Editor: Joseph Sung
2. Gastroesophageal reflux disease (GERD)
Gastroesophageal reflux disease (GERD) is increasingly recognized around the world and has been linked to the development
of esophageal carcinoma. Endoscopy is widely performed not only for diagnosis but also for therapy (i.e. dilation). The majority
of GERD cases do not have endoscopic abnormalities and a complete evaluation with biopsies, esophageal motility, and 24-hour
ambulatory pH monitoring are frequently needed before therapy is initiated. This chapter reviews the endoscopic recognition
of GERD, the various staging classifications of the disease and its complications, and the assessment and management of esophageal
strictures. We further expand on the promising new technologies for endoscopic therapy of GERD and provide some concepts and
trends for the future.
Several studies on the value of symptoms and endoscopic findings in GERD have concluded that it is difficult to establish
the diagnosis by patients' history alone and that reflux disease may be present even with normal endoscopy . Therefore, for the correct diagnosis of GERD and the assessment of its severity, many authorities recommend a complete esophageal
evaluation that includes endoscopy with biopsies, esophageal motility and 24-hour ambulatory pH monitoring (Fig. 1) .
Diagnostic upper endoscopy
Diagnostic upper endoscopy in GERD may reveal either a normal or an abnormal esophagus characterized by ulcers, erosions,
exudates, and friability. There are four widely used systems of grading the severity of the esophageal damage, the SavaryMiller, the HetzelDent, the MUSE, and the Los Angeles classification (Figs 24) . The refinement of endoscopes, the advent of transnasal endoscopy, and the use of absorptive stains to detect and define
abnormalities have facilitated imaging of the esophageal mucosa to a level of excellent detail and resolution. Although diagnostic
upper endoscopy may reveal characteristic abnormalities of GERD, biopsy or brush cytology may be needed to obtain histological
or cytological confirmation .
Despite pathological gastroesophageal reflux, the esophagus may be normal from the cricopharyngeus to the esophagogastric
junction. Since GERD may cause several extraesophageal manifestations (i.e. laryngitis, asthma, difficulty with throat clearing)
endoscopy should always explore the posterior aspect of the pharynx, the glottis, the posterior cricoid cartilage, and both
the pyriform sinuses .
Upon passing the endoscope just beyond that level, one appreciates the concentric, transient effect of the upper esophageal
sphincter (UES) and then the pink appearance of the esophageal mucosa with its longitudinal folds. These folds usually measure
24 mm, and run parallel to each other, converging towards the centre of the lumen. At the level of the middle third of the esophageal
body, a small amount of saliva may be normally appreciated. The presence of a larger amount of liquid or the existence of
a fluid level in the midesophagus suggests significant impairment of esophageal clearance (i.e. scleroderma or achalasia)
The length of the esophagus varies from 35 to 45 cm, depending on the height of the individual. As the endoscope is passed into the distal third of the esophageal body the
esophageal mucosa may become slightly more erythematous.
Hiatus and Z-line
At this level, two landmarks should be specifically assessed: the integrity of the gastroesophageal junction (Z-line) and
the diaphragmatic hiatus. The Z-line marks the transition of the columnar gastric epithelium (reddish colour) to the squamous
esophageal epithelium (whitish-pink colour). It is visualized both in an antegrade fashion as well as during retroflexion
in the stomach (Fig. 5). The Z-line should be at the same level as the diaphragm or a bit below (Fig. 6). It is usually a distinct line, but it can be irregular or exhibit small ectopic islands of reddish mucosa above it. The
endoscope traverses the esophagogastric junction easily upon air insufflation; resistance to passage or friability implies
disease (i.e. stricture). The gastroesophageal junction should remain closed unless swallowing occurs or air is insufflated
through the endoscope. Persistence of a patulous junction is abnormal and implies the presence of reflux.
In contrast, sometimes the gastroesophageal junction is difficult to evaluate because the mucosal folds converge excessively.
This is not a feature of GERD but it can be seen in patients after fundoplication (rosette formation). Rarely, in older individuals
with thoracic aortic dilation, an extrinsic compression of the distal esophagus is seen just above the diaphragmatic orifice
and it should not be misinterpreted as a stricture. At this point, it is also important to measure the distanceif anybetween the Z-line and the diaphragmatic hiatus (Fig. 7). Normally, this distance should be 02 cm; otherwise a sliding hiatal hernia is present.
Glycogenic acanthosis of the esophagus consists of whitish elevations of the squamous mucosa of variable size (13 mm) scattered throughout the esophagus, but mostly in the distal two-thirds of the esophageal body. Histological examination
of these lesions reveals the presence of excess glycogen that is easily demonstrated using the periodic acidSchiff stain (PAS). Chromoendoscopy using Lugol's solution creates a brownish discoloration of these lesions that is more
pronounced than the adjacent esophageal mucosa. The exact significance of glycogenic acanthosis is unknown, but an association
with GERD has been reported .
The presence of erythema in the distal esophagus has created a lot of controversy since it is a poorly reproducible finding.
Because the colour controls of video-endoscopes and image-processing units are variable, it is very difficult to attribute
erythema to the underlying presence of esophagitis unless biopsies are taken. Therefore, the reporting of erythema should
not necessarily be viewed as an abnormal finding, suggestive of GERD. Further, the occasional presence of gastric-like mucosa
within 1 cm above the diaphragmatic hiatus does not imply the presence of Barrett's esophagus, and it may be seen in asymptomatic individuals
as well as patients with GERD .
Several variants of the gastroesophageal junction should not be misinterpreted as contributing to GERD. For example, sometimes
the normal esophagogastric angle is absent and the distal esophageal folds merge directly with the proximal gastric folds
of the lesser curvature . In contrast, the presence of a normal esophagogastric angle, that is, the point where the left esophageal wall merges with
the greater gastric curvature, does not exclude pathological reflux. Occasionally, the Z-line is not easily perceptible as
a result of gastric atrophy or anaemia, and this does not imply distal esophageal inflammation.
Erythematous areas and erosions
Careful distension of the distal esophagus by air insufflation may reveal small superficial erythematous areas or erosions.
These changes are more frequently seen with magnification endoscopes or upon close-up distension view. Unfortunately, the
smaller the surface alteration, the more there is interobserver variation. Sometimes, erythematous lesions are difficult to
distinguish from gastric mucosa or islands of Barrett's esophagus. When there is doubt, biopsies should be done. Depending
on their size, the absence of perceptible depth, and confluence, they are classified as either SavaryMiller stage 1 or Los Angeles grade A [3,4] (Fig. 8).
If biopsies of erythematous lesions reveal intestinal metaplasia, the diagnosis of Barrett's esophagus is made. Regardless
of its length or surface involvement, this condition is associated with an increased risk for malignancy (adenocarcinoma)
Ulcers are characterized by a perceptible depth upon air insufflation, a white base (crater), coating exudates or pseudomembranes,
and surrounding erythema. Close visualization reveals either elevated margins around the ulcer or a depressed appearance.
Surrounding the ulcer(s) there is oedematous, congested mucosa. All these characteristics, namely depth, margins, and surrounding
erythema, help with the assessment of GERD by either the SavaryMiller or the Los Angeles classification .
Specifically, Savary stage 1 or LA grade B: isolated longitudinal erosion or ulcer larger than 5 mm, on red background associated with an elevated mucosa along a longitudinal fold. Savary stage 2 or LA grade C: longitudinal
erosions and ulcers that are confluent but affect only one part of the esophageal wall along the distal esophageal folds (Figs 911). Savary stage 3 or LA grade D: confluent and circumferential ulcers covered by exudates or pseudomembranes with perceptible
depth upon insufflation and surrounding erythematous mucosa (Fig. 12). Savary stage 4: wall thickening and fibrosis with stricture formation with or without associated ulceration.
Sometimes, particularly after empirical therapy with antisecretory drugs, the stricture may be annular, distinct, short in
length (< 1 cm), and without associated mucosal lesions (see strictures below) (Fig. 13).
At other times, the stricture is associated with an ulcer that extends from the Z-line to the level of the stricture in a
longitudinal fashion. In such cases, a necrotic, haemorrhagic base is frequently encountered and is associated with bleeding
and friability. Biopsies are important to rule out malignancy and Barrett's esophagus.
Typically a peptic stricture (SavaryMiller stage 4) is the result of a long-standing reparative process during the course of erosive esophagitis. It is noted
most frequently in the distal esophagus as an annular constriction that impairs the easy passage of the endoscope . However, it may not be easily appreciated with the newer, small caliber endoscopes, and air insufflation may be needed to
outline its presence. A peptic stricture may or may not be associated with an esophageal ulcer, Barrett's metaplasia, or cancer,
and biopsies should be obtained .
The presence of a peptic stricture deserves immediate attention in order to relieve dysphagia and prevent aspiration of stagnant
esophageal contents. When performing endoscopy in patients with dysphagia suspected to have a peptic stricture, it is mandatory
to do it under direct vision. If difficulty is encountered with passing the endoscope, guidewire-assisted dilation should
be performed under fluoroscopic control either with a C-arm-type mobile unit in the endoscopy unit or a dedicated fluoroscopy
table in the radiology suite. Although not always necessary, a barium study may be useful in delineating the severity, location,
length, and complexity of the stricture .
Most peptic strictures are smooth on their surface, short, straight, and most frequently distal (Fig. 14). If such strictures can be traversed with the endoscope, use of a guidewire or balloon system is not needed and Maloney
dilation can be safe and effective. Rarely, complex esophageal strictures are encountered. Such strictures are long, narrow,
tortuous, or associated with esophageal diverticula and do not allow the tips of freely passed dilators to enter the stomach.
These strictures require a guidewire-based system or a balloon dilator under fluoroscopic guidance. A barium swallow may assist
with the localization, length, and diameter of strictures, their complexity, and the coexistence of esophageal diverticula
or hiatal hernia. This in turn determines the preferred dilation technique, the number of sessions required, and the dilation
A hiatal hernia is an intrathoracic ascent of the proximal portion of the greater curvature of the stomach through the esophageal
hiatus of the diaphragm  (Figs 15 and 16). It can be either sliding when the cardia moves up into the thorax, or rolling (paraesophageal) when the cardia remains
In sliding hernias, the upper border of the hernia is the squamocolumnar junction dislocated into the chest for a variable
length, and the lower border is the diaphragmatic indentation that can be appreciatedif possibleby asking the patient to sniff, a maneuver that approximates the diaphragmatic crura. In paraesophageal hernias, a gastric
sac of variable size is displaced into the mediastinum, but the squamocolumnar junction and the cardia remain in place. Sometimes,
a mixed variety is seen.
A sliding hiatal hernia exists in 25% of the population, but with increasing age its prevalence reaches 1015%. It may be found in up to 85% of patients with symptomatic reflux and it plays a pathogenetic role. The retention of acidic
gastric contents within the hernia pouch allows for repetitive episodes of reflux during the transient lower esophageal relaxations
(tLESRs) that happen either spontaneously or in response to swallows. Further, in the presence of sliding hiatal hernia, when
the intra-abdominal pressure increases there is no compensatory, parallel increase in lower esophageal sphincter (LES) pressure.
These two factors contribute to pathological reflux in patients with sliding hiatal hernia . In contrast, paraesophageal hernias are quite rare and may not be associated with GERD.
Endoscopy in esophagitis
Endoscopy is not necessary in every patient with heartburn but it should be performed if the symptoms become chronic and/or refractory to treatment, if the diagnosis is unclear, or if complications are suspected. However, the absence of endoscopic
features of GERD does not exclude the diagnosis. Ambulatory 24-h esophageal pH monitoring should be considered in cases where
endoscopy is negative .
Endoscopic staging of esophagitis
Because of wide observer variability in assessing the severity of esophagitis, the four most common classifications are listed
This is the most widely used grading of esophagitis and distinguishes four grades (14) ranging from erythema to erosions, ulcers, and stricture formation Fig. 2). Because of the ambiguity of grade 4 esophagitis, there are modifications that either offer subdivisions of grade 4 or define
Barrett's esophageal metaplasia as grade 5 (Figs 17 and 18).
Because most patients with GERD either do not have endoscopic lesions or have mild esophagitis, the HetzelDent system focuses on subtle mucosal abnormalities Fig. 3). Of note, esophageal strictures and Barrett's metaplasia are not parts of this grading.
This system is analogous to the TNM classification system used in oncology and describes several independent features: metaplasia
(M), ulceration (U), stricture formation (S), and mucosal erosion (E). Each of these elements is graded independently in four
increments (0, absent; 1, mild; 2, moderate; 4, severe) . The result of an endoscopic examination is described as a grade for each lesion type, i.e. M0U1S0E1.
Los Angeles classification
This system classifies severity by the extent of mucosal abnormalities, and complications are recorded separately , Fig. 4). A mucosal break implies erosion in the squamous epithelium with or without overlying exudate. The system is very sensitive
to early disease and is preferred in drug trials assessing drug efficacy.
Other lesions associated with GERD
Schatzki's ring is a diaphragm-like constriction that results from mucosal hyperplasia of the gastroesophageal junction  (Fig. 19). It can be seen in the antegrade position, upon air insufflation, or during retroflexion at the level of the cardia. Although
its relationship to GERD is not established, many studies have shown associated pathological reflux .
A tear at the gastroesophageal junction (MalloryWeiss tear) typically results from emetogenic injury to the distal esophagus and accounts for approximately 5% of upper gastrointestinal
bleeding episodes . It is usually not seen in conjunction with esophagitis, but it is associated with symptoms of reflux.
Esophageal involvement by scleroderma leads to severe mucosal alterations because of the lack of effective esophageal peristalsis
in the distal two-thirds of the esophageal body and the absence or significant diminution of the lower esophageal sphincter
(LES) pressure (25). This frequently results in severe involvement of the wall of the esophagus, ulcers and exudates in conjunction with a patulous
gastroesophageal junction, and free reflux of gastric contents during endoscopy .
Postoperative changes after fundoplication
After an antireflux operation, the anatomy of the gastroesophageal junction is permanently altered. The endoscopic appearance
of the distal esophagus and cardia, both in the antegrade and retroflexed views, is characterized by confluence of the distal
esophageal folds that create a rosette  (Fig. 20). Significant air insufflation is required to adequately visualize the mucosa and areas of short-segment Barrett's esophagus
may become imperceptible.
In cases of failure of an antireflux procedure, several causes need to be entertained. If GERD symptoms persist or recur,
a laxity of the fundoplication procedure leading to a patulous gastroesophageal junction is frequently found . Rarely, an intrathoracic mobilization or a 'slipped' Nissen fundoplication is seen (Fig. 21). If new symptoms of poor esophageal emptying occur (dysphagia or regurgitation), a very tight fundoplication or scarring
may be noted (Fig. 22).
Endoscopic esophageal mucosal biopsies should be obtained as part of the evaluation of patients with GERD. Changes of reflux
esophagitis (papillary hyperplasia, eosinophilic or chronic inflammatory infiltration) may be present even in the absence
of endoscopic abnormalities  (Fig. 23).
Chromoendoscopy in GERD
Chromoendoscopy in patients with GERD is performed with either Lugol's solution or methylene blue [30,31]. Lugol's solution stains normal esophageal mucosa dark green-brown. Any lesion of the esophagus that does not contain glycogen
(i.e. carcinoma, intestinal metaplasia, or inflammation) does not stain. Spraying 2050 ml of Lugol's solution on the mucosa may therefore reveal dysplasia or early cancer that would not be visible endoscopically.
Endoscopic management of esophageal strictures
Although dysphagia is the main symptom of a peptic stricture, other conditions such as non-obstructive GERD, motility disorder,
infection, malignancy, and esophageal rings should be considered . The goals of therapy for peptic strictures are the relief of dysphagia and the prevention of stricture recurrence with adjunctive,
continuous acid-suppressive therapy . Conditions that may increase the risk of esophageal dilation are cervical deformity, bleeding disorder, recent esophageal
surgery, esophageal perforation, large thoracic aneurysm, or foreign body impaction.
The use of fluoroscopy allows for accurate positioning of the endoscope tip, monitoring the guidewire placement through the
stricture for subsequent Savary-type dilation, or for monitoring the performance of a tapered-tip dilation using either Maloney
or Hurst dilators . Further, fluoroscopy is quite useful in the performance of balloon dilation as it delineates the waist of the balloon at
the level of the stricture and its obliteration during inflation. Upon completion of the dilation, if there is suspicion of
a perforation, a contrast study should be performed using gastrograffin, in order to fluoroscopically look for contrast extravasation
The use of fluoroscopy for esophageal dilation may not improve the outcome. In a randomized trial of benign esophageal stricture
dilation with Maloney dilators with or without fluoroscopic guidance, those who underwent dilation with fluoroscopy more often
tolerated passage of a 12.5 mm barium pill after dilation (62 vs. 42%), and had better dysphagia relief (93 vs. 69%) (36). In another study, however, it was the operator's experience rather than fluoroscopy that was associated with procedural
Principles of esophageal dilation
Esophageal dilation circumferentially stretches the stricture and splits its fibrous composition. Typically, the mechanical
dilators exert both a longitudinal and radial force, and dilate the stricture progressively from the proximal to its distal
end. In contrast, balloon dilators exert their dilating force in a radial fashion and simultaneously over the entire length
of the stricture .
There are two types of mechanical dilators: those that are passed freely, and those that are inserted over a guidewire. The
tapered-tip Maloney (Medovations, Germantown, WI) are the most commonly used dilators; they are available in multiple sizes
and do not require a guidewire for placement. The Hurst dilators have a rounded tip that is harder to pass, and are rarely
used today. Both Maloney and Hurst dilators are filled with tungsten, which provides flexibility and weight. The SavaryGilliard guidewire-assisted dilators (Wilson Cook, Winston-Salem, NC; American Dilatation System by Bard Interventional Products,
Tewksbury, MA) are widely used . They are made from plastic, have a tapered tip, and are available in multiple sizes. The EderPeustow dilator system (Eder Instruments Co., Chicago, IL), uses progressively larger elliptical (olive-shaped) metal dilators
that are passed over a guidewire.
Pneumatic (balloon) dilation
There are two types of balloon dilators: the TTS, a through-the-scope dilator (various manufacturers), which is passed directly through the endoscope, and the OTW, an over-the-guidewire balloon dilator (Boston Scientific Corp., Natick, MA) . Balloons exert a greater radial force and retain their maximum predetermined diameter. The new generation of TTS balloons
(Boston Scientific Corp., Natick, MA) expand to three different diameters at 1.5 mm increments without having to change balloons. Studies comparing mechanical to balloon dilation have shown mixed results
and success depends mostly upon the experience of the endoscopist [41,42]. In general, complex strictures should be dilated with a guidewire-based mechanical or balloon dilating system.
Techniques of dilation
Esophageal dilation is generally performed as an outpatient procedure under conscious sedation and meticulous local pharyngeal
anaesthesia . Some patients with simple peptic strictures who require frequent dilations may not need sedation or may self-dilate at home
using Maloney dilators. Typically Maloney dilation is performed while the patient is seated. In order to improve visualization
and to avoid aspiration, fasting before dilation is important. Drugs that affect platelet function should be stopped 1 week
before the procedure and antibiotic prophylaxis should be given to patients at high-risk for endocarditis.
When using mechanical dilators, the diameter of the initial dilator should be approximately the same width as the stricture.
For balloon dilators, the initial balloon size reflects the estimated stricture diameter: a 10 mm balloon for diameters between
2 and 4 mm; a 12 mm balloon for diameters between 5 and 9 mm; and a 15 mm balloon for a diameter greater than 9 mm. In order to reduce the likelihood of complications, no more than three dilators of progressively increasing size should
be passed in a single session, and the luminal diameter should not be increased by more than 2 mm. The effectiveness of dilation is approximated by the degree of resistance during passage of the dilator.
The need for, and frequency of repeated dilations depends upon the patient's response. If the stricture has a narrow diameter
and exhibits significant resistance, repeated sessions every 57 days may be required. As a general rule, the last dilator used in the previous session is usually passed first. However,
since shrinkage of strictures following dilation may occur, it is useful to evaluate the stricture diameter prior to dilation,
and if needed to revert back to a smaller-sized dilator.
TTS balloon dilators and mechanical dilators are equally safe for dilating esophageal strictures, but recurrences may be less
during the second year following TTS compared to mechanical dilation . TTS balloon dilators are passed through the channel of the endoscope into the stricture under direct vision or during fluoroscopy.
Obliteration of the balloon 'waist' on fluoroscopy reflects effective stricture dilation. Two dilations of 3060 s in each session are usually performed but the optimal number and duration of inflations is not known. The ability to
move the inflated balloon freely through the treated stricture implies a successful dilation. If several sessions are required,
they are usually performed every 35 days .
In general, dilation to 18 mm allows intake of a regular diet; a diameter of 15 mm allows for a modified regular diet and patients should be instructed to chew their food well. In contrast, patients with
an esophageal lumen less than 13 mm will usually experience dysphagia with solids. The free passage of a 12 mm barium tablet into the stomach can be used as
an objective endpoint for dilation [45,46](Figs 2426).
Dilation of distal esophageal (Schatzki's) rings
Given their dense, fibrous nature, Schatzki's rings often fail to respond to standard Savary-type dilation. In these instances,
disruption using balloon dilators that are capable of applying radial force on the ring is preferable. If this approach fails
and the patient remains symptomatic, consideration should be given to ring incision, using electrocautery . Under direct visualization and minimization of movement, four-quadrant diathermy cuts are made using a regular or a needle-knife
sphincterotome, resulting in restoration of the esophageal lumen to its original diameter. However, this procedure carries
the risk of perforation and should only be performed by experienced endoscopists.
Concomitant medical therapy for strictures
Proton pump inhibitors should be used in patients with peptic strictures since they reduce the need for subsequent dilation
better than H2 antagonists. In one study, 336 patients with peptic strictures were randomized to omeprazole 20 mg QD or ranitidine 150 mg BID for 1 year after esophageal dilation to 1218 mm and follow-up endoscopy with dilation was performed as indicated. The omeprazole-treated patients required significantly
fewer repeated dilation sessions (30 vs. 46%) and had improved dysphagia scores compared to the ranitidine-treated group . Patients with recurrent peptic strictures despite use of a proton pump inhibitor may benefit from ambulatory 24-h pH monitoring
while on therapy to assure the adequacy of acid suppression.
Some patients with benign esophageal strictures do not achieve acceptable symptom relief despite an intensive dilation schedule
and aggressive proton pump inhibitor therapy . These patients should be evaluated for, and offered surgery. Those who are poor surgical candidates may benefit from regular
self-dilations with a Maloney dilator. However, home dilation has risks, and many patients are not motivated or suitable candidates.
Intralesional injection of corticosteroids
The injection of corticosteroids into the stricture may reduce stricture recurrence following dilation . Although the mechanism of action is not well understood, corticosteroids may reduce scar tissue formation by inhibiting
collagen deposition. A standard sclerotherapy needle is used to inject an average of 0.2 ml of triamcinolone acetonide (Kenalog, Bristol-Myers Squibb, Princeton, NJ) into all four quadrants at the narrowest region
of the stricture. Some use an ultrasound miniprobe passed through the endoscope to guide the injection into the thickest part
of the stricture .
Other endoscopic methods for strictures
Electrosurgical incision of peptic strictures has been reported but the safety of this technique has not been rigorously tested.
A biodegradable esophageal stent made from a coil of poly L-lactide (Instent, Eden Praire, Minn) has been used for relief
of dysphagia due to a benign refractory, radiation-induced stricture. Because of the possibility for migration or stent-induced
fistula formation, expandable metal stents are not recommended for peptic strictures. A retrievable, expandable stent is under
Complications of esophageal stricture dilation
The major complication of esophageal dilation is esophageal perforation . The incidence of perforation depends on the etiology of the stricture, the technique, and operator experience, and ranges
between 0.1 and 0.3%. The clinical manifestations of esophageal perforation depend upon the location and extent of the perforation
and the duration since the onset of injury. Cervical perforation may be associated with neck pain and tenderness, hoarseness,
and subcutaneous emphysema. Perforation of the thoracic esophagus is most commonly associated with chest, back, or epigastric
pain, which is worse with inspiration or swallowing. There may be associated dysphagia, odynophagia, bleeding, or dyspnea.
Patients may be tachycardic, tachypneic, and febrile, and eventually develop septic shock.
Patients with suspected perforation should undergo chest and neck X-rays to look for subcutaneous emphysema or pneumomediastinum
. Contrast esophagography usually establishes the diagnosis. Water-soluble contrast agents (such as gastrograffin) are used
initially, followed by barium studies if results are negative. Barium has a higher sensitivity for small perforations. If
clinical suspicion remains high despite negative findings on esophageal contrast studies, computed tomography should be performed
as it is highly sensitive for detecting soft tissue air. Patients whose perforation is recognized early have a good prognosis
and, in many cases, can be managed non-surgically. A delay in diagnosis usually necessitates surgery and carries a mortality
rate of 2550%. Esophageal dilation may cause bacteremia in up to 45% of cases and antibiotic prophylaxis is needed for patients at high
risk for endocarditis . Significant bleeding requiring blood transfusions after esophageal dilation occurs in 0.22% of cases.
Endoscopic therapies for GERD
Several endoscopically assisted interventional techniques have emerged for the treatment of GERD. These therapies should be
considered for patients who respond well to proton pump inhibitors (PPIs), but do not wish to take long-term medications,
patients who respond partly to PPIs or have regurgitation not responsive to PPIs but do not want surgery, patients who are
afraid of possible long-term sequelae of PPI therapy, patients intolerant to PPIs, and possibly patients who have failed fundoplication
for GERD .
The best candidates for endoscopic therapies are those who have well-established GERD documented by endoscopy or pH monitoring
and esophageal motility studies and have at least in part responded to PPIs. Other potential candidates are those with PPI-responsive
GERD despite normal 24-h pH study (Non-Erosive Reflux Disease, NERD). Consideration should also be given to patients with
PPI-responsive, extraesophageal manifestations of reflux. The endoscopic procedures currently available are not appropriate for the late, complicated disease states of esophageal shortening or stricture, poor esophageal function, and
Many technique modifications will certainly improve the safety and efficacy profiles of all endoscopic therapies. Efficacy
comparisons and sham trials will be needed in order to show differences among these new endoscopic modalities in the management
of GERD. Comparisons to surgery and drug therapy will probably ensue. Safety and tolerability will continuously be assessed
in a postmarketing surveillance. Longer observations of patients already treated will address the durability of effect over
periods longer than 12 months. The general applicability in all GERD groups and cost-effectiveness will be determined with
wider application and future technological advances .
Many questions about endoscopic therapies for GERD remain unanswered: How do these procedures work? How well do they work?
How safe are they? Who are the best candidates for them? How long does their effect last? Answers to all these questions will
become available with the increased and widespread utilization of these procedures and the design and execution of well-controlled,
randomized clinical trials.
Radiofrequency energy delivery (Stretta®)
Radiofrequency (RF) delivery for GERD, or the Stretta® procedure, is performed using the Stretta® system (Curon Medical Inc., Sunnyvale, CA), which incorporates a flexible catheter with a control module/generator. The catheter has a soft bougie tip and a 6 mm shaft, and contains a balloon/basket that inflates to a maximum 3 cm diameter and deploys four electrodes. The generator delivers RF in an automated fashion under temperature control using
thermocouple monitoring while the power output is regulated by computer algorithm. Target tissue as well as mucosal temperature
are achieved and maintained through a special suction and irrigation system .
Endoscopy is first performed, the distance from the incisors to the squamocolumnar junction (Z-line) is measured, a super-stiff
guidewire is placed in the duodenum, and the endoscope is removed, leaving the guidewire in place.
The Stretta® catheter, comprised of the bougie tip, balloon/basket assembly, and four electrode delivery sheaths positioned radially around the balloon, is then passed through the mouth
block over the guidewire and positioned up to 1 cm above the Z-line. The wire is then removed. The balloon is inflated and four nickeltitanium needle electrodes (22 gauge, 5.5 mm length) are deployed into the muscle of the GEJ. RF energy is delivered to each electrode, while cooling the mucosa with
irrigation, using the temperature controlled RF generator system described above.
Additional lesion sets are created in the region from 1 cm above to 2 cm below the Z-line by rotating the catheter 45° and varying its linear position. A total of 14 lesion sets are created, a number determined by previous animal model investigations
and the individual patient anatomy. Patients then undergo endoscopy immediately after delivery of RF energy to assess the
early post-RF appearance of the mucosa.
Typically, collagen contraction is seen immediately after RF delivery with tightening of the GEJ [59,60] (Fig. 27).
Mechanisms of action
There are two potential mechanisms of action of Stretta®:
- Mechanical: increased gastric yield pressure (GYP) by 75% and lower esophageal sphincter pressure (LESP) by 21% have been shown in a
porcine model of reflux. After Stretta®, increased muscular wall thickness has been shown histopathologically in a canine model and endosonographically in a porcine
model. A modest increase of the lower esophageal sphincter pressure (LESP) 6 months after Stretta® has also been found in a recently reported human trial.
- Neurological: decreases in the tLESR frequency by 54% in a canine model and by 2544% in two human Stretta® studies incorporating 3-h postprandial esophageal manometry and pH monitoring after a standard meal have been reported .
The following complications have been encountered with Stretta®: bleeding 0.17%, mucosal ulceration 0.08%, pleural effusion 0.08%, perforation 0.33%, aspiration/death 0.17%. The total number of complications with 1200 procedures is 0.83%. In order to prevent such complications patient
selection is paramount. Technical considerations, such as catheter placement < 1 cm above the Z-line, balloon distension to ~2.5 psi, proper sedation, endoscopy confirmation after the first set or therapy, guidewire catheter placement, and adherence
to patient management guidelines have played a role in curtailing the number of complications .
Endoscopic implantation of bulking agents
The injection of bulking agents that are of low viscosity to traverse a needle and then change to a solid state at the local
injection site has been studied for many years . The site of injection is near the squamocolumnar junction in a circumferential fashion.
The injection needle diameter must match implant viscosity. Preferably, 2327 per cent gauges are used since they are easier to manipulate and atraumatic enough to minimize back-leak of the implantable
material from the puncture site.
The depth of implant (submucosal or intramuscular) also varies depending on the material, which tends to flow 12 cm up or down from the injection site. If a submucosal injection is made, the endoscopist observes a bulging effect.
If not, and a deeper implantation is desired, fluoroscopy is used. Initial trials with bulking agents were performed using
Teflon paste and bovine dermal collagen in a refluxing dog model. These trials showed that there is a transient increase in
gastric yield pressure and a decrease in esophagitis 
Inert polymer microspheres
Inert polymer microspheres made of polymethyl-acrylate (PMMA, Plexiglass) dispersed in gelatin solution have been injected
into the mucosa of the lower esophageal sphincter region in 10 patients, aiming at persistent bulking of the gastroesophageal
junction barrier. The microspheres resist phagocytosis and do not migrate, thereby providing durability for the effect. The
mean follow-up of patients in that study was 7.2 months and 70% of patients were off medications at last follow-up. The procedure
has not been approved in the US, and wide-application and long-term data are lacking .
Deep implantation of ethinyl-vinyl alcohol (Enteryx, Enteric Medical Technologies, Palo Alto, CA), an inert, biocompatible polymer, through a sclerotherapy needle under fluoroscopy
has been recently studied. Seventy-five patients received the biopolymer injection under fluoroscopic guidance to confirm
intramuscular injection. The procedure lasted about 1 h and there were no serious complications other than chest pain for
up to 1 week following the procedure  (Fig. 28).
Expandable hydrogel prosthesis (Gatekeeper)
The procedure involves submucosal placement of an expandable miniature hydrogen prosthesis in the region of the gastroesophageal
junction under direct endoscopic visualization. After placement, the prosthesis swells up and bulks the LES region (Medtronics,
Minneapolis, MN) . A pilot study with nine patients reported significant improvement of GERD health-related quality of life scores at 1 month.
Proper positioning of the prosthesis was confirmed by endoscopic ultrasound in eight of the patients. Minimal complications
were reported. Long-term data are awaited.
The placement of the prostheses in the submucosa of the esophagus can be performed under conscious sedation. After endoscopic
inspection of the esophagus, stomach, and duodenum a guidewire is placed in the duodenum.
The Gatekeeper System uses a 16 mm over-tube as a conduit for the endoscope and for the 2.4 mm diameter hydrogel delivery system. Distally
in the over-tube a shelf is present in a rigid segment. The endoscope (contained within the lumen of the over-tube) and over-tube
are passed into the lower esophagus over a guidewire.
Once in position, suction is applied via the endoscope, which pulls the esophageal wall into a shelf at the end of the over-tube.
A conventional injection needle is passed through a second channel in the over-tube and saline is injected into the submucosal
tissue, creating a tissue bleb or submucosal pocket. The injection needle is removed and the prosthesis delivery system (1
mm diameter needle, dilator and 2.4 mm diameter trocar) is passed through the same channel and advanced into the tissue bleb.
The needle assembly and dilator are then removed, leaving the sheath in the submucosal plane. A dry 1.5 mm diameter by 18 mm long hydrogel rod is then loaded into the proximal end of the sheath and advanced with a push rod through
the sheath into the submucosa. Once the hydrogel has been delivered the push rod and sheath are removed. Finally, the sheath
can be pulled out of the submucosa and the fold is removed from the chamber by inflating some air, and slightly twisting the
over-tube. Axial rotation or further insertion or removal of the over-tube repositions the shelf to place additional prostheses.
The complete procedure takes approximately 15 min for one hydrogel and 5 min for each additional hydrogel. Regardless of the number of deliveries only one pass of the over-tube and endoscope is required.
Within 24 h the prostheses expand to their full state, creating submucosal swellings in the esophageal wall, thus creating
a mechanical anti-reflux barrier (Fig. 29).
Endoscopic plication systems
Endoluminal gastric plication (ELGP)
This is an endoscopic suturing method introduced by CR Bard, Inc. (Murray Hill, NJ) under the name Endocinch. The procedure requires two endoscopes and an over-tube . The first endoscope carries the metal sewing capsule on its tip. The second endoscope cinches the sutures through a catheter
device that deploys a ceramic plug and ring through which the sutures are threaded. A short, 18 mm OD over-tube allows for repeated (~10) intubations.
Two to three plications are usually performed either longitudinally (one above the other), radially (next to each other),
or spirally at the lesser curvature side of the cardia within 1 cm below the squamocolumnar junction. Each plication is formed by two sutures which are placed into the gastric submucosa,
about 1.5 cm apart, and then pulled together.
After correct placement of the sewing capsule, suction is applied, the gastric wall is pulled into the hollow chamber of the
capsule, and a straight needle loaded with non-absorbable prolene 3-0 suture is fired through the suctioned tissue. After
placement of the second suture, the two stitches are pulled together and cinched by the ceramic plug and ring using the second
endoscope. Depending on anatomy and technical expertise, the procedure takes 4060 min  (Fig. 30).
The procedure intends to alter the anatomy of the gastric cardia and the angle of His by tightening the lax open end of the
cardia within the lesser curve accentuating the angle of His. The majority of the stitches are placed submucosally, not transmurally,
just below the squamocolumnar junction. Complications may include sore throat, minor bleeding, transient dysphagia, and mucosal
Currently undergoing human clinical trials and not yet FDA-approved, this device (NDO Surgical Inc., Mansfield, MA) uses a
small caliber endoscope to visually guide the plication device . Both are then retroflexed to view the cardia region at the greater curvature side, just 1 cm below the squamocolumnar junction. After such positioning, a set of jaws is opened and a catheter with a corkscrew tip
is advanced and screwed into the muscularis propria of that area bringing the gastric wall into the span of the jaws.
Upon closure of the jaws, one large plication is accomplished using a double-pronged rivet-like implant opposing two full
thickness portions of the cardia wall (Fig. 31). Over time, the serosal sides of the gastric wall fuse and tighten the cardia, and accentuate the angle of His.
The procedure was introduced at DDW 2001 and its efficacy with six patients in India was reported. All plications were successful
and there were no complications. These patients had 80% reduction of GERD scores at 3 months, five out of six were completely
off medications, and pH scores were improved.
Boston Scientific device
Using a special device (Boston Scientific/Microvasive, Natick, MA) the distal esophagus and proximal fundus are grasped, folded, and remodeled to create a valvular
structure comparable to that of a Nissen fundoplication. A small caliber gastroscope is advanced through the lumen of the
grasping device so that the procedure can be performed under endoscopic visualization. Bioabsorbable clips are used to fasten
the esophageal and gastric tissue together. Clinical experience thus far is limited to adult baboons but the method appears
Outstanding issues and future trends
GERD is a Western world pandemic and will remain a major health problem in the near future as the developing world modernizes.
Although of lesser impact on morbidity and mortality, GERD will continue to chronically compromise quality of life and thus
will contribute to large health-care costs. An increasingly sophisticated set of tools and devices will be available that
will allow easier and more accurate diagnosis and definition of disease severity.
Endoscopic enhancement technologies (chromoendoscopy, magnification endoscopy, etc.) will allow easier, more specific recognition
of inflammatory, metaplastic, or neoplastic changes of the esophageal mucosa. In vivo functional measurements (such as intracellular pH, cell permeability, cell integrity) and optical measurements of the depth
and nature of injury will provide an additional dimension of the dysfunction associated with a given endoscopic appearance
Barrett's esophagus will be detected more and more frequently as transnasal endoscopy enters daily office practice as a screening
tool, and surveillance practices will be better defined and provide maximum benefits with minimization of costs.
Peptic strictures will probably vanish because of early therapy. Pharmacological therapy will continue aiming at complete
symptom control in GERD, but it will carry with it the need for chronic medication use.
Quick-fix approaches, such as endoscopic therapy, fundoplication, or laparoendoscopic approaches will continue to evolve and
will play a major role for this chronic disease.
All this progress will require an increasingly frequent exchange between gastroenterologists and surgeons, who will work together
in centres of excellence to care for such patients.
Dr Triadafilopoulos is a consultant to almost all the major pharmaceutical companies that are active in the area of gastroesophageal
reflux. He has received funding for studies, seminars, and travel from such companies and has an equity position in Curon
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