Title: The Efficacy of Retrograde and Antegrade Enemas in the Management of Low Anterior
Resection Syndrome in Patients Undergoing Rectal Resection: A Systematic Review and Meta-
analysis
Version: 0 Date: 23 Mar 2025
Reviewer's report:
This is a nicely presented manuscript with good description of methodology. However, there
are several points in the presented work that raise questions on its suitability to be published
in the current state.
Minor points as follows:
In the protocol, the study was open for inclusion of randomised and non-randomised studies.
But, in final manuscript, only RCTs were included.
I noted from the PRISMA that there were observational studies excluded. Could author provide
information on what were these 6 observational/retrospective studies excluded from the final
review? Were they comparative enema vs standard treatment studies? If yes, according to the
protocol they should have been included.
Noted RoB2 assessment of included studies. I would be interested to see the whole RoB
assessment algorithm in the supporting files to understand whether RoB assessment was
performed correctly or not. RoB2 is designed to be performed for each individual outcomes
separately? Which outcome did authors analyse to assess the risk of bias?
I have re-evaluated the RoB2 for the outcome LARS score for the study Alvandipour et al30.
I disagree with authors that this study is low risk of bias. Specifically, for example, there is no
information to suggest that allocation sequence was concealed and therefore one cannot give
low risk of bias in the domain 1 for this study.
The study was set up to analyse measurement of other scores: Wexner score, Cleveland
Clinic Florida Fecal Incontinence Score, Rockwood (ASCRS) questionnaires, Vaizey, Alto-
mare, the Memorial Sloan-Kettering Cancer Center Bowel Function Instrument (MSKCC BFI)
questionnaires, etc. as well as additional outcomes were supposed to be studied:
(1)Quality of life pre- and post-enema
(2)Rate of complications with the enema
(3)Patient satisfaction
(4)rate of treatment failure
(5)health service costs
There is little analysis on these additional outcomes and measurements of effect, apart from
LARS score. This makes me conclude the study has not completed aims drawn in the registered
protocol.
The study will benefit from additional table on reporting results of individual studies in one
summary table.
Major problem:
The studies included are very heterogenic in terms of interventional and control arm descriptions.
More importantly, the study of Alvandipour M. Et al.  used completely different design to other
studies by analysing how novel intervention will prevent (rather than treat) LARS. I doubt this
was appropriate to do meta-analysis given such high heterogeneity between included studies.
In summary, after addressing above mentioned points this study can be a good systematic review
for publishing, but should not have meta-analysis component in it.
Advice: revise as above and re-submit as systematic review only (exclude meta-analysis part)
Title: The Efficacy of Retrograde and Antegrade Enemas in the Management of Low Anterior
Resection Syndrome in Patients Undergoing Rectal Resection: A Systematic Review and Meta-
analysis
Version: 0 Date: 23 Mar 2025
Reviewer's report:
This is a nicely presented manuscript with good description of methodology. However, there
are several points in the presented work that raise questions on its suitability to be published
in the current state.
Minor points as follows:
In the protocol, the study was open for inclusion of randomised and non-randomised studies.
But, in final manuscript, only RCTs were included.
I noted from the PRISMA that there were observational studies excluded. Could author provide
information on what were these 6 observational/retrospective studies excluded from the final
review? Were they comparative enema vs standard treatment studies? If yes, according to the
protocol they should have been included.
Noted RoB2 assessment of included studies. I would be interested to see the whole RoB
assessment algorithm in the supporting files to understand whether RoB assessment was
performed correctly or not. RoB2 is designed to be performed for each individual outcomes
separately? Which outcome did authors analyse to assess the risk of bias?
I have re-evaluated the RoB2 for the outcome LARS score for the study Alvandipour et al30.
I disagree with authors that this study is low risk of bias. Specifically, for example, there is no
information to suggest that allocation sequence was concealed and therefore one cannot give
low risk of bias in the domain 1 for this study.
The study was set up to analyse measurement of other scores: Wexner score, Cleveland
Clinic Florida Fecal Incontinence Score, Rockwood (ASCRS) questionnaires, Vaizey, Alto-
mare, the Memorial Sloan-Kettering Cancer Center Bowel Function Instrument (MSKCC BFI)
questionnaires, etc. as well as additional outcomes were supposed to be studied:
(1)Quality of life pre- and post-enema
(2)Rate of complications with the enema
(3)Patient satisfaction
(4)rate of treatment failure
(5)health service costs
There is little analysis on these additional outcomes and measurements of effect, apart from
LARS score. This makes me conclude the study has not completed aims drawn in the registered
protocol.
The study will benefit from additional table on reporting results of individual studies in one
summary table.
Major problem:
The studies included are very heterogenic in terms of interventional and control arm descriptions.
More importantly, the study of Alvandipour M. Et al.  used completely different design to other
studies by analysing how novel intervention will prevent (rather than treat) LARS. I doubt this
was appropriate to do meta-analysis given such high heterogeneity between included studies.
In summary, after addressing above mentioned points this study can be a good systematic review
for publishing, but should not have meta-analysis component in it.
Advice: revise as above and re-submit as systematic review only (exclude meta-analysis part)
Please review this paper.
user
Title: The Efficacy of Retrograde and Antegrade Enemas in the Management of Low Anterior
Resection Syndrome in Patients Undergoing Rectal Resection: A Systematic Review and Meta-
analysis
Version: 0 Date: 23 Mar 2025
Reviewer's report:
This is a nicely presented manuscript with good description of methodology. However, there
are several points in the presented work that raise questions on its suitability to be published
in the current state.
Minor points as follows:
In the protocol, the study was open for inclusion of randomised and non-randomised studies.
But, in final manuscript, only RCTs were included.
I noted from the PRISMA that there were observational studies excluded. Could author provide
information on what were these 6 observational/retrospective studies excluded from the final
review? Were they comparative enema vs standard treatment studies? If yes, according to the
protocol they should have been included.
Noted RoB2 assessment of included studies. I would be interested to see the whole RoB
assessment algorithm in the supporting files to understand whether RoB assessment was
performed correctly or not. RoB2 is designed to be performed for each individual outcomes
separately? Which outcome did authors analyse to assess the risk of bias?
I have re-evaluated the RoB2 for the outcome LARS score for the study Alvandipour et al30.
I disagree with authors that this study is low risk of bias. Specifically, for example, there is no
information to suggest that allocation sequence was concealed and therefore one cannot give
low risk of bias in the domain 1 for this study.
The study was set up to analyse measurement of other scores: Wexner score, Cleveland
Clinic Florida Fecal Incontinence Score, Rockwood (ASCRS) questionnaires, Vaizey, Alto-
mare, the Memorial Sloan-Kettering Cancer Center Bowel Function Instrument (MSKCC BFI)
questionnaires, etc. as well as additional outcomes were supposed to be studied:
(1)Quality of life pre- and post-enema
(2)Rate of complications with the enema
(3)Patient satisfaction
(4)rate of treatment failure
(5)health service costs
There is little analysis on these additional outcomes and measurements of effect, apart from
LARS score. This makes me conclude the study has not completed aims drawn in the registered
protocol.
The study will benefit from additional table on reporting results of individual studies in one
summary table.
Major problem:
The studies included are very heterogenic in terms of interventional and control arm descriptions.
More importantly, the study of Alvandipour M. Et al.  used completely different design to other
studies by analysing how novel intervention will prevent (rather than treat) LARS. I doubt this
was appropriate to do meta-analysis given such high heterogeneity between included studies.
In summary, after addressing above mentioned points this study can be a good systematic review
for publishing, but should not have meta-analysis component in it.
Advice: revise as above and re-submit as systematic review only (exclude meta-analysis part)
assistant