A 48-year-old man presents for evaluation of burning epigastric and substernal pain that has recurred almost daily for the past 4 months. He says that these symptoms seem to be worse when he lies down and after meals. He denies difficulty swallowing or weight loss. The patient has been taking a proton pump inhibitor (PPI) regularly over the past 12 weeks with partial resolution of his symptoms. His past medical history is significant for frequent early morning wheezing and hoarseness that have been present for the past few months. The patient has no other known medical problems, and he has had no prior surgeries. He consumes alcohol occasionally but does not use tobacco. On examination, he is moderately obese. No abnormalities are identified on the cardiopulmonary or abdominal examination.
What is the most likely diagnosis?
What are the mechanisms contributing to this disease process?
What are the complications associated with this disease process?
ANSWERS TO CASE 2: Gastroesophageal Reflux Disease
Summary: A 48-year-old man complains of a 4-month history of daily burning epigastric pain. It is worse after eating and lying down and minimally improved with the use of a PPI. He also has symptoms of reactive airway disease and hoarseness.
• Most likely diagnosis: Gastroesophageal (GE) reflux associated with silent aspiration and pharyngitis.
• Mechanisms contributing to this disease process: Diminished lower esophageal sphincter (LES) function, impaired esophageal clearance, excess gastric acidity, diminished gastric emptying, and abnormal esophageal barriers to acid exposure.
• Complications associated with the disease process: Peptic stricture, Barrett esophagus, and extraesophageal complications.
1. Learn the physiologic mechanisms that prevent the pathologic processes that lead to gastroesophageal reflux disease (GERD).
2. Learn a rational diagnostic and therapeutic approach to suspected GERD.
This patient’s history of substernal chest pain associated with meals is typical for GERD. Hoarseness and wheezing are atypical symptoms that may be related to pharyngeal reflux with silent aspiration. Evaluation by an otolaryngologist may be needed to rule out oropharyngeal and vocal cord pathology.
One of the most concerning features in the history is the lack of response to the PPI, which produces symptoms relief in more than 95% of treated patients; therefore it is extremely important to confirm the diagnosis of GERD and to rule out other pathology. Endoscopy should be performed. A 24-hour pH monitoring, while the patient is off medication, is appropriate to correlate the symptoms with episodes of reflux and quantify the severity of the reflux. Pharyngeal pH monitoring, which measures proximal esophageal acid exposure, may help support a diagnosis of silent aspiration.
Although H2 blockers can provide symptomatic relief for mild reflux, PPIs are far more effective for the relief of GERD symptoms. Patients with extraesophageal symptoms and pharyngeal reflux are generally less responsive to medical treatment than patients with typical GERD symptoms. Surgical therapy is an alternative to medical therapy and may be considered if the patient does not respond to medical therapy, cannot tolerate the medications, or prefers surgical intervention. Patients with GERD symptoms that do not resolve with high-dose PPI treatment are a difficult subset of patients from the management standpoint because their symptoms could be due to motility disorders and/or excessive visceral pain responses to acid exposure; therefore, it is important to communicate to the patients that surgical fundoplication could produce less favorable results.
APPROACH TO: Gastroesophageal Reflux Disease
GASTROESOPHAGEAL REFLUX DISEASE: May include typical symptoms of heartburn caused by acid regurgitation from the stomach into the distal esophagus. Alternatively, patients also may present with atypical symptoms that include pulmonary symptoms such as reactive airway, chronic cough, and silent aspiration.
BARRETT ESOPHAGUS: Replacement of the normal squamous epithelium of the distal esophagus with columnar epithelium with intestinal metaplasia, which places the patient at risk for esophageal adenocarcinoma.
MANOMETRY AND pH MONITORING: Combined procedure in which a small electronic pressure transducer is swallowed by the patient to be positioned in the vicinity of the LES. The most commonly used pH monitor involves a 24-hour ambulatory device that measures pH at 5 cm above the LES.
Occasional GE reflux, or heartburn, occurs in approximately 20% to 40% of the adult population. Not all patients with typical GERD-like symptoms have reflux (60%); therefore, it is important to look for alternative causes of symptoms in patients with atypical symptoms or inappropriate response to PPI. Patients with long-standing GERD may develop complications such as peptic strictures, Barrett esophagus, and extraesophageal complications. Barrett esophagus is associated with an increased risk for esophageal adenocarcinoma. Extraesophageal complications, postulated to be caused by pharyngeal reflux and silent aspiration, include laryngitis, reactive airway disease, recurrent pneumonia, and pulmonary fibrosis.
Normal physiologic mechanisms are important in preventing abnormal GE reflux. For example, abnormalities in the resting pressure, intra-abdominal length, or number of relaxations of the LES can contribute to abnormal reflux. The LES normally serves as a zone of increased pressure between the positive pressure in the stomach and the negative pressure in the chest. A hypotensive or incompetent LES can result in increased reflux. The crural diaphragm, which is attached to the esophagus by the phrenoesophageal ligament, also contributes to the normal barrier against reflux. When the LES is abnormally located in the chest, as with a hiatal hernia, the antireflux mechanism may be compromised at the GE junction. Also, the esophagus normally undergoes transient relaxations, but patients with abnormal GERD experience an increased number and duration of relaxations. Other potential contributory factors include excess acid production, abnormal esophageal clearance of acid, delayed gastric emptying, and decreased mucosal resistance to acid injury.
Patients with self-limiting or mild GERD symptoms do not automatically require further workup. Those with long-standing or atypical symptoms (wheezing, cough, hoarseness), recurrence of disease after the cessation of medical therapy, or unrelieved symptoms when taking maximal-dose PPIs should undergo diagnostic testing to confirm the diagnosis and to rule out complications of GERD. Also, patients being considered for a surgical antireflux procedure should undergo further evaluation. Although not all surgeons routinely perform all four studies, a standard workup prior to a surgical antireflux procedure includes endoscopy, manometry, 24-hour pH probe testing, and barium esophagography (Table 2–1).
Table 2–1 • DIAGNOSIS OF GASTROESOPHAGEAL REFLUX DISEASE
The initial treatment of patients with GERD consists of lifestyle modifications (Table 2–2) and medications as needed. For patients with esophagitis or frequent symptoms, the mainstay of treatment is acid suppression therapy with PPI. High-dose PPI therapy is often required for severe symptoms or refractory esophagitis. Most patients with frequent severe GERD symptoms will likely need lifelong high-dose PPI therapy. A lack of any symptomatic relief with PPIs suggests the possibility of an alternative diagnosis.
Table 2–2 • TREATMENT OF GASTROESOPHAGEAL REFLUX DISEASE
Some of the newer pharmacologic treatments currently under investigation for patients with refractory GERD include medications to improve LES pressures and reduce occurrence of transient LES relaxation, medications to modulate visceral pain receptor responses to acid exposure, and medications to improve esophageal mucosal protection.
Surgical therapy is an alternative to medical therapy and should be considered in patients with documented GERD who have persistent symptoms when taking maximal doses of PPI. Although several antireflux operations are available, the standard operation is laparoscopic Nissen fundoplication, which involves performing a 360-degree wrap of the fundus of the stomach around the GE junction to create a valve effect (Figure 2–1). Long-term success with antireflux surgery exceeds 90%. Two newer endoscopic endoluminal techniques have been developed to treat reflux: delivery of radiofrequency energy to the GE junction and endoluminal suturing of the GE junction. Further prospective data are required for these newer procedures.
Figure 2–1. Nissen fundoplication. The fundus of the stomach is wrapped around the distal esophagus and sutured.
A problem that has limited the broader application of operative fundoplication such as the Nissen fundoplication is that over half of the patients develop recurrent GI symptoms postoperatively, which often requires the patients to remain on PPI or H2 blockers for symptomatic relief. Unfortunately, the cause of the problem is not completely understood at this time.
2.1 A 62-year-old man with congestive heart failure (CHF) and emphysema has symptoms of substernal chest pain and regurgitation after meals and at bedtime. He obtains incomplete relief of his symptoms with ranitidine. An endoscopy confirms mild esophagitis. Which of the following is the most appropriate next step?
A. Reassure him that continued occurrence of symptoms while receiving therapy is normal.
B. Prescribe omeprazole 20 mg per day.
C. Schedule him for 24-hour pH monitoring, manometry, and a barium esophagogram for further evaluation.
D. Schedule him for a laparoscopic Nissen fundoplication.
E. Recommend dietary changes.
2.2 A 51-year-old woman has a 6-month history of substernal chest pain and vague upper abdominal discomfort. She has been taking antacid therapy with minimal relief and has had a negative upper endoscopy. Which of the following is the best next step in her workup?
A. Barium esophagogram to evaluate for a hiatal hernia
B. Performing manometry to rule out a motility disorder such as diffuse esophageal spasm or achalasia
C. Referring the patient for cardiac workup as a potential cause of her chest pain
D. Referring to a psychiatrist for a possible conversion reaction
E. Performing a CT of the chest and abdomen
2.3 A 45-year-old man has had a diagnosis of GERD for 3 years with treatment with H2-blocking agents. Recently, he has complained of epigastric pain. An upper endoscopy was performed showing Barrett esophagus at the distal esophagus. Which of the following is the best next step in the treatment of this individual?
A. Initiate a PPI.
B. Advise the patient to continue to take the H2 blocker.
C. Perform a laparoscopic Nissen fundoplication.
D. Advise surgical therapy involving gastrectomy and esophageal bypass.
E. Discontinue the H2 blocker and initiate antacids.
2.4 A 24-year-old man with long-standing GERD, currently taking PPIs, is being evaluated for possible surgical therapy. Which of the following is an indication for surgery?
A. Inability to tolerate PPIs
B Inability to afford PPIs
C. Incomplete relief of symptoms despite a maximum dosage of medical therapy
D. The patient’s desire to discontinue medication
E. All of the above
2.1 B. Given the patient’s comorbidities (CHF and emphysema), he is not a good candidate for surgical therapy. An important piece of this patient’s history is his history of partial relief with H2 blocker as opposed to no response at all; therefore, this history suggests that the diagnosis of GERD is a correct one and the patient may simply need to have escalation of GERD treatment. This patient should be switched to a PPI because the relapse rate associated with H2 blockers is much higher than that associated with PPI.
2.2 C. When chest or epigastric pain does not respond to antacid therapy, and especially with a negative upper endoscopy, etiologies other than GERD (such as cardiac pain) should be considered. This patient’s history qualifies as atypical chest pain and may benefit from an exercise stress test. Documentation of a hiatal hernia does not necessarily correlate causally to her symptoms. Cardiac disease would be the most concerning disease, and that is why this disorder should be ruled out first. CT of the abdomen and chest may be helpful to identify other potential anatomic causes of her chest and abdominal pain but should only be done after appropriate cardiac evaluations.
2.3 A. The next step in medical therapy for GERD is the addition of a PPI, which is a more effective medication for GERD. The patient has been symptomatic and developed Barrett esophagitis on an H2blocker, and therefore additional therapy is needed for relief of symptoms and to decrease the progression of the Barrett esophagitis to adenocarcinoma. An antireflux surgery (such as the Nissen fundoplication) is an option but not gastrectomy and esophageal bypass. In general, most practitioners would elect to place the patient on the more appropriate medical treatment at this time rather than proceed with fundoplication. This patient also needs endoscopic surveillance of the Barrett esophagus.
2.4 E. The indications for surgery are relative and determined in part by the patient; thus, inability to tolerate, inability to pay for, or a desire to discontinue medical therapy is a consideration for operative management.
Diagnostic endoscopy should be performed when patients have longstanding GERD symptoms and when their symptoms are refractory to medical treatment.
The long-term efficacy of PPI and antireflux operations in reducing esophageal cancer development appears to be equivalent.
Adenocarcinoma of the esophagus is a complication of long-standing GERD.
Surgical therapy for GERD is indicated in patients with documented GERD who have persistent symptoms while taking maximal dose PPIs, cannot tolerate PPIs, or do not wish to take lifelong medications.
The response to PPI is one of the most reliable clinical indicators of GERD.
A 24-hour pH monitoring is the most reliable objective indicator of GERD.
Armstrong D, Sifrim D. New pharmacologic approaches in gastroesophageal reflux disease. Gastroenterol Clin North Am. 2010;39:393-418.
Bhanot P, Soper NJ. Gastroesophageal reflux disease. In: Cameron JL, ed. Current Surgical Therapy. 9th ed. Philadelphia, PA: Mosby Elsevier; 2008:34-41.
Jobe BA, Hunter JG, Peters JH. Esophagus and diaphragmatic hernia. In: Brunicardi FC, Andersen DK, Billiar TR, et al, eds. Schwartz’s Principles of Surgery. 9th ed. New York, NY: McGraw-Hill; 2010: 803-887.
Spechler SJ, Lee E, Ahnen D, et al. Long-term outcome of medical and surgical therapies for gastroesophageal reflux disease: follow-up of a randomized controlled trial. JAMA. 2001;285:2331-2338.