Title: Title: Differentiation of small (#3 cm) hepatocellular carcinomas from benign nodules in
cirrhotic liver: The added additive value of MRI-based radiomics analysis to LI-RADS version
2018 algorithm
Version: 2 Date: 08 Feb 2021
Reviewer's report:
SPECIFIC COMMENTS
This manuscript is clear and exhaustive without appreciable major issues.
Although language used is already appropriate and pleasant, I (I am not a native English
speaker) only recommend to Authors to obtain a certified native speaker with proficiencies in
the scientific-medical field to properly complete this paper.
TITLE
The title is clearly explanatory and, in my opinion, it suddenly shows the main topic of the paper.
I would like to propose only a little language observation that could be adopted from Authors
if they are pleased of that.
In my opinion it may be more pleasurable to adopt this slimmer title: “Differentiation of small
(#3 cm) hepatocellular carcinomas from benign nodules in cirrhotic liver: the added additive
value of MRI-based radiomics analysis to LI-RADS vversion 2018 algorithm”.
ABSTRACT
The abstract results globally precise and properly reflecting the main text, consequently no major
adjustments are needed.
Style and length reflect the “Author Guidelines” presented on the website except for the absence
of “Trial Registration”: as indicated in the authors guidelines, since this is a retrospective study
the authors should indicate the wording “retrospectively registered” in this section.
In the Methods section Authors may also specify the retrospective study design and the period
of study comprise as well.
KEYWORDS
Keywords are completely missing, so Authors should indicate from three to ten keywords
representing the main content of the article (as indicated in authors guidelines). If possible, to
enhance the finding process of this paper (and consequently of the Journal) by Readers and
Stakeholders, I would like to suggest the selection of keywords directly on MeSH Browser.
BACKGROUND
The introduction is well structured and interesting to read, although some clarifications could
be added.
For example, in page 3 line 17 it could be useful to underline that the theme regarding
the use (or not) of LI-RADS is still open, because this system in the present form
demonstrated many limitations [Eur J Gastroenterol Hepatol. 2019;31(3):283-288. doi:10.1097/
MEG.0000000000001269]. It is important, in my opinion, if the Authors highlight the limits
of LI-RADS, adding the great potential of radiomics combined with LI-RADS in order to
overcome some of the LI-RADS limitations [Eur J Gastroenterol Hepatol. 2019;31(3):283-288.
doi:10.1097/MEG.0000000000001269].
The aim needs to be re-written. In fact, it seems to be a result and not an aim.
MATERIALS & METHODS
It is not well clear, nor in the aim (background) nor in the m&m, why the Authors apply their
scientific idea only on nodules <3 cm. it is important that this point is clarify!
In the “Qualitative Image Analysis” the authors stated that: “Two radiologists (observer 1, JSL,
with 15 years of experience; and observer 2, BGL, with 10 years of experience) independently
analyzed all MR images and reached a consensus.”. how they reached the consensus? Please,
explain.
I think that data reported in the “radiomics analysis” subsection (starting from Page 7-8) may
result highly complex to all readers and I want to suggest to Authors to try reaching a more slim
and usable form for these content because it may confuse non-expert readers in this field.
If it is necessary to reduce the size of the paper in terms of words count, it is possible to eliminate
all the part that explains the LI-RADS, adding a simple bibliographic entry that refers to them.
RESULTS
The population of this study is composed largely of HBV patients. This is more typical of
the Asian world, while it is less common in the Western countries where the hepatitis B mass
vaccination has allowed the consequent reduction of patients with HBV-related cirrhosis. This
difference could lead the data from this study to be unappetizing in the Western world. Therefore,
authors, in my opinion, could either make a comparison of their results between the HBV group
and the HCV group, or (more simply), they may address these issues in the discussion.
In particular, in the Western world, the issue of treating hepatitis C is much discussed, in
particular regarding the oncological possible consequences. On page 4 lines 21 Authors could
explain if their HCV patients underwent anti-viral therapies that may have changed the natural
history of the disease. Consequently, I would like to ask them if they speculated on these or other
important clinical-therapeutic features that have an important role on the prognosis and evolution
of HCC such as showed in [World J Gastroenterol. 2018 Jun 28;24(24):2582-2595] and [J
Gastroenterol 2020 Oct;55(10):927-943]. Could the Authors please disclose this important topic
here and/or in the “Discussion” section?
I would like to ask if Authors, who stated in page 11 line 10 that they collected histopathologic
data deriving from resections or biopsies samples, investigated some of the most important
molecular feature that potentially have a big impact on the imaging appearance of these lesions
such as the case of OATP1B1/B3 expression, which is a well-known influencing factor of the
HCC imaging appearance, especially in small HCCs. In fact, it was demonstrated that HCCs
showing a progressive loss in OATP immunoreactivity correlates with the gain of a biliary
phenotype. Moreover, OATP could be used together with K7/19 to identify a phenotypical
"spectrum" in HCC progression. [Virchows Arch. 2011 Aug;459(2):141-6]. Have the Authors
thought of analyzing this topic more in depth, and discuss this theme in the discussion section?
Authors also excluded from the study patients with “a nodule with a diameter larger than 3 cm”
and I think that this approach could create a sort of “selection bias” because the model presented
by Authors could not be such effective in larger lesions patients. Have the Authors considered
this topic? I think that this topic could be disclosed in the limitation section of the discussion.
Anyway, results remain clear and well-structured, and no further adjustments are needed.
DISCUSSION
The discussion section is well structured and clear, but I want to suggest to Authors to enrich
this section with some considerations that could easily be disclosed.
In page 18 from lines 10-11 Authors disclose a lot of important informations about the increase
in performance given by the adoption of radiomics signature based on MRI texture, which leads
to an improvement in both sensitivity and specificity, potentially making it better than LI-RADS.
Basing on these considerations and study results, I would like to ask to Authors if they thought
it was possible to speculate on the fact that MRI-based radiomics could also help in realizing a
better identification and classification of HCC substages [Sci Rep 2019 Oct 14;9(1):14749] that
clearly demonstrated a great clinical value in the assessment of critical patients with untreated
HCCs as demonstrated in [Am J Gastroenterol 2016 Jan;111(1):70-77].
No further modifications are required for this section. My only reminder to Authors is to that a
native speaker English revision is recommended.
REFERENCES
References do not perfectly reflect the style showed in Authors guidelines, so Authors should
try to adjust them. Modulate the reference style according to this journal.
In particular Ref #8 and #9 are repeated and consequently reference order must be checked and
fixed along the main text.
FIGURES AND TABLES
All figures and tables are satisfactory and didactic, and they correctly match the quality standard
of this Journal.
Title: Title: Differentiation of small (#3 cm) hepatocellular carcinomas from benign nodules in
cirrhotic liver: The added additive value of MRI-based radiomics analysis to LI-RADS version
2018 algorithm
Version: 2 Date: 08 Feb 2021
Reviewer's report:
SPECIFIC COMMENTS
This manuscript is clear and exhaustive without appreciable major issues.
Although language used is already appropriate and pleasant, I (I am not a native English
speaker) only recommend to Authors to obtain a certified native speaker with proficiencies in
the scientific-medical field to properly complete this paper.
TITLE
The title is clearly explanatory and, in my opinion, it suddenly shows the main topic of the paper.
I would like to propose only a little language observation that could be adopted from Authors
if they are pleased of that.
In my opinion it may be more pleasurable to adopt this slimmer title: “Differentiation of small
(#3 cm) hepatocellular carcinomas from benign nodules in cirrhotic liver: the added additive
value of MRI-based radiomics analysis to LI-RADS vversion 2018 algorithm”.
ABSTRACT
The abstract results globally precise and properly reflecting the main text, consequently no major
adjustments are needed.
Style and length reflect the “Author Guidelines” presented on the website except for the absence
of “Trial Registration”: as indicated in the authors guidelines, since this is a retrospective study
the authors should indicate the wording “retrospectively registered” in this section.
In the Methods section Authors may also specify the retrospective study design and the period
of study comprise as well.
KEYWORDS
Keywords are completely missing, so Authors should indicate from three to ten keywords
representing the main content of the article (as indicated in authors guidelines). If possible, to
enhance the finding process of this paper (and consequently of the Journal) by Readers and
Stakeholders, I would like to suggest the selection of keywords directly on MeSH Browser.
BACKGROUND
The introduction is well structured and interesting to read, although some clarifications could
be added.
For example, in page 3 line 17 it could be useful to underline that the theme regarding
the use (or not) of LI-RADS is still open, because this system in the present form
demonstrated many limitations [Eur J Gastroenterol Hepatol. 2019;31(3):283-288. doi:10.1097/
MEG.0000000000001269]. It is important, in my opinion, if the Authors highlight the limits
of LI-RADS, adding the great potential of radiomics combined with LI-RADS in order to
overcome some of the LI-RADS limitations [Eur J Gastroenterol Hepatol. 2019;31(3):283-288.
doi:10.1097/MEG.0000000000001269].
The aim needs to be re-written. In fact, it seems to be a result and not an aim.
MATERIALS & METHODS
It is not well clear, nor in the aim (background) nor in the m&m, why the Authors apply their
scientific idea only on nodules <3 cm. it is important that this point is clarify!
In the “Qualitative Image Analysis” the authors stated that: “Two radiologists (observer 1, JSL,
with 15 years of experience; and observer 2, BGL, with 10 years of experience) independently
analyzed all MR images and reached a consensus.”. how they reached the consensus? Please,
explain.
I think that data reported in the “radiomics analysis” subsection (starting from Page 7-8) may
result highly complex to all readers and I want to suggest to Authors to try reaching a more slim
and usable form for these content because it may confuse non-expert readers in this field.
If it is necessary to reduce the size of the paper in terms of words count, it is possible to eliminate
all the part that explains the LI-RADS, adding a simple bibliographic entry that refers to them.
RESULTS
The population of this study is composed largely of HBV patients. This is more typical of
the Asian world, while it is less common in the Western countries where the hepatitis B mass
vaccination has allowed the consequent reduction of patients with HBV-related cirrhosis. This
difference could lead the data from this study to be unappetizing in the Western world. Therefore,
authors, in my opinion, could either make a comparison of their results between the HBV group
and the HCV group, or (more simply), they may address these issues in the discussion.
In particular, in the Western world, the issue of treating hepatitis C is much discussed, in
particular regarding the oncological possible consequences. On page 4 lines 21 Authors could
explain if their HCV patients underwent anti-viral therapies that may have changed the natural
history of the disease. Consequently, I would like to ask them if they speculated on these or other
important clinical-therapeutic features that have an important role on the prognosis and evolution
of HCC such as showed in [World J Gastroenterol. 2018 Jun 28;24(24):2582-2595] and [J
Gastroenterol 2020 Oct;55(10):927-943]. Could the Authors please disclose this important topic
here and/or in the “Discussion” section?
I would like to ask if Authors, who stated in page 11 line 10 that they collected histopathologic
data deriving from resections or biopsies samples, investigated some of the most important
molecular feature that potentially have a big impact on the imaging appearance of these lesions
such as the case of OATP1B1/B3 expression, which is a well-known influencing factor of the
HCC imaging appearance, especially in small HCCs. In fact, it was demonstrated that HCCs
showing a progressive loss in OATP immunoreactivity correlates with the gain of a biliary
phenotype. Moreover, OATP could be used together with K7/19 to identify a phenotypical
"spectrum" in HCC progression. [Virchows Arch. 2011 Aug;459(2):141-6]. Have the Authors
thought of analyzing this topic more in depth, and discuss this theme in the discussion section?
Authors also excluded from the study patients with “a nodule with a diameter larger than 3 cm”
and I think that this approach could create a sort of “selection bias” because the model presented
by Authors could not be such effective in larger lesions patients. Have the Authors considered
this topic? I think that this topic could be disclosed in the limitation section of the discussion.
Anyway, results remain clear and well-structured, and no further adjustments are needed.
DISCUSSION
The discussion section is well structured and clear, but I want to suggest to Authors to enrich
this section with some considerations that could easily be disclosed.
In page 18 from lines 10-11 Authors disclose a lot of important informations about the increase
in performance given by the adoption of radiomics signature based on MRI texture, which leads
to an improvement in both sensitivity and specificity, potentially making it better than LI-RADS.
Basing on these considerations and study results, I would like to ask to Authors if they thought
it was possible to speculate on the fact that MRI-based radiomics could also help in realizing a
better identification and classification of HCC substages [Sci Rep 2019 Oct 14;9(1):14749] that
clearly demonstrated a great clinical value in the assessment of critical patients with untreated
HCCs as demonstrated in [Am J Gastroenterol 2016 Jan;111(1):70-77].
No further modifications are required for this section. My only reminder to Authors is to that a
native speaker English revision is recommended.
REFERENCES
References do not perfectly reflect the style showed in Authors guidelines, so Authors should
try to adjust them. Modulate the reference style according to this journal.
In particular Ref #8 and #9 are repeated and consequently reference order must be checked and
fixed along the main text.
FIGURES AND TABLES
All figures and tables are satisfactory and didactic, and they correctly match the quality standard
of this Journal.
Please review this paper.
user
Title: Title: Differentiation of small (#3 cm) hepatocellular carcinomas from benign nodules in
cirrhotic liver: The added additive value of MRI-based radiomics analysis to LI-RADS version
2018 algorithm
Version: 2 Date: 08 Feb 2021
Reviewer's report:
SPECIFIC COMMENTS
This manuscript is clear and exhaustive without appreciable major issues.
Although language used is already appropriate and pleasant, I (I am not a native English
speaker) only recommend to Authors to obtain a certified native speaker with proficiencies in
the scientific-medical field to properly complete this paper.
TITLE
The title is clearly explanatory and, in my opinion, it suddenly shows the main topic of the paper.
I would like to propose only a little language observation that could be adopted from Authors
if they are pleased of that.
In my opinion it may be more pleasurable to adopt this slimmer title: “Differentiation of small
(#3 cm) hepatocellular carcinomas from benign nodules in cirrhotic liver: the added additive
value of MRI-based radiomics analysis to LI-RADS vversion 2018 algorithm”.
ABSTRACT
The abstract results globally precise and properly reflecting the main text, consequently no major
adjustments are needed.
Style and length reflect the “Author Guidelines” presented on the website except for the absence
of “Trial Registration”: as indicated in the authors guidelines, since this is a retrospective study
the authors should indicate the wording “retrospectively registered” in this section.
In the Methods section Authors may also specify the retrospective study design and the period
of study comprise as well.
KEYWORDS
Keywords are completely missing, so Authors should indicate from three to ten keywords
representing the main content of the article (as indicated in authors guidelines). If possible, to
enhance the finding process of this paper (and consequently of the Journal) by Readers and
Stakeholders, I would like to suggest the selection of keywords directly on MeSH Browser.
BACKGROUND
The introduction is well structured and interesting to read, although some clarifications could
be added.
For example, in page 3 line 17 it could be useful to underline that the theme regarding
the use (or not) of LI-RADS is still open, because this system in the present form
demonstrated many limitations [Eur J Gastroenterol Hepatol. 2019;31(3):283-288. doi:10.1097/
MEG.0000000000001269]. It is important, in my opinion, if the Authors highlight the limits
of LI-RADS, adding the great potential of radiomics combined with LI-RADS in order to
overcome some of the LI-RADS limitations [Eur J Gastroenterol Hepatol. 2019;31(3):283-288.
doi:10.1097/MEG.0000000000001269].
The aim needs to be re-written. In fact, it seems to be a result and not an aim.
MATERIALS & METHODS
It is not well clear, nor in the aim (background) nor in the m&m, why the Authors apply their
scientific idea only on nodules <3 cm. it is important that this point is clarify!
In the “Qualitative Image Analysis” the authors stated that: “Two radiologists (observer 1, JSL,
with 15 years of experience; and observer 2, BGL, with 10 years of experience) independently
analyzed all MR images and reached a consensus.”. how they reached the consensus? Please,
explain.
I think that data reported in the “radiomics analysis” subsection (starting from Page 7-8) may
result highly complex to all readers and I want to suggest to Authors to try reaching a more slim
and usable form for these content because it may confuse non-expert readers in this field.
If it is necessary to reduce the size of the paper in terms of words count, it is possible to eliminate
all the part that explains the LI-RADS, adding a simple bibliographic entry that refers to them.
RESULTS
The population of this study is composed largely of HBV patients. This is more typical of
the Asian world, while it is less common in the Western countries where the hepatitis B mass
vaccination has allowed the consequent reduction of patients with HBV-related cirrhosis. This
difference could lead the data from this study to be unappetizing in the Western world. Therefore,
authors, in my opinion, could either make a comparison of their results between the HBV group
and the HCV group, or (more simply), they may address these issues in the discussion.
In particular, in the Western world, the issue of treating hepatitis C is much discussed, in
particular regarding the oncological possible consequences. On page 4 lines 21 Authors could
explain if their HCV patients underwent anti-viral therapies that may have changed the natural
history of the disease. Consequently, I would like to ask them if they speculated on these or other
important clinical-therapeutic features that have an important role on the prognosis and evolution
of HCC such as showed in [World J Gastroenterol. 2018 Jun 28;24(24):2582-2595] and [J
Gastroenterol 2020 Oct;55(10):927-943]. Could the Authors please disclose this important topic
here and/or in the “Discussion” section?
I would like to ask if Authors, who stated in page 11 line 10 that they collected histopathologic
data deriving from resections or biopsies samples, investigated some of the most important
molecular feature that potentially have a big impact on the imaging appearance of these lesions
such as the case of OATP1B1/B3 expression, which is a well-known influencing factor of the
HCC imaging appearance, especially in small HCCs. In fact, it was demonstrated that HCCs
showing a progressive loss in OATP immunoreactivity correlates with the gain of a biliary
phenotype. Moreover, OATP could be used together with K7/19 to identify a phenotypical
"spectrum" in HCC progression. [Virchows Arch. 2011 Aug;459(2):141-6]. Have the Authors
thought of analyzing this topic more in depth, and discuss this theme in the discussion section?
Authors also excluded from the study patients with “a nodule with a diameter larger than 3 cm”
and I think that this approach could create a sort of “selection bias” because the model presented
by Authors could not be such effective in larger lesions patients. Have the Authors considered
this topic? I think that this topic could be disclosed in the limitation section of the discussion.
Anyway, results remain clear and well-structured, and no further adjustments are needed.
DISCUSSION
The discussion section is well structured and clear, but I want to suggest to Authors to enrich
this section with some considerations that could easily be disclosed.
In page 18 from lines 10-11 Authors disclose a lot of important informations about the increase
in performance given by the adoption of radiomics signature based on MRI texture, which leads
to an improvement in both sensitivity and specificity, potentially making it better than LI-RADS.
Basing on these considerations and study results, I would like to ask to Authors if they thought
it was possible to speculate on the fact that MRI-based radiomics could also help in realizing a
better identification and classification of HCC substages [Sci Rep 2019 Oct 14;9(1):14749] that
clearly demonstrated a great clinical value in the assessment of critical patients with untreated
HCCs as demonstrated in [Am J Gastroenterol 2016 Jan;111(1):70-77].
No further modifications are required for this section. My only reminder to Authors is to that a
native speaker English revision is recommended.
REFERENCES
References do not perfectly reflect the style showed in Authors guidelines, so Authors should
try to adjust them. Modulate the reference style according to this journal.
In particular Ref #8 and #9 are repeated and consequently reference order must be checked and
fixed along the main text.
FIGURES AND TABLES
All figures and tables are satisfactory and didactic, and they correctly match the quality standard
of this Journal.
assistant