Chapter 31 Esophageal Disorders
Clinical Case Problem 1: A 33-Year-Old Man with Substernal and Retrosternal Pain and Hypertension
Select the best answer to the following questions
1. Which of the following must be considered in the differential diagnosis of this patient’s problem?
2. Given the history and physical examination, which of the following conditions is (are) most likely responsible for the symptoms noted?
3. What is the major pathophysiologic mechanism underlying the chronic symptoms described in this case?
4. Which of the following is not an acceptable treatment of gastroesophageal reflux disease (GERD)?
5. Which of the following is not associated with severe chronic GERD?
Clinical Case Problem 2: A 68-Year-Old Man Who Finds Swallowing Difficult
Vital signs are normal. No abnormalities are discerned on physical examination.
6. Which of the following is the least likely cause of his dysphagia?
7. Which of the following is (are) not true concerning malignant dysphagia?
Answers
1. f. All choices should be considered.
2. e. It is most important to rule out myocardial ischemia with further testing, including blood analysis of cardiac enzymes or troponins and perhaps hospitalization and an exercise stress test. However, the most likely cause of the symptoms described is GERD complicated by anxiety brought about by job-related stress coupled with his fresh chest pain. When he awoke, his underlying anxiety was increased because of chest pain. This raised his blood pressure, inducing a feeling of heaviness in his chest, further raising his anxiety level to that of panic, which in turn further increased his blood pressure. The nitroglycerin helped break this vicious circle, allowing him to calm down, to think more rationally, and to remember past symptoms, which included a history of probable GERD. Although a final diagnosis cannot be made on the basis of the described symptoms alone, the absence of abnormal cardiac examination findings and the normal ECG point away from heart problems. Moreover, a number of factors point toward GERD as an underlying cause, including (1) the relatively high prevalence of GERD in the population (in one study, 25% to 40% of adults were found to be affected at least monthly and 7% to 10% daily), (2) his history of acid reflux symptoms relieved by antacids, and (3) his indulgence in “comfort eating” of GERD-inducing foods the previous night. In addition, the stress of being laid off and a night of poor sleep made conditions ripe for onset of his symptoms.
Although GERD is usually manifested as heartburn, a sizable minority report chest pain with minimal or no burning sensation, making diagnosis more difficult. Others report hoarseness or even shortness of breath as the presenting symptom. Peptic ulcer can produce aching discomfort in the upper abdomen or lower chest and thus must be included in the differential. However, it rarely is described as retrosternal pain radiating to the neck; moreover, eating generally relieves, not worsens, symptoms. Panic disorder is also a consideration. Further history is necessary to rule this out.
3. a. The most common cause of acid reflux is a transient relaxation of the LES. However, permanent relaxation and increased abdominal pressure that overcomes the LES may also be causative factors. Transient relaxation may be caused by foods (chocolates, coffee and other sources of caffeine, alcohol, fatty meals, and peppermint or spearmint), drugs (beta blockers, nitrates, calcium channel blockers, and anticholinergics), and smoking (nicotine).
In addition to relaxation of the LES, other potential precipitants are poor esophageal motility and delayed gastric emptying. Hiatal hernias are also found in high frequency in patients with symptoms of GERD. Achalasia is characterized by dysphagia, not by acid regurgitation. Although excess gastric acid may exacerbate symptoms, GERD can occur with normal acid secretion. Esophageal spasm can cause acid reflux, but it is a relatively rare condition and not a major mechanism.
Although some of the symptoms were due to anxiety, it was described as an acute attack, not a chronic condition.
4. d. The prokinetic motility agents are generally inappropriate drugs of choice for treatment of GERD. Antacids or over-the-counter H2 antagonists coupled with certain lifestyle changes represent the most conservative line of treatment. The following lifestyle changes were found to be effective in an evidence-based review: weight loss and elevation of the head of the bed by approximately 6 inches. Commonsense measures are to avoid lying down after meals, to avoid late night meals or midnight snacks, and to avoid tight-fitting clothes. Interestingly, commonly made recommendations, such as the avoidance of dietary irritants (e.g., fat, chocolate, caffeine, spearmint or peppermint, and alcohol), avoidance of drugs that lower LES pressure (e.g., calcium channel blockers, beta blockers, and theophylline), and discontinuation of tobacco use, had little effect on outcome. Nevertheless, if the patient encounters a pattern of known precipitants, such as use of antiinflammatory drugs, certainly recommend avoidance of the irritant.
If symptoms persist despite lifestyle changes, a PPI can be added to increase the pH of the material being regurgitated. Many patients have tried H2 receptor blockers before seeing the physician. H2 receptor blockers are available mostly without prescription: cimetidine (Tagamet), ranitidine (Zantac), nizatidine (Axid), and famotidine (Pepcid). The PPIs include omeprazole (Prilosec), lansoprazole (Prevacid), rabeprazole (Aciphex), esomeprazole (Nexium), pantoprazole (Protonix), and others. PPIs are more effective than H2 receptor antagonists but (with the exception of certain generics) cost more, even though they need to be taken only once a day. Although PPIs effectively reduce symptoms, they do so by reducing the gastric acidity, which may in the long term lead to other problems, such as reducing the ability to absorb vitamin B12 and to protect against ingested pathogens. Also, PPIs interfere with the bioavailability of many other drugs dependent on low gastric pH for absorption, such as digoxin and ketoconazole.
As in the case described, anxiety can provoke additional symptoms and can also exacerbate the gastric reflux symptoms. Supportive counseling and possibly the temporary addition of an anxiolytic can also be considered. Panic disorder should be ruled out.
Patients should be evaluated every 8 to 12 weeks, and if symptoms are alleviated, the dosage of the drug used may be decreased with the aim of titrating to the lowest possible dose and, ideally, eventual discontinuation. Should a relapse occur, treatment can be started again.
If patients do not have an adequate response to therapy, or for patients 50 years old or older, endoscopy should be considered because of the higher incidence of gastric malignant neoplasms and peptic ulcer disease.
5. d. Esophageal varices are a byproduct of portal hypertension, not esophageal reflux disease.
The potential pathologic sequence of events associated with chronic GERD is as follows: (1) the acid irritates the esophageal lining, causing inflammation and esophagitis; (2) the esophagitis can lead to ulcer and stricture formation, causing difficulty in swallowing; (3) chronic inflammation may also induce metaplasia and transformation of the cells lining the esophageal lumen, causing Barrett syndrome; and (4) Barrett syndrome esophageal cells can transform into malignant cells. Only approximately 5% of people with GERD develop Barrett syndrome, but once it is diagnosed, there is at least a 30-fold greater chance for development of a malignant neoplasm.
6. d. All listed choices are potential causes of dysphagia. An additional cause for consideration in this case is malignant dysphagia. Although it is not listed in this question, it is critical always first to rule out malignant change as a potential cause of even mild dysphagia because failure to diagnose and to start treatment of esophageal cancer in a timely manner is almost a certain death sentence. Moreover, the patient described in Clinical Case Problem 2 has several risk factors for esophageal cancer, including his age, sex, and smoking and drinking habits. (See answer 7 for further discussion.)
However, among the five conditions listed, pharyngeal paralysis is the least likely cause of dysphagia in the case described. This condition is produced by weakness and incoordination of the muscles in the pharynx that propel food into the esophagus. Both liquids and solids are difficult to swallow, and aspiration into the windpipe and regurgitation into the nose commonly occur. It is a result of faulty transmission of nerve impulses to the pharyngeal muscles generally caused by an associated neuromuscular disease, such as myasthenia gravis, amyotrophic lateral sclerosis, or stroke. No such neurologic condition was described.
Achalasia, meaning failure to relax, is a rare disorder with an incidence in the United States of approximately 1 per 100,000. It is caused by incoordination of the esophageal peristaltic muscles and the failure of the LES to relax due to a lack of inhibitory input from nonadrenergic, noncholinergic, ganglionic cells. As a consequence, food cannot pass into the stomach. The cause is not known, and swallowing of liquids and solids is affected. The most effective treatment is endoscopic dilation, including injection of botulinum toxin into the LES to block acetylcholine release, with the aim of restoring the balance between excitatory and inhibitory stimulation. A less effective but less abrasive treatment worth trying as the first line of treatment, particularly for elderly or other more fragile patients, is the use of medications that relax the LES. Calcium channel blockers or nitrates are the drugs of choice. However, such treatment is successful in only approximately 10% of the cases. If all else fails, the patient can be advised to hold his or her arms straight up in the air. This has been alleged to facilitate swallowing.
Diffuse esophageal spasm is characterized by multiple high-pressure, poorly coordinated esophageal contractions that usually occur after a swallow. The cause is unknown, and symptoms mimic GERD. However, if the cause is spasm, the symptoms will continue intermittently for a period of years and may become progressively worse. Esophageal dilation may provide relief. If not, surgery may be necessary.
A Schatzki ring is a diaphragm-like mucosal ring that forms at the esophagogastric junction (the B ring). If the lumen of this ring becomes too small, symptoms occur. The cause is not clear, but such rings are usually found in older individuals and have been observed in 6% to 15% of patients undergoing a barium swallow study; however, only 0.5% of those being examined have significant symptoms. Symptoms correlate with the size of the lumen of the ring: a lumen of more than 20 mm in diameter provides few if any symptoms; if it is less than 13 mm in diameter, chronic and more severe symptoms occur. Most patients have an intermittent, nonprogressive dysphagia for solid foods that occurs in consuming of a heavy meal with meat that was “wolfed down,” hence the pseudonym the “steakhouse syndrome.” Sometimes the meal is regurgitated, relieving the block, and eating can be resumed. Patients with a Schatzki ring are also at risk for GERD. A diagnosis is confirmed by radiographic barium swallow or endoscopic means, and if symptoms are sufficiently troublesome, the treatment of choice is rupture of the ring by dilation.
An esophageal stricture is a narrowing of the lumen of the esophagus preventing the passage of foods. Typically, it is at the distal end of the tube and is the result of scarring after chronic exposure to gastric juice due to GERD. Scarring and consequently stricture formation can also occur in response to other types of trauma, including swallowing of caustic solutions, chronic swallowing of pills without water, or residual scarring after surgery. Usual treatment is dilation.
7. e. Before 1970 in the United States, and still in many areas of the world, squamous cell carcinoma accounted for 90% to 95% of the cases of esophageal cancer. However, since that time, the relative incidence of adenocarcinoma has increased markedly in the United States; by the early 1990s, it accounted for approximately 50% of all cases. Currently, the proportion of adenocarcinomas is probably even higher.
In the United States, the incidence of all types of esophageal cancer is 3 to 6 cases per 100,000. It is more prevalent in males (male-to-female ratio is 7:1) and in African American males than in white males. It is generally diagnosed in the sixth or seventh decade.
Nonkeratinizing stratified epithelial squamous cells line the esophagus. Irritations of these cells and exposure to carcinogens cause a malignant transformation inducing a squamous cell carcinoma. Tobacco use and excess alcohol consumption account for most squamous cell cases and are the major modifiable risk factors in the United States. Other potential factors include nitrosamines and other nitrosyl compounds commonly found in smoked or pickled foods. In some environments, there are nitrosyl compounds in the water and certain mineral deficiencies lead to the accumulation of these compounds in ceratin food plants. Both events have been suggested to cause squamous cell carcinoma. It has also been reported that chronic ingestion of very hot liquids, very spicy foods, or other irritants promotes squamous cell tumors. Long-standing cases of achalasia or strictures as well as radiation and a host of other relatively uncommon factors have also been reported to induce squamous cell carcinomas, but squamous cell cancer does not arise from Barrett syndrome. A diet rich in fruits and vegetables seems to protect against this malignant neoplasm.
In contrast to the multiple causes of the squamous cell malignant neoplasms, adenocarcinomas arise from a well-characterized sequence. In response to chronic exposure to acid reflux, the normal stratified epithelium first becomes inflamed, and then metaplasia occurs and these columnar epithelial cells are transformed into a specialized glandular epithelium called Barrett epithelium. The Barrett epithelial cells can then undergo a progressive dysplasia from low to high grade and ultimately to adenocarcinoma. Most adenocarcinomas occur in the more distal parts of the esophagus because this area is more likely to be exposed to regurgitated acid.
Because very early symptoms are only a mild dysphagia, early cancers tend to be ignored. Unfortunately, both squamous cell carcinomas and adenocarcinomas are aggressive, and by the time the tumors have grown large enough to obscure the lumen and to produce severe symptoms, they also are likely to have grown through the esophageal wall and to have invaded other tissues. The fact that the esophageal wall is thin, composed of only two tissue layers, facilitates this escape. Because of this tendency to overlook early symptoms, many patients have a stage IV cancer at the time of diagnosis with a 5-year survival rate of only 5%; the overall 5-year survival rate at all stages is 20% to 25%, and it is the same for both squamous cell carcinoma and adenocarcinoma.
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