Review for 10.1186/s12876-022-02418-3 (2022)

Reviewer’s report
Title: 
Segmental reversal of the distal small intestine in a short bowel syndrome
model in piglets showed detrimental effect on weight gain
Version: 
1 
Date: 
27 Jan 2022
Reviewer's report:
The manuscript BMGE-D-21-00839 "Segmental reversal of the distal small
intestine in a short bowel syndrome model in piglets showed detrimental effect
on weight gain" explores the concept of segmental reversal as a viable surgical
approach in the treatment of short bowel syndrome. 
The subject matter is
important and relevant to the field of intestinal failure as bowel lengthening
procedures are the most common type of surgical intervention but can only be
completed when dilated bowel is present. 
An alternative approach when there is
high output and non-dilated bowel would be a significant advance to the field.
While there is some literature on the subject of segmental reversals in animals
and humans, results have been mixed with regard to outcome suggesting that the
variables in predicting successful outcome are not yet known. 
The study
described in this manuscript utilizes a well known piglet model of short bowel
syndrome and the methods are clearly described. 
The authors took great care to
provide details of the study and discuss limitations such as the measurement of
small bowel length using a flexible liner along the anti-mesenteric border. 
Given
the details of the methods, the reviewer feels that this study would be
reproducible. 
Unfortunately, for the most part, the study yielded negative results
in that there was no apparent benefit and likely a negative effect with the use of
the reversed segment. 
Despite this, the study has merit in that it does further add
to the literature findings that lead to a greater understanding of reversed segment
procedures. 
The major limitation of the study, which the authors address in the
discussion, is that it is possible that the length of the reversed segment was too
long. 
It was clear that the length of the reversed segment was carefully
considered prior to the study. 
Unfortunately, the results seemed to suggest the
reversed segment led to essentially a functional obstruction as demonstrate by a
lack of adaptation as seen in the histology of the proximal segments, the
demonstration of muscular hypertrophy presumably from working against a
reversed segment, and the observation of dilation in the reversed segment in the
interventional group. 
The authors introduce a novel concept in the measurement
of GLP-2 and GIP in reversed segments. 
As the intervention group did not show
evidence of adaptation, it is not surprising that the GLP-2 and GIP levels did not
increase (and actually tended to decrease). 
The control animals, for the most
part, did appear to respond as expected with evidence of adaptation.
Unfortunately, there is very little that can be done with regard to additional data
analysis or the introduction of another variable (such as citrulline) 
that would
lead to an alternative interpretation of the data.
It is interesting that the authors tended to focus on markers/measurement of
adaptation as a potential benefit of segmental reversal would be decreased
output. 
There was no measurement of output and whether there was a significant
change in intervention versus control animals. 
The authors main outcome was
weight gain over time. 
As the model essentially demonstrated a functional
obstruction, it might explain the decreased weight gain in the interventional
group. 
Piglets were allowed to feed ad libitum and it is unclear if the piglets in
the interventional group ate less than there counterparts.
This study was well contrived, but unfortunately did not support the hypothesis
that segmental reversal is beneficial in short bowel syndrome in this animal
model. 
It is hoped that the authors continue their work in determining the
variables, such as length of reversed segment, that could provide more promising
results.
Specific comments with regard to the manuscript include:
1. In the methods section it appears that the post-operative management included
the use of methadone q4hr continuously throughout the length of the experiment.
If this is correct, it may have altered bowel motility. 
I suspect that the methadone
was given for a limited period of time post-operatively. 
This should be clarified.
2. Weight gain (or lack thereof) was the main outcome measure. 
In the text, the
difference in weight gain was stated in kilograms. 
It is assumed that these are 28
day weights. 
The statistics suggest a students-t test was used 
and if so, there
should be an associated p-value (the authors state it was significant). 
The figure
is then referenced which displays the weight gain as a percentage of weight gain
which is a very clear graph, but not explained in the text. 
As this is the major
finding in the study, it should be more thoroughly explained.
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Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes