Reviewer’s report  
Title: Evidence of surgical outcomes fluctuates over time: results from a cumulative meta -
analysis  of laparoscopic versus open appendectomy for acute appendicitis  
 
Version: 0 Date: 21 Nov 2015  
 
Reviewer: Ramon Gorter  
Reviewer’s report:  
This report is on the the fact that established evidence through meta -analyses at one point might 
fluctuate and therefore the authors opt for cumulative meta -analysis of RCTs  
 
We would like to congratulate the authors on this excellent manuscript and the c oncept of their 
idea. They have done an extensive search and meta -analysis.  
 
We do have however some minor questions to the authors:  
 
1. The authors state in their conclusion that evidence might change overtime. This is 
especially true for surgical resear ch due to the fact that surgical innovations are more 
prone to confounders such as learning curve, procedural variables etcetera. Therefore 
although there is some form of standardisation, the RCTs conducted on the topic of 
appendectomy might slightly diffe r. For instance the handling of purulent fluid intra -
abdominally differs between authors (aspiration versus washout versus drainage). In our 
opinion all these variables might lead to different outcomes after an appendectomy. 
Moreover surgical procedures ar e influenced by the learning curve and optimisation of 
the strategy. In my opinion this is one of the main reasons why results from clinical trials 
on this topic might fluctuate. In our opinion it is therefore more crucial that instead of 
single (national)  center studies on a subject, we should conduct multi (international) 
center studies on a topic in which we all follow the same protocol. The conclusions from 
these RCT's can than be meta -analysed between continents.  
 
2. We need to realise however them in surgical research once evidence has been established 
by a meta -analysis the topic is prone to publication bias. Only the clinical trials/researchs 
with contradicting results will be published in contrast to those confirming the evidence. 
This will be of gr eat influence on the meta analysis performed. The authors should 
outline this more in their discussion and in our opinion should soften their conclusions  
 
3. We would suggest that the authors in the results section change the term"database" into 
the search yielded  
 
4. In our opinion their are some inconsistencies; Regarding the intra -abdominal abscess 
section in the results, the authors state that the cumulat ive meta analysis was in favour of 
the open appendectomy published in 2001. After this year, the CI shifted to the left in 
favour of laparoscopic appendectomy eventually leading to no significant difference. Can 
the authors maybe elaborate in which year th e CI included the value of one? As 
Saulerland published  his meta -analysis (cochrane) in which studies were included from 
1983 -2009. He concluded that LA was associated with more IAA than open 
appendectomy. In which year did the authors found no difference  any more  
 
5. How many studies were needed to change the effect regarding the IAA  
 
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 spe cify 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.  
 
No 
 
Are you able to assess any statistics in the manuscript o r 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 recommend additional statistical review  
 
Quality of written Engl ish 
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, consideri ng 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, e ither now or in the future?  
 
2. Do you hold any stocks or shares in an organis ation that may in any way gain or lose 
financially from the publication of this manuscript, e ither 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 received 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 fin ancial competing interests?  
 
6. Do you have any non -financial competing interests  in relation to this pa per? 
 
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 authors' 
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 do not wish to be inc luded 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: Evidence of surgical outcomes fluctuates over time: results from a cumulative meta -
analysis  of laparoscopic versus open appendectomy for acute appendicitis  
 
Version: 0 Date: 21 Nov 2015  
 
Reviewer: Ramon Gorter  
Reviewer’s report:  
This report is on the the fact that established evidence through meta -analyses at one point might 
fluctuate and therefore the authors opt for cumulative meta -analysis of RCTs  
 
We would like to congratulate the authors on this excellent manuscript and the c oncept of their 
idea. They have done an extensive search and meta -analysis.  
 
We do have however some minor questions to the authors:  
 
1. The authors state in their conclusion that evidence might change overtime. This is 
especially true for surgical resear ch due to the fact that surgical innovations are more 
prone to confounders such as learning curve, procedural variables etcetera. Therefore 
although there is some form of standardisation, the RCTs conducted on the topic of 
appendectomy might slightly diffe r. For instance the handling of purulent fluid intra -
abdominally differs between authors (aspiration versus washout versus drainage). In our 
opinion all these variables might lead to different outcomes after an appendectomy. 
Moreover surgical procedures ar e influenced by the learning curve and optimisation of 
the strategy. In my opinion this is one of the main reasons why results from clinical trials 
on this topic might fluctuate. In our opinion it is therefore more crucial that instead of 
single (national)  center studies on a subject, we should conduct multi (international) 
center studies on a topic in which we all follow the same protocol. The conclusions from 
these RCT's can than be meta -analysed between continents.  
 
2. We need to realise however them in surgical research once evidence has been established 
by a meta -analysis the topic is prone to publication bias. Only the clinical trials/researchs 
with contradicting results will be published in contrast to those confirming the evidence. 
This will be of gr eat influence on the meta analysis performed. The authors should 
outline this more in their discussion and in our opinion should soften their conclusions  
 
3. We would suggest that the authors in the results section change the term"database" into 
the search yielded  
 
4. In our opinion their are some inconsistencies; Regarding the intra -abdominal abscess 
section in the results, the authors state that the cumulat ive meta analysis was in favour of 
the open appendectomy published in 2001. After this year, the CI shifted to the left in 
favour of laparoscopic appendectomy eventually leading to no significant difference. Can 
the authors maybe elaborate in which year th e CI included the value of one? As 
Saulerland published  his meta -analysis (cochrane) in which studies were included from 
1983 -2009. He concluded that LA was associated with more IAA than open 
appendectomy. In which year did the authors found no difference  any more  
 
5. How many studies were needed to change the effect regarding the IAA  
 
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 spe cify 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.  
 
No 
 
Are you able to assess any statistics in the manuscript o r 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 recommend additional statistical review  
 
Quality of written Engl ish 
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, consideri ng 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, e ither now or in the future?  
 
2. Do you hold any stocks or shares in an organis ation that may in any way gain or lose 
financially from the publication of this manuscript, e ither 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 received 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 fin ancial competing interests?  
 
6. Do you have any non -financial competing interests  in relation to this pa per? 
 
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 authors' 
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 do not wish to be inc luded 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: Evidence of surgical outcomes fluctuates over time: results from a cumulative meta -
analysis  of laparoscopic versus open appendectomy for acute appendicitis  
 
Version: 0 Date: 21 Nov 2015  
 
Reviewer: Ramon Gorter  
Reviewer’s report:  
This report is on the the fact that established evidence through meta -analyses at one point might 
fluctuate and therefore the authors opt for cumulative meta -analysis of RCTs  
 
We would like to congratulate the authors on this excellent manuscript and the c oncept of their 
idea. They have done an extensive search and meta -analysis.  
 
We do have however some minor questions to the authors:  
 
1. The authors state in their conclusion that evidence might change overtime. This is 
especially true for surgical resear ch due to the fact that surgical innovations are more 
prone to confounders such as learning curve, procedural variables etcetera. Therefore 
although there is some form of standardisation, the RCTs conducted on the topic of 
appendectomy might slightly diffe r. For instance the handling of purulent fluid intra -
abdominally differs between authors (aspiration versus washout versus drainage). In our 
opinion all these variables might lead to different outcomes after an appendectomy. 
Moreover surgical procedures ar e influenced by the learning curve and optimisation of 
the strategy. In my opinion this is one of the main reasons why results from clinical trials 
on this topic might fluctuate. In our opinion it is therefore more crucial that instead of 
single (national)  center studies on a subject, we should conduct multi (international) 
center studies on a topic in which we all follow the same protocol. The conclusions from 
these RCT's can than be meta -analysed between continents.  
 
2. We need to realise however them in surgical research once evidence has been established 
by a meta -analysis the topic is prone to publication bias. Only the clinical trials/researchs 
with contradicting results will be published in contrast to those confirming the evidence. 
This will be of gr eat influence on the meta analysis performed. The authors should 
outline this more in their discussion and in our opinion should soften their conclusions  
 
3. We would suggest that the authors in the results section change the term"database" into 
the search yielded  
 
4. In our opinion their are some inconsistencies; Regarding the intra -abdominal abscess 
section in the results, the authors state that the cumulat ive meta analysis was in favour of 
the open appendectomy published in 2001. After this year, the CI shifted to the left in 
favour of laparoscopic appendectomy eventually leading to no significant difference. Can 
the authors maybe elaborate in which year th e CI included the value of one? As 
Saulerland published  his meta -analysis (cochrane) in which studies were included from 
1983 -2009. He concluded that LA was associated with more IAA than open 
appendectomy. In which year did the authors found no difference  any more  
 
5. How many studies were needed to change the effect regarding the IAA  
 
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 spe cify 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.  
 
No 
 
Are you able to assess any statistics in the manuscript o r 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 recommend additional statistical review  
 
Quality of written Engl ish 
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, consideri ng 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, e ither now or in the future?  
 
2. Do you hold any stocks or shares in an organis ation that may in any way gain or lose 
financially from the publication of this manuscript, e ither 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 received 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 fin ancial competing interests?  
 
6. Do you have any non -financial competing interests  in relation to this pa per? 
 
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 authors' 
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 do not wish to be inc luded 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