Reviewer’ s report
Title: An assessment of chromosomal alterations detected by fluorescence in situ hybridisation in
pancreatobiliary tract malignancy
Version: 1Date: 23 May 2019
Reviewer: David F. Chhieng
Reviewer's report:
The authors described their experience of using FISH to evaluate biliary brushing cytology in
diagnosing pancreatobiliary malignancy. Similar studies have been published in the Englishliterature during the past decades. The authors did not offer new insight to the subject except thatthe test was applied to the Chinese patient population. In addition, the number of specimen wasrelatively small which was further compounded by the fact that the majority (3/4) of cases weremalignant. The latter contributed to significant bias in the estimation of PPV and NPV since theyare both dependent on the disease prevalence.In addition, the English is difficult to read and there are substantial grammatical errors.Page 6: What classification system was used for reporting cytology? Why did the authors use"atypical" to report cytology cases that were considered "reactive", should they be classified as"negative" In addition, if the specimen was considered unequivocal for carcinoma, why did theauthors classify them as "suspicious" and what would be the difference between cases that wereclassified as "suspicious" vs "positive".Page 6: What was the rationale to obtain a separate cytologic sample for FISH after the initialsample for cytology was obtained? How was the quality of the 2 samples compared with eachother? Why did the authors choose cytospin preparation and not ThinPrep preparation for FISH
test?
Page 8: Was the same reviewer evaluated both the cytology and FISH samples? Was he/she blindto the results? If there was only one reviewer, how did the authors account for reviewer bias? Ifthere was more than one reviewer, how did the authors resolve discrepancies among reviewers?Page 8: the authors described using 2-cm thick section for FISH. That would be a very thicksection. Please clarify! What scoring criteria did the authors use to evaluate FISH testing onFFPE?Page 9: What was the cut off value for cytology results in determining sensitivity and specificity?Only cases that were classified as "positive" were considered positive; the remaining cases wereconsidered negative?Section of discussion: The authors should compare their observations with those reported in theliterature.Section of discussion (page 14): The authors offered plausible explanation of the one false positiveFISH test as a result of the presence of high grade dysplasia. If this was the situation as suggestedby the authors, the cytology should demonstrate rare atypical cells derived from high gradedysplasia. Did the authors review the cytologic samples to determine if there were any atypicalcells that were missed in the initial preparation.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
NoDoes 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 your comments to the authors.
NoAre you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?If an additional statistical review is recommended, please specify what aspects require furtherassessment in your comments to the editors.
I am able to assess the statisticsQuality of written English
Please indicate the quality of language in the manuscript:
Not suitable for publication unless extensively edited
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, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of thismanuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that 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 currently 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.
I declare that I have no competing interests.I agree to the open peer review policy of the journal. I understand that my name will be included
on my report to the authors and, if the manuscript is accepted for publication, my named reportincluding 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 Commons
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 included as confidential commentsto the editors, which will not be published.
I agree to the open peer review policy of the journal
Reviewer’ s report
Title: An assessment of chromosomal alterations detected by fluorescence in situ hybridisation in
pancreatobiliary tract malignancy
Version: 1Date: 23 May 2019
Reviewer: David F. Chhieng
Reviewer's report:
The authors described their experience of using FISH to evaluate biliary brushing cytology in
diagnosing pancreatobiliary malignancy. Similar studies have been published in the Englishliterature during the past decades. The authors did not offer new insight to the subject except thatthe test was applied to the Chinese patient population. In addition, the number of specimen wasrelatively small which was further compounded by the fact that the majority (3/4) of cases weremalignant. The latter contributed to significant bias in the estimation of PPV and NPV since theyare both dependent on the disease prevalence.In addition, the English is difficult to read and there are substantial grammatical errors.Page 6: What classification system was used for reporting cytology? Why did the authors use"atypical" to report cytology cases that were considered "reactive", should they be classified as"negative" In addition, if the specimen was considered unequivocal for carcinoma, why did theauthors classify them as "suspicious" and what would be the difference between cases that wereclassified as "suspicious" vs "positive".Page 6: What was the rationale to obtain a separate cytologic sample for FISH after the initialsample for cytology was obtained? How was the quality of the 2 samples compared with eachother? Why did the authors choose cytospin preparation and not ThinPrep preparation for FISH
test?
Page 8: Was the same reviewer evaluated both the cytology and FISH samples? Was he/she blindto the results? If there was only one reviewer, how did the authors account for reviewer bias? Ifthere was more than one reviewer, how did the authors resolve discrepancies among reviewers?Page 8: the authors described using 2-cm thick section for FISH. That would be a very thicksection. Please clarify! What scoring criteria did the authors use to evaluate FISH testing onFFPE?Page 9: What was the cut off value for cytology results in determining sensitivity and specificity?Only cases that were classified as "positive" were considered positive; the remaining cases wereconsidered negative?Section of discussion: The authors should compare their observations with those reported in theliterature.Section of discussion (page 14): The authors offered plausible explanation of the one false positiveFISH test as a result of the presence of high grade dysplasia. If this was the situation as suggestedby the authors, the cytology should demonstrate rare atypical cells derived from high gradedysplasia. Did the authors review the cytologic samples to determine if there were any atypicalcells that were missed in the initial preparation.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
NoDoes 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 your comments to the authors.
NoAre you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?If an additional statistical review is recommended, please specify what aspects require furtherassessment in your comments to the editors.
I am able to assess the statisticsQuality of written English
Please indicate the quality of language in the manuscript:
Not suitable for publication unless extensively edited
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, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of thismanuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that 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 currently 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.
I declare that I have no competing interests.I agree to the open peer review policy of the journal. I understand that my name will be included
on my report to the authors and, if the manuscript is accepted for publication, my named reportincluding 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 Commons
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 included as confidential commentsto 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: An assessment of chromosomal alterations detected by fluorescence in situ hybridisation in
pancreatobiliary tract malignancy
Version: 1Date: 23 May 2019
Reviewer: David F. Chhieng
Reviewer's report:
The authors described their experience of using FISH to evaluate biliary brushing cytology in
diagnosing pancreatobiliary malignancy. Similar studies have been published in the Englishliterature during the past decades. The authors did not offer new insight to the subject except thatthe test was applied to the Chinese patient population. In addition, the number of specimen wasrelatively small which was further compounded by the fact that the majority (3/4) of cases weremalignant. The latter contributed to significant bias in the estimation of PPV and NPV since theyare both dependent on the disease prevalence.In addition, the English is difficult to read and there are substantial grammatical errors.Page 6: What classification system was used for reporting cytology? Why did the authors use"atypical" to report cytology cases that were considered "reactive", should they be classified as"negative" In addition, if the specimen was considered unequivocal for carcinoma, why did theauthors classify them as "suspicious" and what would be the difference between cases that wereclassified as "suspicious" vs "positive".Page 6: What was the rationale to obtain a separate cytologic sample for FISH after the initialsample for cytology was obtained? How was the quality of the 2 samples compared with eachother? Why did the authors choose cytospin preparation and not ThinPrep preparation for FISH
test?
Page 8: Was the same reviewer evaluated both the cytology and FISH samples? Was he/she blindto the results? If there was only one reviewer, how did the authors account for reviewer bias? Ifthere was more than one reviewer, how did the authors resolve discrepancies among reviewers?Page 8: the authors described using 2-cm thick section for FISH. That would be a very thicksection. Please clarify! What scoring criteria did the authors use to evaluate FISH testing onFFPE?Page 9: What was the cut off value for cytology results in determining sensitivity and specificity?Only cases that were classified as "positive" were considered positive; the remaining cases wereconsidered negative?Section of discussion: The authors should compare their observations with those reported in theliterature.Section of discussion (page 14): The authors offered plausible explanation of the one false positiveFISH test as a result of the presence of high grade dysplasia. If this was the situation as suggestedby the authors, the cytology should demonstrate rare atypical cells derived from high gradedysplasia. Did the authors review the cytologic samples to determine if there were any atypicalcells that were missed in the initial preparation.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
NoDoes 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 your comments to the authors.
NoAre you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?If an additional statistical review is recommended, please specify what aspects require furtherassessment in your comments to the editors.
I am able to assess the statisticsQuality of written English
Please indicate the quality of language in the manuscript:
Not suitable for publication unless extensively edited
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, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of thismanuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that 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 currently 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.
I declare that I have no competing interests.I agree to the open peer review policy of the journal. I understand that my name will be included
on my report to the authors and, if the manuscript is accepted for publication, my named reportincluding 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 Commons
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 included as confidential commentsto the editors, which will not be published.
I agree to the open peer review policy of the journal
assistant