GORD

Question 1

Compare and contrast physiological and pathological reflux.

Answer 1

Some degree of reflux is physiologic. Physiologic reflux episodes typically occur postprandially, are short-lived, asymptomatic, and rarely occur during sleep. Pathologic reflux is associated with symptoms or mucosal injury, often including nocturnal episodes.

Question 2

Compare and contrast GORD with reflux oesophagitis.

Answer 2

In general, the term gastroesophageal reflux disease (GERD) is applied to patients with symptoms suggestive of reflux or complications thereof, but not necessarily with esophageal inflammation. Reflux esophagitis describes a subset of patients with symptoms of GERD who also have endoscopic or histopathologic evidence of esophageal inflammation.

Question 3

How does the Montreal Working Group define ‘GORD’?

Answer 3

A consensus statement (the Montreal Classification) defines GERD as a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. According to the Montreal Working Group, heartburn is considered troublesome if mild symptoms occur two or more days a week, or moderate to severe symptoms occur more than one day a week.

Question 4

What is the prevalence of GORD?

Answer 4

GERD prevalence was found to be 10 to 20 percent in the Western world and less than 5 percent in Asia.

Question 5

What are the most common symptoms of GORD?

Answer 5

The most common symptoms of gastroesophageal reflux disease (GERD) are heartburn (pyrosis), regurgitation, and dysphagia.

Question 6

What other GIT-related symptoms may be caused by GORD? Elaborate a bit on each one.

Answer 6

Other symptoms of GERD include chest pain, water brash, globus sensation, odynophagia, and nausea.

●Patients with reflux-induced chest pain may also have typical reflux symptoms. However, heartburn is a poor predictor of whether patients with chest pain have evidence of GERD by objective reflux testing (eg, esophageal pH monitoring).
●Water brash or hypersalivation is a relatively unusual symptom in which patients can foam at the mouth, secreting as much as 10 mL of saliva per minute in response to reflux.
●Globus sensation is the almost constant perception of a lump in the throat (irrespective of swallowing), which has been related to GERD in some studies. However, the role of esophageal reflux in globus is uncertain. One study suggested that globus was associated with a hyper-reactive upper esophageal sphincter rather than with reflux.
●Odynophagia is an unusual symptom of GERD but, when present, usually indicates an esophageal ulcer.
●Nausea is infrequently reported with GERD, but a diagnosis of GERD should be considered in patients with otherwise unexplained nausea.

Question 7

What extra-oesophageal symptoms may be caused by GORD?

Answer 7

A variety of potential extraesophageal manifestations have also been described including bronchospasm, laryngitis, and chronic cough.

Question 8

What is typically found at endoscopy in a patient with GORD?

Answer 8

Upper endoscopy may be normal in patients with GERD, or there may be evidence of esophagitis of varying degrees. Other endoscopic findings in patients with longstanding GERD include peptic strictures, Barrett’s metaplasia, and esophageal adenocarcinoma.

Question 9

What is typically found on histology in patients biopsied for GORD? What does this likely represent?

Answer 9

The most consistently observed histologic finding in this study was dilation of the intercellular spaces seen on transmission electron microscopy. This finding is also present in patients with reflux esophagitis and eosinophilic esophagitis. The mild histologic findings noted in GERD represent the reparative capacity of the esophageal epithelium after cell damage due to acid exposure.

Question 10

How does one make a diagnosis of GORD?

Answer 10

The diagnosis of gastroesophageal reflux disease (GERD) can be based upon clinical symptoms alone. In patients presenting with any of the clinical manifestations described above, a presumptive diagnosis of GERD can be made.

Question 11

What, importantly, is not a diagnostic criterion for GORD?

Answer 11

Response to antisecretory therapy is not a diagnostic criterion for GERD. A meta-analysis of diagnostic test characteristics found that a response to proton pump inhibitors (PPIs) did not correlate well with objective measures of GERD such as ambulatory pH monitoring

Question 12

What are some conditions that should be considered in the differential diagnosis of GORD?

Answer 12

The differential diagnosis of gastroesophageal reflux disease (GERD) includes infectious esophagitis, pill esophagitis, eosinophilic esophagitis, peptic ulcer disease, non-ulcer dyspepsia, biliary tract disease, coronary artery disease, and esophageal motor disorders. Symptoms alone do not reliably distinguish among these disorders.

Question 13

Provide a rationale for additional investigations in the diagnosis/management of GORD.

Answer 13

The goal of additional testing is to confirm the diagnosis of gastroesophageal reflux disease (GERD) in patients refractory to therapy, assess for complications of GERD, or to establish alternative diagnoses.

Question 14

Which modalities are available for further evaluation of a patient with GORD? Give a broad/rough overview of their indications.

Answer 14

• Endoscopy:
  Endoscopy with biopsy should be done at presentation for patients with an esophageal GERD syndrome with troublesome dysphagia and to evaluate patients with a suspected esophageal GERD syndrome who have not responded to an empirical trial of twice-daily PPI therapy.
• Ambulatory pH monitoring
  Is useful for confirming gastroesophageal reflux disease in those with persistent symptoms (whether typical or atypical) who do not have evidence for mucosal damage on endoscopy, particularly if a trial of twice-daily PPI has failed or to monitor the adequacy of treatment in those with continued symptoms.
• Manometry is useful in ensuring that ambulatory pH probes are placed correctly, to evaluate peristaltic function before antireflux surgery, and to exclude major motor disorders as an alternative diagnosis in patients with chest pain and/or dysphagia.
• Biliary tract ultrasonography should be considered in patients with nausea and/or epigastric pain.
• Unexplained chest pain should be evaluated with at least an electrocardiogram and exercise stress test prior to a gastrointestinal evaluation.

Question 15

What are the two broad categories of endoscopic findings in GORD?

Answer 15

Erosive oesophagitis and nonerosive reflux disease.

Question 16

Outline the Los Angeles classification of oesophagitis.

Answer 16

The Los Angeles classification is the most thoroughly evaluated classification for esophagitis and is the most widely used.
●Grade A – one or more mucosal breaks each ≤5 mm in length.
●Grade B – at least one mucosal break >5 mm long, but not continuous between the tops of adjacent mucosal folds.
●Grade C – at least one mucosal break that is continuous between the tops of adjacent mucosal folds, but which is not circumferential.
●Grade D – mucosal break that involves at least three-fourths of the luminal circumference.

Question 17

Outline how biopsies should be taken in oesophagitis patients.

Answer 17

On upper endoscopy, biopsies should target any areas of suspected metaplasia, dysplasia, or, in the absence of visual abnormalities, normal mucosa (at least five samples to evaluate for eosinophilic esophagitis).

Question 18

List the oesophageal complications of GORD.

Answer 18

Erosive esophagitis, Barrett’s esophagus, esophageal stricture.

Question 19

List the extra-oesophageal complications of GORD.

Answer 19

Asthma, otolaryngologic complications (chronic laryngitis, laryngeal and tracheal stenosis), other (chronic cough, dental erosions, chronic sinusitis, and recurrent pneumonitis).

Question 20

Fully describe the indications for endoscopy in patients with GORD.

Answer 20

Upper endoscopy is not required in the presence of typical GERD symptoms of heartburn or regurgitation. We recommend an upper endoscopy if the diagnosis of GERD is unclear and in the following individuals:

●In patients with heartburn and alarm features to rule out complications of GERD and other diagnoses. Alarm features include dysphagia, odynophagia, gastrointestinal bleeding, anemia, weight loss, and recurrent vomiting.
●Patients with severe erosive esophagitis (Los Angeles classification Grade C and D) on initial endoscopy should undergo a follow-up endoscopy after a two-month course of proton pump inhibitor (PPI) therapy to assess healing and rule out Barrett’s esophagus. Repeat endoscopy after this follow-up examination is not indicated in the absence of Barrett’s esophagus unless patients have bleeding, dysphagia, or a significant change in symptoms while on effective therapy for GERD.
●To screen for Barrett’s esophagus in patients with multiple risk factors for esophageal adenocarcinoma, including chronic GERD, hiatal hernia, age ≥50 years, male gender, white race, elevated body mass index, and intra-abdominal body fat distribution.
●Patients with typical GERD symptoms that persist despite a therapeutic trial of four to eight weeks of twice-daily PPI therapy.

Question 21

What are the major therapeutic groups in GORD and what are the two basic approaches to therapy?

Answer 21

Those with mild and intermittent symptoms and those with severe or frequent symptoms or erosive oesophagitis.

Step-Up and step-down approaches.

Question 22

Describe the therapeutic approach to patients with mild and intermittent symptoms.

Answer 22

We suggest step-up therapy for GERD in patients with mild and intermittent symptoms (fewer than two episodes per week) who have no evidence of erosive esophagitis on upper endoscopy, if performed. We make incremental changes in therapy at two- to four-week intervals.

In patients who are naïve to treatment, we initially recommend lifestyle and dietary modification and, as needed, low-dose histamine 2 receptor antagonists (H2RAs). We suggest concomitant antacids as needed if symptoms occur less than once a week. For patients with continued symptoms despite these measures, we increase the dose of H2RAs to standard dose, twice daily for a minimum of two weeks.

Therefore, if symptoms of GERD persist, we discontinue H2RAs and initiate once-daily PPIs at a low dose and then increase to standard doses if required. Once symptoms are controlled, treatment should be continued for at least eight weeks.

Question 23

Outline the lifestyle and dietary measures used in the management of GORD.

Answer 23

●Weight loss for patients with GERD who are overweight or have had recent weight gain.
●Elevation of the head of the bed in individuals with nocturnal or laryngeal symptoms (eg, cough, hoarseness, throat clearing). We also suggest a corollary to this recommendation: refraining from assuming a supine position after meals and avoidance of meals two to three hours before bedtime.
●Dietary modification should not be routinely recommended in all patients with GERD. However, we suggest selective elimination of dietary triggers (fatty foods, caffeine, chocolate, spicy foods, food with high fat content, carbonated beverages, and peppermint) in patients who note correlation with GERD symptoms and an improvement in symptoms with elimination.

Question 24

Outline the use of antacids in the management of GORD.

Answer 24

As antacids do not prevent GERD, their role is limited to intermittent (on-demand) use for relief of mild GERD symptoms that occur less than once a week. Antacids usually contain a combination of magnesium trisilicate, aluminum hydroxide, or calcium carbonate, which neutralize gastric pH, thereby decreasing the exposure of the esophageal mucosa to gastric acid during episodes of reflux.

Question 25

Outline the use of H2RAs in the management of mild/intermittent GORD.

Answer 25

Histamine 2 receptor antagonists (H2RAs) decrease the secretion of acid by inhibiting the histamine 2 receptor on the gastric parietal cell. However, the development of tachyphylaxis within two to six weeks of initiation of H2RAs limits their use as maintenance therapy for GERD.

However, H2RAs have limited efficacy in patients with erosive esophagitis.

Question 26

Describe the therapeutic approach to the management of severe GORD.

Answer 26

We use step-down therapy in patients with erosive esophagitis, frequent symptoms (two or more episodes per week), and/or severe symptoms that impair quality of life in order to optimize symptom relief. We begin with standard-dose PPI once daily for eight weeks in addition to lifestyle and dietary modification.

We subsequently decrease acid suppression to low-dose PPIs and then to H2RAs if patients have mild or intermittent symptoms. We discontinue acid suppression in all asymptomatic patients with the exception of patients with severe erosive esophagitis or Barrett’s esophagus, in whom we suggest maintenance PPI therapy.

Question 27

Outline the use of PPIs in the management of severe GORD. Cover:

• Indications
• Mechanism of action
• Optimal dosing
• Efficacy

Answer 27

Proton pump inhibitors (PPIs) should be used in patients who fail twice-daily H2RA therapy and in patients with erosive esophagitis and/or frequent (two or more episodes per week) or severe symptoms of GERD that impair quality of life.

PPIs are the most potent inhibitors of gastric acid secretion by irreversibly binding to and inhibiting the hydrogen-potassium (H-K) ATPase pump. PPIs are most effective when taken 30 minutes before the first meal of the day because the amount of H-K-ATPase present in the parietal cell is greatest after a prolonged fast.

PPIs at standard doses for eight weeks relieve symptoms of GERD and heal esophagitis in up to 86 percent of patients with erosive esophagitis.

Question 28

Comment on the treatment of H. pylori infection in patients with GORD.

Answer 28

It is uncertain whether chronic acid suppression with PPIs increases the risk for atrophic gastritis in patients with H. pylori. Therefore, routine screening for H. pylori infection and empiric eradication of H. pylori are not recommended in patients with GERD.

Question 29

What percentage of patients relapse after first-line treatment?

Answer 29

Approximately two-thirds of patients with nonerosive reflux disease (NERD), and nearly all patients with erosive esophagitis (EE), relapse when acid suppression is discontinued.

Question 30

How is relapse treated?

Answer 30

Patients with recurrent symptoms should be managed with acid suppressive therapy with the medication and dose used to initially control symptoms.

In patients with recurrent symptoms three or more months after discontinuing acid suppression, we suggest repeated, eight-week courses of acid suppressive therapy, as needed. However, if recurrent symptoms occur within three months, we suggest an upper endoscopy to rule out complications of GERD and long-term maintenance therapy for acid suppression. For patients who require long-term PPI therapy, we suggest that the lowest effective dose be used.

Question 31

How should GORD be managed in pregnant/lactating women?

Answer 31

Initial management of gastroesophageal reflux disease (GERD) in pregnancy consists of lifestyle and dietary modification (eg, elevation of the head end of the bed, avoidance of dietary triggers). In patients with persistent symptoms, pharmacologic therapy should begin with antacids followed by sucralfate. In patients who fail to respond, similar to nonpregnant patients, histamine 2 receptor antagonists (H2RAs) and then proton pump inhibitors (PPIs) should be used to control symptoms.

Most antacids are considered safe in pregnancy and are compatible with breastfeeding. However, antacids containing sodium bicarbonate and magnesium trisilicate should be avoided in pregnancy.

Question 32

From when in pregnancy can endoscopy be considered?

Answer 32

Upper endoscopy should be performed during pregnancy only if there is a strong indication (eg, significant gastrointestinal bleeding). When possible, endoscopy should be postponed until the second trimester.

Question 33

What percentage of GORD patients fail therapy with a PPI?

Answer 33

Approximately 10 and 40 percent of patients with GERD fail to respond symptomatically, either partially or completely, to a standard dose PPI.

Question 34

What is the definition of PPI failure?

Answer 34

We suggest that lack of satisfactory symptomatic response to PPI once a day is sufficient to consider patients as PPI failures.

Question 35

What are the major drug factors in PPI failure?

Answer 35

Timing adherence (should be taken 30mins prior to meals) and compliance.

Question 36

What are the major factors non-drug factors in PPI failure?

Answer 36

Functional heartburn (most common) and reflux hypersensitivity, weakly acidic or alkaline reflux (non-acidic reflux), delayed gastric emptying (in those with risk factors).

Question 37

Describe functional heartburn.

Answer 37

According to the Rome IV criteria, a diagnosis of functional heartburn requires all of the following criteria be fulfilled for the last three months with symptom onset at least six months prior to the diagnosis:
●Burning retrosternal discomfort or pain
●Absence of symptom relief despite optimal antisecretory therapy
●Absence of evidence that gastroesophageal reflux (abnormal acid exposure and symptom reflux association) or eosinophilic esophagitis is the cause of symptoms
●Absence of major esophageal motor disorders (achalasia/EGJ outflow obstruction, diffuse esophageal spasm, jackhammer esophagus, absent peristalsis)

Question 38

Describe reflux hypersensitivity.

Answer 38

Reflux hypersensitivity is characterized by retrosternal symptoms including heartburn and chest pain with normal acid exposure but a positive symptom association with acid or weakly acid reflux. According to the Rome IV criteria, a diagnosis of reflux hypersensitivity requires all of the following criteria be fulfilled for the last three months with symptom onset at least six months prior to the diagnosis:
●Retrosternal symptoms including heartburn and chest pain.
●Normal endoscopy and absence of evidence that eosinophilic esophagitis is the cause for symptoms
●Absence of major esophageal motor disorders (achalasia/EGJ outflow obstruction, diffuse esophageal spasm, jackhammer esophagus, absent peristalsis)
●Evidence of triggering of symptoms by reflux events despite normal acid exposure on pH or pH–impedance monitoring (response to antisecretory therapy does not exclude the diagnosis).

Question 39

Which conditions should be considered in the differential diagnosis of refractory GORD?

Answer 39

●Achalasia
●Stricture
●Esophageal cancer
●Patients who are taking nonsteroidal antiinflammatory drugs (NSAIDs) can experience pyrosis and may be more susceptible to acid-related esophageal disease
●Patients with rumination syndrome may be thought to have GERD.
●In addition to acid, a variety of caustic and infectious causes are associated with esophagitis. Examples include pill-induced esophagitis, caustic ingestion, Candida, herpes, and radiation. These causes should be excluded.
●Patients who have impaired gastric emptying are predisposed to reflux. Symptoms may be improved after appropriate treatment.
●Eosinophilic esophagitis in adults is commonly associated with dysphagia while only about one-third of patients report classic heartburn symptoms [57-62]. Heartburn alone is uncommon.
●In one study, patients with GERD who also had irritable bowel syndrome (IBS) perceived their symptoms as more severe and tended not to achieve the same degree of symptom improvement during PPI treatment compared with patients with GERD without IBS.

Question 40

When should the diagnostic evaluation for refractory GORD be undertaken?

Answer 40

Diagnostic evaluation for refractory GERD should be considered in patients after an evaluation of proper compliance and reinforcement of lifestyle modification. In patients without alarm symptoms (eg, dysphagia, odynophagia, anorexia, weight loss, or upper GI bleeding), an empiric trial of doubling the dose of a PPI, or switching to a different PPI should be considered prior to initiating diagnostic testing.

Question 41

Outline the 3 modalities used in the diagnostic evaluation of refractory GORD.

Answer 41

Upper endoscopy — Patients who fail a PPI once daily and also have alarm symptoms should undergo upper endoscopy. The value of endoscopy in patients with refractory GERD without alarm symptoms is limited; there is no evidence that PPI failure is associated with an increased likelihood of a life-threatening esophageal or gastric lesion. There is some evidence that if endoscopy is performed, biopsies assessing for dilated intercellular spaces might help to separate true refluxers from those who have functional heartburn.

Esophageal pH testing — Patients who fail PPI twice daily should undergo esophageal pH testing. The pH test can be performed while off treatment in patients without typical GERD symptoms, to determine if reflux is the cause of their symptoms or while on treatment and together with impedance testing in patients with a partial response to PPIs to determine if there is continued pathological acid or non-acid exposure despite a PPI.

Esophageal manometry — The value of esophageal manometry in refractory GERD is very limited. This is primarily because most of treatment failure patients have NERD or functional heartburn. However, in those with suspected achalasia and in all patients undergoing surgery for GERD, esophageal manometry should be performed.

Question 42

What are the general therapeutic measures used in patients with refractory GORD?

Answer 42

Optimizing therapy:
Evaluation of proper compliance and adequate dosing time should be the first management step.
Lifestyle modifications:
As for ordinary GORD.

Question 43

What are the 3 major therapeutic groups for patients with refractory GORD?

Answer 43

Those whom tests show to have:

• Continued acidic reflux
• Weakly acidic/Alkaline reflux
• Oesophageal hypersensitivity/Functional heartburn

Question 44

How does one manage a patient with refractory GORD for whom additional diagnostic testing reveal that they have continued acidic reflux?

Answer 44

Adjustment of proton pump inhibitor — Switching to another PPI or doubling the PPI dose are options in treating residual acid reflux in patients on once daily PPI. We usually double the dose for eight weeks before considering an alternative PPI, although either option is effective. There is no evidence to support further escalation of the PPI dose in those who failed PPI twice daily. When doubling the PPI dose, one PPI should be given before breakfast and the other before dinner.

Bedtime H2 receptor antagonist — Another strategy that has been suggested is to add a bedtime H2 receptor antagonist (H2RA) only in patients who failed PPI twice daily. The hope is to significantly reduce nocturnal acid breakthrough in patients who failed PPI twice daily. However, the enthusiasm about the value of adding H2RA at bedtime has been subsequently tempered by studies demonstrating rapid development of tolerance to H2RA. On the other hand, observational data and clinical experience have suggested that long-term use of an H2RA at bedtime can be clinically beneficial, at least for some patients. Thus, a nighttime H2RA may be an option in patients who do not respond to PPI twice daily; if clinical tolerance has been encountered, then using the H2RA intermittently or on demand could theoretically be helpful.

In patients with persistent acid reflux after the addition of an H2RA, antacids (eg, aluminum hydroxide, magnesium hydroxide), sodium alginate, or sucralfate may provide some relief.

Question 45

How does one manage a patient with refractory GORD for whom additional diagnostic testing reveal that they have weakly acidic/alkaline reflux?

Answer 45

Treatments aimed at reducing weakly acidic reflux — A variety of compounds reduce the rate of transient lower esophageal sphincter relaxation (TLESR) and thus the number of reflux events. However, only baclofen, a gamma-aminobutyric acid B receptor agonist, was introduced into the clinical arena as a potential add-on treatment for patients who failed PPI treatment (once or twice daily).

The side effects are an important limiting factor in the routine usage of baclofen in clinical practice.

We suggest a trial of baclofen in patients with refractory GERD on PPI twice daily who demonstrate symptoms associated with non-acidic reflux on an esophageal impedance pH study. If access to an esophageal impedance pH study is unavailable, we suggest an empiric trial of baclofen in those whose symptoms are primarily regurgitation. We usually begin by giving 10 mg at bedtime, which can be increased slowly to 20 mg three times daily while carefully monitoring for side effects.

Question 46

How does one manage a patient with refractory GORD for whom additional diagnostic testing reveal that they have oesophageal hypersensitivity or functional heartburn?

Answer 46

In patients with refractory GERD who have an unremarkable esophageal impedance pH study and in patients with non-acid reflux, we suggest a trial of visceral analgesics (pain modulators), such as a tricyclic antidepressant, selective serotonin uptake inhibitor, serotonin-norepinephrine reuptake inhibitors, or trazodone. If access to esophageal impedance pH is not available, and patients primarily report heartburn, we generally begin with a trial of an H2 receptor antagonist (H2RA) at bedtime, suggesting it be used intermittently to avoid tachyphylaxis. In those who do not respond, we then suggest a trial of a tricyclic antidepressant, trazodone, serotonin-norepinephrine reuptake inhibitors, or a selective serotonin reuptake inhibitor.

Question 47

What other/experimental approaches to therapy are available?

Answer 47

●The role of bile acid binders such as cholestyramine or sucralfate in patients with GERD who failed PPI treatment remains unclear. Reducing bile reflux in this patient population is desirable, but it is unclear if any of the currently available bile acid binders are sufficiently effective to improve symptoms.
●Acupuncture.
●Two endoscopic approaches for treating GERD include application of controlled radiofrequency (RF) energy to the lower esophageal sphincter region (Stretta procedure) and transoral incisionless fundoplication. Both techniques have demonstrated a significant decrease in PPI dose. However, the role of both techniques in patients with non-acid reflux remains to be elucidated.

Question 48

What are the indications for surgery in patients with GORD?

Answer 48

The most frequent indication for surgery for patients with GERD is severe GERD unresponsive to optimal medical therapy, which consists of both drug therapy and lifestyle modifications. Other reasons for operative management include noncompliance, severe esophagitis by endoscopy, benign stricture, Barrett’s columnar-lined epithelium (without severe dysplasia or carcinoma), dental erosion by acid exposure, and recurrent pulmonary symptoms.

Question 49

What is the recommended procedure for GORD surgery?

Answer 49

There is no consensus on which is the best antireflux operative procedure for all patients.

Question 50

Which surgical options are currently preferred?

Answer 50

We recommend the laparoscopic posterior fundoplication (LPF) as the surgical approach for the treatment of GERD (Grade 1A). Patients undergoing a LPF had fewer short-term adverse outcomes (eg, esophageal acid exposure time, heart burn, and reoperation rate) and fewer long-term adverse outcomes (eg, heartburn, reoperation rate) compared with patients undergoing a laparoscopic anterior repair..