Osteopenia Is Associated with Shorter Survival in Patients with Intrahepatic Cholangiocarcinoma

Round 1

Reviewer 1 Report

Authors performed a retrospective study trying to find an association of osteopenia with disease free survival in patients with intrahepatic cholangiocarcinoma. I have the following questions to the authors.

What is the role of liver in osteopenia; although there is an association from the study are there any biochemical/molecular feedback from liver towards osteopenia?

What is the nutritional status of these patients in terms calclium uptake? 

How does the chemotherapy influence BMD? Can you comment on this?

Did you find any positive correaltion betweeen nutrition index and osteopenia?

how do you associate osteopenia with cholongiocarcinoma?

How do you account for postmenopausal status in women?

Based on the past drug history were there drugs that could have affected the BMD including any chemotherapy?

Author Response

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Reviewer 2 Report

1. Methods; 2.4; "The cutoff value for CEA and CA-199 were 4.5 and 37.." Please add unit for 2 data. These 2 data were upper normal range or other? 

2. Please apply to used "ICC" for "intrahepatic cholangiocarcinoma" due to frequent appearances, and  others will be the same

3. The last paragraph of Methods 2.1; Prognostic nutrition index(PNI), NL ratio and PL ratio need to be descripted clearly for readers especial PNI.

4. The age of non- and osteopenia patients (Table ) was with a sgnificant difference and may be due to athe aging process. Please mentioned in the "Discussion"

Author Response

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Reviewer 3 Report

I felt your paper added useful information about factors surgeons, hepatologists, and oncologists can use to advise and treat patients with cholangiocarcinoma. I have a few issues with your grammar and wording which I will address below:

1.) In the abstract, line 17, I believe you meant to write "units" instead of "unite".

2.) In the abstract, line 18, I suggest inserting "was" after "test".

3.) In the Introduction, line 29, I do not understand why you have the sentence about Cholangiolocellular carcinoma. It seems out of place and it confuses the reader about for which cancer does "Complete surgical resection remains the only method ...".

4.) In the Introduction, line 52, I suggest adding "alone" after osteopenia.

5.) In Materials and Methods, line 66, I believe your definition of a R2 resection is incomplete and should include "resection of the tumor visible grossly but leaving macroscopic residual disease." I also would like an explanation of why the surgeons had to do so.

6.) In Materials and Methods, line 86, I suggest changing "was" to "were".

7.) In Results, in Table 1, line 9, I suggest replacing "bleeding" with "blood loss".

8.) In Results, in Table 1, line 14, I suggest changing "por" to "poorly", which is what I assumed you meant.

9.) In Results, lines 129, 131, and Tables 1a and 1b, I suggest changing "non-osteopenia" to either "without osteopenia" or "normal BMD".

10.) In Discussion, I became confused about your thinking expressed in lines 173 to 181. The sentence "One possibility is the NF-kappaB is a key molecule associated with sarcopenia" is actually a statement and no explanation is given why that molecule is key. The next sentence, line 174, should begin with "The" states that RANKL "activates osteoclastogenesis" but no explanation of that that word means for osteopenia. The next sentence, line 176, begins with "RANK", which I assume you meant to be "RANKL", suggest it leads to muscle loss, although that is not stated, and causes sarcopenia. Etc. I believe I understand what you are saying but I would like you to spell it out more clearly.

Author Response

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Author Response File: Author Response.docx