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Disorders of the Esophagus TABLE 1. Causes of Dysphagia Condition Diagnostic Clues Oropharyngeal Dysphagia Structural disorders Cervical osteophytes High dysphagia, degenerative joint disease Cricoid webs High dysphagia, iron deficiency Pharyngoesophageal (Zenker) diverticulum Aspiration, neck mass, and regurgitation of foul-smelling food Goiter Neck mass Neurologic/myogenic disorders Amyotrophic lateral sclerosis Upper and lower motoneuron signs, fasciculations Central nervous system tumor Headache, vision changes, nausea, seizures, balance problem Stroke Focal neurologic deficits Muscular dystrophy Slow progression of muscular weakness over years Myasthenia gravis Weakness with repetitive activity Multiple sclerosis Episodes of neurologic dysfunction with variable degrees of recovery Parkinson disease Bradykinesia, rigidity, tremor Dementia Altered cognition Sjogren syndrome Dry mouth, dry eyes Esophageal Dysphagia Structural disorders Dysphagia lusoria (vascular dysphagia) Vascular extrinsic compression of the esophagus on imaging Epiphrenic/traction diverticulum Outpouching of the esophagus at any level on imaging Esophageal strictures Progressive dysphagia, especially for solid food; history of reflux Eosinophilic esophagitis Food impactions, atopic history, rings or strictures on endoscopy Esophageal webs or rings Intermittent dysphagia; upper esophageal webs may be associated with iron deficiency anemia Neoplasms Rapidly progressive dysphagia for solids, then liquids; anorexia; weight loss Motility disorders Achalasia Concomitant liquid and solid dysphagia Diffuse esophageal spasm Chest pain

Esophageal webs or rings Intermittent dysphagia; upper esophageal webs may be associated with iron deficiency anemia Neoplasms Rapidly progressive dysphagia for solids, then liquids; anorexia; weight loss Motility disorders Achalasia Concomitant liquid and solid dysphagia Diffuse esophageal spasm Chest pain Systemic sclerosis Skin hardening, telangiectasias, sclerodactyly, gastroesophageal reflux disease, Raynaud phenomenon

Achalasia Concomitant liquid and solid dysphagia Diffuse esophageal spasm Chest pain Systemic sclerosis Skin hardening, telangiectasias, sclerodactyly, gastroesophageal reflux disease, Raynaud phenomenon appropriate diagnostic test to determine the degree of inflam- Treatment with acid suppression or cognitive behavioral mation and underlying cause. therapy may be initiated once a structural cause has been ruled out. Globus Sensation Patients commonly report globus sensation as a lump in the Reflux and Chest Pain throat or throat tightness, usually not linked to meals. The development of chest pain from an esophageal cause can Causes of globus include GERD (with or without heartburn), mimic chest pain from cardiac disease. A cardiac cause must motility disorders, stress, and psychiatric conditions be ruled out first. The most common cause of noncardiac chest (e.g., anxiety disorder, panic disorder, and somatic symptom pain is GERD. Another possible cause is an esophageal motility disorder). Globus should not be diagnosed if the patient disorder, particularly hypercontractile motility disorders. reports other esophageal symptoms, such as dysphagia or Reports of heartburn with a history of Raynaud phenomenon odynophagia. Assessment for the cause should include eval- could signify a systemic condition, such as systemic sclerosis. uation for thyroid goiter and an underlying pharyngeal Starting a course of an acid-reducing agent can be both lesion, which can be diagnosed by transnasal endoscopy or diagnostic and therapeutic. Patients whose symptoms do barium swallow. not respond require further evaluation, including upper 2

Disorders of the Esophagus TABLE 2. Factors Associated With Reflux Category Factor Lifestyle Cigarette smoking Eating habits Eating large meals Eating late at night Lying supine shortly after eating Foods and Alcohol beverages Chocolate Citrus fruits and juices Coffee Fatty and fried foods Onions Peppermint Medications Anticholinergic agents Aspirin and NSAIDs Calcium channel blockers Nitrates Progesterone Opioids (due to delayed gastric emptying) Body position Bending over, exercising (both result in increased intra-abdominal pressure) Other Obesity Pregnancy Tight-fitting clothing Hiatal hernia FIGURE 1. Barium esophagram showing a Schatzki ring, a subtype of esophageal ring located at the squamocolumnar junction and a common cause of dysphagia. Nonmalignant Disorders of the Esophagus endoscopy, and possibly ambulatory pH testing with or with- Gastroesophageal Reflux Disease out esophageal manometry. GERD is characterized by contents refluxing from the stomach

FIGURE 1. Barium esophagram showing a Schatzki ring, a subtype of esophageal ring located at the squamocolumnar junction and a common cause of dysphagia. Nonmalignant Disorders of the Esophagus endoscopy, and possibly ambulatory pH testing with or with- Gastroesophageal Reflux Disease out esophageal manometry. GERD is characterized by contents refluxing from the stomach See Gastroesophageal Reflux Disease for information into the esophagus. It has a prevalence of 10% to 20% in the about diagnosis and management. Western world. There is a strong relationship between GERD and obesity. The most common symptoms reported are heart- burn, regurgitation, and chest pain, for which a cardiac cause ¢ Oropharyngeal dysphagia occurs when the patient must be excluded. Many factors can trigger reflux (Table 2). cannot transfer the food bolus from the mouth into Protective mechanisms to minimize esophageal exposure to the upper esophagus by swallowing and should be acid and its effects include swallowed salivary bicarbonate, evaluated with a modified barium swallow with video peristalsis, a competent lower esophageal sphincter (LES), and fluoroscopy. gastric emptying; reflux occurs when these physiologic pro- e Esophageal dysphagia with solids alone suggests a tectors become ineffective. Uncontrolled GERD can negatively mechanical obstruction, whereas dysphagia with liq- affect quality of life because of poor sleep, low productivity, uids alone or with liquids and solids favors a motility and work absences. Long-standing GERD can lead to compli- disorder. cations, including reflux esophagitis, stricture, Barrett esopha-

See Gastroesophageal Reflux Disease for information into the esophagus. It has a prevalence of 10% to 20% in the about diagnosis and management. Western world. There is a strong relationship between GERD and obesity. The most common symptoms reported are heart- burn, regurgitation, and chest pain, for which a cardiac cause ¢ Oropharyngeal dysphagia occurs when the patient must be excluded. Many factors can trigger reflux (Table 2). cannot transfer the food bolus from the mouth into Protective mechanisms to minimize esophageal exposure to the upper esophagus by swallowing and should be acid and its effects include swallowed salivary bicarbonate, evaluated with a modified barium swallow with video peristalsis, a competent lower esophageal sphincter (LES), and fluoroscopy. gastric emptying; reflux occurs when these physiologic pro- e Esophageal dysphagia with solids alone suggests a tectors become ineffective. Uncontrolled GERD can negatively mechanical obstruction, whereas dysphagia with liq- affect quality of life because of poor sleep, low productivity, uids alone or with liquids and solids favors a motility and work absences. Long-standing GERD can lead to compli- disorder. cations, including reflux esophagitis, stricture, Barrett esopha- ¢ Upper endoscopy is diagnostic and may be therapeutic gus, and esophageal adenocarcinoma. Commonly attributed

See Gastroesophageal Reflux Disease for information into the esophagus. It has a prevalence of 10% to 20% in the about diagnosis and management. Western world. There is a strong relationship between GERD and obesity. The most common symptoms reported are heart- burn, regurgitation, and chest pain, for which a cardiac cause ¢ Oropharyngeal dysphagia occurs when the patient must be excluded. Many factors can trigger reflux (Table 2). cannot transfer the food bolus from the mouth into Protective mechanisms to minimize esophageal exposure to the upper esophagus by swallowing and should be acid and its effects include swallowed salivary bicarbonate, evaluated with a modified barium swallow with video peristalsis, a competent lower esophageal sphincter (LES), and fluoroscopy. gastric emptying; reflux occurs when these physiologic pro- e Esophageal dysphagia with solids alone suggests a tectors become ineffective. Uncontrolled GERD can negatively mechanical obstruction, whereas dysphagia with liq- affect quality of life because of poor sleep, low productivity, uids alone or with liquids and solids favors a motility and work absences. Long-standing GERD can lead to compli- disorder. cations, including reflux esophagitis, stricture, Barrett esopha- ¢ Upper endoscopy is diagnostic and may be therapeutic gus, and esophageal adenocarcinoma. Commonly attributed for esophageal dysphagia. extraesophageal conditions include chronic cough, hoarseness (laryngitis), wheezing (asthma), and dental erosions. Pregnant ¢ Chest pain is common in patients with gastroesophageal women may experience GERD during any trimester of preg- reflux disease, but a cardiac cause of chest pain must be nancy, symptoms may worsen as the pregnancy progresses, ruled out first. and symptoms typically resolve after delivery.

Disorders of the Esophagus Diagnosis Lifestyle Changes Strategies for diagnosing GERD include consideration of clini- Patients with recent weight gain or who are overweight cal history and response to medical therapy; testing, such as should have a weight-loss plan. Patients with nocturnal GERD endoscopy and ambulatory pH monitoring; and exclusion of should not eat within at least 3 hours before going to sleep a motility disorder by manometry. There is no single gold- and should consider raising the head of the bed. Avoiding standard diagnostic test. Clinical symptoms of heartburn and large meals and rich or fatty foods that stay in the stomach for regurgitation strongly suggest GERD. Alarm features include longer periods is helpful. dysphagia, weight loss, hematemesis, or melena. Patients with Additional dietary modification should focus on elimi- GERD symptoms but without alarm features may undergo an nating specific foods that trigger an individual patient’s GERD empiric trial of a proton pump inhibitor (PPI). In patients with symptoms rather than globally eliminating all common trigger alarm features or failure to respond to treatment, upper endos- foods (caffeine; chocolate; spicy foods; acidic foods, such as copy is warranted to rule out an underlying ring, web, malig- citrus fruits; and fatty foods). Cessation of alcohol and tobacco nancy, eosinophilic esophagitis, erosive esophagitis, stricture, use is recommended. or Barrett esophagus. Most patients with GERD have normal findings on upper endoscopy. Medical Therapy Ambulatory pH monitoring can quantify acid exposure in Pharmacologic therapy includes antacids, H, blockers, and the esophagus. Impedance-pH testing can help differentiate PPIs. A PPI once daily for 8 weeks is the therapy of choice for between acid and nonacid reflux. Testing to detect active acid symptom relief and for treatment of erosive esophagitis. Most reflux can be done with a 24-hour transnasal catheter or 48-hour PPIs should be taken once daily, 30 to 60 minutes before the or 96-hour wireless capsule endoscopy. pH monitoring may be first meal of the day. Patients with partial response to PPI performed while the patient is not receiving acid-suppressive therapy should increase the dosage to twice daily. Given the therapy to confirm acid exposure and support a diagnosis of risks and potential adverse effects of PPI therapy (Table 3), the GERD. Esophageal manometry should be considered as part of the goal should be to use the lowest dose required to control evaluation for patients with dysphagia or atypical reflux symp- symptoms and to discontinue if there is not an appropriate toms and before antireflux surgery to rule out motility disorders. indication. Similarly, patients requiring long-term mainte- nance therapy should be prescribed the lowest effective PPI Treatment dose, including on-demand or intermittent use. For patients An algorithm outlining evaluation of GERD is presented in with uncomplicated GERD, stopping or reducing long-term Figure 2. PPI therapy should be attempted once a year.

Diagnosis Lifestyle Changes Strategies for diagnosing GERD include consideration of clini- Patients with recent weight gain or who are overweight cal history and response to medical therapy; testing, such as should have a weight-loss plan. Patients with nocturnal GERD endoscopy and ambulatory pH monitoring; and exclusion of should not eat within at least 3 hours before going to sleep a motility disorder by manometry. There is no single gold- and should consider raising the head of the bed. Avoiding standard diagnostic test. Clinical symptoms of heartburn and large meals and rich or fatty foods that stay in the stomach for regurgitation strongly suggest GERD. Alarm features include longer periods is helpful. dysphagia, weight loss, hematemesis, or melena. Patients with Additional dietary modification should focus on elimi- GERD symptoms but without alarm features may undergo an nating specific foods that trigger an individual patient’s GERD empiric trial of a proton pump inhibitor (PPI). In patients with symptoms rather than globally eliminating all common trigger alarm features or failure to respond to treatment, upper endos- foods (caffeine; chocolate; spicy foods; acidic foods, such as copy is warranted to rule out an underlying ring, web, malig- citrus fruits; and fatty foods). Cessation of alcohol and tobacco nancy, eosinophilic esophagitis, erosive esophagitis, stricture, use is recommended. or Barrett esophagus. Most patients with GERD have normal findings on upper endoscopy. Medical Therapy Ambulatory pH monitoring can quantify acid exposure in Pharmacologic therapy includes antacids, H, blockers, and the esophagus. Impedance-pH testing can help differentiate PPIs. A PPI once daily for 8 weeks is the therapy of choice for between acid and nonacid reflux. Testing to detect active acid symptom relief and for treatment of erosive esophagitis. Most reflux can be done with a 24-hour transnasal catheter or 48-hour PPIs should be taken once daily, 30 to 60 minutes before the or 96-hour wireless capsule endoscopy. pH monitoring may be first meal of the day. Patients with partial response to PPI performed while the patient is not receiving acid-suppressive therapy should increase the dosage to twice daily. Given the therapy to confirm acid exposure and support a diagnosis of risks and potential adverse effects of PPI therapy (Table 3), the GERD. Esophageal manometry should be considered as part of the goal should be to use the lowest dose required to control evaluation for patients with dysphagia or atypical reflux symp- symptoms and to discontinue if there is not an appropriate toms and before antireflux surgery to rule out motility disorders. indication. Similarly, patients requiring long-term mainte- nance therapy should be prescribed the lowest effective PPI Treatment dose, including on-demand or intermittent use. For patients An algorithm outlining evaluation of GERD is presented in with uncomplicated GERD, stopping or reducing long-term Figure 2. PPI therapy should be attempted once a year. GERD symptoms

Diagnosis Lifestyle Changes Strategies for diagnosing GERD include consideration of clini- Patients with recent weight gain or who are overweight cal history and response to medical therapy; testing, such as should have a weight-loss plan. Patients with nocturnal GERD endoscopy and ambulatory pH monitoring; and exclusion of should not eat within at least 3 hours before going to sleep a motility disorder by manometry. There is no single gold- and should consider raising the head of the bed. Avoiding standard diagnostic test. Clinical symptoms of heartburn and large meals and rich or fatty foods that stay in the stomach for regurgitation strongly suggest GERD. Alarm features include longer periods is helpful. dysphagia, weight loss, hematemesis, or melena. Patients with Additional dietary modification should focus on elimi- GERD symptoms but without alarm features may undergo an nating specific foods that trigger an individual patient’s GERD empiric trial of a proton pump inhibitor (PPI). In patients with symptoms rather than globally eliminating all common trigger alarm features or failure to respond to treatment, upper endos- foods (caffeine; chocolate; spicy foods; acidic foods, such as copy is warranted to rule out an underlying ring, web, malig- citrus fruits; and fatty foods). Cessation of alcohol and tobacco nancy, eosinophilic esophagitis, erosive esophagitis, stricture, use is recommended. or Barrett esophagus. Most patients with GERD have normal findings on upper endoscopy. Medical Therapy Ambulatory pH monitoring can quantify acid exposure in Pharmacologic therapy includes antacids, H, blockers, and the esophagus. Impedance-pH testing can help differentiate PPIs. A PPI once daily for 8 weeks is the therapy of choice for between acid and nonacid reflux. Testing to detect active acid symptom relief and for treatment of erosive esophagitis. Most reflux can be done with a 24-hour transnasal catheter or 48-hour PPIs should be taken once daily, 30 to 60 minutes before the or 96-hour wireless capsule endoscopy. pH monitoring may be first meal of the day. Patients with partial response to PPI performed while the patient is not receiving acid-suppressive therapy should increase the dosage to twice daily. Given the therapy to confirm acid exposure and support a diagnosis of risks and potential adverse effects of PPI therapy (Table 3), the GERD. Esophageal manometry should be considered as part of the goal should be to use the lowest dose required to control evaluation for patients with dysphagia or atypical reflux symp- symptoms and to discontinue if there is not an appropriate toms and before antireflux surgery to rule out motility disorders. indication. Similarly, patients requiring long-term mainte- nance therapy should be prescribed the lowest effective PPI Treatment dose, including on-demand or intermittent use. For patients An algorithm outlining evaluation of GERD is presented in with uncomplicated GERD, stopping or reducing long-term Figure 2. PPI therapy should be attempted once a year. GERD symptoms y Y Esophageal symptoms Extraesophageal symptoms (heartburn, acid regurgitation) (cough, laryngitis, asthma)

y Y Esophageal symptoms Extraesophageal symptoms (heartburn, acid regurgitation) (cough, laryngitis, asthma) | | ‘ 4y ¥ ¥ Alarm symptoms? Alarm symptoms? Esophageal features Esophageal symptoms/ absent present present complications absent Therapeutic trial Refer toa Therapeutic trial Explore alternative of a PPI gastroenterologist of a PPI causes for endoscopy and | other evaluation

Therapeutic trial Refer toa Therapeutic trial Explore alternative of a PPI gastroenterologist of a PPI causes for endoscopy and | other evaluation y y y \ If clinical response, If clinical response, - : No or No or ‘: é pes sig et incomplete SIME Mae TOW! response miccmnplets response tai g! effective dose effective dose FIGURE 2. Management of gastroesophageal reflux disease. GERD = gastroesophageal reflux disease; PPI = proton pump inhibitor. 7 —— "Alarm include dysphagia, I weight loss, h is, and melena. 4

Disorders of the Esophagus TABLE 3. Adverse Effects of Proton Pump Inhibitors should be considered before a PPI trial. Surgery is less effective in this group and should be considered only in patients whose Common Unusual Proposed | Associations symptoms respond to PPI therapy. Headache Vitamin B,2 deficiency Kidney injury? | Refractory GERD Diarrhea Hypomagnesemia Dementia@ | The first step in addressing refractory GERD is to optimize j

Headache Vitamin B,2 deficiency Kidney injury? | Refractory GERD Diarrhea Hypomagnesemia Dementia@ | The first step in addressing refractory GERD is to optimize j Dyspepsia Community-acquired | PPI therapy by emphasizing the importance of taking pneumonia? medication 30 to 60 minutes before eating, increasing the Clostridioides difficile infection? dosage to twice daily, or switching to another PPI. If symp- Hip fracture toms are still unresponsive, alternative causes must be considered. For typical symptoms, endoscopy is used to 2A large randomized controlled trial published in 2019 failed to demonstrate increased risk for these outcomes over 3 years (Moayyedi P, Eikelboom JW, Bosch rule out eosinophilic esophagitis or erosive esophagitis. J, et al; COMPASS Investigators. Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin. Adequacy of acid suppression therapy may be confirmed Gastroenterology. 2019; 157:682-691.e2. [PMID: 31152740] doi:10.1053/j. gastro.2019.05.056). by esophageal impedance-pH testing while the patient is receiving optimized PPI therapy. For atypical symptoms, other causes should be evaluated, and referral to otorhino- Switching to a different PPI may be warranted for adverse laryngology, pulmonary, or allergy specialists to identify reactions or unresponsive symptoms. PPIs are safe in pregnant and treat the cause should be considered. In these patients, patients. impedance-pH testing conducted off acid-suppression Prokinetic agents, such as metoclopramide, should not be therapy may help confirm the diagnosis of acid reflux. If used to treat GERD unless gastroparesis is present. results of impedance-pH and pH testing are normal but symptoms persist, therapy for functional heartburn may Antireflux Surgery be attempted with selective serotonin reuptake inhibitors, Surgery is infrequently required; indications include failure of serotonin-norepinephrine reuptake inhibitors, or tricyclic optimal PPI therapy, a desire to stop the medication, and intol- antidepressants. erable medication side effects. Patients should undergo objec- tive testing, such as pH monitoring and manometry, before Eosinophilic Esophagitis surgery. Surgical treatments for GERD are laparoscopic Eosinophilic esophagitis (EoE) is commonly associated with fundoplication or bariatric surgery for obesity as well as mag- dysphagia and food bolus obstruction, which may be recur- netic sphincter augmentation (a magnetic ring is placed rent. Most patients are diagnosed between the second and fifth around the LES without surgical alteration of the stomach). decades of life, and EoE is more common in men. Patients Surgery is most effective in patients with typical symptoms of often have other atopic conditions, such as asthma, rhinitis, heartburn and regurgitation that respond to PPI therapy. dermatitis, and seasonal or food allergies. The reported U.S. However, about one third of patients require resumption of a prevalence is 40 to 90 per 100,000. The diagnostic criteria for PPI 5 to 10 years after surgery. Postoperative complications EoE are esophageal symptoms (dysphagia), esophageal biopsy include dysphagia, diarrhea, and inability to belch because of specimens showing persistent eosinophil counts of 15/hpf or a tight fundoplication. greater, and exclusion of other causes of eosinophilia. Other causes include GERD, hypereosinophilic syndrome, infections Endoscopic Therapy (fungal, viral), autoimmune and connective tissue disorders, Transoral incisionless fundoplication (an endoscopic fun- Crohn disease with esophageal involvement, and drug hyper- doplication created with full-thickness suture) has had initial sensitivity reactions. EoE is diagnosed in the absence of eosin- success; long-term data are limited. Additional endoscopic ophilia elsewhere. therapies for GERD are based on thermal radiofrequency Endoscopic findings include rings, longitudinal furrows, energy, silicone injection, suturing, and endoscopic resection, luminal narrowing, and sometimes strictures (Figure 3). If but long-term benefits are unproven. assessment identifies no other causes of eosinophilia, EoE can be diagnosed and appropriate therapy initiated with a Extraesophageal Manifestations PPI and/or swallowed topical glucocorticoids (fluticasone or Asthma, chronic cough, and laryngitis are linked to GERD budesonide). Limited evidence suggests that diet modifica- (see Figure 2). When these symptoms are present, other non- tion may be effective in the prevention of EoE. An empiric GERD causes should be eliminated. Laryngoscopy should not elimination diet-removing the foods most commonly associ- be used to diagnose GERD-related laryngitis, and edema and ated with food allergies, such as egg, soy, wheat, peanuts, erythema as potential signs of reflux-induced laryngitis are cow’s milk, and fish/shellfish—has been used. Endoscopic nonspecific. A PPI trial is recommended in patients who have dilation should be considered in patients with continued concomitant typical GERD symptoms. For patients with atyp- dysphagia caused by esophageal stricture not responding to ical symptoms only, ambulatory esophageal pH monitoring medical therapy.

Disorders of the Esophagus Herpes simplex virus and cytomegalovirus are seen in immunodeficient or immunosuppressed individuals but rarely occur in immunocompetent patients. Endoscopy with biopsy is needed to confirm the diagnosis. Herpes simplex virus infection is treated with acyclovir, and cytomegalovirus infection is treated with ganciclovir; oral valganciclovir is also an option.

Herpes simplex virus and cytomegalovirus are seen in immunodeficient or immunosuppressed individuals but rarely occur in immunocompetent patients. Endoscopy with biopsy is needed to confirm the diagnosis. Herpes simplex virus infection is treated with acyclovir, and cytomegalovirus infection is treated with ganciclovir; oral valganciclovir is also an option. Pill-Induced Esophagitis Medications can cause esophageal injury that results in esophagitis. Risk factors for pill-induced esophagitis include decreased salivary output, esophageal dysmotility, large pills, medications that increase the LES tone (opioids), and inges- tion of medications in the supine position. Patients commonly report chest pain, dysphagia, and odynophagia several hours to days after taking the medication. Pill-induced esophagitis has occurred with alendronate, quinidine, tetracycline, doxy- FIGURE 3. The characteristic findings of eosinophilic esophagitis on endoscopy cycline, potassium chloride, ferrous sulfate, and mexiletine. include rings and longitudinal furrows; strictures may also be seen. Medications associated with stricture formation include alen- dronate, ferrous sulfate, NSAIDs, and potassium chloride. Pill- Infectious Esophagitis induced esophagitis can be diagnosed by history alone, but

Pill-Induced Esophagitis Medications can cause esophageal injury that results in esophagitis. Risk factors for pill-induced esophagitis include decreased salivary output, esophageal dysmotility, large pills, medications that increase the LES tone (opioids), and inges- tion of medications in the supine position. Patients commonly report chest pain, dysphagia, and odynophagia several hours to days after taking the medication. Pill-induced esophagitis has occurred with alendronate, quinidine, tetracycline, doxy- FIGURE 3. The characteristic findings of eosinophilic esophagitis on endoscopy cycline, potassium chloride, ferrous sulfate, and mexiletine. include rings and longitudinal furrows; strictures may also be seen. Medications associated with stricture formation include alen- dronate, ferrous sulfate, NSAIDs, and potassium chloride. Pill- Infectious Esophagitis induced esophagitis can be diagnosed by history alone, but Infectious esophagitis can be caused by fungal, viral, bacte- upper endoscopy should be performed for severe symptoms, rial (uncommon), or parasitic pathogens. It most commonly persistent symptoms, or atypical symptoms (such as hemate- occurs in immunocompromised patients. Patients most mesis or abdominal pain). Preventive strategies include drink- often present with odynophagia or dysphagia. Candida ing sufficient water with medications and remaining upright

rial (uncommon), or parasitic pathogens. It most commonly persistent symptoms, or atypical symptoms (such as hemate- occurs in immunocompromised patients. Patients most mesis or abdominal pain). Preventive strategies include drink- often present with odynophagia or dysphagia. Candida ing sufficient water with medications and remaining upright esophagitis frequently causes dysphagia with or without for 30 minutes after pill ingestion. odynophagia, whereas viral esophagitis produces odynopha- gia. Other organisms associated with esophagitis include Esophageal Motility Disorders Lactobacillus, B-hemolytic streptococci, Cryptosporidium The esophagus is a muscular tube that passes a food bolus species, Pneumocystis jirovecii, Mycobacterium avium from the hypopharynx to the stomach through peristalsis. The complex, and Mycobacterium tuberculosis. upper third of the esophagus is composed of skeletal muscle Candida infection can occur in immunocompetent or innervated by axons of lower motor neurons. The lower two immunocompromised hosts. Diagnosis is usually made clini- thirds is smooth muscle innervated by the vagus nerve. High- cally on the basis of compatible symptoms and oral candidia- resolution esophageal manometry is used to evaluate sus- sis, although not all patients have oral involvement. Endoscopy pected esophageal motility disorders. and biopsy can be considered for patients who do not respond to empiric therapy or who have atypical symptoms. Endoscopy Hypertonic Motility Disorders shows small, white, raised plaques, and esophageal brushings Hypertonic motility disorders are characterized by dysphagia confirm the diagnosis (Figure 4). The most common species is with both liquids and solids. Other symptoms can include Candida albicans, which is treated with oral fluconazole. regurgitation of undigested food, particularly when the patient is in a recumbent position.

confirm the diagnosis (Figure 4). The most common species is with both liquids and solids. Other symptoms can include Candida albicans, which is treated with oral fluconazole. regurgitation of undigested food, particularly when the patient is in a recumbent position. Achalasia and Pseudoachalasia Achalasia is defined by inadequate relaxation of the LES and aperistalsis. Achalasia can be idiopathic or associated with viral, autoimmune, and neurodegenerative disorders and infection (Chagas disease). Damage to the ganglion cells and myenteric plexus in the esophageal body and LES leads to uncontested cholinergic nerve activation, which prevents LES relaxation. Achalasia affects men and women equally, with an annual incidence of 1 in 100,000 individuals. It commonly occurs between 30 and 60 years of age. Patients have dysphagia bn with both solids and liquids along with nonacidic regurgitation FIGURE 4. White adherent plaques suggesting Candida esophagitis, as seen on of undigested food. Additional symptoms include heartburn, upper endoscopy. weight loss, and chest pain unresponsive to acid-reducing 6

Disorders of the Esophagus Endoscopy with botulinum toxin injection into the LES inhibits acetylcholine release, relaxing the LES. However, after 1 year, only 40% of patients have continued symptom relief. Botulinum toxin injection can be repeated, but successive

Endoscopy with botulinum toxin injection into the LES inhibits acetylcholine release, relaxing the LES. However, after 1 year, only 40% of patients have continued symptom relief. Botulinum toxin injection can be repeated, but successive treatments are often less effective for symptom management. Pneumatic dilation is an effective nonsurgical therapy. Dilators ranging from 30 mm to 40 mm are used to disrupt the circular muscle. Clinical symptom relief ranges from 50% to 90%, and the most common complication is perforation. Surgical treatment consists of laparoscopic myotomy of the circular muscle fibers. A partial fundoplication may also be done laparoscopically to prevent reflux symptoms after myotomy. Advantages of laparoscopic myotomy include the ability to address any hiatal hernia, if present, and perform a concurrent antireflux procedure. Peroral endoscopic myotomy (POEM) is a newer procedure that entails creation of an esoph- ageal submucosal tunnel extending to the LES and then a myotomy. Advantages of POEM include the lack of skin inci- sions and ability to perform a longer myotomy, which may be beneficial in spastic achalasia. Disadvantages include risk for FIGURE 5. Barium esophagram showing the typical appearance of a dilated reflux. Choice of therapy depends on patient factors, type of esophagus and “bird's beak” narrowing at the gastroesophageal junction in a patient with achalasia. disease, and available local expertise. Medical therapy is reserved for poor candidates for endo- scopic or surgical therapy. LES pressure can be reduced with agents. Extrinsic compression from surgical procedures, such medical therapy, including calcium channel blockers (nifedi- as fundoplication or bariatric surgery (gastric band), can also pine) or long-acting nitrates. cause secondary achalasia. Patients with achalasia for more than 10 years have There is a spectrum of achalasia-type disorders. Classic increased risk for squamous cell carcinoma and may benefit achalasia is characterized by a hypertonic LES and aperistalsis. from surveillance endoscopy, but there are no established Another subtype may include hypertonic LES, aperistalsis, and guidelines for frequency of surveillance. panesophageal pressurization (increased pressure of the entire esophageal body between the lower and upper esophageal Diffuse Esophageal Spasm and Jackhammer Esophagus sphincters). Spastic disorders of the esophagus may present with chest The initial diagnostic test is barium esophagography, pain or dysphagia. Diffuse esophageal spasms are character- which shows dilation of the esophagus with narrowing at the ized by premature contractions, and the esophagus has a gastroesophageal junction, known as a “bird’s beak” (Figure 5). “corkscrew” (Figure 6) or “rosary bead” appearance on esoph- Upper endoscopy reveals retained food and saliva, no signs of agography. Jackhammer esophagus occurs in patients with mechanical obstruction or mass, and “tightness” at the gas- high-vigor peristaltic contractions. troesophageal junction while the scope is advanced into the Symptoms often respond to nitroglycerin, suggesting a stomach. In classic achalasia, esophageal manometry shows flaw in esophageal nitric oxide production. Any GERD symp- incomplete LES relaxation and aperistalsis and confirms the toms should be treated with a PPI. In patients without GERD diagnosis. Manometry may also detect evolving achalasia vari- symptoms, medical therapy with antidepressants (trazadone, ants or spastic achalasia variants. imipramine) or a phosphodiesterase inhibitor (sildenafil) can Pseudoachalasia results from malignant tumor infiltra- relieve chest pain. Dysphagia may respond to calcium channel tion or other secondary causes leading to myenteric plexus blockers. Botulinum toxin injection has alleviated dysphagia damage and can present similarly to achalasia. Unlike acha- symptoms. lasia, pseudoachalasia has been associated with sudden weight loss later in life. Three clinical features suggest cancer as a Hypotonic Motility Disorders cause of pseudoachalasia: short duration of dysphagia Hypotonic disorders of the esophagus are marked by lack of (<1 year), weight loss (>6.8 kg), and age older than 55 years. contractility and incomplete peristalsis. Patients may report Suspected pseudoachalasia should be evaluated with CT, GERD symptoms, which result from decreased LES pressure endoscopy, or endoscopic ultrasonography. or dysphagia from incomplete peristalsis. In most cases, the Treatment of achalasia includes endoscopic or surgical cause of hypotonic esophageal disease is unknown. However, intervention with the goal of lowering LES pressure, which secondary causes include smooth-muscle relaxants, relieves symptoms. Medical therapy is uncommonly used. anticholinergic agents, estrogen, progesterone, connective

treatments are often less effective for symptom management. Pneumatic dilation is an effective nonsurgical therapy. Dilators ranging from 30 mm to 40 mm are used to disrupt the circular muscle. Clinical symptom relief ranges from 50% to 90%, and the most common complication is perforation. Surgical treatment consists of laparoscopic myotomy of the circular muscle fibers. A partial fundoplication may also be done laparoscopically to prevent reflux symptoms after myotomy. Advantages of laparoscopic myotomy include the ability to address any hiatal hernia, if present, and perform a concurrent antireflux procedure. Peroral endoscopic myotomy (POEM) is a newer procedure that entails creation of an esoph- ageal submucosal tunnel extending to the LES and then a myotomy. Advantages of POEM include the lack of skin inci- sions and ability to perform a longer myotomy, which may be beneficial in spastic achalasia. Disadvantages include risk for FIGURE 5. Barium esophagram showing the typical appearance of a dilated reflux. Choice of therapy depends on patient factors, type of esophagus and “bird's beak” narrowing at the gastroesophageal junction in a patient with achalasia. disease, and available local expertise. Medical therapy is reserved for poor candidates for endo- scopic or surgical therapy. LES pressure can be reduced with agents. Extrinsic compression from surgical procedures, such medical therapy, including calcium channel blockers (nifedi- as fundoplication or bariatric surgery (gastric band), can also pine) or long-acting nitrates. cause secondary achalasia. Patients with achalasia for more than 10 years have There is a spectrum of achalasia-type disorders. Classic increased risk for squamous cell carcinoma and may benefit achalasia is characterized by a hypertonic LES and aperistalsis. from surveillance endoscopy, but there are no established Another subtype may include hypertonic LES, aperistalsis, and guidelines for frequency of surveillance. panesophageal pressurization (increased pressure of the entire esophageal body between the lower and upper esophageal Diffuse Esophageal Spasm and Jackhammer Esophagus sphincters). Spastic disorders of the esophagus may present with chest The initial diagnostic test is barium esophagography, pain or dysphagia. Diffuse esophageal spasms are character- which shows dilation of the esophagus with narrowing at the ized by premature contractions, and the esophagus has a gastroesophageal junction, known as a “bird’s beak” (Figure 5). “corkscrew” (Figure 6) or “rosary bead” appearance on esoph- Upper endoscopy reveals retained food and saliva, no signs of agography. Jackhammer esophagus occurs in patients with mechanical obstruction or mass, and “tightness” at the gas- high-vigor peristaltic contractions. troesophageal junction while the scope is advanced into the Symptoms often respond to nitroglycerin, suggesting a stomach. In classic achalasia, esophageal manometry shows flaw in esophageal nitric oxide production. Any GERD symp- incomplete LES relaxation and aperistalsis and confirms the toms should be treated with a PPI. In patients without GERD diagnosis. Manometry may also detect evolving achalasia vari- symptoms, medical therapy with antidepressants (trazadone, ants or spastic achalasia variants. imipramine) or a phosphodiesterase inhibitor (sildenafil) can Pseudoachalasia results from malignant tumor infiltra- relieve chest pain. Dysphagia may respond to calcium channel tion or other secondary causes leading to myenteric plexus blockers. Botulinum toxin injection has alleviated dysphagia damage and can present similarly to achalasia. Unlike acha- symptoms. lasia, pseudoachalasia has been associated with sudden weight loss later in life. Three clinical features suggest cancer as a Hypotonic Motility Disorders cause of pseudoachalasia: short duration of dysphagia Hypotonic disorders of the esophagus are marked by lack of (<1 year), weight loss (>6.8 kg), and age older than 55 years. contractility and incomplete peristalsis. Patients may report Suspected pseudoachalasia should be evaluated with CT, GERD symptoms, which result from decreased LES pressure endoscopy, or endoscopic ultrasonography. or dysphagia from incomplete peristalsis. In most cases, the Treatment of achalasia includes endoscopic or surgical cause of hypotonic esophageal disease is unknown. However, intervention with the goal of lowering LES pressure, which secondary causes include smooth-muscle relaxants, relieves symptoms. Medical therapy is uncommonly used. anticholinergic agents, estrogen, progesterone, connective 7

Disorders of the Esophagus Metaplastic and Neoplastic Disorders of the Esophagus Barrett Esophagus Epidemiology and Screening Barrett esophagus is the replacement of the squamous epithe- lium with metaplastic columnar epithelium in the esophagus. It is a consequence of GERD, even in patients without clinical symptoms, and is a precursor lesion for esophageal cancer. Risk factors associated with Barrett esophagus include chronic GERD (for >5 years), age older than 50 years, male sex, white race, tobacco use, and obesity. Drinking alcohol is not associ- ated with increased risk for Barrett esophagus, and wine con- sumption might be protective. The annual cancer risks are 0.2% to 0.5% per year for Barrett esophagus without dysplasia, 0.7% per year for Barrett esophagus with low-grade dysplasia, and 7% per year for Barrett esophagus with high-grade dysplasia. About 10% of patients with GERD are found to have Barrett esophagus on endoscopy. Evidence does not support routine screening for Barrett esophagus based on GERD

Metaplastic and Neoplastic Disorders of the Esophagus Barrett Esophagus Epidemiology and Screening Barrett esophagus is the replacement of the squamous epithe- lium with metaplastic columnar epithelium in the esophagus. It is a consequence of GERD, even in patients without clinical symptoms, and is a precursor lesion for esophageal cancer. Risk factors associated with Barrett esophagus include chronic GERD (for >5 years), age older than 50 years, male sex, white race, tobacco use, and obesity. Drinking alcohol is not associ- ated with increased risk for Barrett esophagus, and wine con- sumption might be protective. The annual cancer risks are 0.2% to 0.5% per year for Barrett esophagus without dysplasia, 0.7% per year for Barrett esophagus with low-grade dysplasia, and 7% per year for Barrett esophagus with high-grade dysplasia. About 10% of patients with GERD are found to have Barrett esophagus on endoscopy. Evidence does not support routine screening for Barrett esophagus based on GERD FIGURE 6. Findings of a “corkscrew” esophagus (caused by multiple symptoms for the general population. Studies suggest that simultaneous contractions) on esophagography are typical of diffuse esophageal individuals with multiple risk factors for esophageal carci- spasm. noma and chronic GERD might benefit from screening. Men older than 50 years with GERD symptoms for more than tissue disorders (e.g., systemic sclerosis), and pregnancy. 5 years and additional risk factors (nocturnal reflux symp- Esophageal manometry shows weak nonperistaltic contrac- toms, hiatal hernia, elevated BMI, intra-abdominal distribu- tions in the distal esophagus. Findings can mimic those of tion of body fat, tobacco use) may benefit from screening achalasia. endoscopy. Women generally do not require routine endo- Treatment includes lifestyle changes, such as eating upright scopic screening for Barrett esophagus and should be selected and consuming liquid or semisolid rather than solid food. for screening on a case-by-case basis. Medical therapy includes acid-reducing agents for GERD and low-dose antidepressants to reduce chest discomfort. Prokinetic Diagnosis and Management agents (e.g., metoclopramide) are not recommended. Barrett esophagus is diagnosed by endoscopic findings (Figure 7) with biopsy, which are then confirmed by pathology showing specialized intestinal metaplasia with acid-mucin-containing HVC ¢ In patients with symptoms of gastroesophageal reflux goblet cells. Barrett esophagus is categorized by endoscopy disease but without alarm features, an empiric trial of a measurements as short-segment (<3 cm) or long-segment proton pump inhibitor is the initial management. (>3 em). Long segments are at a higher risk for cancer progres- ¢ The diagnostic criteria for eosinophilic esophagitis are sion than are short segments. esophageal symptoms (most commonly dysphagia), Barrett esophagus progresses along a continuum: intesti- esophageal biopsy specimens showing persistent eosin- nal metaplasia, indefinite for dysplasia, low-grade dysplasia, ophil counts of 15/hpf or greater, and exclusion of other high-grade dysplasia, intramucosal carcinoma, and, finally, causes of eosinophilia. invasive adenocarcinoma. The stage informs surveillance and HVC * Candida esophagitis can be diagnosed clinically on the treatment recommendations (Table 4). basis of compatible symptoms, such as dysphagia and In patients with Barrett esophagus, medical therapy oral candidiasis. should be used to treat reflux symptoms and to heal reflux

FIGURE 6. Findings of a “corkscrew” esophagus (caused by multiple symptoms for the general population. Studies suggest that simultaneous contractions) on esophagography are typical of diffuse esophageal individuals with multiple risk factors for esophageal carci- spasm. noma and chronic GERD might benefit from screening. Men older than 50 years with GERD symptoms for more than tissue disorders (e.g., systemic sclerosis), and pregnancy. 5 years and additional risk factors (nocturnal reflux symp- Esophageal manometry shows weak nonperistaltic contrac- toms, hiatal hernia, elevated BMI, intra-abdominal distribu- tions in the distal esophagus. Findings can mimic those of tion of body fat, tobacco use) may benefit from screening achalasia. endoscopy. Women generally do not require routine endo- Treatment includes lifestyle changes, such as eating upright scopic screening for Barrett esophagus and should be selected and consuming liquid or semisolid rather than solid food. for screening on a case-by-case basis. Medical therapy includes acid-reducing agents for GERD and low-dose antidepressants to reduce chest discomfort. Prokinetic Diagnosis and Management agents (e.g., metoclopramide) are not recommended. Barrett esophagus is diagnosed by endoscopic findings (Figure 7) with biopsy, which are then confirmed by pathology showing specialized intestinal metaplasia with acid-mucin-containing HVC ¢ In patients with symptoms of gastroesophageal reflux goblet cells. Barrett esophagus is categorized by endoscopy disease but without alarm features, an empiric trial of a measurements as short-segment (<3 cm) or long-segment proton pump inhibitor is the initial management. (>3 em). Long segments are at a higher risk for cancer progres- ¢ The diagnostic criteria for eosinophilic esophagitis are sion than are short segments. esophageal symptoms (most commonly dysphagia), Barrett esophagus progresses along a continuum: intesti- esophageal biopsy specimens showing persistent eosin- nal metaplasia, indefinite for dysplasia, low-grade dysplasia, ophil counts of 15/hpf or greater, and exclusion of other high-grade dysplasia, intramucosal carcinoma, and, finally, causes of eosinophilia. invasive adenocarcinoma. The stage informs surveillance and HVC * Candida esophagitis can be diagnosed clinically on the treatment recommendations (Table 4). basis of compatible symptoms, such as dysphagia and In patients with Barrett esophagus, medical therapy oral candidiasis. should be used to treat reflux symptoms and to heal reflux ¢ Herpes simplex virus and cytomegalovirus esophagitis esophagitis. No strong evidence suggests that antireflux

FIGURE 6. Findings of a “corkscrew” esophagus (caused by multiple symptoms for the general population. Studies suggest that simultaneous contractions) on esophagography are typical of diffuse esophageal individuals with multiple risk factors for esophageal carci- spasm. noma and chronic GERD might benefit from screening. Men older than 50 years with GERD symptoms for more than tissue disorders (e.g., systemic sclerosis), and pregnancy. 5 years and additional risk factors (nocturnal reflux symp- Esophageal manometry shows weak nonperistaltic contrac- toms, hiatal hernia, elevated BMI, intra-abdominal distribu- tions in the distal esophagus. Findings can mimic those of tion of body fat, tobacco use) may benefit from screening achalasia. endoscopy. Women generally do not require routine endo- Treatment includes lifestyle changes, such as eating upright scopic screening for Barrett esophagus and should be selected and consuming liquid or semisolid rather than solid food. for screening on a case-by-case basis. Medical therapy includes acid-reducing agents for GERD and low-dose antidepressants to reduce chest discomfort. Prokinetic Diagnosis and Management agents (e.g., metoclopramide) are not recommended. Barrett esophagus is diagnosed by endoscopic findings (Figure 7) with biopsy, which are then confirmed by pathology showing specialized intestinal metaplasia with acid-mucin-containing HVC ¢ In patients with symptoms of gastroesophageal reflux goblet cells. Barrett esophagus is categorized by endoscopy disease but without alarm features, an empiric trial of a measurements as short-segment (<3 cm) or long-segment proton pump inhibitor is the initial management. (>3 em). Long segments are at a higher risk for cancer progres- ¢ The diagnostic criteria for eosinophilic esophagitis are sion than are short segments. esophageal symptoms (most commonly dysphagia), Barrett esophagus progresses along a continuum: intesti- esophageal biopsy specimens showing persistent eosin- nal metaplasia, indefinite for dysplasia, low-grade dysplasia, ophil counts of 15/hpf or greater, and exclusion of other high-grade dysplasia, intramucosal carcinoma, and, finally, causes of eosinophilia. invasive adenocarcinoma. The stage informs surveillance and HVC * Candida esophagitis can be diagnosed clinically on the treatment recommendations (Table 4). basis of compatible symptoms, such as dysphagia and In patients with Barrett esophagus, medical therapy oral candidiasis. should be used to treat reflux symptoms and to heal reflux ¢ Herpes simplex virus and cytomegalovirus esophagitis esophagitis. No strong evidence suggests that antireflux are seen in immunodeficient or immunosuppressed surgery can prevent progression of Barrett esophagus to

FIGURE 6. Findings of a “corkscrew” esophagus (caused by multiple symptoms for the general population. Studies suggest that simultaneous contractions) on esophagography are typical of diffuse esophageal individuals with multiple risk factors for esophageal carci- spasm. noma and chronic GERD might benefit from screening. Men older than 50 years with GERD symptoms for more than tissue disorders (e.g., systemic sclerosis), and pregnancy. 5 years and additional risk factors (nocturnal reflux symp- Esophageal manometry shows weak nonperistaltic contrac- toms, hiatal hernia, elevated BMI, intra-abdominal distribu- tions in the distal esophagus. Findings can mimic those of tion of body fat, tobacco use) may benefit from screening achalasia. endoscopy. Women generally do not require routine endo- Treatment includes lifestyle changes, such as eating upright scopic screening for Barrett esophagus and should be selected and consuming liquid or semisolid rather than solid food. for screening on a case-by-case basis. Medical therapy includes acid-reducing agents for GERD and low-dose antidepressants to reduce chest discomfort. Prokinetic Diagnosis and Management agents (e.g., metoclopramide) are not recommended. Barrett esophagus is diagnosed by endoscopic findings (Figure 7) with biopsy, which are then confirmed by pathology showing specialized intestinal metaplasia with acid-mucin-containing HVC ¢ In patients with symptoms of gastroesophageal reflux goblet cells. Barrett esophagus is categorized by endoscopy disease but without alarm features, an empiric trial of a measurements as short-segment (<3 cm) or long-segment proton pump inhibitor is the initial management. (>3 em). Long segments are at a higher risk for cancer progres- ¢ The diagnostic criteria for eosinophilic esophagitis are sion than are short segments. esophageal symptoms (most commonly dysphagia), Barrett esophagus progresses along a continuum: intesti- esophageal biopsy specimens showing persistent eosin- nal metaplasia, indefinite for dysplasia, low-grade dysplasia, ophil counts of 15/hpf or greater, and exclusion of other high-grade dysplasia, intramucosal carcinoma, and, finally, causes of eosinophilia. invasive adenocarcinoma. The stage informs surveillance and HVC * Candida esophagitis can be diagnosed clinically on the treatment recommendations (Table 4). basis of compatible symptoms, such as dysphagia and In patients with Barrett esophagus, medical therapy oral candidiasis. should be used to treat reflux symptoms and to heal reflux ¢ Herpes simplex virus and cytomegalovirus esophagitis esophagitis. No strong evidence suggests that antireflux are seen in immunodeficient or immunosuppressed surgery can prevent progression of Barrett esophagus to individuals; endoscopy with biopsy is needed to confirm adenocarcinoma when compared with medical therapy

¢ Herpes simplex virus and cytomegalovirus esophagitis esophagitis. No strong evidence suggests that antireflux are seen in immunodeficient or immunosuppressed surgery can prevent progression of Barrett esophagus to individuals; endoscopy with biopsy is needed to confirm adenocarcinoma when compared with medical therapy the diagnosis. with PPIs. Endoscopy-based therapies for patients with confirmed e Treatments for achalasia include botulinum toxin injec- dysplasia include endoscopic mucosal resection for all visible tion, pneumatic dilation, and surgical myotomy; botuli- lesions and radiofrequency ablation; experience with other num toxin injection is associated with high relapse rates. ablative methods, such as cryotherapy, is growing.

Disorders of the Esophagus Risk Factors Risk factors for adenocarcinoma include male sex, older age, GERD, Barrett esophagus, obesity, and tobacco use. Risk factors for squamous cell carcinoma include tobacco and alcohol use, caustic injury, achalasia, past thoracic radiation, nutritional deficiencies (zinc, selenium), poor socioeconomic status, poor oral hygiene, nonepidermolytic palmoplantar keratoderma (an autosomal dominant disorder associated with yellow wax-like hyperkeratosis on the palms and soles, also known as tylosis), human papillomavirus infection, and nitrosamine exposure.

Risk Factors Risk factors for adenocarcinoma include male sex, older age, GERD, Barrett esophagus, obesity, and tobacco use. Risk factors for squamous cell carcinoma include tobacco and alcohol use, caustic injury, achalasia, past thoracic radiation, nutritional deficiencies (zinc, selenium), poor socioeconomic status, poor oral hygiene, nonepidermolytic palmoplantar keratoderma (an autosomal dominant disorder associated with yellow wax-like hyperkeratosis on the palms and soles, also known as tylosis), human papillomavirus infection, and nitrosamine exposure. Diagnosis and Staging The most common initial presentation of esophageal carcinoma is dysphagia with solid foods, but asymptomatic individuals have been diagnosed according to surveillance endoscopic find- ings. Other symptoms include weight loss, anorexia, anemia (secondary to gastrointestinal bleeding), and chest pain. Upper endoscopy with biopsy is the preferred diagnostic test. Squamous cell carcinoma is most commonly located in the proximal esophagus, and adenocarcinoma is usually found in the distal esophagus.

Diagnosis and Staging The most common initial presentation of esophageal carcinoma is dysphagia with solid foods, but asymptomatic individuals have been diagnosed according to surveillance endoscopic find- ings. Other symptoms include weight loss, anorexia, anemia (secondary to gastrointestinal bleeding), and chest pain. Upper endoscopy with biopsy is the preferred diagnostic test. Squamous cell carcinoma is most commonly located in the proximal esophagus, and adenocarcinoma is usually found in the distal esophagus. FIGURE 7. Upper endoscopic view of Barrett mucosa (salmon-colored) versus TNM staging is often done with endoscopic ultrasonogra- normal squamous mucosa (pink-colored). phy for locoregional disease and with CT and PET to identify metastatic disease. For treatment of esophageal carcinoma, see MKSAP 19 Oncology. Esophageal Carcinoma Superficial tumors that are limited to the mucosal lining Epidemiology (T1a), show no evidence of lymph node metastasis, and have The global incidence of esophageal cancer varies widely; high- low-risk features in terms of differentiation and lymphovascu- prevalence areas include Asia and southern and eastern Africa. lar invasion may be treated with endoscopic resection in an The two types of esophageal carcinoma are squamous cell organ-sparing manner. carcinoma and adenocarcinoma. Worldwide, squamous cell carcinoma makes up about 90% of all esophageal cancers; however, the incidence has been decreasing, whereas the inci- e Barrett esophagus is a precursor cancer lesion caused by dence of adenocarcinoma has been rising. Esophageal cancer long-standing gastroesophageal reflux disease (GERD). occurs in the fifth to seventh decades of life and is three to four ¢ Routine screening for Barrett esophagus in patients with times more common in men. In the United States, about GERD symptoms is not recommended but should be 16,000 new cases are reported annually, with 15,000 deaths considered in men older than 50 years with GERD symp- occurring in the same year. The overall 5-year survival rate toms for more than 5 years and additional risk factors. ranges from 15% to 25%, depending on the cancer stage at (Continued) initial presentation.

FIGURE 7. Upper endoscopic view of Barrett mucosa (salmon-colored) versus TNM staging is often done with endoscopic ultrasonogra- normal squamous mucosa (pink-colored). phy for locoregional disease and with CT and PET to identify metastatic disease. For treatment of esophageal carcinoma, see MKSAP 19 Oncology. Esophageal Carcinoma Superficial tumors that are limited to the mucosal lining Epidemiology (T1a), show no evidence of lymph node metastasis, and have The global incidence of esophageal cancer varies widely; high- low-risk features in terms of differentiation and lymphovascu- prevalence areas include Asia and southern and eastern Africa. lar invasion may be treated with endoscopic resection in an The two types of esophageal carcinoma are squamous cell organ-sparing manner. carcinoma and adenocarcinoma. Worldwide, squamous cell carcinoma makes up about 90% of all esophageal cancers; however, the incidence has been decreasing, whereas the inci- e Barrett esophagus is a precursor cancer lesion caused by dence of adenocarcinoma has been rising. Esophageal cancer long-standing gastroesophageal reflux disease (GERD). occurs in the fifth to seventh decades of life and is three to four ¢ Routine screening for Barrett esophagus in patients with times more common in men. In the United States, about GERD symptoms is not recommended but should be 16,000 new cases are reported annually, with 15,000 deaths considered in men older than 50 years with GERD symp- occurring in the same year. The overall 5-year survival rate toms for more than 5 years and additional risk factors. ranges from 15% to 25%, depending on the cancer stage at (Continued) initial presentation. TABLE 4. Practice Guidelines for Endoscopic Surveillance and Treatment of Barrett Esophagus

FIGURE 7. Upper endoscopic view of Barrett mucosa (salmon-colored) versus TNM staging is often done with endoscopic ultrasonogra- normal squamous mucosa (pink-colored). phy for locoregional disease and with CT and PET to identify metastatic disease. For treatment of esophageal carcinoma, see MKSAP 19 Oncology. Esophageal Carcinoma Superficial tumors that are limited to the mucosal lining Epidemiology (T1a), show no evidence of lymph node metastasis, and have The global incidence of esophageal cancer varies widely; high- low-risk features in terms of differentiation and lymphovascu- prevalence areas include Asia and southern and eastern Africa. lar invasion may be treated with endoscopic resection in an The two types of esophageal carcinoma are squamous cell organ-sparing manner. carcinoma and adenocarcinoma. Worldwide, squamous cell carcinoma makes up about 90% of all esophageal cancers; however, the incidence has been decreasing, whereas the inci- e Barrett esophagus is a precursor cancer lesion caused by dence of adenocarcinoma has been rising. Esophageal cancer long-standing gastroesophageal reflux disease (GERD). occurs in the fifth to seventh decades of life and is three to four ¢ Routine screening for Barrett esophagus in patients with times more common in men. In the United States, about GERD symptoms is not recommended but should be 16,000 new cases are reported annually, with 15,000 deaths considered in men older than 50 years with GERD symp- occurring in the same year. The overall 5-year survival rate toms for more than 5 years and additional risk factors. ranges from 15% to 25%, depending on the cancer stage at (Continued) initial presentation. TABLE 4. Practice Guidelines for Endoscopic Surveillance and Treatment of Barrett Esophagus | Dysplasia Grade Recommendation | None If no dysplasia is present, repeat upper endoscopy every 3 to 5 years | | Indefinite Start or adjust proton pump inhibitor therapy, then repeat endoscopy in 3 to 6 months If still present, then repeat endoscopy in 1 year

| Dysplasia Grade Recommendation | None If no dysplasia is present, repeat upper endoscopy every 3 to 5 years | | Indefinite Start or adjust proton pump inhibitor therapy, then repeat endoscopy in 3 to 6 months If still present, then repeat endoscopy in 1 year | Low-grade Confirmation by expert pathologist. Start or adjust proton pump inhibitor therapy. Repeat endoscopy in 3 | | to 6 months to rule out a visible lesion that should prompt resection; with confirmed low-grade dysplasia, | endoscopic eradication therapy or annual surveillance endoscopy is an acceptable option High-grade Confirmation by expert pathologist Endoscopic eradication therapy is preferred Data obtained from Shaheen NJ, Falk GW, lyer PG, Gerson LB; American College of Gastroenterology. ACG clinical guideline: diagnosis and management of Barrett's esophagus. Am J Gastroenterol. 2016;111:30-50; quiz 51. [PMID: 26526079] doi:10.1038/ajg.2015.322; and Sharma P, Shaheen NJ, Katzka D, et al. AGA clinical practice update on endoscopic treatment of Barrett's esophagus with dysplasia and/or early cancer: expert review. Gastroenterology. 2020; 158:760-769. [PMID: 31730766] doi:10.1053/j.gastro.2019.09.051.