ESOPHAGEAL FUNCTION TESTING
The function of the esophagus is to facilitate the passage of food and drink to the stomach and to ensure that they stay there. Disorders of this function are complex and are caused by a variety of anatomic or intrinsic issues that can be measured and diagnosed with esophageal function tests. Esophageal dysfunction can be present at any level of the esophagus, although most patients evaluated by surgeons have issues with lower esophageal sphincter (LES) function. Common symptoms such as dysphagia, regurgitation, reflux, and pain prompt a diagnostic work up workup, and esophageal function tests are essential for optimal surgical intervention. A detailed history from patients with dysphagia is imperative; many patients suffer unnecessarily because physicians are unfamiliar with this topic.
This chapter provides a brief overview of commonly encountered esophageal function disorders and a review of the primary esophageal function tests used in their diagnosis.
DISORDERS OF ESOPHAGEAL FUNCTION
Gastroesophageal reflux disease (GERD) is a common disorder that often brings patients to medical attention for acid-suppressing medication. Chronic reflux, Barrett’s esophagus, stricture, and regurgitation of stomach contents into the mouth or pharynx are common symptoms that lead to surgical referral. The etiology with aspiration of the reflux or regurgitation can be complex and may be related to the amount and type of dietary consumption or to an anatomic problem, usually a hiatal hernia that alters the geometry of the gastroesophageal junction (GEJ). A mechanically defective LES is diagnosed when one of the anatomic components is abnormal (pressure, <6 mm Hg; total length, <2 cm; abdominal length, <1 cm). As one expects, the chance of GERD increases with the increasing number of defective components and is more than 90% when all three LES components are abnormal. The etiology and severity of reflux varies with every patient and can be investigated with pH studies, impedance testing, and motility or manometry studies. Newer technologies can combine these tests into one catheter.
Achalasia is the most common esophageal motility disorder and is defined as relaxation failure or incomplete relaxation of the LES accompanied by an absence of peristalsis in the esophageal body. The LES is hypertensive in about 50% and almost always shows a failure of normal relaxation of patients with achalasia. Patients need to know that although swallowing is improved after surgery or pneumatic dilation of the LES, it is never normal because of the abnormal peristalsis. The cause of achalasia remains unknown, but a decreased number of inhibitory ganglion cells is seen on pathologic review. An esophagram is a good screening test for a patient with dysphagia; the classic findings are a dilated esophagus with smooth tapering at the GEJ, to the classic “bird’s beak” appearance (Figure 1). The diagnosis of achalasia should always rule out pseudoachalasia, any condition that can masquerade as achalasia, such as a malignant disease. Endoscopic examination is an imperative part of this evaluation and usually shows some resistance at the GEJ, with a classic “popping” feeling as the scope passes into the stomach. Endoscopy can also include the placement of a wire to facilitate the passage of a manometric catheter, where blind passage proves difficult. Manometry is the gold standard for confirmation of the diagnosis and classically shows aperistalsis and incomplete relaxation of the LES after a swallow (Figure 2). Medical therapy can include calcium channel blockers, nitrates, and sildenafil. However, these are minimally effective. Endoscopic therapies include botulinum toxin and pneumatic dilation. Botulinum toxin is effective but only works for 3 to 6 months. Pneumatic dilation is slightly less effective than surgery, and many radiologists and gastroenterologists no longer are comfortable performing this procedure. Importantly, pneumatic dilation makes surgery considerably more difficult. Surgery involves a myotomy of the LES, which can usually be performed laparoscopically, from the stomach, across the LES, and well on to the esophagus. Some patients with end-stage achalasia and a dilated nonfunctional esophagus may need an esophagectomy.
Hypertensive Lower Esophageal Sphincter
Hypertensive LES is diagnosed when a patient has an LES pressure above the 95th percentile of normal and has symptoms of dysphagia or noncardiac chest pain. The exact value differs according to the method used for measurement, but this condition can only be diagnosed with manometry. In hypertensive LES, relaxation of the LES and peristalsis are present, unlike in achalasia.
Diffuse Esophageal Spasm
Diffuse esophageal spasm (DES) is an uncommon condition that accounts for less than 10% of esophageal motility abnormalities. DES is characterized by uncoordinated contractions of the esophagus that typically result in symptoms of chest pain, dysphagia, or both. The esophagram may be abnormal, but manometry is usually necessary for the diagnosis. Manometric findings, however, may not correlate with symptoms. DES is usually characterized by disordered rather than high pressure esophageal contractions.
Medical treatment options include nitrates and sildenafil and tri-cyclic antidepressants, which help with noncardiac chest pain. Valium and Ativan are also frequently effective if both the drugs fail to control symptoms. Use of proton pump inhibitors (PPIs) for treatment of concomitant GERD may also be helpful. A long myotomy can be effective in many patients with refractory DES but has a very high morbidity rate.
Hypercontractile “Nutcracker” Esophagus
Hypercontractile, or “nutcracker,” esophagus is a manometric diagnosis defined by high pressure (>180 mm Hg) or long duration of swallow responses (>7 seconds) in patients who have either chest pain or dysphagia (Figures 3 and 4). The peristaltic contractions propagate normally, and the LES relaxes appropriately. Diltiazem has been shown to lower distal peristaltic pressures and may reduce chest pain; however, these results are not reliably reproducible. As in DES, nitrates, sildenafil, PPIs, and tricyclic antidepressants may be useful in the treatment of noncardiac chest pain.
Ineffective Esophageal Motility
Ineffective esophageal motility is characterized by decreased distal esophageal peristaltic wave pressures (amplitudes <30 mm Hg) or an absence of esophageal contractions in more than 30% of wet swallows. A distinguishing feature between ineffective esophageal motility and achalasia is that resting LES pressure is typically decreased in ineffective esophageal motility. Systemic conditions, such as scleroderma, can be associated with ineffective esophageal motility. Unfortunately, no standard treatment options exist, besides PPIs and lifestyle modifications. Patients are advised to eat small meals, remain upright after eating, chew food well, and take acid-suppressing medication.
Nonspecific Esophageal Motility
Nonspecific esophageal motility disorder refers to an esophageal motility disorder that does not have features of a named motility disorder. These abnormalities are often not associated with dysphagia and are nonspecific. Examples of frequently encountered nonspecific esophageal motility disorders are triple-peaked and retrograde contractions. Systemic diseases such as diabetes mellitus, hypothyroidism, eosinophilic esophagitis, and amyloidosis can be associated with nonspecific esophageal motor abnormalities. These abnormalities may also be seen in patients with paraesophageal hernia who have a shortened esophagus.
The presence of a hiatal hernia alters the usual location and structure of the LES, displacing it into the negatively pressured thorax and disrupting the reinforcement offered by the diaphragmatic crura. The manometric profile often shows the LES and the crura and intra-abdominal stomach as having increased pressure, a “double hump.” High resolution manometry makes the diagnosis of hiatal hernia by manometry relatively easy. Manometry in paraesophageal hernias can be unpredictable depending on the anatomy of the hernia and the stomach because the esophagus may be shortened or of normal length. Manometry guides surgeons in repair of the hiatal hernia and helps them to choose the type of fundoplication to perform. Although a paucity of evidence is found, most esophageal surgeons avoid a complete wrap for patients with abnormal peristalsis and perform a partial, 180-degree, or 270-degree, fundoplication to prevent postoperative dysphagia.
DIAGNOSTIC TESTS FOR ESOPHAGEAL DISEASES
Radiographic tests of the esophagus include the fluoroscopic esophagram and cross-sectional imaging. An esophagram, or barium swallow, is often performed as a biphasic examination in which double or single contrast techniques are used and should always have a solid bolus administered as a 13 mm barium tablet. Liquid and solid contrast agents are used in most diagnostic tests for dysphagia. Because the act of swallowing is a dynamic process, the inclusion of video or cine recording is imperative for better assessment of oropharyngeal function and esophageal motility.
A properly conducted videoesophagram allows the physician to comment on oropharyngeal function, morphology of the esophagus, esophageal motility, appearance of the mucosal surface, evaluation of the GEJ, presence and degree of reflux, and efficiency of secondary wave clearance. A videoesophagram is sensitive for detection of certain motility disorders, such as achalasia (94%) and scleroderma (100%); however, it is relatively insensitive for detection of most other motility disorders. The decision of whether to obtain radiographic imaging before endoscopic examination or to proceed directly to esophagogastroduodenoscopy (EGD) can be difficult. The authors recommend a videoesophagram as the initial diagnostic test in conditions such as a suspected cricopharyngeal bar, esophageal web, diverticulum, Schatzki’s ring, early achalasia, or complex stricture, where an esophagram may provide the endoscopist a “road map.”
Cross-sectional imaging with computed tomographic (CT) scan is helpful for evaluation of extraluminal esophageal disease, including staging for esophageal cancer and evaluation of esophageal trauma. However, the videoesophagram is still the gold standard in evaluation for esophageal leak. CT scan is used in evaluation of esophageal changes of the wall, such as thickening, but is not accurate in the evaluation of esophageal mucosal disease or motility disorders. Magnetic resonance imaging can produce high-quality multiplanar images without use of ionizing radiation but has limited utility for most esophageal diseases because of motion artifact and long imaging times.
Although not strictly an esophageal function test, endoscopic examination is often necessary for evaluation or treatment for esophageal disorders. The authors routinely perform an on-table endoscopy before esophageal surgery because the surgeon is ultimately responsible for the diagnosis and treatment option selected. For example, endoscopic evaluation in achalasia rules out pseudoachalasia and can confirm the diagnosis with the characteristic “pop” on passing through the LES. For hiatal hernia surgery, it can identify Barrett’s esophagus, rule out early malignant disease of the stomach or esophagus that has been missed, and help identify the presence of a short esophagus that may need an esophageal lengthening procedure as part of the hernia repair.
Endoscopic evaluation for esophageal disorders begins with a good view of the vocal cords and aryepiglottic folds, which can appear inflamed in patients with chronic GERD. The upper esophageal sphincter (UES) consists of the cricopharyngeal muscle and is best seen on the final withdrawal of the endoscope. As the esophagus is entered, the mucosa can be carefully inspected for signs of mucosal inflammation or luminal irregularities, such as esophageal webs, rings, strictures, or esophagitis. Evaluation of the esophagus for distension or tonicity is also important because an atonic or patulous appearance may indicate the presence of a motility disorder.
At the level of the aortic arch, the striated muscle of the upper esophagus transitions to smooth muscle in the distal half of the esophagus. Patients with dysphagia should have random biopsies sampled from the distal and proximal esophagus for evaluation for eosinophilic esophagitis, particularly if the endoscopic examination shows the corrugated “feline” esophagus, with multiple concentric rings and linear furrows (Figure 5). In patients with longstanding GERD, the squamocolumnar junction proximal to the LES should be carefully inspected for signs of Barrett’s esophagus (Figure 6), which appears as intestinal mucosa, with a pinker or salmon-colored appearance. The length of the Barrett’s mucosa should be quantified, and multiple biopsies should be taken for assessment for dysplasia or malignancy.
The LES should really be called the LES complex because it is not one discrete muscle but rather a combination of esophageal muscle, phrenoesophageal ligament, and diaphragm. On endoscopy, it appears as a flap valve. Once the endoscope has entered the stomach, the endoscopist notes whether the gastric wall is poorly distensible and uses retroflex to examine the cardia and GEJ. The flap valve of the GEJ may be seen and assessed for competence under air pressure or for whether a hiatal hernia has expanded this area and allowed reflux and regurgitation.
Endoscopy offers multiple therapeutic maneuvers, from dilation to biopsy to botulinum toxin injection. Mucosal ablative techniques are also used for Barrett’s esophagus, and endoscopic ultrasound scan (EUS) has become the gold standard for the local and regional lymph node staging of esophageal cancer.
Esophageal manometry is the gold standard for assessment of esophageal motor function. It is the only modality that can define the pressure profile of peristalsis and measure LES pressure. Conventional manometry uses eight sensors, placed at various points of the esophagus, typically four in the esophageal body and four at the level of the GEJ. High-resolution manometry, specifically the Manoscan (Sierra Scientific Instruments, LLC, Los Angeles, Calif), is vastly superior and will replace older manometry equipment. High-resolution manometry provides a much clearer picture of esophageal pressure changes during swallowing and includes pressure monitors every centimeter along the catheter. This new technology offers the ability to simplify the procedural setup, eliminate motion artifact, simplify the ability to interpret data, and allow for a more sophisticated interpretation of esophageal motility. Indications for esophageal manometry are summarized in Box 1.
Box 1: Indications for esophageal manometry:
- Dysphagia: For the assessment of functional disorders after structural causes have been ruled out.
- Noncardiac chest pain: For assessment for esophageal dysmotility as a cause of symptoms.
- Diagnosis or confirmation of a suspected motility disorder.
- Preoperative assessment of esophageal motility before planned esophageal surgery.
- Postoperative assessment: For detection of response to surgery or confirmation of response to treatment or for assessment of the cause of persistent symptoms after surgery.
For conventional manometry, a solid-state or water-perfused catheter is used. The manometry catheter is swallowed until all of the sensors are in the stomach, and the catheter is then pulled back in increments of 0.5 to 1 cm for measurement of the resting pressure of the LES, esophageal body, and UES (Figure 7). Once the resting pressures have been calibrated, the catheter is positioned across the entire esophagus for recording of pressure changes during swallowing. The contraction and relaxation of the UES, the body of the esophagus, and the LES are recorded with 10 consecutive swallows of a 5-mL bolus of water. These pressure values are compared with standardized normal values (Figure 8; Table 1). Plotting of the pressure values with the passage of the water bolus down the esophagus allows for the detection of abnormal peristalsis and sphincter dysfunction. These patterns form the basis of esophageal dysmotility conditions.
The high-resolution manometry catheters have sensors every 1 cm. These catheters are able to span from the pharynx to the stomach, which obviates the need to retract the catheter to measure resting pressures. Pressure measurements are recorded both in the resting phase and for 10 swallows in a similar fashion to the olden equipment. However, these pressure measurements are displayed as a topographic pressure reading over time. A typical scan of a high-resolution swallow in achalasia is shown in Figure 9. This figure also shows impedance in magenta, as the catheter used included impedance monitoring. Figures 4 and 9 are also examples of high-resolution manometry.
Table 1: Normal LES parameters in 50 healthy volunteers.
Diagnostic Tests for Gastroesophageal Reflux
A surgeon performing a procedure for GERD should order four principal tests before performing a fundoplication or hiatal hernia repait First, an acid exposure test is used to document the presence of reflux because many patients with heartburn do not actually have GERD. Second, manometry is essential to ensure that esophageal dysmotility is not contributing to reflux as patients with dysmotility may not be able to clear physiologic reflux. Surgeons need to be careful when operating on patients with documented GERD and impaired motility because postoperative dysphagia can be a significant problem. A partial fundoplication or a floppy complete fundoplication may prevent dysphagia in these patients. Third, a barium swallow helps with identification of the presence and size of a hiatal hernia and may alert the surgeon to the presence of a short esophagus. A tension-free intra-abdominal GEJ at the end of the procedure is imperative, and a variety of esophageal lengthening procedures can be used if necessary. Finally, an EGD should be performed to rule out malignant disease and to identify Barrett’s esophagus in patients with severe GERD. The authors typically perform the EGD in the operating room at the same setting as the procedure.
Acid exposure in the esophagus is measured with an intraluminal pH probe with one of two methods: either an intraluminal tube with a nasopharyngeal catheter or a wireless Bravo pH probe (Medtronic, Minneapolis, Minn). Both methods provide the physician with similar data, particularly relating to the amount of time the esophagus is exposed to acid reflux. When the information is correlated with a symptom log, determination is possible of whether the patient’s symptoms are related to acid exposure within the esophagus. This information is commonly expressed with use of six standard parameters (Box 2) to calculate a DeMeester score, or a composite pH score. A score of less than 14.72 (95th percentile of normal) is considered physiologic reflux, whereas a score greater than 14.72 is considered abnormal. Acid exposure in the esophagus may be physiologic, and it is recorded according to the position of the patient (supine or upright) and the relation of acid exposure to meals. pH monitoring may also be used while the patient is on acid-suppressing therapy to determine whether there is adequate acid suppression with the current medication regimen. The data collected from each individual’s tests are compared with normal values derived from data from healthy volunteers. The Bravo probe is often preferred by patients for pH monitoring because it is placed at the time of upper endoscopy and does not require an extended time with a nasopharyngeal catheter. The Bravo probe is placed 5 cm above the LES and wirelessly transmits data to a recorder worn by the patient. It measures ph for 48 hours while a wired probe is worn for 24 hours which gives a larger sampling of ph changes in the esophagus and is more accurate.
Box 2: Measured parameters during 24-hour esophageal pH monitoring:
- Percent total time pH <4
- Percent upright time pH <4
- Percent supine time pH <4
- Number of reflux episodes
- Number of reflux episodes ≥5 minutes
- Longest reflux episode (in minutes)
Impedance monitoring measures bolus transport by measuring the resistance to electrical conductivity ofthe esophagus and its contents. Impedance testing is an important adjunct to traditional pH testing because it can be useful for patients taking PPIs and for evaluation of bile (nonacid) reflux. Impedance measurement works by using low AC voltage to apply an electrical potential between two electrodes on a catheter separated by an isolator. The circuit is then closed by the surrounding material spanning the electrodes. Because air, liquid, and esophageal mucosa have unique impedance characteristics, identification of the material that is bridging the electrodes is easy. Air is resistant to current flow and has a high impedance; liquid has a low impedance value. Esophageal tissue has an indeterminate range and is used as a baseline during monitoring. With multiple electrodes along a catheter system, identification of changes in impedance makes possible determination of the direction of bolus transport within the esophagus and identification of reflux of a bolus that has cleared the esophagus but comes back up from the stomach (Figure 10).
Multichannel intraluminal impedance (MII) is a new technology that incorporates impedance transducers for pressure measurement and a pH probe in one catheter. As a result, MII is used for the same indications as esophageal manometry and for detection and measurement of acid and nonacid reflux.
The diagnosis of esophageal function disorders can be made from a careful history and the use of appropriate diagnostic testing. Several tests are frequently needed for the thorough evaluation of these disorders. Surgeons must understand the utility of these tests to evaluate whether a patient is a good surgical candidate for intervention and to determine the best treatment for a particular patient. A surgeon who is not familiar with these tests is not able to achieve optimal outcomes in the management of complex esophageal disorders. The authors also stress the importance of close collaboration between the radiologist, gastroenterologist, and surgeon in evaluating and treating this complicated group of patients.
Kuo P, Holloway RH, Nguyen NQ: Current and future techniques in the evaluation of dysphagia, J Gastroenterol Hepatol 27(5):873-881, 2012.
Lacy BE, Weiser K, Chertoff J, et al: The diagnosis of gastroesophageal reflux disease, Am J Med 123(7):583-592, 2010.
Stein HJ, Barlow AP, DeMeester TR, et al: Complications of gastroesophageal reflux disease: role of the lower esophageal sphincter, esophageal acid and acid/alkaline exposure and duodenogastric reflux, Ann Surg 216:35—45, 1992.
Stein HK, DeMeester TR: Indications, technique and clinical use of ambulatory 24 hour esophageal motility monitoring in a surgical practice, Ann Surg 217:128-137, 1993.
Acknowledgment: The authors recognize Vinay Chandrasekhara, MD, and Sanjay Jagannath, MD, the authors of this chapter in the 10th edition, as they have revised and updated their excellent work.