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Keywords
Endoluminal gastroplication (ELGP), endotherapy,
gastroesophageal reflux disease (GERD).
Introduction
There is an ongoing rebirth of interest
in the endoscopic management of gastroesophageal reflux disease
(GERD) which will ultimately succeed in providing dependable,
reasonably durable, and repeatable procedures for the endoscopic
management of this problem. We are in the infancy of endotherapy
for GERD.
Early efforts at endoscopic control of GERD
were reported in the 1980s and 1990s. These are well summarized
in a Gastrointestinal Endoscopy editorial by Glen Lehman (1).
The methods studied can be divided into two approaches--bulking
and scarification at the esophagogastric junction (EGJ). Tissue
bulking attempts in dogs using bovine dermal collagen and
Teflon paste at the University of Indiana reported encouraging
results in 1984 (2). This experience translated into a human
pilot study using the collagen preparation injected submucosally
at the EGJ with clinical benefits lasting up to six months
in duration (3). In 1990 a team from the University of Chicago
reported the use of 5% sodium morrhuate injected submucosally
into the cardia of dogs followed four years later by a small
experience in 15 humans (4,5). A report surfaced in 1990 describing
an attempt at scarifying the cardia in dogs with an Nd:YAG
laser (6).
Paul Swain began his development of the
endoscopic suturing device in the 1980s. His device is a miniature
sewing machine in design. In 2000 he submitted an abstracted
report of the use of this device in slightly over 100 patients,
some of whom were followed for four years (7). In this same
year the multicenter US trial using the same device in 64
patients was reported during DDW and subsequently after six
months of follow-up, this same experience was published in
Gastrointestinal Endoscopy (8). Two other mechanical methods
for altering the EGJ have been presented in abstract form
which differ significantly from the Swain suturing device
(9-11).
Coagulation of the LES was reported initially
in a porcine model and subsequently in human trials in 2001
(12-14). Injection therapy into the submucosa and the LES
have been resurrected most recently (15,16). Self-expanding
implants into the LES has also been recently reported (17)
(Figures 1 and 2).
The Challenge of the Anatomy
The lower esophageal sphincter from the
endoluminal view involves the distal rosette of esophageal
folds or “cushions” within the distal 2 cm to
3 cm of the esophagus and extends down below the normally
located “Z-line” into the cardia for 1 cm to 2
cm. This is the anatomic region targeted for endoscopic intervention.
Perhaps more important than the distribution of the entire
LES is the lowest component endoluminally viewed as the collar
of cardia tissues which comprise the angle of His along with
the open area within this horseshoe-shaped collar, the lesser
curvature component of the cardia (Figure 3). This anatomy
has been well described (18,19). In the majority of patients
with GERD this collar of tissue is patulous and may have a
flattened appearance as well, ultimately disappearing in the
presence of a hiatal hernia (20).
The options for endoscopic treatment include
(Figure 4):
1. Altering the LES
2. Creating a barrier at the EGJ
3. Altering the cardia and angle of HIS
There are no suturing or other mechanical
methods reported which alter the actual LES. The earlier methods
mentioned above have attempted to create a barrier in the
region of the LES by means of bulking the area or stimulating
contraction and fibrosis of the cardia submucosal tissues
(i.e. a stricture).
Inducing fibrosis of the submucosal gastric cardia has failed
to result in any clinical improvement. This is not surprising
since this region will rapidly replace the damaged tissues
with normal tissue. It is conceivable that inducing a stricture
of the esophagus akin to that encountered subsequent to sclerotherapy
of varices can improve reflux symptoms. A fibrosing or other
type of stricture of the esophagus is more durable compared
to the cardia, but unfortunately results in dysphagia. Soft
and compressible (i.e. with passage of swallowed materials)
bulking within the cardia may provide the necessary barrier
and avoid dysphagia.
Bulking with collagen at the esophagogastric junction resulted
in measurable clinical improvement for the ten patients involved
in the single reported clinical study over a six month period
(3). Although the investigators abandoned this method because
of the multiple sessions required to achieve clinical improvement
and the six month maximum symptom control, the study offered
a very important observation. This observation was that bulking
can alter the cardia/His anatomy sufficiently to improve symptoms.
It predicted that other methods such as suturing should be
effective. Experience with the control of urinary incontinence
by means of submucosal injection has identified that the dissipation
of injected materials can be prevented if the injected material
consists of particulate matter > 80 µ in diameter.
This has stimulated the use of micro (Plexiglas) and macro
(polymer) therapies.
There are currently two prevailing FDA approved therapies
for GERD- endoluminal gastroplication by suture and radiofrequency
coagulation of the LES and the neuronal elements within the
esophagogastric junction.
The goal for successful endoscopic suture or single plication
therapy for GERD is to mechanically alter the cardia/His anatomy.
This can be accomplished several ways:
1. Tightening the lax open end of the cardia horseshoe within
the lesser curve
2. Creating a barrier (“speed bump”) within the
lesser curve at the level of the cardia (simulating bulking)
3. Altering the angle of His by accentuating it
4. Altering the angle of His by lengthening it
The goal for coagulation therapy is to:
1. Created a tightening of the LES by scarring
2. Impair sensation of reflux by neuronal destruction
3. Impair the physiology of the LES by reducing transient
lower esophageal sphincter relaxations
Endoluminal Gastroplication (ELGP)
This is the endoscopic suturing method initially
made available by CR Bard, Inc.—Endocinch.
It is the commercial version of Swain’s miniature endoscopic
sewing machine. A new device is also available, the ESD by
Wilson Cook Medical (Winston-Salem, NC).
The Endocinch method requires two endoscopes and an overtube.
One endoscope carries the metal sewing capsule offset and
attached to the endoscope tip. The second endoscope allows
“cinching” of the sutures by means of a catheter
device which deploys a ceramic plug and ring through which
the sutures are threaded (Figures 5-7).
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Figure
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Figure
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Figure
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Figure
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Video
Clip 1: Endocinch endoluminal
gastroplication. A case is provided which illustrates
the creation of three plications within the gastric
cardia.
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ELGP is performed by creating two to three
“plications” arranged variably, side-by-side (circumferentially)
and/or in a row one above the other (longitudinally). These
are placed within the open end (lesser curvature) of the cardia
within one to two centimeters of the squamocolumnar junction.
Each plication is formed by two stitches placed into the gastric
wall approximately 15 mm apart and then drawn together. Stitch
depth is variable but in the majority they are at the level
of the submucosa. Stitch depth is dependent upon suction of
the gastric wall into the hollow chamber of the sewing capsule
at which point a straight needle loaded with non-absorbable
prolene 3-0 suture is driven through the suctioned gastric
tissue. The two stitches and associated mounds of gastric
tissue are then “cinched” together under tension
by placement of the ceramic plug and ring. The procedure is
dependent upon the placement of a short 18 mm OD overtube
which allows the 7-10 intubations to be performed over an
overall procedure time of 40-60 minutes. Hiatal hernias up
to 4 cm have been included in these procedures (Figure 8 and
Video Clip 1).
The same procedure can be performed with the Wilson Cook ESD
(Figures 9 and 10). This device is modeled after a laparoscopic
suturing system. Similar to the Bard Endocinch device, a non-absorbable
suture is placed into the gastric wall by a straight driven
needle after the gastric tissues have been suctioned into
the hollow at the tip of the device. The ESD allows two stitches
and consequently a plication to be created with a single passage
of the suturing device which is an improvement in the efficiency
of endoscopic suturing. The sutures are similarly cinched
under tension by means of crimping a short metal cylinder
through which the sutures have been threaded via a second
semiflexible “knotting” device. Unlike the Bard
system, the ESD is operated through a side sleeve attached
along the length and tip of the endoscopic insertion tube.
This offers more maneuverability of the endoscope and a full
viewing field. The ESD is manipulated, in and out, and can
be rotated, independent of the endoscope. Stitch depth with
the ESD is may be more variable than with the Endocinch device,
although the latest version offers a dramatic improvement
in stitch depth consistency. The suturing device at present
is more flexible than the crimping device. Manipulation of
the later device to stitch sites can be challenging at times.
This more often occurs when the ESD is being used for reasons
other than GERD therapy, e.g. closure of fistulas.
Single Full Thickness Plication Method
The latest mechanical device which is currently
undergoing a clinical trial, ultimately to acquire FDA approval,
is the NDO Endoscopic Plication System (NDO Surgical, Inc.,
Masfield, MA) (9,10) (Figure 11). This device was originally
dependent upon an overtube for its operation. A small caliber
endoscope is used to visually guide operation. Both endoscope
and the plication device are operated in a retroflexed position
to view the cardia anteriorly, within 1 cm of the squamocolumnar
junction. Once position is obtained, a set of jaws are opened,
spanning this area. A catheter with a corkscrew-type tip is
advanced and screwed into the muscularis propria. This allows
the entire thickness of the gastric wall to be drawn into
the span of the jaws at which point the jaws are closed creating
one large plication opposing two full thickness portions of
the cardia wall. A set of hollow spikes (akin to a snake’s
fangs) is driven through these tissues which places a knotted
loop of prolene suture with each T-bar end pre-loaded into
the spikes, under sufficient tension to appose both layers
of serosa from each portion of gastric wall. In time the serosal
layers fuse creating a (probably permanent) large plication
which both tightens the collar of cardia tissue and probably
also accentuates the angle of His. There is no experience
with hiatal hernias.
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Video
Clip 2: NDO transmural gastroplication
procedure. Creation of this large plication involves
the angle of HIS, anteriorly. The procedure is
performed with the stomach hyperdistended with
air and the endoscope in a retroflexed position
in order to carefully monitor each step of the
procedure. The transmural plication is held together
by placing non-absorble sutures with the large
jaws of the device, also operated in a retroflexed
position.
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The device used in the multicenter clinical
trial was not user friendly. It required multiple labor intensive
steps to complete a plication and carried significant risk.
The procedure was often performed with two endoscopists--one
to operate the endoscope and the other to operate the device.
Both device and endoscope must be passed through a very large,
23 mm diameter overtube, which alone carried inherent risk.
In order to successfully retroflex the plication device, the
stomach must be hyper-distended using a supplemental air flow
via the working channel of the endoscope which can lead to
pneumoperitoneum if more than one set of punctures are created
(Video Clip 2).
The results of the multicenter study were very encouraging.
At one year nearly three-fourths of patients were completely
off of PPIs. Ambulatory pH normalized in one-third of patients.
The manufacturers of the plication device
have developed a commercial version of the device which is
not overtube dependent, is more user friendly, and has a smaller
outer diameter. These modifications will be very appealing.
This second generation device is currently undergoing testing
in Canada and South America.
Coalgulation Injury
The Stretta procedure surfaced at nearly
the same time as the Endocinch procedure. Both the technique
and the device have undergone modification since its first
release as an FDA approved device. The goal for this procedure
is to thermally injure the LES and the nerve plexus in close
apposition by means of multiple sets of radially placed radiofrequency
(monopolar) point coagulations. The mechanism by which this
injury produces benefit is to reduce the number of transient
lower esophageal sphincter relaxations, alter tissue compliance
and wall thickness of the LES and gastroesophageal junction.
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12 |
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Figure
13 |
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Figure
14 |
The procedure is dependent upon exact measurements
of the squamocolumnar junction and the passage of the wire-guided
device which is a semi-flexible catheter with a bougie-type
tip, 18 mm basketed distal balloon (proximal to the bougie
tip), and four nitinol 5.5 mm retractable needles. The coagulating
current is passed through these needles (Figure 12).
The delivery of the coagulating injury is continuously monitored
on a screen which provides feedback on impedence (needle tip
position), tissue temperature, and mucosal temperature (graphically
displayed). The mucosal temperature can be controlled by water
flow from the basket straps overlying the balloon.
The procedure requires meticulous attention to the distance
of the squamocolumnar junction from the incisors, the monitor
screen, balloon inflation pressure, and patient sedation.
The procedure is painful for the patient, especially during
injury of the esophageal component of the LES. Coagulation
is begun 1 cm above the “Z-line” and proceeds
in 0.5 cm increments into the cardia. After the cardia has
undergone the step-wise coagulations for a 2 cm distance,
a traction-type series of additional coagulations are performed.
After each set of 4 point coagulations (which take 90 seconds
to perform each set), the device is rotated 45 degrees and
another set is performed. Approximately 15–25 sets of
coagulations are performed in each patient. The procedure
takes approximately 45–50 minutes to perform (Figures
13 and 14).
Polymer Injection
The most simple method involves the needle injection of a
polyvinyl alcohol polymer suspended in DMSO and admixed with
tantalum powder for radiopacity—Enteryx (Boston Scientific
Corp, MA). The polymer is in a liquid state at room temperature
and after injection transforms into an expanded spongy semisolid
material. Animal histologic studies indicated that this material
eventually becomes encapsulated by fibrous tissue similar
to a foreign body response (Figure 15). For durability, the
polymer must be injected deeply into the cardia, ideally within
the muscularis propria, and in close proximity to the squamocolumnar
junction. The mechanism by which this material is effective
is unknown. It intuitively alters compliance at the level
of the esophagogastric junction.
The technique requires a few minutes and is monitored by fluoroscopy.
An average amount of material used in a treatment session
is 4 ml. Successfully injected polymer will be seen by fluoroscopy
to be concentrated in a focal area (Figure 16). There is no
obvious change seen intraluminally.
There is experience with this method for two years in Europe
with very favorable results. The FDA is soon to decide on
release of Enteryx for widespread clinical use in the US.
Its use will be controlled by the manufacturer and similar
to Endocinch and Stretta, it will require completion of a
training program.
The Outcome of Endotherapy
The first published clinical experience
involving the Bard Endocinch method was on the original FDA
approval study. This method provided significant improvement
in heartburn scores and regurgitation. Sixty-two percent of
the 64 patients either stopped or significantly reduced their
medications. There were no significant changes in pretreatment
esophagitis of grade 2 in or 3 in classification (Savary-Miller
scale). There was no significant change in the 24-hour ambulatory
pH except for a significant reduction in the number of reflux
episodes. Plications were not intact at in those patients
who experienced no symptomatic improvement. A long-term domestic
follow-up experience is soon to be reported and a sham control
study has been completed but not reported. A 12 month follow-up
experience with Endocinch was reported in a study group of
26 patients from abroad. In this experience PPI use was reduced
in 64%. There was a measurable but not statistically significant
reduction in pH with a statistically significant improvement
in the DeMeester score (21). In our own experience of over
100 patients, improvement in heartburn and regurgitation was
observed in 68% with benefits lasting from two weeks to over
three years. Sixty-five percent of patients have reduced medication
usage to less than one dose per month and of those patients
using PPIs, only 20% have been completely off of this type
of medication. Complications include universal sore throat,
bleeding, and, in our own experience, two incomplete perforations
(capsule induced intramural dissections)- gastric and esophageal.
The NDO method was introduced at DDW 2001 in an experience
involving six patients in whom the procedure was performed
in India. At three months there was an 80% reduction in GERD
symptom scores. Five of the six patients were completely off
of medications. Ambulatory pH scores were improved. All plications
were intact. In our own experience with this method, all patients
have at one year follow-up been free of symptoms, have normalized
their ambulatory pH tests, and in one patient who underwent
an endoscopy for other reasons, had an intact plication.
Six and twelve month follow-up data was reported on the Stretta
procedure (14). This experience looked at GERD symptom scores,
quality of life (SF-36), and medication use. Significant improvement
was reported in all areas. PPI use was reduced to 30%. Esophageal
acid exposure was improved (10.2% to 6.4%). No serious complications
were reported. There have however been serious and fatal complications
associated with this procedure, predominantly related to perforation
and sedation. Stretta has also been studied via a sham protocol
with results supporting the benefit of the procedure.
There is currently no reported experience with the Wilson
Cook ESD device in humans for control of GERD. This experience
is just occurring and will likely increase as the newer improved
version of the device is made available. In personal use of
this device for closure of postoperative fistulas in the esophagus
and duodenal bulb, there have been no complications.
Enteryx, based upon the European experience, has been safe
and has had results as favorable or better than the other
modalities in symptom control, elimination of PPI usage (80%),
lengthening of LES by manometry, and normalization of pH (35%).
There is no experience with these methods specifically addressing
Barrett’s esophagus. All of these methods have specifically
excluded all but short segment Barrett’s esophagus in
their clinical studies. Hiatal hernias up to 2 cm have been
included in treatment with all of these procedures. Endocinch
has been performed in hernias as large as 4 cm.
There have been no studies with any of these methods looking
at healing of esophagitis. All of the techniques have included
patients with up to grade II esophagitis, with some exceptions.
None of these methods have been able to demonstrate healing
of pre-existing erosions. This may not be important depending
on whom the target population for this type of therapy is
intended.
SUMMARY
Endoscopic techniques for control of GERD have potential for
effective control of symptoms. This potential for success
has been demonstrated by these early groundbreaking efforts
which are vast improvements over the much earlier attempts
in the 1980s and early 1990s. Emerging methods such as ELGP
and Stretta offer greater potential for successful control
of GERD than earlier efforts. Full thickness mechanical methods
are the most appealing but must be proven to be safe, especially
from the perspective of perforation, sepsis, and injury to
the vagal nerve trunks. Larger hiatal hernias are likely to
be problematic for all methods. The use of these methods in
patients with Barrett’s esophagus must be resolved.
At the present time, the ideal patient for whom endoscopic
therapy for control of GERD is an option is the patient with
typical uncomplicated reflux symptoms who is well controlled
on prescription medications who is seeking an alternative
to drug therapy. These are the patients who face lifelong
symptoms and predictably are unlikely to have complications.
These are the patients with non-erosive reflux disease (NERD)
for whom endotherapy becomes a viable option.
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