Reviewer ’s report  
 
Title: The development of early ascites is associated with shorter ov erall survival in patients 
with hepatocellular carcinoma treated with drug -eluting embolic chemoembolization  
 
Version: 1 Date: 27 Apr 2020  
 
Reviewer: Fabio Piscaglia  
 
Reviewer's report:  
 
The revised version of the ma nuscript is very much improved and now more consistent with the 
clinical practice.  
 
I am not sure that anemia has the same meaning in HCC on cirrhosis as it has in other cancer 
types. Therefore I disagree with the interpretation given at 2.12. In fact in other cancer types 
anemia does indeed reflect the worsening of general condition. In HCC in cirrhosis anemia 
reflext hypersplenism which in turns reflect the severity of portal hypertension. Therefore it is 
not unexpected that it was a predictor of decompe nsation in previous studies. The mechanisms 
are probably different in HCC and in other cancers. I would be very cautions in assigning any 
independent predictive role related to HCC.  
 
Engligh text would benefit from a revision by a native speaker.  
 
 
Minor p oints.  
 
Page 10, line 2. I think albumin &gt;35 g/L; should instead be inferior to 35 (albumin &lt;35) 
since the Hazard Ratio is 1.5. Therefore the patient beloding to the group (according to the 
current text &gt;35 g/L of albumin) are associated with a wor se prognosis, which seem 
impossibile to explain. Rather low albumin is expected to be associated with worse prognosis. A 
few lines later for the same reason developmento of ascites (HR 0.43) should read "absence of 
developement of ascites…" in my view.  
 
Table 1. The range should report the lowest and highest value. In these tables this is not the case 
for several variable (e.g. biliubin, albumin, AFP, etc). Please verify and correct.  
 
Table 1. Prior radiological ascites no /yes is 198 / 18., whereas in Ta ble 2 ascites preTACE no / 
yes was 197 / 19, in Table 3 it is 198 / 18. Therefore please decide whether you had 18 or 19 
patients with previous ascites, as the current data are confusing and verify the entire manuscript 
consistently.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your c omments to the authors.  
 
Yes 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in yo ur comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in y our comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1.  Have you in the past five years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financially from the 
publi cation of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organisation t hat may in any way gain or 
lose financially from the publication of this manuscript, either now or in the 
future?  
 
3.  Do you hold or are you curr ently applying for any patents  relating to the content 
of the manuscript?  
 
4.  Have you received reimbursements, fees, funding, or salary from an organization 
that holds or has applied for patents relating to the content of the manuscript?  
 
5.  Do you have any  other financial competing interests?  
 
6.  Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have  no competing interests' 
below. If your reply is yes to any, please give details below.  
 
• Esaote (Genova, Ita lia):Research contract with the department  
 
Occasional honoraria  
 
• Astrazeneca (Milano, Italy): advisory board  
 
• Bayer (Leverkusen, Germania): speaker bureau, advisory board.  
 
• Bracco (Milano, Italy): speaker bureau  
 
• BMS (UK): speaker bureau  
 
• La Force Gu erbet (Minneapolis, USA): speaker bureau.  
 
• EISAI (Milano, Italy): speaker bureau, advisory board  
 
• GE (Milwaukee, USA): consultant  
 
• Tiziana Life Sciences (United Kingdom)  
 
• Siemens Healthcare (Germany)  
 
• Alkermes (USA)  
 
• IPSEN (Italy / Europe): speaker bureau  
 
• Roche (Italy): advisory board  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commo ns 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: The development of early ascites is associated with shorter ov erall survival in patients 
with hepatocellular carcinoma treated with drug -eluting embolic chemoembolization  
 
Version: 1 Date: 27 Apr 2020  
 
Reviewer: Fabio Piscaglia  
 
Reviewer's report:  
 
The revised version of the ma nuscript is very much improved and now more consistent with the 
clinical practice.  
 
I am not sure that anemia has the same meaning in HCC on cirrhosis as it has in other cancer 
types. Therefore I disagree with the interpretation given at 2.12. In fact in other cancer types 
anemia does indeed reflect the worsening of general condition. In HCC in cirrhosis anemia 
reflext hypersplenism which in turns reflect the severity of portal hypertension. Therefore it is 
not unexpected that it was a predictor of decompe nsation in previous studies. The mechanisms 
are probably different in HCC and in other cancers. I would be very cautions in assigning any 
independent predictive role related to HCC.  
 
Engligh text would benefit from a revision by a native speaker.  
 
 
Minor p oints.  
 
Page 10, line 2. I think albumin &gt;35 g/L; should instead be inferior to 35 (albumin &lt;35) 
since the Hazard Ratio is 1.5. Therefore the patient beloding to the group (according to the 
current text &gt;35 g/L of albumin) are associated with a wor se prognosis, which seem 
impossibile to explain. Rather low albumin is expected to be associated with worse prognosis. A 
few lines later for the same reason developmento of ascites (HR 0.43) should read "absence of 
developement of ascites…" in my view.  
 
Table 1. The range should report the lowest and highest value. In these tables this is not the case 
for several variable (e.g. biliubin, albumin, AFP, etc). Please verify and correct.  
 
Table 1. Prior radiological ascites no /yes is 198 / 18., whereas in Ta ble 2 ascites preTACE no / 
yes was 197 / 19, in Table 3 it is 198 / 18. Therefore please decide whether you had 18 or 19 
patients with previous ascites, as the current data are confusing and verify the entire manuscript 
consistently.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your c omments to the authors.  
 
Yes 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in yo ur comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in y our comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1.  Have you in the past five years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financially from the 
publi cation of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organisation t hat may in any way gain or 
lose financially from the publication of this manuscript, either now or in the 
future?  
 
3.  Do you hold or are you curr ently applying for any patents  relating to the content 
of the manuscript?  
 
4.  Have you received reimbursements, fees, funding, or salary from an organization 
that holds or has applied for patents relating to the content of the manuscript?  
 
5.  Do you have any  other financial competing interests?  
 
6.  Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have  no competing interests' 
below. If your reply is yes to any, please give details below.  
 
• Esaote (Genova, Ita lia):Research contract with the department  
 
Occasional honoraria  
 
• Astrazeneca (Milano, Italy): advisory board  
 
• Bayer (Leverkusen, Germania): speaker bureau, advisory board.  
 
• Bracco (Milano, Italy): speaker bureau  
 
• BMS (UK): speaker bureau  
 
• La Force Gu erbet (Minneapolis, USA): speaker bureau.  
 
• EISAI (Milano, Italy): speaker bureau, advisory board  
 
• GE (Milwaukee, USA): consultant  
 
• Tiziana Life Sciences (United Kingdom)  
 
• Siemens Healthcare (Germany)  
 
• Alkermes (USA)  
 
• IPSEN (Italy / Europe): speaker bureau  
 
• Roche (Italy): advisory board  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commo ns 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: The development of early ascites is associated with shorter ov erall survival in patients 
with hepatocellular carcinoma treated with drug -eluting embolic chemoembolization  
 
Version: 1 Date: 27 Apr 2020  
 
Reviewer: Fabio Piscaglia  
 
Reviewer's report:  
 
The revised version of the ma nuscript is very much improved and now more consistent with the 
clinical practice.  
 
I am not sure that anemia has the same meaning in HCC on cirrhosis as it has in other cancer 
types. Therefore I disagree with the interpretation given at 2.12. In fact in other cancer types 
anemia does indeed reflect the worsening of general condition. In HCC in cirrhosis anemia 
reflext hypersplenism which in turns reflect the severity of portal hypertension. Therefore it is 
not unexpected that it was a predictor of decompe nsation in previous studies. The mechanisms 
are probably different in HCC and in other cancers. I would be very cautions in assigning any 
independent predictive role related to HCC.  
 
Engligh text would benefit from a revision by a native speaker.  
 
 
Minor p oints.  
 
Page 10, line 2. I think albumin &gt;35 g/L; should instead be inferior to 35 (albumin &lt;35) 
since the Hazard Ratio is 1.5. Therefore the patient beloding to the group (according to the 
current text &gt;35 g/L of albumin) are associated with a wor se prognosis, which seem 
impossibile to explain. Rather low albumin is expected to be associated with worse prognosis. A 
few lines later for the same reason developmento of ascites (HR 0.43) should read "absence of 
developement of ascites…" in my view.  
 
Table 1. The range should report the lowest and highest value. In these tables this is not the case 
for several variable (e.g. biliubin, albumin, AFP, etc). Please verify and correct.  
 
Table 1. Prior radiological ascites no /yes is 198 / 18., whereas in Ta ble 2 ascites preTACE no / 
yes was 197 / 19, in Table 3 it is 198 / 18. Therefore please decide whether you had 18 or 19 
patients with previous ascites, as the current data are confusing and verify the entire manuscript 
consistently.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your c omments to the authors.  
 
Yes 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in yo ur comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in y our comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1.  Have you in the past five years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financially from the 
publi cation of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organisation t hat may in any way gain or 
lose financially from the publication of this manuscript, either now or in the 
future?  
 
3.  Do you hold or are you curr ently applying for any patents  relating to the content 
of the manuscript?  
 
4.  Have you received reimbursements, fees, funding, or salary from an organization 
that holds or has applied for patents relating to the content of the manuscript?  
 
5.  Do you have any  other financial competing interests?  
 
6.  Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have  no competing interests' 
below. If your reply is yes to any, please give details below.  
 
• Esaote (Genova, Ita lia):Research contract with the department  
 
Occasional honoraria  
 
• Astrazeneca (Milano, Italy): advisory board  
 
• Bayer (Leverkusen, Germania): speaker bureau, advisory board.  
 
• Bracco (Milano, Italy): speaker bureau  
 
• BMS (UK): speaker bureau  
 
• La Force Gu erbet (Minneapolis, USA): speaker bureau.  
 
• EISAI (Milano, Italy): speaker bureau, advisory board  
 
• GE (Milwaukee, USA): consultant  
 
• Tiziana Life Sciences (United Kingdom)  
 
• Siemens Healthcare (Germany)  
 
• Alkermes (USA)  
 
• IPSEN (Italy / Europe): speaker bureau  
 
• Roche (Italy): advisory board  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commo ns 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant