• CASE 2

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 hut 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 Retlux 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 improves slightly with the use of a PPI. He also has symptoms of reactive airway disease and hoarseness.

• Most likely diagnosis: Gastroesophageal 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’s esophagus, and extraesophageal complications.

Analysis

Objectives

1. Describe the physiologic mechanisms that prevent and the pathologic processes that lead to gastroesophageal reflux disease (GERD).

2. Understand a rational diagnostic and therapeutic approach to suspected

GERD.

Considerations

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 alarming features in the history is the lack of response to the PPI, which produces symptoms relief in >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 I-I, blockers can provide symptomatic relief for mild reflux, PPI is far more effective for the relief of GERD symptoms. However, patients with extraesophageal symptoms and pharyngeal reflux may be less responsive to medical treatment. 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.

APPROACH TO GASTROESOPHAGEAL

REFLUX DISEASE

Definitions

Gastroesophageal reflux disease: Symptoms of heartburn caused by acid regurgitation from the stomach into the distal esophagus.

Barrett’s 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.

Nianornetry 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 measure pH at 5 cm above the LES.

Clinical Approach

Occasional gastroesophageal retlux, or heartburn, occurs in approximately 20% to 40% of the adult population. However, abnormal GERD occurs in only

60% of patients with reflux symptoms. Patients with long-standing GERD may develop complications such as peptic strictures. Barrett’s esophagus, and extraesophageal complications. Barrett’s esophagus is associated with an increased risk for esophageal adenocarcinoma. Extraesophageal coniplications, postulated to be caused by pharyngeal reflux and silent aspiration, include laryngitis, reactive airway disease, recurrent pneumonia, and pulmonary fibrosis.

Pathophysiology

Normal physiologic mechanisms are important in preventing abnormal gastroesophageal reflux. For example, abnormalities in the resting pressure, intraabdominal length. or number of relaxations of the LES can contribute to abnormal retlux. 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 gastroesophageal (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.

Workup Patients with self-limiting or mild GERD symptoms do not automatically require a 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 aritireflux 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, inanometry, 24-hour pH probe testing, and barium esophagography (Table 2—I).

Treatment 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 syniptoms 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 PPls suggests the possibility of an alternative diagnosis.

Surgical therapy is an alternative to medical therapy and indicated in patients with documented GERD who have persistent symptoms when taking maximal-dose PPIs, are intolerant to PPIs, or who do not wish to take lifelong medications. 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.

Table 2—1

DIAGNOSIS OF GASTROESOPHAGEAL REFLUX DISEASE

Endoscopy

Evaluates for erosive esophagitis or Barrett’s esophagus, or alternative pathology. Biopsy for suspected dysplasia or malignancy.

Barium esophagogram

Identifies the location of the gastroesophageal junction in relation to the diaphragm.

Identifies a hiatal hernia or shortened esophagus.

Evaluates for gastric outlet obstruction (in which

case fundoplication is contraindicated).

Can demonstrate spontaneous reflux.

pH monitoring for 24 h

Correlates symptoms with episodes of reflux. Quantitates reflux severity.

Pharyngeal pH monitoring

Correlates respiratory symptoms with abnormal pharyngeal acid exposure.

Manometry

Evaluates the competency of the lower esophageal sphincter.

Evaluates the adequacy of peristalsis prior to planned antireflux surgery. Partial fundoplication may be indicated if apcristalsis is noted. Can diagnose motility disorders such as achalasia or diffuse esophageal spasm.

Nuclear scintigraphy

May confirm retlux if pH monitoring cannot be performed.

Evaluates gastric emptying.

Table 2—2

TREATMENT OF GASTROESOPHAGEAL REFLUX DISEASE

Behavioral therapy

Avoidance of caffeine, alcohol, and

high-fat metals

Avoidance of meals within 2—3 h of bedtime

Elevation of the head of the bed

Weight loss in obese individuals

Smoking cessation

Medical therapy

Antacids

H, blockers

Proton pump inhibitors

Prokinetic agents

Surgical therapy

Laparoscopic or open antireflux procedure

Endoscopic therapy

Radiofrequency energy directed to the

gastroesophageal junction

Endoscopic endoluminal gastroplication

Comprehension Questions

12.1] A 62-year-old man with congestive heart failure 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 a PH.

C. Schedule him for 24-hour pH monitoring. manometry. and a barium esophagogram for further evaluation.

0. Schedule him for a laparoscopic Nissen fundoplication.

[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 manornetry 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

[2.3] A 45-year-old man has had a diagnosis of GERD for 3 years with treat

ment with H, blocking agents. Recently. he has complained of epigastric

pain. An upper endoscopy was performed showing Barrett’s 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 H, blocker.

C. Advise surgical therapy involving gastrectomy and esophageal bypass.

D. Discontinue the H, 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 PPls

B. Incomplete relief of symptoms despite a maximum dosage of medical therapy

C. The patient’s desire to discontinue medication

D. All of the above

Answers

[2.1] B. Given the patient’s comorbidities, he is not a good candidate for sur

gical therapy. Patient should be switched to a PPI because the relapse

rate associated with H, blockers is much higher than those 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. Documentation of a

hiatal hernia does not necessarily correlate causally to her symptoms.

[2.31 A. The next step in medical therapy for GERD is the addition of a PPI.

The patient has been symptomatic and developed Barrett’s esophagitis

on an H, blocker, and therefore additional therapy is needed for relief

of symptoms and to decrease the progression of the Barrett’s esophagi

tis to adenocarcinoma. An antireflux surgery (such as the Nissen

fundoplication) is an option but not gastrectomy and esophageal

bypass. This patient also needs endoscopic surveillance of the Barrett’s

esophagus.

[2.4] D. The indications for surgery are relative and determined in part by

the patient: thus, inability to tolerate or a desire to discontinue medical

therapy is a consideration for operative management.

CLINICAL PEARLS

Diagnostic endoscopy should be performed when patients have longstanding GERD symptoms and when patients’ symptoms are refractory to medical treatment.

The long-term efficacy of PPI and antiretlux 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.