Review for 10.1186/s12876-022-02348-0 (2022)

Reviewer’s report
Title: 
Utility of mean platelet volume in differentiating intrahepatic
cholangiocarcinoma from hepatocellular carcinoma
Version: 
0 
Date: 
30 Dec 2021
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
OBJECTIVE - Full research articles: is there a clear objective that addresses a
testable research question(s) (brief or other article types: is there a clear
objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols)
appropriate for the objective?
No - there are major issues
EXECUTION - Are the experiments and analyses performed with technical rigor
to allow confidence in the results?
No - there are major issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results
reasonable and not overstated?
No - there are major issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work
technically sound? If not, can revisions be made to make the work technically
sound?
Maybe - with major revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: 
The authors aim to assess the utility of MPV in distinguishing ICC versus HCC.
There are a number of limitations to this observational study in terms of its
design and discussion.
REQUESTED REVISIONS: 
1. The introduction is weak and language needs working on. Authors need to
make it clearer how often there is diagnostic doubt between HCC v ICC based on
radiology (CT/MR) and conventional biomarkers (aFP/ca199) ie % needing a
biopsy for confirmation of diagnosis in their management. 
2. The selection of the training and validation cohort is very stringent. The
authors need to expand on this in the methodology and in the discussion ie how
many cases did they exclude as a consequence, the risk of overfitting, the
clinical limitations of MPV as so many physiological variables influence MPV
such as gender, smoking, medications etc.
3. No comment on whether the instrument used to measure MPV differed
between the 2 centres. No comment in discussion how sample collection and
analysis can influence MPV. The technical challenges of reproducibility in MPV
again needs to be highlighted in the discussion
4. No comment on background liver, all cases have been managed by resection
so this variable needs to be included (ie cirrhotic/fibrotic) in the analysis. As
underlying liver disease severity will be a confounding factor on MPV.
5. Result section needs to be expanded on, the authors need to highlight relevant
points from their tables. Authors need to make sure all abbreviations used are
defined and normal ranges are included for all variables measured.
6. Discussion is very weak. From the way the authors have phrased things, they
give the impression that FNA (fine needle aspirate) is the gold standard when
there is diagnostic doubt in HCC v ICC. If this is the case for the 2 centres
involved in the study, please state this here. Otherwise amend, as globally the
gold standard is tru-cut liver biopsy when there is diagnostic doubt.
The involvement of platelets in tumor biology and chronic liver disease is
extremely complex. This aspect needs to be expanded on and put into clinical
context ie a number of observational papers over the years that have commented
on MPV as a surrogate marker of cancer/inflammatory state but because of so
many aspects of disease/life style/drugs/physiology influencing MPV limits the
clinical utility of this measurement.
ADDITIONAL REQUESTS/SUGGESTIONS: 
Have highlighted main points of concerns earlier. A minor comment is the
language that makes reading sections of the manuscript difficult to read and
follow.
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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?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes