World J Surg (2010) 34:750757
DOI 10.1007/s00268-010-0394-7
Effect of Transoral Incisionless Fundoplication on Symptoms,
PPI Use, and pH-Impedance Refluxes of GERD Patients
Pier Alberto Testoni Maura Corsetti
Salvatore Di Pietro Antonio Gianluca Castellaneta
Cristian Vailati Enzo Masci Sandro Passaretti
Published online: 21 January 2010
Societe Internationale de Chirurgie 2010
Abstract
Background Three previous studies from the same insti-
tution have reported that transoral incisionless fundopli-
cation (TIF) with the EsophyX device is effective for
creating a continent gastroesophageal valve and for good
functional results as measured only by pH-metry in patients
with gastroesophageal reflux disease (GERD). The objec-
tive of the present study was to evaluate the effect of TIF
on symptoms, use of proton pump inhibitors (PPI),
esophageal motility, and pH-impedance in patients with
symptomatic GERD.
Methods Twenty consecutive patients were enrolled to
complete the GERD-HRQL and GERD-QUAL question-
naires while on and off PPI. They were also examined by
upper gastrointestinal (GI) endoscopy to determine Hill
grade and Jobe length of the gastroesophageal valve, and to
check for hiatal hernia and esophagitis, esophageal
manometry, and pH-impedance before and 6 months after
TIF.
Results Six months after TIF, the GERD-HRLQ and
GERD-QUAL scores off-PPI therapy and the number of
total and acid pH-impedance refluxes were significantly
reduced (p \ 0.05). The PPI had been completely stopped
in 55% of the patient and was reduced in 22% of the
patients.
Conclusions At 6-month follow-up, TIF performed using
the EsophyX device reduces symptoms and pH-impedance
P. A. Testoni (&)
M. Corsetti
S. Di Pietro

A. G. Castellaneta
C. Vailati
E. Masci
S. Passaretti
Division of Gastroenterology and Gastrointestinal Endoscopy,
San Raffaele Scientific Institute, Vita-Salute San Raffaele
University, via Olgettina 58, 20132 Milan, Italy
e-mail: testoni.pieralberto@hsr.it
123
refluxes, allowing interruption or reduction of PPI use in
78% of patients with GERD.
Introduction
Gastroesophageal reflux disease (GERD) is a very common
disorder caused by reflux of the gastric content into the
esophagus. The disease clinically presents mainly with
heartburn, retrosternal pain, or regurgitation, and endo-
scopic examination may or may not find esophagitis. These
symptoms can significantly impair the quality of life [13]
and generally recur once medical therapy is stopped. Reflux-
related long-term complications are Barretts esophagus and
in some cases esophageal adenocarcinoma [4, 5].
The goals of treatment are to relieve symptoms, heal
esophagitis, and prevent the recurrence of symptoms and
complications. Antisecretory drugs and surgery relieve
symptoms and improve the patients quality of life, pre-
venting endoscopic and symptomatic relapse [57]. Con-
cerns related to medical therapy are the need for continued
long-term medication to prevent the recurrence of esoph-
agitis and/or symptoms, drug intolerance or unresponsive-
ness, and the need for high dosages for long periods to heal
the lesions and relieve symptoms or prevent relapses in
patients with extra-esophageal symptoms.
In the last decade, technological innovations for the
treatment of GERD have led to the transoral endoluminal
approach. A variety of endoscopic techniques aimed at
reinforcing the barrier function of the lower esophageal
sphincter (LES) have been proposed or are under study as
alternatives to antisecretory therapy or antireflux surgery
[8, 9]. These endoscopic strategies all appeared promising
to begin with, but many were abandoned because of dis-
appointing long-term results [10].
World J Surg (2010) 34:750757
A novel transoral incisionless fundoplication (TIF)
technique can now create an omega-shaped, full-thickness
gastroesophageal valve from the inside of the stomach,
using the EsophyX device (Endogastric Solutions, Inc.,
Redmond, WA), that delivers multiple fasteners under
direct endoscopic view. Transoral incisionless fundoplica-
tion with the EsophyX device was documented in a canine
model as a feasible, effective, safe, and natural means of
performing orifice surgery for GERD [11]. Three studies in
humans from the same institution confirmed these findings,
showing both the persistence of the newly created valve at
1 and 2 years and good functional results as measured only
by pH-metry [1214].
The aim of the present study was to assess the effect of
TIF on symptoms, PPI use, esophageal motility, and pH-
impedance findings in a consecutive series of patients with
symptomatic GERD.
Materials and methods
Patients
Over an 18-month period we enrolled 20 consecutive
patients (12 men, age 45 14 years, body mass index
[BMI] 24 3), with symptomatic GERD, as defined
according to Rome III criteria [15] and as judged by GERD
health-related quality of life (GERD-HRQL) scores of 20
or more after discontinuation of proton pump inhibitors
(PPI) for at least 14 days. Eight patients were completely
responsive to PPI at a standard dose twice a day for at least
4 weeks, eight were partially responsive (as defined by a
GERD-HRQL [12 on a standard dose twice a day for at
least 4 weeks), two were not responsive at all, and two
were intolerant to PPI.
Exclusion criteria were esophagitis grade D in the Los
Angeles classification; hiatal hernia [3 cm long;
BMI C 35; biopsy-proven Barretts esophagus; esophageal
stricture; previous esophageal, gastric, or major abdominal
surgery; and other severe co-morbidity (including cardio-
pulmonary disease and collagen disease).
Written informed consent for the procedure and data
management for scientific purposes was obtained from all
patients, and the protocol was approved by the medical
ethics committee of the San Raffaele Scientific Institute of
Milan.
Study protocol
At enrolment a full medical history was taken for all
patients, including GERD medication usage, and they
completed the GERD-HRQL and the GERD-QUAL ques-
tionnaires while on a standard dose of PPI (20, 30, or
751
40 mg) twice a day. The PPI was then discontinued for
14 days, and the patients were asked to complete the two
questionnaires once again. Any drugs influencing gastro-
intestinal motility were also discontinued 14 days before
each study. The patients then underwent: upper gastroin-
testinal (GI) endoscopy to determine the Hill grade and
Jobe length of the gastroesophageal valve, the presence and
size of hiatal hernia, the presence and severity of esopha-
gitis according to the Los Angeles grading system [16];
scintigraphic recording of gastric emptying time; stationary
esophageal manometry and 24 h ambulatory pH-imped-
ance monitoring.
The GERD-HRQL and GERD-QUAL questionnaires,
upper GI endoscopy, esophageal manometry and pH-
impedance were repeated 6 months after the TIF. During
these 6 months, patients were asked to keep a daily diary
reporting the use of PPI. This was defined as continued
when the daily drug dose was the same as before the
procedure; reduced when any daily dose of PPI was
taken for less than 50% of the total number of days during
follow-up; and completely stopped when not a single
dose of PPI was taken during the follow-up.
GERD-HRQL and GERD-QUAL questionnaires
The GERD-HRLQ is a validated 15-item questionnaire that
measures the symptom severity of GERD patients. Six
items measure satisfaction with the degree of heartburn;
two, dysphagia; one, with the impact of medication on
daily life; and six, with regurgitation. Each item is scored
from 0 to 5. One item measures overall satisfaction with
the present condition [17]. The GERD-HRLQ total score
was calculated for each patient as the sum of the individual
item scores [17].
The GERD-QUAL is a validated 37-item questionnaire
that measures the quality of life in GERD patients; each
item is scored from 1 to 5 [18]. The GERD-QUAL total
score was calculated for each patient as the sum of the
scores for the individual items [18].
Geometric aspects of the gastroesophageal valve
The geometry of the gastroesophageal valve were deter-
mined by measuring the Jobe length, defined as the dis-
tance (in centimeters) from the apex of the fundus to the
valve lip [19, 20], assessed by means of a standard biopsy
forceps with open valves (4 mm wide), and the Hill grades
[21], determined as follows:
Grade I: a prominent tissue fold surrounding the
endoscopic shaft;
Grade II: a moderately prominent tissue fold that rarely
opens with respiration and closes promptly;
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752
Grade III: a barely present fold that fails to close around
the endoscope;
Grade IV: lack of a muscular fold; the esophageal lumen
stays open all the time, allowing the squamous epithe-
lium to be viewed from below.
Jobe length and Hill grade of the gastroesophageal valve
were determined before the procedure and during the fol-
low-up period by an endoscopist involved in the study but
not in the fundoplication procedure.
Gastric emptying time by scintigraphy
Gastric emptying time was measured by scintigraphy, as
previously reported, after patients had ingested a Tc-99
standardized meal [22]. The half-emptying time (t1/2) was
recorded for each patient.
Stationary esophageal manometry
After an overnight fast, a 12-French diameter, PVC water-
perfused catheter for esophageal manometry with six
recording side holes (Bioengineering Laboratories SpA,
Meda, Italy) was introduced transnasally. Esophageal
manometry was then performed in the usual way with a
stationary pull-through technique for localization and
measurement of the resting pressure of the LES and
esophageal motor function [23]. The mean LES pressure
and distal esophageal amplitude (DEA) were calculated.
24 h pH-impedance
After removal of the manometry catheter, a 24 h ambula-
tory pH-impedance catheter (VersaFlex Z, Alpine Biomed
Corporation/Natus Medical, San Carlos, CA) was intro-
duced transnasally and placed 5 cm above the LES.
Patients were given a personal diary in which to note meal
times and record time spent in the recumbent position. Data
from the MII-pH probe was transmitted and recorded on a
portable data recorder (Ohmega, Ambulatory pH &
impedance recorder, Medical Measurement System, MMS,
Netherlands). Meal periods were excluded from the anal-
ysis. Liquid reflux, gas reflux, mixed liquidgas reflux, acid
reflux, weakly acidic reflux, and weakly alkaline reflux
were defined as previously reported [24]. The following
parameters were obtained from the impedance and pH
recordings: number of total, acid, weakly acidic, weakly
alkaline reflux episodes, number and percentage of refluxes
with proximal extent (reflux reaching the 15-cm impedance
site), and Johnson-De Meesters score. For comparison,
normal values were obtained from the study by Zerbib
et al. [25] in 72 healthy subjects followed in ambulatory
conditions with non-standardized meals. The 95th
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World J Surg (2010) 34:750757
percentiles obtained in this series were considered the
upper limit of normal. Values of the Johnson-De Meesters
score [14.7 were considered abnormal.
Transoral incisionless fundoplication (TIF 2.0)
with the EsophyX device
Transoral incisionless fundoplication using the EsophyX
device (EndoGastric Solutions, Redmond, WA) is classified
as a suturing technique. It reconfigures the tissue for creation
of the gastroesophageal valve. The procedure was designed
to create full-thickness serosa-to-serosa plications and con-
struct valves 34 cm long and 200300 degrees in circum-
ference. During a single insertion, the neo-valve is created
by retracting tissue from the fundus of the stomach with a
helical retractor. Sufficient tissue can be retracted by mas-
saging the fundus with the mold while simultaneously
pulling on the helical retractor; this gives a 34 cm long full-
thickness serosa-to-serosa plication, which includes the
muscular layers. The retracted tissue is secured by deploying
multiple non-absorbable polypropylene fasteners through
the two layers in a circumferential pattern, around the gas-
troesophageal junction [12]. If there is a hiatal hernia not
exceeding 23 cm in length, it can be reduced by returning
the squamo-columnar junction to its natural position below
the diaphragm by means of a built-in vacuum invaginator.
In our procedure the EsophyX device was inserted
transorally over a standard front-view endoscope (Pentax
EG 2770 K) with the patient in the supine position. The
procedure was done under general anesthesia; one endos-
copist operated the device and controlled the implantation
of fasteners, while another operated the endoscope and
ensured continuous visualization throughout the procedure.
The fasteners were deployed starting at the posterior and
anterior sides of the gastroesophageal valve at the level of
the greater curvature of the stomach, then continuing cir-
cumferentially around the gastroesophageal valve, in order
to create an omega-shaped valve with 200300 degrees of
circumference [12]. This technique (TIF 2.0) differs from a
previous one (TIF 1.0) in which fasteners were deployed
starting at the middle of the gastroesophageal valve.
At the end of the procedure, Hill grade and Jobe length
of the newly created valve and the number of fasteners
deployed were recorded. Patients were scheduled to stay in
hospital overnight and were discharged the next day after
clinical and laboratory examinations; broad-spectrum
antibiotics and PPI were given after the procedure in all
cases. Patients were instructed to follow a liquid diet for
the first 2 weeks and a soft diet for the next 4 weeks. The
PPIs were discontinued 7 days after the procedure.
Outpatient assessment was scheduled by telephone at
postoperative weeks 1 and 2, and again 6 months after the
procedure, as established by the study protocol.
World J Surg (2010) 34:750757 753

Endoscopic fundoplication was performed in all cases Table 2 Esophageal motility and pH-impedance findings in GERD
by the same endoscopist, who had previous experience in patients before and 6 months after TIF
in vivo animal models and human beings. Before TIF 6 months after TIF p Value

Esophageal manometry
Statistical analysis
LES pressure (mmHg) 85 10 3 0.13
Intra- and inter-patient characteristics, GERD-HRLQ and DEA (mmHg) 69 28 73 29 0.74
GERD-QUAL total scores, Jobe valve length, t1/2, LES pH-metry
pressure and DEA, and esophageal pH-impedance findings DeMeester score 20 13 18 17 0.57
were compared by Wilcoxons test and the MannWhitney Impedance
test. Fishers exact test was used to compare frequencies. A Total refluxes (no.) 63 43 43 41 0.02
p value \0.05 was considered statistically significant. Data Acidic 31 19 14 15 0.001
are presented as mean SD. Weakly acidic 31 38 98 0.25
Weakly alkaline 6 11 9 33 0.65
Proximal 26 22 15 16 0.11
Results % Proximal 43 19 31 17 0.06
LES lower esophageal sphincter, DEA distal esophageal amplitude
Clinical and morphofunctional findings before TIF 2.0

Symptoms and medications

All patients had symptoms of heartburn and/or regurgita-
tion at enrolment and had been on PPI maintenance therapy
with a standard dose of PPI (20, 30, or 40 mg) twice a day
for at least 3 months during the period before the
enrolment.
The mean GERD-HRLQ and GERD-QUAL scores off
PPI therapy were significantly higher than the mean score
on PPI therapy (p \ 0.01) (Table 1).
Geometry of the gastroesophageal valve
Esophageal motility, gastric emptying time, and 24 h
pH-impedance
Table 2 illustrates the esophageal motility and 24 h pH-
impedance findings. Eighteen patients had pathological
esophageal reflux as measured by pH-impedance, and two
were within the normal range. The mean gastric emptying
time was 81 44 min.
TIF 2.0 details and geometry of the new
gastroesophageal valve at the end of the procedure

Eleven of the 20 patients had a hiatal hernia 12 cm long, All procedures were successful, with a mean operative time
one had a 2.5-cm hiatal hernia, and another had a 3-cm of 77 21 min. A mean of 10 2 fasteners were
hiatal hernia. Three of these patients suffered from grade A deployed to construct each valve. In all cases hiatal hernias
esophagitis. The Hill grade was II in 16 patients, III in 3 were reduced and the Hills grade of the newly created
patients, and IV in 1 patient. The mean Jobe valve length valve was I; the mean Jobe length of the valve was sig-
was 1.17 0.8 cm. nificantly greater (2.5 0.8 vs. 1.17 0.8 cm; p \ 0.01).
Figure 1 shows the gastroesophageal valve before the TIF
procedure, soon thereafter, and 6 months thereafter in one
patient.
Table 1 GERD-HRLQ and GERD-QUAL mean scores on and off Hospital stay was one day in all cases, as required by the
therapy before TIF and off therapy after TIF
protocol, and no serious complications arose, such as per-
Before TIF p Value* 6 months p Value** foration, bleeding, or severe infection. All patients com-
after TIF plained of mild to moderate epigastric pain in the 6 hours
ON OFF OFF
after the procedure, requiring analgesics in 12 cases (60%);
GERD- 20 14 45 20 0.0006 16 14 \0.001 and 15/20 patients (75%) complained of a 24 h pharyngeal
HRLQ irritation, a result of insertion and manipulation of the
GERD- 80 25 114 29 0.001 74 21 \0.001 device. Four patients (20%) reported mild epigastric pain
QUAL persisting for 35 days, but not requiring analgesics. White
* p ON versus OFF therapy cell count 24 h after the procedure was slightly high
** p OFF after versus OFF before transoral incisionless fundoplica- (12,000 2,700, normal values 4,80010,800) in 18/20
tion (TIF) patients (90%).

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754
Fig. 1 Gastroesophageal valve before (a), soon after (b), and
6 months after the transoral incisionless fundoplication (TIF) proce-
dure (c) in one patient
Clinical and morphofunctional findings 6 months after
TIF 2.0
All patients undergoing the TIF procedure did the tests, as
scheduled in the study protocol; however, the present
analysis included only the 18 patients with pathological
gastroesophageal reflux before the TIF procedure, as
measured by pH-impedence. The two patients with 24 h
pH-impedance within the normal range were excluded
from this follow-up study.
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World J Surg (2010) 34:750757
Symptoms and medication use
The GERD-HRLQ and GERD-QUAL scores off PPI
therapy were significantly lower than before treatment
(p \ 0.01) (Table 1). Six months after treatment, 10 of the
18 patients had completely stopped daily PPI altogether
(55.6%), four had reduced it by more than 50% (22.2%),
and four continued with the same dose as before the pro-
cedure. Esophagitis disappeared in two patients; in one it
was still present, and in three it appeared (Table 3).
Geometry of the gastroesophageal valve
Eight patients (61.5%) no longer had hiatal hernia after
TIF. The Hills grade remained I in 10 patients (55.6%),
but it returned to II in 4, III in 3, and IV in 1. Four of 14
(28.6%) patients with pre-procedure Hills grade II and all
those with grades III and IV returned to the pre-procedure
grade (Table 3). In no cases was the grade worse than
before the procedure. The mean Jobe length of the newly
created valve remained at the immediate post-procedure
value in the 10 patients with persisting Hills grade I, but it
was smaller in the others.
Esophageal motility and 24 h pH-impedance
As reported in Table 1, the LES pressure and the DEA did
not change significantly after treatment. There were sig-
nificantly fewer total and acid refluxes after treatment. The
percentage of refluxes reaching the proximal extent tended
to be lower, whereas the number of weakly alkaline re-
fluxes was not significantly different. The number of
weakly acidic refluxes decreased after treatment, though
not to a significant extent. The De Meesters score did not
change significantly.
Subgroup analysis
Dividing the patients on the basis of PPI use 6 months after
TIF and considering as responders only those who com-
pletely stopped the therapy, comparison of the patients
main characteristics brought to light some differences
before and after the procedure (Fig. 2). Of all the patients
with hiatal hernia, 46% were responders and 54% were
non-responders. The only two patients with a hiatal hernia
[2 cm were non-responders. Further, 72% of all the
patients with a before-TIF Hills grade B2 were responders
and 28% were non-responders (p = 0.05). All the patients
with a before-TIF Hills grade [2 were non-responders,
whereas none of them were responders (p = 0.02). All
responders had Hills grade I at 6 months. Of the patients
with esophagitis before TIF, 33% were responders and
67% were non-responders. Esophagitis persisted or
World J Surg (2010) 34:750757 755

Table 3 Hills grade, presence

Patients Hill grade Hill grade Hiatal hernia Hiatal hernia Esophagitis Esophagitis
(1) or absence (0) of hiatal
before after before after grade before grade after
hernia and esophagitis and Los
Angeles Classification grade, 1 II II 1 1 1a 1b
before and 6 months after TIF
2 II II 1 1 0 0
3 IV IV 1 1 0 1d
4 III III 1 1 1a 0
5 III III 1 1 0 1b
6 II II 1 0 0 0
7 II II 1 0 0 1a
8 III III 0 0 0 0
9 II I 1 0 0 0
10 II I 0 0 0 0
Responders, if they completely 11 II I 1 0 0 0
stopped proton pump inhibitors 12 II I 0 0 0 0
(PPI), are reported in gray 13 II I 1 0 0 0
(entries 918); non-responders,
14 II I 0 0 0 0
in white (entries 18)
15 II I 1 0 0 0
The two patients excluded from
the analysis because of pre- 16 II I 1 0 0 0
treatment esophageal reflux 17 II I 0 0 0 0
within the normal range are not 18 II I 1 0 1a 0
reported

100% barrier function of the LES. However, compared with PPI

Responders Non responders
therapy or surgical fundoplication, endoscopic approaches
72% have not proved so successful in reducing reflux, measured
67%
by 24 h pH-metry and healing esophagitis [5]. A limitation
54% * of these endoscopic techniques was that they did not permit
46%
modifiable, patient-tailored approaches, as can be done
33% with surgical fundoplication.
28%
Transoral incisionless findoplication with the EsophyX
* device was found in a canine model to offer feasible,
0% effective, and safe natural orifice surgery for GERD, cre-
ating a valve similar in shape and circumference to the
Hiatal hernia Hill grade 2 Hill grade >2 Esophagitis valve created by Nissen fundoplication [12].
Fig. 2 Pre-TIF endoscopic findings in responders and non-respond-
Three studies from the same institution in humans have
ers, as defined according to complete cessation of proton pump confirmed the results in the canine model, showing at 1 and
inhibitors (PPI) use at 6 months. * p \ 0.05 2 years the persistence of the newly created valve and good
functional results, as measured only by pH-metry [1214].
recurred after the TIF procedure only in non-responders The present study assessed for the first time the effect of
(Fig. 2). During the TIF procedure itself, significantly TIF 2.0 by means of the EsophyX device in patients with
fewer fasteners were employed in the non-responders than symptomatic GERD, evaluating pH-impedance. Clinical
in the responders (9 1 vs. 10 3; p = 0.02). evaluation 6 months after the TIF procedure showed that
As regards manometry and pH-impedance findings, the GERD-HRLQ and GERD-QUAL scores of patients
responders and non-responders did not differ except for LES off-PPI therapy were significantly lower than before
tone, which was significantly lower in non-responders than in treatment. The numbers of total and acid refluxes as mea-
responders at baseline (5 5 vs. 10 5 mmHg; p = 0.03). sured by pH-impedance were significantly lower, too,
whereas the LES basal pressure did not change; 55.6% of
patients had completely stopped and 22.2% reduced their
Discussion daily PPI use.
The discordance between the relief of overall symptoms
The concept of endoscopic therapies for gastroesophageal and conflicting motility test findings has also been reported
reflux, just like surgery, is to control reflux by boosting the in previous studies evaluating other endoscopic procedures

123
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for gastroesophageal reflux [5]. However, with the present
technique it can be argued that it is more the greater length
of the newly created valve than its pressure that acts as a
barrier to gastroesophageal reflux.
The findings obtained by pH-metry and impedance could
seem contradictory when considered separately. However,
as recently stated, the analysis of the number of refluxes and
their proximal extent allows a quantitative evaluation of the
efficiency of the anti-reflux barrier, while the esophageal
exposure time could express a combination of both anti-
reflux barrier and esophageal clearance failure [26]. A recent
study has demonstrated that the odds of normalizing 24-h
pH-metry after endoluminal gastroplication is significantly
greater in thinner patients with mild reflux disease [27]. Our
results could suggest that the newly created anti-reflux
barrier is efficient while the characteristics of the enrolled
patients (presence of hiatal hernia in the majority of cases),
suggestive of a moderate GERD, do not allow normalization
of pH-metry. Further studies should clarify this aspect of the
treatment in order to define the selection criteria for endo-
luminal therapy in the treatment of GERD patients.
From the technical point of view, 6 months after TIF,
hiatal hernia was no longer detectable in 61.5% of those
who had had it before the procedure; the Hill grade of the
newly created valve was still I in 55.6% of cases and the
Jobe valve was significantly longer in all cases with Hills
grades I and II. In 38.5% of patients with hiatal hernia the
competence of the newly created valve, judging from the
Hills grade, declined over the 6-month period, whereas it
remained unchanged (Hills grade I) in all patients without
hiatal hernia. Hiatal hernia[2 cm was associated with poor
technical results.
The evaluation of Hills grade is subjective, and this
could be a limitation in assessing technical results. In
particular it is difficult to differentiate between a prominent
and a moderately prominent tissue fold surrounding the
endoscopic shaft (Hills grades I and II), while the differ-
entiation between Hills grade III and the more advanced
degrees is easier and reliable in experienced hands. How-
ever, it is the only tool, together with the Jobe length of the
valve, with which to evaluate the morphology of the fun-
doplication by upper GI endoscopy.
Looking at the correlation between anatomical and
clinical data, we observed that only the persistence over
time of a Hills grade I valve allowed patients to stop using
PPIs completely. Considering altogether the 14 patients
with pre-TIF Hills grades I and II, we found that 71.4% of
them (10 cases) completely stopped PPI use. In contrast, a
finding associated with a poor response to TIF was a before-
treatment valve with a Hills grade greater than II, sug-
gesting a seriously impaired gastroesophageal junction. In
these patients the Hills grade returned to the pretreatment
level and the TIF technique in our hands was unable to
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World J Surg (2010) 34:750757
retract sufficient tissue from the fundus to create a robust
valve, as indicated by the smaller number of fasteners we
could fix in these cases. These were the patients in whom
esophagitis recurred or appeared. This observation helps us
to find a possible explanation for poor response to treatment
and suggests, as already reported in previous studies [27],
that patients with more seriously impaired gastroesophageal
junction are probably not the best candidates for endolu-
minal procedures.
The inclusion in the present study of symptomatic GERD
patients, either responsive (completely or not) or non-
responsive to PPI therapy, might be considered question-
able. However, these patients represent a tertiary care cen-
ters normal case mix, so this study could be considered the
first to assess the effect of the EsophyX device on the real
patient every specialist might meet in clinical practice.
The uncontrolled design of the study and the short fol-
low-up period are, of course, a limitation, as they do not
allow exclusion of the placebo effect on the results.
However, the results are in accordance with those of pre-
vious uncontrolled studies with a follow-up period of 1
2 years [13, 14].
In conclusion, the present study found that TIF using the
EsophyX device improved patient symptoms and quality of
life, and that it significantly reduced the number of cases of
gastroesophageal reflux as measured by esophageal pH-
impedance, enabling about 78% of patients to stop or
reduce by less than 50% the PPI use in a 6-month follow-
up. The persistence over time of a robust valve was the
only factor associated with a successful result, and this was
achieved with the current technique only in patients with
pre-procedure hiatal hernia not exceeding 2 cm in length or
with Hills grade \ III valve. Considering our and previous
results, at the moment, the TIF procedure doesnt seem to
represent a substitute for fundoplication surgery but a
complement to medical therapy in those patients with small
hiatal hernias and not severely compromised gastroesoph-
ageal junction who refuse surgery, who partially respond to
PPI therapy (i.e., persistent regurgitation), present esoph-
ageal motility alterations, refuse to continue long-term PPI
therapy, or are intolerant to it. However, long-term and
controlled results on more patients should be obtained
before drawing conclusions about the efficacy of the TIF
procedure and clinical indications for this procedure with
respect to surgical fundoplication.
References
1. Dent J, Armstrong D, Delaney B et al (2004) Symptoms evalu-
ation in reflux disease: workshop background processes; termi-
nology, recommendation and discussion outputs. Gut 53:124
2. De Vault KR, Castell DO (2005) American College of Gastro-
enterology update guidelines for the diagnosis and treatment of
World J Surg (2010) 34:750757
gastroesophageal reflux disease. Am J Gastroenterol 100:
190200
3. Anon R (1999) An evidence-based appraisal of reflux disease
management: the Genval workshop report. Gut 44(Suppl 2):S1
S16
4. Locke GR, Talley NJ, Fett SL et al (1997) Prevalence and clinical
spectrum of gastroesophageal reflux: a population-based study in
Olmsted County, Minnesota. Gastroenterology 112:14481456
5. Richter JE (2007) The many manifestations of gastro-esophageal
reflux disease: presentation, evaluation, and treatment. Gastro-
enterol Clin North Am 36:577599
6. Lundell L, Miettinen P (2001) Continued (5 years) follow up of a
randomized clinical study comparing antireflux surgery and
omeprazole in GERD. J Am Coll Surg 192:171182
7. Draaisma WE, Rijnhart-de Jong HG, Broeders IAMJ et al (2006)
Five-year subjective and objective results of laparoscopic and
conventional Nissen fundoplication. Ann Surg 244:3441
8. Triadafilopoulos G (2007) Endotherapy and surgery for GERD.
J Clin Gastroenterol 41(Suppl 2):S87S96
9. Portale G, Filipi CJ, Peters JH (2004) A current assessment of
endoluminal approaches to the treatment of gastroesophageal
reflux disease. Surg Innov 4:225234
10. Fry LC, Monkemuller K, Malfertheiner P (2007) Systematic
review. Endoluminal therapy for gastro-oesophageal reflux dis-
ease: evidence from clinical trials. Eur J Gastroenterol Hepatol
19:11251139
11. Cadie`re GB, Rajan A, Rquibate M et al (2006) Endoluminal
fundoplication (ELF)evolution of EsophyX, a new surgical
device for transoral surgery. Minimally Invasive Ther 15:348
355
12. Cadiere GB, Rajan A, Germay O et al (2008) Endoluminal fun-
doplication by a transoral device for the treatment of GERD: a
feasibility study. Surg Endosc 22:333342
13. Cadiere GB, Buset M, Muls V et al (2008) Antireflux transoral
incisionless fundoplication using EsophyX: 12-month results of a
prospective multicenter study. World J Surg 32:16761688
14. Cadiere GB, Van Sante N, Graves JE et al (2009) Two-year
results of a feasibility study on antireflux transoral incisionless
fundoplication using EsophyX. Surg Endosc 23:957964
15. Drossman DA (2006) The functional gastrointestinal disorders
and the Rome III process. Gastroenterology 130:13771390
757
16. Lundell LR, Dent J, Bennett JR et al (1999) Endoscopic assess-
ment of oesophagitis: clinical and functional correlates and fur-
ther validation of the Los Angeles classification. Gut 45:172180
17. Velanovich V, Vallance SR, Gusz JR et al (1996) Quality of life
scale for gastroesophageal reflux disease. J Am Coll Surg
183:217224
18. Raymond JM, Marquis P, Bechade D et al (1999) Assessment of
quality of life of patients with gastroesophageal reflux. Elabora-
tion and validation of a specific questionnaire. Gastroenterol Clin
Biol 23:3239
19. Jobe BA, Kahrilas PJ, Vernon AH et al (2004) Endoscopic
appraisal of the gastroesophageal valve after antireflux surgery.
Am J Gastroenterol 99:233243
20. Jobe BA, ORourke RW, McMahon BP et al (2008) Transoral
endoscopic fundoplication in the treatment of gastroesophageal
reflux disease. The anatomic and physiologic basis for recon-
struction of the esophago-gastric junction using a novel device.
Ann Surg 248:6976
21. Hill D, Kozarek RA (1999) The gastroesophageal flap valve.
J Clin Gastroenterol 28:194197
22. Malmud LS, Fischer RS, Knight LC et al (1982) Scintigraphic
evaluation of gastric emptying. Semin Nucl Med 12:116125
23. Passaretti S, Zaninotto G, Di Martino N et al (2000) Standards for
esophageal manometry. A position statement of GISMAD. Dig
Liver Dis 32:4655
24. Sifrim D, Castell D, Dent J et al (2004) Gastroesophageal reflux
monitoring: review and consensus report on detection and defi-
nitions of acid, non-acid and gas reflux. Gut 53:10241031
25. Zerbib F, des Varannes SB, Roman S et al (2005) Normal values
and day-to-day variability of 24-h ambulatory oesophageal
impedance-pH monitoring in a Belgian-French cohort of healthy
subjects. Aliment Pharmacol Ther 22:10111021
26. Fornari F, Sifrim D (2008) Diagnostic options for patients with
refractory GERD. Curr Gastroenterol Rep 10:283288
27. Khajanchee YS, Ujiki M, Dunst CM et al (2009) Patient factors
predictive of 24-h pH normalization following endoluminal
gastroplication for GERD. Surg Endosc [E-pub ahead of publi-
cation Saturday, May 09, 2009]
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