Reviewer’s report
Title: 
A case of intraductal tubulopapillary neoplasm of the pancreas in a branch
duct: a rare case report and literature review
Version: 
0 
Date: 
23 Jan 2021
Reviewer's report:
Authors reported a case of ITPN in a branch duct of the pancreas. There are
some concerns in this report.
1. What is a scientific benefit in this report? ITPNs in BD does not sound so rare.
Even differentiation between BD-origin and the main duct-origin does not seem
to be beneficial clinically. The authors need to make points clear to distinguish
BD-origin and MPD-origin in ITPNs.
2. Patients anonymity should be strictly warranted. Descriptions of exact time
like "November 2016" and "May 2014" should be avoided. 
3. "There are few case reports of ITPN in a branch of the pancreatic duct (BD)"
sounds inappropriate. As the authors described in discussion, ITPNs in BD
account for "9.4%", which does not sound "few" or "very rare". 
4. "known to have little invasion and good prognosis" in introduction; "a disease
with borderline malignancy and do not induce a poor prognosis" and "Most
cases, even with extraductal invasion, have a good prognosis" in discussion may
mislead readers. ITPN does claim patients lives as reported by Yamaguchi et al.
Basturk et al (PMID: 27984235) reported that 71% of their 33 experienced cases
reveled invasion and such invasive cases showed 71% in 5-year survival.
5. "pancreatic intraepitheral neoplasm" should be correctly "pancreatic
intraepithelial neoplasia."
6. "Fine needle biopsy was sent with suspicion of an intraductal lesion." The
biopsy is very critical for diagnosis of ITPN, therefore, it should have been
carefully examined. Is there any possibility that the biopsy could be accurately
diagnosed retrospectively?
7. In Figure 5a, what was indicated by arrows? The main pancreatic duct should
be indicated.
8. According to Figure 5c, the tumor mainly shows tubular pattern, which is not
consistent with descriptions as "the tumor had grown with a complicated
papillary structure, pseudopapillary structure, or cribriform pattern (Fig.5)."
9. A histological image of "an extraductal invasion" should be shown.
10. Regarding Figure 6, negative staining images should be shown with positive
controls.
11. "tubule-papillary pattern" should be replaced with "tubulopapillary pattern".
12. "ITPN is a very rare disease as 0.3% of intraductal tumors" is wrong. ITPNs
account for 3% of intraductal tumors of the pancreas.
13. Split of Table 1 is hard to read. 
14. Data of KI-67 in this case noted in Table 1 should be referred in the results
section.
15. Data in Table 2 should be examined statistically.
16. "Diagnosis of ITPN is difficult if localized in a branch duct" and
"Furthermore, the preoperative pathological diagnosis of ITPN in BD is very
difficult" seem to be redundant
17. "There is possibility" should be "there is a possibility".
18. "there are limitations in a histology from ITPNs in BD" is questionable. As
authours stated, an appropriate immunohistochemical examination may lead to
correct diagnosis.
19. "If tumors in a branch duct is certain to be ITPN, a course observation
without surgery might be one choice of therapy for patients with a poor general
condition" is very controversial; therefore, such description is strongly
discouraged. 
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Yes
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 this manuscript, 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.
Reviewer Publication Consent.
 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
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
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?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
A case of intraductal tubulopapillary neoplasm of the pancreas in a branch
duct: a rare case report and literature review
Version: 
0 
Date: 
23 Jan 2021
Reviewer's report:
Authors reported a case of ITPN in a branch duct of the pancreas. There are
some concerns in this report.
1. What is a scientific benefit in this report? ITPNs in BD does not sound so rare.
Even differentiation between BD-origin and the main duct-origin does not seem
to be beneficial clinically. The authors need to make points clear to distinguish
BD-origin and MPD-origin in ITPNs.
2. Patients anonymity should be strictly warranted. Descriptions of exact time
like "November 2016" and "May 2014" should be avoided. 
3. "There are few case reports of ITPN in a branch of the pancreatic duct (BD)"
sounds inappropriate. As the authors described in discussion, ITPNs in BD
account for "9.4%", which does not sound "few" or "very rare". 
4. "known to have little invasion and good prognosis" in introduction; "a disease
with borderline malignancy and do not induce a poor prognosis" and "Most
cases, even with extraductal invasion, have a good prognosis" in discussion may
mislead readers. ITPN does claim patients lives as reported by Yamaguchi et al.
Basturk et al (PMID: 27984235) reported that 71% of their 33 experienced cases
reveled invasion and such invasive cases showed 71% in 5-year survival.
5. "pancreatic intraepitheral neoplasm" should be correctly "pancreatic
intraepithelial neoplasia."
6. "Fine needle biopsy was sent with suspicion of an intraductal lesion." The
biopsy is very critical for diagnosis of ITPN, therefore, it should have been
carefully examined. Is there any possibility that the biopsy could be accurately
diagnosed retrospectively?
7. In Figure 5a, what was indicated by arrows? The main pancreatic duct should
be indicated.
8. According to Figure 5c, the tumor mainly shows tubular pattern, which is not
consistent with descriptions as "the tumor had grown with a complicated
papillary structure, pseudopapillary structure, or cribriform pattern (Fig.5)."
9. A histological image of "an extraductal invasion" should be shown.
10. Regarding Figure 6, negative staining images should be shown with positive
controls.
11. "tubule-papillary pattern" should be replaced with "tubulopapillary pattern".
12. "ITPN is a very rare disease as 0.3% of intraductal tumors" is wrong. ITPNs
account for 3% of intraductal tumors of the pancreas.
13. Split of Table 1 is hard to read. 
14. Data of KI-67 in this case noted in Table 1 should be referred in the results
section.
15. Data in Table 2 should be examined statistically.
16. "Diagnosis of ITPN is difficult if localized in a branch duct" and
"Furthermore, the preoperative pathological diagnosis of ITPN in BD is very
difficult" seem to be redundant
17. "There is possibility" should be "there is a possibility".
18. "there are limitations in a histology from ITPNs in BD" is questionable. As
authours stated, an appropriate immunohistochemical examination may lead to
correct diagnosis.
19. "If tumors in a branch duct is certain to be ITPN, a course observation
without surgery might be one choice of therapy for patients with a poor general
condition" is very controversial; therefore, such description is strongly
discouraged. 
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
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 this manuscript, 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.
Reviewer Publication Consent.
 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
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
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?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Please review this paper.
user
Reviewer’s report
Title: 
A case of intraductal tubulopapillary neoplasm of the pancreas in a branch
duct: a rare case report and literature review
Version: 
0 
Date: 
23 Jan 2021
Reviewer's report:
Authors reported a case of ITPN in a branch duct of the pancreas. There are
some concerns in this report.
1. What is a scientific benefit in this report? ITPNs in BD does not sound so rare.
Even differentiation between BD-origin and the main duct-origin does not seem
to be beneficial clinically. The authors need to make points clear to distinguish
BD-origin and MPD-origin in ITPNs.
2. Patients anonymity should be strictly warranted. Descriptions of exact time
like "November 2016" and "May 2014" should be avoided. 
3. "There are few case reports of ITPN in a branch of the pancreatic duct (BD)"
sounds inappropriate. As the authors described in discussion, ITPNs in BD
account for "9.4%", which does not sound "few" or "very rare". 
4. "known to have little invasion and good prognosis" in introduction; "a disease
with borderline malignancy and do not induce a poor prognosis" and "Most
cases, even with extraductal invasion, have a good prognosis" in discussion may
mislead readers. ITPN does claim patients lives as reported by Yamaguchi et al.
Basturk et al (PMID: 27984235) reported that 71% of their 33 experienced cases
reveled invasion and such invasive cases showed 71% in 5-year survival.
5. "pancreatic intraepitheral neoplasm" should be correctly "pancreatic
intraepithelial neoplasia."
6. "Fine needle biopsy was sent with suspicion of an intraductal lesion." The
biopsy is very critical for diagnosis of ITPN, therefore, it should have been
carefully examined. Is there any possibility that the biopsy could be accurately
diagnosed retrospectively?
7. In Figure 5a, what was indicated by arrows? The main pancreatic duct should
be indicated.
8. According to Figure 5c, the tumor mainly shows tubular pattern, which is not
consistent with descriptions as "the tumor had grown with a complicated
papillary structure, pseudopapillary structure, or cribriform pattern (Fig.5)."
9. A histological image of "an extraductal invasion" should be shown.
10. Regarding Figure 6, negative staining images should be shown with positive
controls.
11. "tubule-papillary pattern" should be replaced with "tubulopapillary pattern".
12. "ITPN is a very rare disease as 0.3% of intraductal tumors" is wrong. ITPNs
account for 3% of intraductal tumors of the pancreas.
13. Split of Table 1 is hard to read. 
14. Data of KI-67 in this case noted in Table 1 should be referred in the results
section.
15. Data in Table 2 should be examined statistically.
16. "Diagnosis of ITPN is difficult if localized in a branch duct" and
"Furthermore, the preoperative pathological diagnosis of ITPN in BD is very
difficult" seem to be redundant
17. "There is possibility" should be "there is a possibility".
18. "there are limitations in a histology from ITPNs in BD" is questionable. As
authours stated, an appropriate immunohistochemical examination may lead to
correct diagnosis.
19. "If tumors in a branch duct is certain to be ITPN, a course observation
without surgery might be one choice of therapy for patients with a poor general
condition" is very controversial; therefore, such description is strongly
discouraged. 
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
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 this manuscript, 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.
Reviewer Publication Consent.
 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
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
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?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
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