.

Imaging Studies

Endoscopy

Findings consistent with but not pathognomonic for EE include: (1) concentric rings or “trachealization” of the esophagus; (2) longitudinal furrows; (3) friability and esophageal inflammation; (4) multicentric white patches; (5) narrowing or strictures; (6) absence of hiatal hernia or other findings more strongly suggestive of GERD. Biopsies should be performed of any suspicious areas, but should also be performed in any patient with symptoms and history suggestive of EE even in the setting of normal endoscopic findings.

Specials Tests

Mucosal Biopsy

An elevated level of eosinophils (>15/high-power field) has been proposed as a diagnostic criteria for EE. This finding can also be seen in GERD, though usually to a lesser degree. This is particularly true for patients who are currently on antireflux therapy, in whom high levels of esoinophils in the setting of refractory esophagitis should raise suspicion for EE. Patients with EE also tend to have elevated esosinophils in all areas of the esophagus, as compared to typically only the distal esophagus with GERD.

Alloantigen Testing

Skin prick testing has been used to identify food triggers in patients with suspected EE with some success. However not all sensitivities can be identified in this manner. Food elimination testing is the mainstay of food sensitivity testing but requires close partnership between the patient and physician and careful monitoring of food content and symptoms. Consultation with a dietician can be useful in the development of food elimination strategies.

Differential Diagnosis

It is important to rule out GERD and achalasia by esophageal manometry and pH monitoring tests. Other esophageal motility disorders and benign and malignant strictures can present in a similar way.

Treatment

Current therapy for EE consists of identification of food triggers and avoidance. This can be difficult because many patients are sensitized to multiple food allergens. Topical glutocorticoids has been successful in controlling symptoms and reducing inflammation in some patients. Acid reduction therapy should be considered if reflux is present to decrease irritation of the inflamed esophageal lining.

Prognosis

Despite food avoidance and pharmacotherapy demonstrating effectiveness in some patients, eosinophilic esophagitis remains a difficult disease to treat, with relapses in symptoms occurring in the majority of patients even after successful therapy.

Gastroesophageal Reflux Disease

Essentials of Diagnosis

• Heartburn
• Regurgitation
• Sliding hiatal hernia on barium swallow
• Esophagitis on endoscopy
• Abnormal esophageal exposure on ambulatory pH monitoring.

General Considerations

GERD is the most common upper gastrointestinal disorder in the Western world and accounts for approximately 75% of esophageal diseases. Heartburn, usually considered synonymous with the presence of abnormal gastroesophageal reflux, is experienced by 20–40% of the adult population of Western countries. The incidence of reflux symptoms increases with age, and both sexes seem to be equally affected. Symptoms are more common during pregnancy, probably because of hormonal effects on the LES and the increased intraabdominal pressure of the enlarging uterus.

Pathogenesis

GERD is caused by the abnormal retrograde flow of gastric contents into the esophagus, resulting in symptoms, mucosal damage, or both. A defective LES is the most common cause of GERD. Transient LES relaxations account for most reflux episodes in patients either without mucosal damage or with mild esophagitis, whereas a short and hypotensive LES is more frequently found in patients with more severe esophagitis. In 40–60% of patients with GERD, abnormalities of esophageal peristalsis are also present. Because esophageal peristalsis is the main determinant of esophageal acid clearance (ie, the ability of the esophagus to clear gastric contents refluxed through the LES), patients with abnormal esophageal peristalsis have more severe reflux and slower clearance. Therefore, these patients often have more severe mucosal injury and more frequent atypical symptoms such as cough or hoarseness. A hiatal hernia also contributes to the incompetence of the gastroesophageal junction by altering the anatomic relationship between the LES and the esophageal crus. In patients with large hiatal hernias, the LES is usually shorter and weaker and the amount of reflux is greater.

Clinical Findings

Symptoms and Signs

Heartburn, regurgitation, and dysphagia are considered typical symptoms of GERD. However, a clinical diagnosis of GERD, based on typical symptoms such as heartburn and regurgitation, is correct in only 70% of patients when compared with the results of pH monitoring. A good response to therapy with proton pump inhibitors is instead a better predictor of the presence of abnormal reflux. In addition to the typical symptoms, patients with GERD can present with atypical symptoms such as cough, wheezing, chest pain, hoarseness, and dental erosions. These symptoms represent extraesophageal presentations of the disease, including respiratory disorders such as asthma, as well as ear, nose, and throat abnormalities such as laryngitis (Table 36–1). Two mechanisms have been postulated for GERD-induced respiratory symptoms: (1) a vagal reflux arc resulting in bronchoconstriction and (2) microaspiration into the tracheobronchial tree.

Ear, nose, and throat symptoms such as hoarseness, globus sensation, or dental erosions are thought to be secondary to the upward extent of the acid with direct damage. This phenomenon has been termed laryngopharyngeal reflux.

Imaging Studies

Barium Swallow

A barium swallow provides information about the presence and size of a hiatal hernia, the presence and length of a stricture, and the length of the esophagus. This test, however, is not diagnostic of GERD since a hiatal hernia or reflux of barium can be present in patients who do not have GERD.

Endoscopy

The value of endoscopy is mostly limited to the detection of the complications of GERD (eg, esophagitis, Barrett esophagus, and stricture) and to the exclusion of other pathology (esophageal, gastric, or duodenal). The value of endoscopy in diagnosing GERD is limited because only 50% of patients with GERD have esophagitis. In addition, there is major interobserver variation among endoscopists for the low grades of esophagitis.

Specials Tests

Esophageal Manometry

Esophageal manometry provides information about the LES, including the resting pressure, length, and relaxation, as well as about the quality of esophageal peristalsis. In about 40% of patients with GERD, the pressure of the LES and the peristalsis are normal. In addition, manometry is essential for proper placement of the pH probe for ambulatory pH monitoring (5 cm above the upper border of the LES).

Ambulatory pH Monitoring

Ambulatory pH monitoring is the most reliable test in the diagnosis of GERD, with a sensitivity and specificity of about 92%. Acid-suppressing medications must be stopped 3 days (eg, H2-blocking agents) to 14 days (eg, proton pump inhibitors) prior to the study. Diet and exercise are unrestricted during the test in order to mimic a typical day of the patient's life. This test should always be performed (1) in patients who do not respond to medical therapy; (2) in patients who relapse after the discontinuation of medical therapy; (3) before antireflux surgery; (4) when atypical symptoms are present. In patients with atypical symptoms a pH probe with two sensors (5 and 20 cm above the LES) is used to determine the upward extent of the reflux. The tracing should be analyzed for a temporal correlation between symptoms and episodes of reflux (Figure 36–7).

Differential Diagnosis

Irritable bowel syndrome, achalasia, eosinophilic esophagitis, cholelithiasis, and coronary artery disease can present with heartburn. Esophageal manometry and pH monitoring are essential to determine with certainty whether GERD is present.

Complications

Esophagitis is the most common complication. Barrett esophagus (ie, metaplastic changes from squamous to columnar epithelium) is found in about 12% of patients with reflux documented by pH monitoring. This complication may lead to the development of adenocarcinoma. Asthma, aspiration pneumonia, laryngitis, chronic sinusitis, and dental erosions can also occur.

Treatment

Nonsurgical Measures

Lifestyle Modifications

Patients should eat frequent, small meals during the day to avoid gastric distention. They should also avoid fatty foods, spicy foods, and chocolate, because these foods lower the LES pressure. The last meal of the day should be no less than 2 h before going to bed. To increase the effect of gravity, the head of the bed should be elevated over 4- to 6-inch blocks. Patients should also be counseled to lose weight if obese.

Other Nonsurgical Measures

Antacids are useful for patients with mild intermittent heartburn. Acid-suppressing medications are the mainstay of medical therapy. H2 blocking agents are usually prescribed for patients with mild symptoms or mild esophagitis. Proton pump inhibitors are superior to H2 blocking agents because they exert a more profound control of acid secretion—healing of the esophagitis occurs in 80–90% of these patients. However, both the symptoms and esophagitis tend to recur in most patients after therapy is discontinued so that most patients need chronic maintenance therapy. In addition, about 50% of patients on maintenance proton pump inhibitors require increasing doses to maintain healing of the esophagitis. Medical therapy is largely ineffective for the treatment of the extraesophageal manifestations of GERD due to the upward extension of the gastric contents. In these patients, acid-suppressing medications only alter the pH of the gastric refluxate, but reflux and aspiration still occur because of an incompetent LES and an ineffective esophageal peristalsis.

Recent concern has been raised about potential adverse effects of long-term therapy with proton-pump inhibitors, in particular calcium malabsorption leading to osteoporosis, increased risk of gastrointestinal infections and pneumonia. Overall the safety profile of proton pump inhibitors is excellent, but it is recommended that patients are treated with the lowest effective dose to control symptoms.

Surgical Measures

Laparoscopic Fundoplication

The goal of surgical therapy is to restore the competence of the LES. A laparoscopic total fundoplication (360°) is considered the procedure of choice because it increases the resting pressure and length of the LES and decreases the number of transient LES relaxations (Figure 36–8).

Indications for Surgery

A laparoscopic fundoplication provides the same excellent results of open surgery, with symptom resolution in more than 90% of patients. It now requires a 1- to 2-day hospital stay and results in both minimal postoperative discomfort and a fast return to regular activity.

The ideal patient is one who has a good response to proton pump inhibitors. A patient who is nonresponsive to medical therapy requires a thorough work-up to elucidate the cause of the foregut symptoms, and an alternative diagnosis ranging from irritable bowel syndrome to gallbladder disease is frequently found. Young patients might also choose an operation early in the course of their disease to avoid a life-long commitment to lifestyle changes and medications. Long-term follow-up of patients treated with either fundoplication or proton pump inhibitors demonstrates surgery to be superior to medical management with regards to control of symptoms.

Patients who have regurgitation with respiratory symptoms or hoarseness are also ideal candidates for a fundoplication. Even the complete elimination of gastric acid secretion by proton pump inhibitors frequently fails to control these symptoms, since it only alters the pH of the gastric refluxate but does not prevent the regurgitation and upward extent of the reflux. Analyzing the pH tracing for a correlation between the symptoms and the episodes of reflux helps to predict the surgical outcome (see Figure 36–7).

Many surgeons also consider the presence of Barrett esophagus as an indication for surgical rather than medical treatment, based on the following considerations: (1) Proton pump inhibitors, although effective in controlling the acid component of refluxate, do not eliminate the reflux of bile, which is a major contributor to the pathogenesis of Barrett epithelium. (2) Patients with Barrett esophagus have a lower LES pressure and a defective peristalsis more often than patients without Barrett esophagus. As a consequence, their mucosa is exposed to larger amounts of gastric refluxate. (3) Evidence suggests that an effective antireflux operation can prevent the progression from metaplasia to dysplasia. The definite answer, however, awaits the results of further randomized control studies; therefore, endoscopic surveillance after laparoscopic fundoplication is recommended.

Prognosis

After a fundoplication, the control of typical symptoms is obtained in about 90% of patients. The success rate is in the range of 70–90% for patients with atypical symptoms, since it is often more difficult to establish, preoperatively, a strong correlation between gastroesophageal reflux and symptoms.

Barrett Esophagus

Essentials of Diagnosis

• GERD symptoms (typical and atypical)
• Endoscopic evidence of “salmon pink” epithelium above gastroesophageal junction
• Specialized columnar epithelium on esophageal biopsy

General Considerations

Barrett esophagus is a metaplasia of the esophageal mucosa caused by the replacement of the squamous epithelium with columnar epithelium. About 10–12% of patients who undergo endoscopy for symptoms of GERD are found to have Barrett esophagus. It occurs more frequently in white men older than 50 years of age. This metaplasia may progress to high-grade dysplasia and eventually to adenocarcinoma. Thus, adenocarcinoma represents the final step of a sequence of events in which a benign disease (GERD) evolves into a preneoplastic disease and eventually into cancer (Figure 36–9).

Pathogenesis

Barrett esophagus is due to reflux of gastric acid and duodenal juice into the esophagus. Barrett metaplasia is considered an advanced stage of GERD characterized by a panesophageal motor disorder. When compared with patients with GERD with no mucosal injury or less severe esophagitis, patients with Barrett esophagus have a shorter and weaker LES and decreased amplitude of esophageal peristalsis. As a consequence, the amount of reflux is greater and esophageal clearance is slower. In addition, hiatal hernia is more common in patients with Barrett metaplasia.

Clinical Findings

Symptoms and Signs

Patients with Barrett esophagus typically have a long history of GERD. Although most patients experience both typical and atypical symptoms of GERD, other patients may become asymptomatic over time because of the decreased sensitivity of the metaplastic epithelium.

Imaging Studies

Barium swallow may show ulcerations, a hiatal hernia, or a stricture. Endoscopy shows a “salmon pink” epithelium above the gastroesophageal junction, which replaces the whitish squamous epithelium. The diagnosis is confirmed by pathologic examination of the esophageal mucosa and requires the identification of intestinal type epithelium, characterized by the presence of goblet cells.

Special Tests

Esophageal manometry often shows a short and hypotensive LES and abnormal esophageal peristalsis. Ambulatory pH monitoring usually shows a severe amount of acid reflux. Esophageal exposure to duodenal juice can be quantified by a fiberoptic probe that measures intraluminal bilirubin (as a marker for duodenal juice). In patients with GERD, the prevalence of esophageal bilirubin exposure parallels the degree of mucosal injury; the bilirubin exposure is higher in patients with Barrett esophagus.

Treatment

Barrett Esophagus: Metaplasia

The treatment options for patients with Barrett esophagus are similar to those of patients with GERD without metaplasia; they consist of either proton pump inhibitors or a fundoplication. Other chemopreventive agents are being investigated but are still experimental. A surgical approach might offer an advantage over medical therapy for the following reasons: (1) The successful elimination of reflux symptoms with proton pump inhibitors does not guarantee the control of acid reflux. When pH monitoring is performed in patients with asymptomatic Barrett esophagus who are treated with these medications, up to 80% of them still experience abnormal reflux. (2) Proton pump inhibitors do not eliminate the reflux of bile, a major contributor to the pathogenesis of Barrett epithelium. An antireflux operation prevents both acid and bile refluxate by restoring the competence of the gastroesophageal junction. (3) Recent studies have shown regression of short-segment Barrett's epithelium (<3 cm) in 15–50% of patients. However, because there is no definitive evidence that treatment (medical or surgical) prevents disease progression to cancer, regular follow-up should be performed with endoscopic examination and biopsy.

Endoscopic surveillance with four-quadrant biopsy has been demonstrated to result in earlier detection of high-grade dysplasia and esophageal cancer as well improved survival in patients with Barrett esophagus. Newer modalities of screening using narrow-band imaging and targeted, rather than random, biopsies has demonstrated similar detection rates with fewer biopsies per session.

Barrett Esophagus: High-Grade Dysplasia

When high-grade dysplasia is found (and confirmed by two experienced pathologists), two treatment options are available, close surveillance or surgery. Patients unfit for or wishing to delay surgery can enroll in a program of strict endoscopic surveillance, with endoscopy performed every 3 months and four quadrant biopsies obtained for every centimeter of Barrett esophagus. The goal is to detect cancer before it becomes invasive and spreads to lymph nodes. This is best suited to patients who have flat lesions, short segment disease, and/or unifocal disease and are willing to commit to strict follow-up.

For young and medically fit patients, an esophagectomy has traditionally been recommended and still may be appropriate for many patients. The cardinal goal of surgical therapy is to remove the cancer prior to nodal spread, which has a grave effect on prognosis. Early studies of esophagectomy for Barrett esophagus demonstrated invasive cancer in 30% or more of patients thought to have high-grade dysplasia at the time of the operation, prompting strong recommendations for early surgical therapy. However, this number may be much lower according to more recent reviews, lending support for less invasive means of treatment.

Endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) have been used as less-invasive methods to eradicate dysplastic epithelium and prevent progression to cancer. These techniques may also be used to treat adenocarcinoma limited to the mucosa without submucosal invasion (T1a, N0, M0). However, the long-term outcome of this treatment is still under investigation. The rationale for this treatment modality is to ablate the columnar epithelium, allowing regeneration of the squamous mucosa. Photodynamic therapy has also been used, but due to associations with difficult-to-treat esophageal strictures and buried islands Barrett epithelium under the regenerated squamous epithelium, RFA is now preferred over this modality. Endoscopic surveillance is recommended for patients treated with EMR or RFA.

Esophageal Cancer

Essentials of Diagnosis

• Progressive dysphagia, initially for solids and later for liquids
• Progressive weight loss
• Diagnosis confirmed by endoscopy and biopsies

General Considerations

In the United States, esophageal carcinoma accounts for 10,000 to 11,000 deaths per year. The last 30 years have seen a major change in the epidemiology of esophageal cancer in the United States. Until the 1970s, squamous cell carcinoma was the most common type of esophageal cancer, accounting for approximately 90% of the total incidence. It commonly occurred in the thoracic esophagus and mostly affected black men. Over the last three decades, the incidence of adenocarcinoma of the distal esophagus and gastroesophageal junction has progressively increased; currently, it accounts for more than 50% of all new cases of esophageal cancer. Squamous cell cancer is still the most common type worldwide. Esophageal cancer occurs mostly during the sixth and seventh decades of life and is more common in men than in women.

Pathogenesis

The most common contributing factors for squamous cell carcinoma are cigarette smoking and chronic alcohol exposure. Chronic ingestion of hot liquids or foods, poor oral hygiene, and nutritional deficiencies may play a role. Certain medical conditions such as achalasia, caustic injuries of the esophagus, and Plummer–Vinson syndrome are associated with an increased incidence of squamous cell cancer. GERD is the most common predisposing factor for adenocarcinoma of the esophagus. In these cases, adenocarcinoma represents the last event of a sequence that starts with GERD and progresses to metaplasia, high-grade dysplasia, and adenocarcinoma (see Figure 36–9). Obesity has also been identified as an important risk factor.

Esophageal cancer arises in the mucosa and subsequently tends to invade the submucosa and the muscle layers. Eventually, structures located next to the esophagus may be infiltrated (eg, the tracheobronchial tree, the aorta, and the recurrent laryngeal nerve). At the same time, the tumor tends to metastasize to the periesophageal lymph nodes (mediastinal, celiac, and cervical) and eventually to the liver and the lungs.

Clinical Findings

Symptoms and Signs

Dysphagia is the most common presenting symptom. Dysphagia initially manifests with the ingestion of solids, but eventually it is experienced with the consumption of liquids. As a result, weight loss occurs in more than 50% of patients. Patients may have pain when swallowing. Pain over bony structures may be due to metastases. Hoarseness is usually due to invasion of the right or left recurrent laryngeal nerve, with paralysis of the ipsilateral vocal cord. Respiratory symptoms may be due to the regurgitation and aspiration of undigested food or to invasion of the tracheobronchial tree, with development of a tracheoesophageal fistula.

Imaging Studies

Barium Swallow

Barium swallow can show both the location and the extent of the tumor. Esophageal cancer usually presents as an irregular intraluminal mass or a stricture (Figure 36–10).

Endoscopy

Endoscopy allows for the direct visualization and biopsy of the tumor. For tumors of the upper and midesophagus, bronchoscopy is indicated to rule out invasion of the tracheobronchial tree.

Special Tests

After the diagnosis is established, it is important to determine the staging of the cancer. In 2010, the AJCC updated the staging system of esophageal cancer to include histologic grade for both adenocarcinoma and squamous cell carcinoma, and location (upper, middle, or lower esophagus) for squamous cell carcinoma (Table 36–2). Abdominal and chest CT scans are used to rule out metastases and the invasion of structures next to the esophagus. Alternately, positron emission tomography scanning can be used. Endoscopic ultrasound is the most sensitive test to determine the penetration of the tumor, the presence of enlarged periesophageal lymph nodes, and the invasion of structures next to the esophagus. A bone scan is indicated in patients who present with a new onset of bone pain.

Differential Diagnosis

Differential diagnoses include peptic strictures due to reflux, achalasia, and benign esophageal tumors.

Treatment

Surgical Measures

Patients with esophageal cancer are considered candidates for esophageal resection if the following criteria are met: (1) there is no evidence of the spread of the tumor to structures next to the esophagus, such as the tracheobronchial tree, the aorta, or the recurrent laryngeal nerve; (2) there is no evidence of distant metastases; (3) the patient is fit from a cardiac and respiratory point of view.

An esophagectomy can be performed by using (1) an abdominal and a cervical incision with blunt dissection of the thoracic esophagus through the esophageal hiatus (transhiatal esophagectomy) or (2) an incision into the abdomen and the right side of the chest (transthoracic esophagectomy). After removing the esophagus, continuity of the gastrointestinal tract is re-established by using either the stomach or the colon. Many retrospective and prospective randomized studies have shown no difference in the survival rate between the two operations, suggesting that it is not the type of operation that influences survival but the stage of the disease at the time the operation is performed. The morbidity rate of the operation is approximately 30% and is mostly due to cardiac complications (eg, arrhythmias), respiratory complications (eg, atelectasis or pleural effusion), and septic complications (eg, anastomotic leak or pneumonia). The mortality rate in specialized centers is less than 5%. As with other complex operations (cardiac surgery, as well as liver and pancreatic resections), a lower mortality rate is obtained in “high-volume centers” because of the presence of an experienced team composed of surgeons, anesthesiologists, cardiologists, radiologists, and nurses.

Nonsurgical Measures

Neoadjuvant therapy based on a combination of radiation therapy and chemotherapy has been attempted to improve both the local control, via radiation therapy, and the distant control of the disease, via chemotherapy. Unfortunately, with the exception of one study, all the randomized trials have failed to show a survival benefit in patients treated by neoadjuvant therapy followed by surgery compared with patients who had surgery alone. Nonoperative therapy is reserved for patients who are not candidates for surgery because of local invasion of the tumor, metastases, or a poor functional status. The goal of therapy in these patients is palliation of the dysphagia, which will allow them to eat. The following treatment modalities are available to achieve this goal: (1) Expandable, coated, metallic stents can be deployed by endoscopy under fluoroscopic guidance to keep the esophageal lumen open. They are particularly useful when a tracheoesophageal fistula is present. (2) Laser therapy (Nd:YAG laser) relieves dysphagia in up to 70% of patients. However, multiple sessions are usually required to keep the esophageal lumen open. (3) Radiation therapy is successful in relieving dysphagia in about 50% of patients.

Prognosis

The stage of the disease is the most important prognostic factor. The overall 5-year survival rate for esophageal cancer remains approximately 25–30%. Patients without lymph node metastases have a significantly better 5-year survival rate than patients with lymph node involvement.