Reviewer’s report  
 
Title: Durability of pneumatic dilation monotherapy in treatment -naïve achalasia patients  
 
Version: 0 Date: 13 Jun 2019  
 
Reviewer: Tim Vanuytsel  
 
Reviewer's report:  
 
Specific comments:  
 
- Introduction, page 4, line 12: recent studie s indicate that the incidence of achalasia is 
probably 2 -3 rather than 1/100.000 (Samo et al. CGH 2017 and Duffield et al. CGH 
2017). Please add these reference and update the statement.  
 
- Methods, page 5, line 54: can the authors confirm that a 35mm ballo on was used 
irrespective of the time after the first dilation? E.g. would the authors use a 35mm ballon 
if a patient comes back 7 years after the first dilation?  
 
- Methods, page 5, line 59: this is confusing: how can the waist be confirmed before 
introduci ng the guidewire and the balloon? Please clarify.  
 
- Methods, page 6, line 32: which was the definition of symptom remission? Based on 
overall assessment by patient or physician or based on a formal Eckardt score (e.g. less 
than 3)? Please add.  
 
- Results, g eneral comment: It is suprising that none the patients needed more than 3 
dilations in the study period of 12 years. Is this related to the local protocol? (eg sending 
patients to surgery after 3 dilations, which appears to be the case since 5/6 failures a fter 3 
dilations were sent for surgery.  
 
- Results, page 7, line 7: please add a patient flow figure indicating the different reasons 
for which patients could not be included (including the lack of sufficient data in patient 
files, etc).  
 
- Results, page 7, line 9: the time interval is highly variable and a median seems more 
appropriate in this case, unless the data were normally distributed which would be 
surprising.  
 
- Results, page 7, line 14: is the follow -time between 1st and 2nd dilation statistically 
different between those needing only 2 PD and those ending up with 3 PD.  
 
- Results, page 8, line 19: The outcome data are difficult to interpret since sometimes 
patients underwent a second dilation within one year - which arguably could be defined 
as failure  - and hence were not evaluated in the group of 1PD and other patients 
underwent surgery based on unclear criteria. It would be reasonable to assume that the 
timing would be important to choose surgery or repeat PD, but this does not seem the 
case since so me patients underwent a second PD after 14 days already. This level of 
randomness makes it difficult to draw clinically meaningful conclusions. It would be 
more sensible to include need for repeat dilation before a certain period of time also as a 
failure to partially account for this bias.  
 
 The current analysis induces a very important bias since only those refusing a second 
dilation would be counted as 'failures' which is not correct. The same is true for e.g. 
figure 4: only those going to surgery or refu sing additional therapy are included as 
failures if I understand correctly.  
 
- Results, page 9, line 14: 'patients who reported symptom relief at time of clinic follow -
up': which clinic follow -up is this? After 3 months, 1 year, …? Or are these only the 
patients who did not experience relapse of symptoms during the entire study period and 
hence the 'remission duration' is only defined by the study period which seems less 
appropriate. I would suggest to include the entire study group in this analysis or calcu late 
conditional remission in the entire study group: is this the 95% mentioned in the abstract 
or only in the 1PD group? This number does not come back in the manuscript.  
 
- Results page 9, line 24: is the follow -up time the time until surgery or the total  follow -up 
time? Please rephrase.  
 
- Results, page 10, line 9 -15: Stats are needed!  
 
- Results, general: even though I appreciate that not all patients underwent HRM (please 
indicate how many), in the current era the authors should classify those who did 
according to the manometric subtypes and include this analysis.  
 
- Discussion, page 11,  line 52: the authors did not include the Hulselmans et al. CGH 2010 
study which performed a similar analysis in a larger study group.  
 
- Discussion, page 13, line 20: 'our data supports this, especially when looking at those 
who pursued three dilations.' W hen looking at the entire group of patients, age is not 
confirmed as a risk factor for failure and hence the data do not support this statement.  
 
- Abstract, results: 'Patients who underwent two or more PDs were more likely to be &lt;40 
years old (ns), and male (ns).' Although the patients of the 2PD group were younger, I 
cannot find back the numbers on which this statement is based in the results. Moreover, if 
both are 'ns' than the authors should rephrase the statement.  
 
 
 
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or  shares in an organisation that may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the 
manuscript?  
 
4. Have you re ceived reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests i n relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer  review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the website along with the author s' 
responses. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I d o not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer’s report  
 
Title: Durability of pneumatic dilation monotherapy in treatment -naïve achalasia patients  
 
Version: 0 Date: 13 Jun 2019  
 
Reviewer: Tim Vanuytsel  
 
Reviewer's report:  
 
Specific comments:  
 
- Introduction, page 4, line 12: recent studie s indicate that the incidence of achalasia is 
probably 2 -3 rather than 1/100.000 (Samo et al. CGH 2017 and Duffield et al. CGH 
2017). Please add these reference and update the statement.  
 
- Methods, page 5, line 54: can the authors confirm that a 35mm ballo on was used 
irrespective of the time after the first dilation? E.g. would the authors use a 35mm ballon 
if a patient comes back 7 years after the first dilation?  
 
- Methods, page 5, line 59: this is confusing: how can the waist be confirmed before 
introduci ng the guidewire and the balloon? Please clarify.  
 
- Methods, page 6, line 32: which was the definition of symptom remission? Based on 
overall assessment by patient or physician or based on a formal Eckardt score (e.g. less 
than 3)? Please add.  
 
- Results, g eneral comment: It is suprising that none the patients needed more than 3 
dilations in the study period of 12 years. Is this related to the local protocol? (eg sending 
patients to surgery after 3 dilations, which appears to be the case since 5/6 failures a fter 3 
dilations were sent for surgery.  
 
- Results, page 7, line 7: please add a patient flow figure indicating the different reasons 
for which patients could not be included (including the lack of sufficient data in patient 
files, etc).  
 
- Results, page 7, line 9: the time interval is highly variable and a median seems more 
appropriate in this case, unless the data were normally distributed which would be 
surprising.  
 
- Results, page 7, line 14: is the follow -time between 1st and 2nd dilation statistically 
different between those needing only 2 PD and those ending up with 3 PD.  
 
- Results, page 8, line 19: The outcome data are difficult to interpret since sometimes 
patients underwent a second dilation within one year - which arguably could be defined 
as failure  - and hence were not evaluated in the group of 1PD and other patients 
underwent surgery based on unclear criteria. It would be reasonable to assume that the 
timing would be important to choose surgery or repeat PD, but this does not seem the 
case since so me patients underwent a second PD after 14 days already. This level of 
randomness makes it difficult to draw clinically meaningful conclusions. It would be 
more sensible to include need for repeat dilation before a certain period of time also as a 
failure to partially account for this bias.  
 
 The current analysis induces a very important bias since only those refusing a second 
dilation would be counted as 'failures' which is not correct. The same is true for e.g. 
figure 4: only those going to surgery or refu sing additional therapy are included as 
failures if I understand correctly.  
 
- Results, page 9, line 14: 'patients who reported symptom relief at time of clinic follow -
up': which clinic follow -up is this? After 3 months, 1 year, …? Or are these only the 
patients who did not experience relapse of symptoms during the entire study period and 
hence the 'remission duration' is only defined by the study period which seems less 
appropriate. I would suggest to include the entire study group in this analysis or calcu late 
conditional remission in the entire study group: is this the 95% mentioned in the abstract 
or only in the 1PD group? This number does not come back in the manuscript.  
 
- Results page 9, line 24: is the follow -up time the time until surgery or the total  follow -up 
time? Please rephrase.  
 
- Results, page 10, line 9 -15: Stats are needed!  
 
- Results, general: even though I appreciate that not all patients underwent HRM (please 
indicate how many), in the current era the authors should classify those who did 
according to the manometric subtypes and include this analysis.  
 
- Discussion, page 11,  line 52: the authors did not include the Hulselmans et al. CGH 2010 
study which performed a similar analysis in a larger study group.  
 
- Discussion, page 13, line 20: 'our data supports this, especially when looking at those 
who pursued three dilations.' W hen looking at the entire group of patients, age is not 
confirmed as a risk factor for failure and hence the data do not support this statement.  
 
- Abstract, results: 'Patients who underwent two or more PDs were more likely to be &lt;40 
years old (ns), and male (ns).' Although the patients of the 2PD group were younger, I 
cannot find back the numbers on which this statement is based in the results. Moreover, if 
both are 'ns' than the authors should rephrase the statement.  
 
 
 
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or  shares in an organisation that may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the 
manuscript?  
 
4. Have you re ceived reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests i n relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer  review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the website along with the author s' 
responses. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I d o not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer’s report  
 
Title: Durability of pneumatic dilation monotherapy in treatment -naïve achalasia patients  
 
Version: 0 Date: 13 Jun 2019  
 
Reviewer: Tim Vanuytsel  
 
Reviewer's report:  
 
Specific comments:  
 
- Introduction, page 4, line 12: recent studie s indicate that the incidence of achalasia is 
probably 2 -3 rather than 1/100.000 (Samo et al. CGH 2017 and Duffield et al. CGH 
2017). Please add these reference and update the statement.  
 
- Methods, page 5, line 54: can the authors confirm that a 35mm ballo on was used 
irrespective of the time after the first dilation? E.g. would the authors use a 35mm ballon 
if a patient comes back 7 years after the first dilation?  
 
- Methods, page 5, line 59: this is confusing: how can the waist be confirmed before 
introduci ng the guidewire and the balloon? Please clarify.  
 
- Methods, page 6, line 32: which was the definition of symptom remission? Based on 
overall assessment by patient or physician or based on a formal Eckardt score (e.g. less 
than 3)? Please add.  
 
- Results, g eneral comment: It is suprising that none the patients needed more than 3 
dilations in the study period of 12 years. Is this related to the local protocol? (eg sending 
patients to surgery after 3 dilations, which appears to be the case since 5/6 failures a fter 3 
dilations were sent for surgery.  
 
- Results, page 7, line 7: please add a patient flow figure indicating the different reasons 
for which patients could not be included (including the lack of sufficient data in patient 
files, etc).  
 
- Results, page 7, line 9: the time interval is highly variable and a median seems more 
appropriate in this case, unless the data were normally distributed which would be 
surprising.  
 
- Results, page 7, line 14: is the follow -time between 1st and 2nd dilation statistically 
different between those needing only 2 PD and those ending up with 3 PD.  
 
- Results, page 8, line 19: The outcome data are difficult to interpret since sometimes 
patients underwent a second dilation within one year - which arguably could be defined 
as failure  - and hence were not evaluated in the group of 1PD and other patients 
underwent surgery based on unclear criteria. It would be reasonable to assume that the 
timing would be important to choose surgery or repeat PD, but this does not seem the 
case since so me patients underwent a second PD after 14 days already. This level of 
randomness makes it difficult to draw clinically meaningful conclusions. It would be 
more sensible to include need for repeat dilation before a certain period of time also as a 
failure to partially account for this bias.  
 
 The current analysis induces a very important bias since only those refusing a second 
dilation would be counted as 'failures' which is not correct. The same is true for e.g. 
figure 4: only those going to surgery or refu sing additional therapy are included as 
failures if I understand correctly.  
 
- Results, page 9, line 14: 'patients who reported symptom relief at time of clinic follow -
up': which clinic follow -up is this? After 3 months, 1 year, …? Or are these only the 
patients who did not experience relapse of symptoms during the entire study period and 
hence the 'remission duration' is only defined by the study period which seems less 
appropriate. I would suggest to include the entire study group in this analysis or calcu late 
conditional remission in the entire study group: is this the 95% mentioned in the abstract 
or only in the 1PD group? This number does not come back in the manuscript.  
 
- Results page 9, line 24: is the follow -up time the time until surgery or the total  follow -up 
time? Please rephrase.  
 
- Results, page 10, line 9 -15: Stats are needed!  
 
- Results, general: even though I appreciate that not all patients underwent HRM (please 
indicate how many), in the current era the authors should classify those who did 
according to the manometric subtypes and include this analysis.  
 
- Discussion, page 11,  line 52: the authors did not include the Hulselmans et al. CGH 2010 
study which performed a similar analysis in a larger study group.  
 
- Discussion, page 13, line 20: 'our data supports this, especially when looking at those 
who pursued three dilations.' W hen looking at the entire group of patients, age is not 
confirmed as a risk factor for failure and hence the data do not support this statement.  
 
- Abstract, results: 'Patients who underwent two or more PDs were more likely to be &lt;40 
years old (ns), and male (ns).' Although the patients of the 2PD group were younger, I 
cannot find back the numbers on which this statement is based in the results. Moreover, if 
both are 'ns' than the authors should rephrase the statement.  
 
 
 
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or  shares in an organisation that may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the 
manuscript?  
 
4. Have you re ceived reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests i n relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer  review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the website along with the author s' 
responses. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I d o not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant