Reviewer's report
Title:Efficacy of transoral fundoplication for treatment of chronic
gastroesophageal reflux disease incompletely controlled with high-dose
proton-pump inhibitors therapy: a randomized, multicenter, open label, crossover
study
Version:1Date:25 August 2014
Reviewer: Oliver Owen Owen Koch
Reviewer's report:
Comments to the authors:
The aim of your study was to determine if transoral fundoplication (TF) could
further improve clinical outcomes in partial responders to high-dose (HD)
proton-pump inhibitor (PPI) therapy and to evaluate durability of TF. The answer
you give after analysing the results of your study is that in” well selected patients”
TF may work.
The design of the study is interesting and could show that TF can help patients
with symptoms despite optimal treatment with PPI. However the results also
show that TF does not help all of the patients to get free of symptoms and does
not normalize esophageal acid exposure (EAE) in the majority of patients. It is a
shame that you did not use HR-manometry and combined
Multichannel-Impedance-pH-Monitoring in the study. Since I think using these
methods you would have been able to answer questions which remain open.
Major Compulsory Revisions:
Which patients do you mean with “well selected” patients? Patients with normal
LES pressure? Patients with normal esophageal motility? We do not know since
HR-manometry has not been used before and after the procedure. You should
state this in your limitations of the study in the discussion part. In the section
“Association analysis” you show that “only preoperative total number of long
refluxes < 12 stayed significantly associated with normalization of EAE”. Could
this be because of preoperatively not seen poor esophageal motility and
therefore poor esophageal clearance? Could you please comment.
What do you think is the pathophysiologic mechanism of the TF device? You say
that you create an intact valve, but you treated patients who partly had an intact
valve (Hill I). How does the device work in these patients? Could this be the
reason that TF failed to normalize EAE in the majority of the patients, because
you selected the wrong patients? How are the postoperative results if you
analyse Hill grade I and II patients separately? Could you please comment and
discuss.
Furthermore, patients whose symptoms are associated with reflux but not
adequately respond to acid suppressive therapy can be identified by combined
Multichannel-Impedance-pH-Monitoring. However you did not use this method,
as you comment in the discussion. In the methods section you state: “Included
were patients with abnormal 48-hours ambulatory pH test defined as % time pH <
4 greater than 5.3% of the total recording period”. If all your patients had an
abnormal EAE why did the PPI-Therapy not normalize the EAE in almost 50% of
the patients and why did esophagitis only heal in 38% of the patients? In
literature esophagitis heals in virtually all patients if they are sufficiently treated
by acid suppressive medical therapy [Kahrilas PJ, Falk GW, Johnson DA, et al.
Esomeprazole improves healing and symptom resolution as compared with
omeprazole in reflux oesophagitis patients: a randomized controlled trial; Aliment
Pharmacol Ther 2000; 14: 1249-1258] Could you please comment on this
finding.
Endoscopic procedures have been criticized for normalizing esophageal acid
exposure in only 30-40% of the patients treated. Esophageal 24-h pH
normalization is widely considered as a crucial component of GERD treatment,
because one of the goals is to avoid long-term complications. In this study using
the TF device the normalization of EAE was 33% respectively 45% after 12
months, although esophagitis healed and symptoms resolved in the majority of
the patients. This fact is very important considering that there is a subgroup of
individuals with mild symptoms who are not willing to undergo surgery because
of side effects, but seek an effective, minimally invasive therapy. From the
patient’s point of view, the so-called heuristic endpoints, such as symptom
resolution, duration of convalescence, patient satisfaction, well-being, and quality
of life, are at least as important as the “classical” outcomes.
This study shows that endoscopic therapy can help patients with symptoms of
GERD despite PPI therapy, and therefore it should be published. However there
are a few lacks in the study design (Methods), and many questions remain
unanswered especially which patients we should select to achieve optimal
outcome.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
'I declare that I have no competing interests'
Reviewer's report
Title:Efficacy of transoral fundoplication for treatment of chronic
gastroesophageal reflux disease incompletely controlled with high-dose
proton-pump inhibitors therapy: a randomized, multicenter, open label, crossover
study
Version:1Date:25 August 2014
Reviewer: Oliver Owen Owen Koch
Reviewer's report:
Comments to the authors:
The aim of your study was to determine if transoral fundoplication (TF) could
further improve clinical outcomes in partial responders to high-dose (HD)
proton-pump inhibitor (PPI) therapy and to evaluate durability of TF. The answer
you give after analysing the results of your study is that in” well selected patients”
TF may work.
The design of the study is interesting and could show that TF can help patients
with symptoms despite optimal treatment with PPI. However the results also
show that TF does not help all of the patients to get free of symptoms and does
not normalize esophageal acid exposure (EAE) in the majority of patients. It is a
shame that you did not use HR-manometry and combined
Multichannel-Impedance-pH-Monitoring in the study. Since I think using these
methods you would have been able to answer questions which remain open.
Major Compulsory Revisions:
Which patients do you mean with “well selected” patients? Patients with normal
LES pressure? Patients with normal esophageal motility? We do not know since
HR-manometry has not been used before and after the procedure. You should
state this in your limitations of the study in the discussion part. In the section
“Association analysis” you show that “only preoperative total number of long
refluxes < 12 stayed significantly associated with normalization of EAE”. Could
this be because of preoperatively not seen poor esophageal motility and
therefore poor esophageal clearance? Could you please comment.
What do you think is the pathophysiologic mechanism of the TF device? You say
that you create an intact valve, but you treated patients who partly had an intact
valve (Hill I). How does the device work in these patients? Could this be the
reason that TF failed to normalize EAE in the majority of the patients, because
you selected the wrong patients? How are the postoperative results if you
analyse Hill grade I and II patients separately? Could you please comment and
discuss.
Furthermore, patients whose symptoms are associated with reflux but not
adequately respond to acid suppressive therapy can be identified by combined
Multichannel-Impedance-pH-Monitoring. However you did not use this method,
as you comment in the discussion. In the methods section you state: “Included
were patients with abnormal 48-hours ambulatory pH test defined as % time pH <
4 greater than 5.3% of the total recording period”. If all your patients had an
abnormal EAE why did the PPI-Therapy not normalize the EAE in almost 50% of
the patients and why did esophagitis only heal in 38% of the patients? In
literature esophagitis heals in virtually all patients if they are sufficiently treated
by acid suppressive medical therapy [Kahrilas PJ, Falk GW, Johnson DA, et al.
Esomeprazole improves healing and symptom resolution as compared with
omeprazole in reflux oesophagitis patients: a randomized controlled trial; Aliment
Pharmacol Ther 2000; 14: 1249-1258] Could you please comment on this
finding.
Endoscopic procedures have been criticized for normalizing esophageal acid
exposure in only 30-40% of the patients treated. Esophageal 24-h pH
normalization is widely considered as a crucial component of GERD treatment,
because one of the goals is to avoid long-term complications. In this study using
the TF device the normalization of EAE was 33% respectively 45% after 12
months, although esophagitis healed and symptoms resolved in the majority of
the patients. This fact is very important considering that there is a subgroup of
individuals with mild symptoms who are not willing to undergo surgery because
of side effects, but seek an effective, minimally invasive therapy. From the
patient’s point of view, the so-called heuristic endpoints, such as symptom
resolution, duration of convalescence, patient satisfaction, well-being, and quality
of life, are at least as important as the “classical” outcomes.
This study shows that endoscopic therapy can help patients with symptoms of
GERD despite PPI therapy, and therefore it should be published. However there
are a few lacks in the study design (Methods), and many questions remain
unanswered especially which patients we should select to achieve optimal
outcome.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
'I declare that I have no competing interests'
Please review this paper.
user
Reviewer's report
Title:Efficacy of transoral fundoplication for treatment of chronic
gastroesophageal reflux disease incompletely controlled with high-dose
proton-pump inhibitors therapy: a randomized, multicenter, open label, crossover
study
Version:1Date:25 August 2014
Reviewer: Oliver Owen Owen Koch
Reviewer's report:
Comments to the authors:
The aim of your study was to determine if transoral fundoplication (TF) could
further improve clinical outcomes in partial responders to high-dose (HD)
proton-pump inhibitor (PPI) therapy and to evaluate durability of TF. The answer
you give after analysing the results of your study is that in” well selected patients”
TF may work.
The design of the study is interesting and could show that TF can help patients
with symptoms despite optimal treatment with PPI. However the results also
show that TF does not help all of the patients to get free of symptoms and does
not normalize esophageal acid exposure (EAE) in the majority of patients. It is a
shame that you did not use HR-manometry and combined
Multichannel-Impedance-pH-Monitoring in the study. Since I think using these
methods you would have been able to answer questions which remain open.
Major Compulsory Revisions:
Which patients do you mean with “well selected” patients? Patients with normal
LES pressure? Patients with normal esophageal motility? We do not know since
HR-manometry has not been used before and after the procedure. You should
state this in your limitations of the study in the discussion part. In the section
“Association analysis” you show that “only preoperative total number of long
refluxes < 12 stayed significantly associated with normalization of EAE”. Could
this be because of preoperatively not seen poor esophageal motility and
therefore poor esophageal clearance? Could you please comment.
What do you think is the pathophysiologic mechanism of the TF device? You say
that you create an intact valve, but you treated patients who partly had an intact
valve (Hill I). How does the device work in these patients? Could this be the
reason that TF failed to normalize EAE in the majority of the patients, because
you selected the wrong patients? How are the postoperative results if you
analyse Hill grade I and II patients separately? Could you please comment and
discuss.
Furthermore, patients whose symptoms are associated with reflux but not
adequately respond to acid suppressive therapy can be identified by combined
Multichannel-Impedance-pH-Monitoring. However you did not use this method,
as you comment in the discussion. In the methods section you state: “Included
were patients with abnormal 48-hours ambulatory pH test defined as % time pH <
4 greater than 5.3% of the total recording period”. If all your patients had an
abnormal EAE why did the PPI-Therapy not normalize the EAE in almost 50% of
the patients and why did esophagitis only heal in 38% of the patients? In
literature esophagitis heals in virtually all patients if they are sufficiently treated
by acid suppressive medical therapy [Kahrilas PJ, Falk GW, Johnson DA, et al.
Esomeprazole improves healing and symptom resolution as compared with
omeprazole in reflux oesophagitis patients: a randomized controlled trial; Aliment
Pharmacol Ther 2000; 14: 1249-1258] Could you please comment on this
finding.
Endoscopic procedures have been criticized for normalizing esophageal acid
exposure in only 30-40% of the patients treated. Esophageal 24-h pH
normalization is widely considered as a crucial component of GERD treatment,
because one of the goals is to avoid long-term complications. In this study using
the TF device the normalization of EAE was 33% respectively 45% after 12
months, although esophagitis healed and symptoms resolved in the majority of
the patients. This fact is very important considering that there is a subgroup of
individuals with mild symptoms who are not willing to undergo surgery because
of side effects, but seek an effective, minimally invasive therapy. From the
patient’s point of view, the so-called heuristic endpoints, such as symptom
resolution, duration of convalescence, patient satisfaction, well-being, and quality
of life, are at least as important as the “classical” outcomes.
This study shows that endoscopic therapy can help patients with symptoms of
GERD despite PPI therapy, and therefore it should be published. However there
are a few lacks in the study design (Methods), and many questions remain
unanswered especially which patients we should select to achieve optimal
outcome.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
'I declare that I have no competing interests'
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