hour score being 16.0.51

Table 42-1 Normal Manometric Values of the Distal Esophageal Sphincter in 50

Subjects

In patients with symptoms of chronic cough, hoarseness, or pulmonary aspiration, placement of an

additional pH electrode in the proximal part of the esophagus or pharynx can be helpful.53 Such dualprobe catheters are particularly helpful in determining if gastroesophageal reflux events extend

proximally, which could give indirect evidence of acid exposure into pharyngeal area and subsequent

irritation. If the accumulated acid exposure in the proximal esophagus is greater than 1% or the number

of reflux episodes is more than 24 (particularly if there is a temporal relationship between the reflux

episodes and the onset of the symptoms), reflux can be documented and assumed to be the cause of the

patient’s RSs.53 A composite score has been developed for proximal pH monitoring, analogous to that

developed for the distal probe, with the normal threshold composite score being 16.4.52

Additional testing is sometimes necessary if the standard methods of assessing esophageal function

fail to yield conclusive results, particularly when investigating the relationship of acid reflux and

extraesophageal symptoms. A novel pharyngeal pH system has been developed that allows a pH probe

to be positioned directly into the pharynx just below the uvula (Restech pH probe, Respiratory

Technology Corp, San Diego, CA, USA).53 This probe utilizes a novel antimony sensor that allows

measurement of pH within the humidified air of that environment without drying out and creating

artifacts. Early clinical experience with this technique indicates that it is a useful adjunct diagnostic test

in patients suspected of having laryngopharyngeal reflux (LPR).

Testing for reflux that is nonacidic or weakly acidic can be gained by multichannel intraluminal

esophageal impedance monitoring. This type of measurement determines the resistance to the flow of

current through a given medium (impedance). The impedance to current changes as the composition of

the medium in which the current is traveling changes (i.e., air, liquids, or solids). Coupled with a pH

probe, it can differentiate acid reflux from nonacid reflux, which may be particularly useful in patients

who remain symptomatic on acid suppression therapy.

Lastly, the assessment of gastric function can be important in many patients with ESs. Disorders of

gastric emptying frequently can contribute to or be confused with esophageal disease, especially GERD.

Nuclear medicine radioisotope with solid food matter such as scrambled eggs has been utilized for this

purpose, and is indicated in any patient being evaluated for GERD who also has a history of nausea,

early satiety, and vomiting. Such information may be invaluable to prevent performing an antireflux

operation in the setting of gastroparesis. The most reliable results are obtained with the use of a 4-hour

study rather than one that just determines a half-time of emptying.

CONCLUSIONS

Although seemingly simple, the anatomy and physiology of the esophagus is complex. Understanding

the anatomic relationships is critical to enable safe surgery on the esophagus. Functional studies allow

identification of abnormalities in the upper or lower esophageal sphincter as well as the esophageal

body, and pH testing can determine the presence of increased exposure of the esophagus to refluxed

gastric juice. An understanding of the relevant pathophysiology is critical to allow functional restoration

of LES competence in patients with reflux disease, or to reduce the LES outflow resistance in patients

with achalasia. While complex, restoration of esophageal function can bring tremendous improvements

in quality of life and social satisfaction for patients, and is gratifying for esophageal surgeons.

GASTROESOPHAGEAL REFLUX DISEASE

Definition and Epidemiology

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GERD is a very common disease, but developing an accurate definition of GERD is surprisingly difficult.

In 2004, a group of experts came together in Montreal and concluded that GERD can be best defined as

“a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or

complications.”54 Population-based studies have reported that one-third of Western populations

experience the symptoms of GERD at least once a month, with 4% to 7% of the population experiencing

daily symptoms.55,56 Its prevalence varies considerably around the globe and is highest in North

America, Australia, and Western Europe and lowest in Africa and Asia.57 It is also likely that both the

prevalence and severity of GERD are increasing in many parts of the world. Time trend analyses have

shown that the prevalence of GERD symptoms has increased progressively in most longitudinal studies,

including those from the United States, Singapore, and China (Fig. 42-22).58 Further, recent data

reported by the Agency for Healthcare Research and Quality (AHRQ) indicate a marked increase (103%)

in hospitalizations for treating disorders caused by GERD; a 216% increase in hospitalization of patients

who, in addition to the ailment for which they were admitted, have milder forms of GERD; and a 39%

increase in admission for GERD with severe symptoms including anemia, weight loss, and vomiting.59

These data suggest that the current therapeutic approach to GERD may be inadequate.

Figure 42-22. Time trends for the prevalence of weekly heartburn from 1980 to 2005. (Reproduced with permission from El-Serag

H. Time trends of gastroesophageal reflux disease: a systematic review. Clin Gastroenterol Hepatol 2007;5:17–26.)

Most patients with mild symptoms self-medicate with over-the-counter antacids or antisecretory

agents, whereas those with more severe and persistent symptoms seek out medical attention. In contrast

to duodenal ulcer disease, where the prevalence has markedly decreased, the prevalence and severity of

GERD seem to be increasing (Fig. 42-23).60 The diagnosis of a CLE is also increasing at a rapid rate, and

deaths from end-stage benign esophageal disease are on an upward trend.61 These changes have

occurred despite dramatic improvements in the efficacy of treatment options.

Two epidemiologic trends may be contributing to the increasing prevalence and severity of GERD

over the past several decades. Population-based studies have shown that GERD is positively associated

with obesity and negatively associated with gastric colonization with Helicobacter pylori. Over the past

20 to 30 years, the former has increased and the latter has decreased markedly in most Western

countries. The relationship between GERD and body mass index (BMI) has been evaluated in a number

of well-designed clinical studies. The frequency, duration, and severity of reflux symptoms were studied

in 10,500 women of the Nurses’ Health Study and a dose-dependent relationship between increasing

BMI frequency of GERD symptoms was identified.62 Compared to normal-weight women (BMI 20 to

22.4), underweight women (BMI <20) were one-third less likely and overweight women (BMI 25 to

27.4) two times more likely to have frequent GERD symptoms. Obese women (BMI >30) had a nearly

three times higher risk of frequent GERD symptoms. Recent meta-analyses confirm these findings, with

studies from the United States demonstrating an association between increasing BMI and the presence of

GERD.63 High-resolution motility studies have shown a significant correlation with BMI and both

intragastric pressure and gastroesophageal pressure gradients, providing a physiologic explanation for

the BMI–GERD association.64 These studies suggest that obese subjects are more likely to have

esophagogastric junction disruption and abnormal pressure gradients favoring the development of

reflux. Finally, the risk of Barrett esophagus has been correlated with the presence of central obesity.

Measures of central obesity, including waist circumference and waist-to-hip ratios, were associated with

both short- and long-segment Barrett esophagus, with a 4.1 higher odds ratio of long-segment Barrett in

patients with a high waist-to-hip ratio.65

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Figure 42-23. Trends in hospitalization for duodenal ulcer and gastroesophageal reflux disease from the 1970s to 1990s in U.S.

veterans. (Reproduced with permission from El-Serag HB, Sonnenberg A. Opposing time trends of peptic ulcer and reflux disease.

Gut 1998;43:327–333.)

The possible pathogenic role of helical-shaped bacteria found in gastric fluids was first suggested in

the late 19th century by the Polish scientist Walery Jaworski of the University of Krakow.66 It was the

publication of two Australian scientists in 1983 that convincingly demonstrated the pathogenic role of

H. pylori.67 These pioneering studies of Barry Marshall and Robin Warren from Perth, Australia,

included self-experiments and were later awarded the Nobel Prize. H. pylori induces a significant

inflammatory and immune response in the affected host, resulting in persistent inflammation in

virtually all infected subjects.

The relationship between H. pylori and GERD has been of interest for decades. The observation that

gastric mucosal atrophy was less frequent in patients with reflux esophagitis was made well before the

H. pylori era. Evolutionary hypotheses assume, and the majority of available epidemiologic data show,

that the decline of H. pylori infection is one of the reasons behind the increasing incidence of GERDrelated diseases including esophageal and cardia adenocarcinoma in the Western world. This inverse

relationship is strongest between H. pylori and esophageal adenocarcinoma, although significant

evidence relates H. pylori and the development of Barrett esophagus and GERD. Over the period from

1970 to 1995, the incidence of both duodenal ulcer, compared to erosive esophagitis, and distal gastric

cancer, compared to gastric cardia cancer, displays strikingly opposing time trends. It has been

postulated that H. pylori–induced chronic corpus gastritis may protect against the development of GERD

and its malignant transformation. A detailed report by Labenz et al.68 in 1997 provided some of the first

evidence in support of this theory. In a case-control study of 460 duodenal ulcer patients, new-onset

GERD symptoms were significantly higher in patients who had successful H. pylori eradication than in

those with persisting infection. Although a number of subsequent studies have raised doubts as to

whether a true relationship exists, the available evidence suggests that the prevalence of H. pylori

infection in patients with GERD is lower than non-GERD control populations and that there is likely an

inverse epidemiologic relationship between GERD and H. pylori.

The relationship of Barrett esophagus to gastric H. pylori colonization is also debated, although most

studies show an even stronger inverse relationship than that of GERD alone. Bowrey et al. reported an

H. pylori prevalence of 27% in patients with Barrett esophagus compared to 41% in healthy control

subjects.69 Werdmuller and Loffeld70 also found significantly lower H. pylori infection rates in Barrett

than non-Barrett patients (23% vs. 51%), whereas Loffeld et al.71 reported very high rates (62%) in a

retrospective analysis of 107 consecutive patients with CLE. Investigations focused on the role of

subpopulations of H. pylori have implicated cagA+ strains as particularly relevant to the development of

GE reflux and its complications.72 Vicari et al.73 demonstrated that in patients with H. pylori infection,

the prevalence of cagA+ strains progressively decreased with the severity of GERD, including Barrett

esophagus and esophageal adenocarcinoma. Other studies have confirmed an inverse relationship

between the presence of cagA positivity and adenocarcinoma of the esophagus and the GE junction.74

Most authors postulate that cagA+ strains may protect from the development of adenocarcinoma by

inducing more severe mucosal inflammation and atrophic gastritis and thereby decreasing acid reflux.

Present data regarding gastric acid secretion are conflicting, however, and further studies are required

to test whether this hypothesis is true.

Previously there was a concept that GERD was a categorical disease with little movement between

categories. In other words, patients with nonerosive disease (NERD) seldom developed erosive

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esophagitis. This concept was disproven by one of the most detailed studies on the natural history of

GERD from investigators in Europe.75 The progression or regression of GERD complications was

assessed in a cohort of nearly 4,000 patients with predominant heartburn over a 2-year period. After 2

years, 25% of patients with nonerosive GERD progressed to erosive disease, 1.6% with mild erosive

esophagitis worsened to more severe esophagitis, and nearly 8% progressed to Barrett esophagus, the

latter predominantly in patients with Los Angeles grade C/D erosive disease at baseline. On the other

hand, 50% to 60% of patients with baseline esophagitis improved to a milder grade or no erosive

disease and 22% were off medications at 2 years. Given that virtually all patients were receiving

significant antisecretory therapy, the study shows that a substantial minority of patients will continue to

worsen despite pharmacologic treatment. A follow-up study at 5 years on 2,721 of the originally

enrolled patients reported that while in most the disease was stable or esophagitis had improved, a

sizeable portion of patients progressed.76 At 5 years, 6% of patients with NERD, 12% with LA grade A/B

esophagitis, and 20% of those with LA grade C/D esophagitis had developed Barrett esophagus. On

multivariable analysis risk factors for progression to esophagitis or Barrett esophagus were family

history of GERD, baseline esophagitis or remaining unhealed after initial treatment, alcohol intake, and

regular use of PPI medication.76

Investigators in Lausanne, Switzerland, reported an intensive endoscopic follow-up of a defined

population of 959 patients over a 30-year period.77 The study involved only patients who had

endoscopic esophagitis and did not include those who had symptoms without mucosal injury. In 42% of

patients esophagitis progressed on therapy to more severe mucosal injury. Further, 18% of the initial

population acquired a columnar-lined lower esophagus with intestinal metaplasia at late follow-up.

Clinical Presentation

The most common complaints in patients with GERD are heartburn, regurgitation, and dysphagia. These

represent the so-called typical symptoms of GERD. Although none of these are specific to GERD,

dysphagia may be an indication of more serious underlying pathology, including esophageal carcinoma,

and should prompt an upper endoscopy. Heartburn means different things to different people and it is

important to ask a patient what heartburn means to them. Typically, heartburn should be characterized

as a substernal “burning” discomfort often radiating from the epigastrium to sternal notch. Occasionally

patients will refer to it as chest or epigastric pain or indigestion. The typical pattern for early reflux

disease is heartburn that occurs postprandially and made worse by “spicy” foods such as tomato sauce,

citrus juices, chocolate, coffee, and alcohol. It is commonly relieved by antacids, histamine-2 blockers or

PPIs. Importantly, the severity of symptoms is not necessarily related to the severity of the underlying

disease (Fig. 42-24).

Figure 42-24. Prevalence of erosive esophagitis in 994 patients with varying severity and frequency of reflux symptoms.

(Reproduced with permission from Venables TL, Newland RD, Patel AC, et al. Omeprazole 10 mg once daily, omeprazole 20 mg

once daily, or ranitidine 150 mg twice daily, evaluated as initial therapy for the relief of symptoms of gastro-oesophageal reflux

disease in general practice. Scand J Gastroenterol 1997;32:965.)

Regurgitation is the spontaneous return of gastric contents proximal to the GE junction. Its

spontaneous nature distinguishes it from vomiting. The patient often gets a sensation that fluid or food

is returning into the esophagus, even if it does not reach as high as the pharynx or mouth. It is typically

worse at night in the recumbent position or when bending over or lying down after a meal. Patients

commonly compensate by not eating late at night or by sleeping partially upright with several pillows

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