Review for 10.1186/s12876-023-02799-z (2023)

Reviewer’s report
Title: 
Preoptimisation in patients with acute obstructive colon cancer
(PREOCC) – a prospective registration study protocol.
Version: 
1 
Date: 
07 Feb 2023
Reviewer's report:
"PEER REVIEWER ASSESSMENTS: 
OBJECTIVE - Full research articles: is there a clear objective that addresses one
or several testable research questions? (Brief or other article types: is there a
clear objective?)
No - there are minor issues
DESIGN - Is the current approach (including controls and analysis protocols)
appropriate for the objective?
Not sure - key details are missing from the manuscript
EXECUTION - Are the experiments and analyses performed with sufficient
technical rigor to allow confidence in the results?
No - there are minor issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics in the study
INTERPRETATION - Is the current interpretation/discussion of the results
reasonable and not overstated?
No - there are major issues
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your
concerns sufficiently for you to now recommend the work as a technically sound
contribution? If not, can further revisions be made to make the work technically
sound?
Maybe - with major revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: HAVE THE AUTHORS RESPONDED
ADEQUATELY TO EACH OF THE QUESTIONS YOU RAISED IN YOUR
COMMENTS 
In large part yes 
HAVE THEY MADE THE APPROPRIATE CHANGES IN THE
MANUSCRIPT 
in part yes but there are still many other changes that this reviewer feels are
important and crucial see my extensive suggestions 
WHAT IS YOUR OVERALL IMPRESSION OF THE REVISED
MANUSCRIPT 
I support such a study but with several what I consider serious reservations.
1. need for an interim analysis
2. Assurance of proximal colonic decompression
3. Clarification 
of 
whether the patients have a complete large bowel obstruction
or only a partially or impending obstruction
In what ways does it not meet best practice?
There are many places ion the manuscript that need clarification in terms of the
methods and esp patient selection. 1) 
I believe very strongly that 
a Data Safety
Monitoring Board (DSMB) of unbiased nonparticipants in the study is important
and remain surprised that the institutional review committee didn't mandate such
a board 2) the authors need also to suggest an appropriated number of right and
left sided cancers in the final cohort because I think they may find that the
majority of possible patients may indeed have left sided cancers which are
managed a bit differently
REQUESTED REVISIONS: 
ARE THERE ANY ADDITIONAL REVISIONS THE AUTHORS SHOULD
MAKE 
I will start with the disclosure that I did not review the prior submission. I will
review this aubmissoon as a primary submission 
1. 
Why are you submitting a protocol before the actual study is done? Is the
journal to which you plan to submit this amenable to protocols?
2. 
Lines 40-41. Don't you really mean "Right hemicolectomy and ileocolostomy"
3. Line 37 when you say "small bowel decompression" do you mean an NG
tube, a small bowel decompression 
tube, or. ( or even an/or ) a trans RECTAL
tube or a trans RECTAL my 
placed stent to allow decompression of the proximal
colon and small bowel? As a surgeon these are important points and best to
address these points here to start to avoid these concerns from the reader who has
only read the abstract. For instance, if the OCC is at the hepatic flexure and all
you do is decompress the small bowel what if the ileocecal 
valve is competent?
Could the ascending colon rupture?
4. Please define your term OCC in much more depth-does this mean total
obstruction, partial obstruction, or impending obstruction- crucial points cc even
#3 above. This is especially important when one reads lines 52-53 cc "
emergency operation". The way I am reading this is that you are targeting
patients with partially obstructing or impending obstruction and NOT WITH
COMPLETE LARGE BOWEL OBSTRUCTION— am I correct? You need to
state this much more definitively because if you plan to include patients with a
completely obstruction colon cancer , then an NG tube will NOT decompress the
small bowel and certainly not the proximal colon in all patients.
5. Line 50 delete the commas
6. Line 57 what do you mean by screening? Genomic studies, colonoscopy to
look for other lesions/cancers/polyps as well as medical Comorbidities
7. Line 63 and 330 "surgeries" should be changed to "operations". Surgery is the
practice of surgery much of which is non operative while operations are 
what we
do in the operating room
8. Line 64 what data? Refs 22-28 do not specifically address OCC why isn't ref
43 identified here?
9. Why concentrate on r sided lesions. Obstruction seems to be more common on
left sided lesions where the colon has a smaller diameter. Is this because
otherwise with left sided lesions you would leave a stent? 
10. Lines 107-108. Does this include large bowel obstruction with proximal
dilated colon? Also will all patients with a dilated colon be included? How will
you determine if their ileocecal valve is competent ?
11. Line 131 what is probe feeding? Define
12. Line 135. What do you mean by a "substantial size of NG tube"? I must say
as a reviewer I have never seen something like this written- most surgeons will
place a 16Fr or larger diameter tube when placing it for decompression
13. Line 136 what do you define as an adequate volume of NG output per day
and quite frankly lines 137-139 are routine nursing and physician management
understandings for anyone with an NG tube -delete this sentence this should be
understood 
with any hospital service I understand that the prior reviewer quite
correctly asked for more details in the methodology section but this is a waste of
space 
14. Line 140 do you do surveillance abdominal X-rays to follow colonic
distinction? What if the proximal dilated colon reaches a dilated of >10cm? How
would you know unless you visualize it?
15. Line 156 how will the diverting colostomy be performed? Where will it be
performed in the colon? And define SEMS here like you did online 321? I am
assuming you mean intralumenal stent placement. I would suggest that you also
use this term in figure 3b to be consistent 
16. Lines 157-158 why will the SEMS ONLY be used in high risk patients as
you describe? What about a ASA2 patient of 50 years who has a complete large
bowel obstruction in the defending colon -wouldn't that patient be an ideal
candidate for a SEMS?
17. I remain uncertain of whether all patients will be included or only 
those in
whom the nutritional status or physical condition is borderline or poor.
18. Is once a day supervised specific physical activity 
adequate? This reviewer
doubts it's efficacy and esp if the patient is discharged to do this at home-
compliance how would you monitor this?
19. Line 213. What breathing exercises will you use? Incentive spirometer?
20. 
Line 218 "may" or "will"?
21. lines 40-41 and 245 Will the "need for" a colostomy also be an end point- is
this what you mean by the term 
"definitive?"" if so I would rephrase it to
something more easily understood by the reader like "need for proximal bowel
diversion". 
This seems to a surgeon and to a patient as a definite improvement in
outcome 
22. Lines 305-306. This sentence as worded is obvious 
do you really mean that
staged resection after preoptimization rather than elective and if so what
reference can you provide see #8 above
23. Line 321 delete the abbreviation it is not a common one
24. Line 323 don't you mean "the literature is absent or minimal"
25. Line 352 decompressing ileostomy will work well for an incompetent
ileocecal valve but may not for those with a competent valve. Reword this a bit
26. I 
am quite 
worried about your seeming lack of concern for what you call
colonic blow out esp when your reference 43 still has a 25% risk of the need for
emergency surgery. You never address the competency of the ileocecal valve!
And I question your contention on lines 363-364 about feasibility when 25% of
patients required emergency surgery
27. are you planning an interim 
analysis by a data management committee , a
DSMB 
COMMITTEE; if 
not ,this reviewer strongly suggests that you need an
interim analysis to address #35 above and is very surprised that the institutional
review committee did not require such a review.
28. Line 336. Did 
any of these patients have a complete r sided colonic
obstruction? 
A bit more data of these patients is necessary
29. Table 
1 
A) gender should be changed to sex. Gender is 
the phenotype yet in this (
scientific) study you are interested in the genotype 
cc outcomes 
B) what about measurement of the colonic diameter at say the 
cecum. A diameter
of an acute presentation with a cecum>10 cm is so often used as a parameter to
require colonic decompression either by diversion or resection?
30. Finally are you goi g to require a minimum number of patiwnts with each of
the proximal and distal obstructing cancers - my suspicion is that there will be
many more totally obstructing left sided cancers than r sided and thus the
definition of total vs partial obstruction.
AUTHORS I have been quite critical of this protocol and this reviewer is a bit
surprised that many of the questions I have raised were not either discussed by
the MEC-U or not elaborated in this protocol, esp a interim analysis in light 
of
ref 43. . Sorry but I think my comments are justified. Yes this reviewer IS
supportive of such a study in partially obstruction colon cancer 
and in totally
obstructing colon cancers provided proximal colonic decompression can 
be
assured
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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?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
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