Reviewer’s report
Title: 
Pancreaticopleural Fistula in a Child with Chronic Pancreatitis Harboring
Compound SPINK1 Variants
Version: 
1 
Date: 
18 Mar 2021
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
RELEVANCE - Does this case report make a contribution to medical
knowledge, have educational value, or highlight the need for a change in clinical
practice or diagnostic/prognostic approaches? 
Yes, this report contributes to medical knowledge
CASE DESCRIPTION - Are the details of the case sufficiently well described to
understand the patient's symptoms and course of treatment? 
No - there are minor issues
DIAGNOSIS/INTERPRETATION - Based on the facts presented, are the
diagnosis, interpretation, and course of treatment medically sound?
Yes, the work described is medically sound
DISCUSSION OF THE CASE - Does the discussion appropriately analyse the
importance of the findings and their relevance to future understanding of disease
processes, diagnosis or treatment? Has an adequate literature review pertinent to
the case been included?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Could an appropriately REVISED
version of this work represent a technically sound contribution?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: What is your overall impression of the report? 
Though extremely rare, there have been few reported cases. This report stresses
two things 1. Treatment of a PPF and 2. The fact that it should stimulate the
evaluation of the patients esp a child for a pancreatic genomic mutation which
will be important to the family and his/her offspring
Are you confident in the authors' description and interpretation of the report? 
I have made many suggestions to more precisely and specifically describe the
findings. Somewhere in the text the authors should mention that figure 3 really
shows a posterior mediastinal 
pseudocyst that ruptured into the right pleural
cavity and functioned as a PPF
Have the authors clearly outlined the need for publication by novelty of the case
or the specific adverse event? 
Yes I believe so for the reasons I outlined above in impression- teaching case cc
treatment and diagnosis
REQUESTED REVISIONS: 
Suggested changes
P-LEASE NORTE I 
HAEBV 
MADE MANY SUIGGESTIONS BUT THEY
ARE ALL C0NSRUCTIVE
1. In the future, Please either number 
your pages or number the lines
progressively across all pages 
this will make any correspondence with the
journal or the peer reviewers easier for everyone
2. 
Page 1 abstract( I will refer to the pages after this 
order) 
Line 13 ( your
numbers) delete "manifested" change to "who presents with a "
3.page 1 line 22 best to explain what endoscopic treatment you did 
4. Page 1 line 26 add at the end of the sentence. "in an appropriate clinical
situation related to pancreatic pathology" 
5. Page 1 lines 17 and 29 when you say "conservative treatment" what do you
mean? Just observation or TPN, NPO, etc 
6. Page 1 conclusions. 
This is too long, shorten some of this- you have already
said above
7. Page 2 line 7 add also "acute necrotizing pancreatitis" as a potential cause
8 page 2 line 18 why not refer to the specific pediatric 
cases in the literature refs
8,9,11, and 15?
9. Page 2 lines 14 and 32 and page 3 line 21 
delete the word "scan" 
tomography
is a "scan"
10. Page 3 line 1 add the word "chain of lakes" after the word 
" dilatations" also
"dilations" would be more correct than dilatations
11. Page 3 line 12 is there any evidence that antioxidants have any role on
treatment? If so I would add a reference to support this treatment; I know of no
good data on this! 
Also was he sent home in oral feeding or was the TPN and the
octreotide continued ? Were there any restrictions on types of food intake? Did
you consider enteral feeding distal to duodenum? 
Need to explain all this
12 page 3 line 23 was he also put on TPN?
13. page 3 line 24 and 28 change to "ERP" 
no need to inject the bile duct
14 figure 2 need to label a and b, 
15. Figure 3. Need to label the panels. 
I cannot be convinced that the arrow
shows the PPF track-- it does show a mediastinal fluid collection 
but this
collection is nowhere near the pancreas on this scan. The track to this posterior
mediastinal pseudocyst 
is further caudal I suggest that you consider this fluid
collection as a mediastinal pseudocyst that ruptured into the right pleural space. 
16. 
Figure 4 I do not see a stricture 
in the PD just after the neck of the gland on
the duodenal side even though that is where it usually is and should be in this
patient 
17. Page3 Lines26 and 27 did you have to dilate the PD structure?
18. Page 4 line 2 I do not understand the sentence. What do you mean by a
discrepancy? Do you mean that only 4 to 40% of families of a patient with a
SPINK 1 mutation have an identifiable family history?
19. Page 4 line 6 the disruption is not always "posterior" 
Delete the word 
20. Page 4 line 14. Liver cirrhosis ? Really? That is unlikely and especially when
the increase in amylase activity 
is so great! I would delete that reference to liver
cirrhosis in fact I would delete the rest of the entire sentence starting 
on line 12
these other causes are really really rare
21 page 4 lines 19 and 29. Quite frankly I think that you mean not "the fistula"
but rather the "pseudocyst"-- in truth most PPFs are small in diameter
22. Page 4 line 29 please add the references
23. Page 4 line 30 what type of complications? Add them briefly so anyone
planning this can be aware of these complications 
24. Page 4 line 31 I would add after the word "management" the following
phrase "such as pancreatic resection or formal operative pancreatic ductal
drainage procedures"
ADDITIONAL REQUESTS/SUGGESTIONS: 
see above
Publons Reviewer Recognition
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No
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
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. 
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.
This reviewer has been recruited by a partner organization, Research Square.
Reviewers with declared or apparent competing interests are not utilized for
these reviews. This reviewer has agreed to publication of their comments online
under a Creative Commons Attribution License attributed to Research Square
and was paid a small honorarium for completing the review within a specified
timeframe. Honoraria for reviews such as this are paid regardless of the reviewer
recommendation.
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?
Yes
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: 
Pancreaticopleural Fistula in a Child with Chronic Pancreatitis Harboring
Compound SPINK1 Variants
Version: 
1 
Date: 
18 Mar 2021
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
RELEVANCE - Does this case report make a contribution to medical
knowledge, have educational value, or highlight the need for a change in clinical
practice or diagnostic/prognostic approaches? 
Yes, this report contributes to medical knowledge
CASE DESCRIPTION - Are the details of the case sufficiently well described to
understand the patient's symptoms and course of treatment? 
No - there are minor issues
DIAGNOSIS/INTERPRETATION - Based on the facts presented, are the
diagnosis, interpretation, and course of treatment medically sound?
Yes, the work described is medically sound
DISCUSSION OF THE CASE - Does the discussion appropriately analyse the
importance of the findings and their relevance to future understanding of disease
processes, diagnosis or treatment? Has an adequate literature review pertinent to
the case been included?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Could an appropriately REVISED
version of this work represent a technically sound contribution?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: What is your overall impression of the report? 
Though extremely rare, there have been few reported cases. This report stresses
two things 1. Treatment of a PPF and 2. The fact that it should stimulate the
evaluation of the patients esp a child for a pancreatic genomic mutation which
will be important to the family and his/her offspring
Are you confident in the authors' description and interpretation of the report? 
I have made many suggestions to more precisely and specifically describe the
findings. Somewhere in the text the authors should mention that figure 3 really
shows a posterior mediastinal 
pseudocyst that ruptured into the right pleural
cavity and functioned as a PPF
Have the authors clearly outlined the need for publication by novelty of the case
or the specific adverse event? 
Yes I believe so for the reasons I outlined above in impression- teaching case cc
treatment and diagnosis
REQUESTED REVISIONS: 
Suggested changes
P-LEASE NORTE I 
HAEBV 
MADE MANY SUIGGESTIONS BUT THEY
ARE ALL C0NSRUCTIVE
1. In the future, Please either number 
your pages or number the lines
progressively across all pages 
this will make any correspondence with the
journal or the peer reviewers easier for everyone
2. 
Page 1 abstract( I will refer to the pages after this 
order) 
Line 13 ( your
numbers) delete "manifested" change to "who presents with a "
3.page 1 line 22 best to explain what endoscopic treatment you did 
4. Page 1 line 26 add at the end of the sentence. "in an appropriate clinical
situation related to pancreatic pathology" 
5. Page 1 lines 17 and 29 when you say "conservative treatment" what do you
mean? Just observation or TPN, NPO, etc 
6. Page 1 conclusions. 
This is too long, shorten some of this- you have already
said above
7. Page 2 line 7 add also "acute necrotizing pancreatitis" as a potential cause
8 page 2 line 18 why not refer to the specific pediatric 
cases in the literature refs
8,9,11, and 15?
9. Page 2 lines 14 and 32 and page 3 line 21 
delete the word "scan" 
tomography
is a "scan"
10. Page 3 line 1 add the word "chain of lakes" after the word 
" dilatations" also
"dilations" would be more correct than dilatations
11. Page 3 line 12 is there any evidence that antioxidants have any role on
treatment? If so I would add a reference to support this treatment; I know of no
good data on this! 
Also was he sent home in oral feeding or was the TPN and the
octreotide continued ? Were there any restrictions on types of food intake? Did
you consider enteral feeding distal to duodenum? 
Need to explain all this
12 page 3 line 23 was he also put on TPN?
13. page 3 line 24 and 28 change to "ERP" 
no need to inject the bile duct
14 figure 2 need to label a and b, 
15. Figure 3. Need to label the panels. 
I cannot be convinced that the arrow
shows the PPF track-- it does show a mediastinal fluid collection 
but this
collection is nowhere near the pancreas on this scan. The track to this posterior
mediastinal pseudocyst 
is further caudal I suggest that you consider this fluid
collection as a mediastinal pseudocyst that ruptured into the right pleural space. 
16. 
Figure 4 I do not see a stricture 
in the PD just after the neck of the gland on
the duodenal side even though that is where it usually is and should be in this
patient 
17. Page3 Lines26 and 27 did you have to dilate the PD structure?
18. Page 4 line 2 I do not understand the sentence. What do you mean by a
discrepancy? Do you mean that only 4 to 40% of families of a patient with a
SPINK 1 mutation have an identifiable family history?
19. Page 4 line 6 the disruption is not always "posterior" 
Delete the word 
20. Page 4 line 14. Liver cirrhosis ? Really? That is unlikely and especially when
the increase in amylase activity 
is so great! I would delete that reference to liver
cirrhosis in fact I would delete the rest of the entire sentence starting 
on line 12
these other causes are really really rare
21 page 4 lines 19 and 29. Quite frankly I think that you mean not "the fistula"
but rather the "pseudocyst"-- in truth most PPFs are small in diameter
22. Page 4 line 29 please add the references
23. Page 4 line 30 what type of complications? Add them briefly so anyone
planning this can be aware of these complications 
24. Page 4 line 31 I would add after the word "management" the following
phrase "such as pancreatic resection or formal operative pancreatic ductal
drainage procedures"
ADDITIONAL REQUESTS/SUGGESTIONS: 
see above
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
No
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.
This reviewer has been recruited by a partner organization, Research Square.
Reviewers with declared or apparent competing interests are not utilized for
these reviews. This reviewer has agreed to publication of their comments online
under a Creative Commons Attribution License attributed to Research Square
and was paid a small honorarium for completing the review within a specified
timeframe. Honoraria for reviews such as this are paid regardless of the reviewer
recommendation.
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?
Yes
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: 
Pancreaticopleural Fistula in a Child with Chronic Pancreatitis Harboring
Compound SPINK1 Variants
Version: 
1 
Date: 
18 Mar 2021
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
RELEVANCE - Does this case report make a contribution to medical
knowledge, have educational value, or highlight the need for a change in clinical
practice or diagnostic/prognostic approaches? 
Yes, this report contributes to medical knowledge
CASE DESCRIPTION - Are the details of the case sufficiently well described to
understand the patient's symptoms and course of treatment? 
No - there are minor issues
DIAGNOSIS/INTERPRETATION - Based on the facts presented, are the
diagnosis, interpretation, and course of treatment medically sound?
Yes, the work described is medically sound
DISCUSSION OF THE CASE - Does the discussion appropriately analyse the
importance of the findings and their relevance to future understanding of disease
processes, diagnosis or treatment? Has an adequate literature review pertinent to
the case been included?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Could an appropriately REVISED
version of this work represent a technically sound contribution?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: What is your overall impression of the report? 
Though extremely rare, there have been few reported cases. This report stresses
two things 1. Treatment of a PPF and 2. The fact that it should stimulate the
evaluation of the patients esp a child for a pancreatic genomic mutation which
will be important to the family and his/her offspring
Are you confident in the authors' description and interpretation of the report? 
I have made many suggestions to more precisely and specifically describe the
findings. Somewhere in the text the authors should mention that figure 3 really
shows a posterior mediastinal 
pseudocyst that ruptured into the right pleural
cavity and functioned as a PPF
Have the authors clearly outlined the need for publication by novelty of the case
or the specific adverse event? 
Yes I believe so for the reasons I outlined above in impression- teaching case cc
treatment and diagnosis
REQUESTED REVISIONS: 
Suggested changes
P-LEASE NORTE I 
HAEBV 
MADE MANY SUIGGESTIONS BUT THEY
ARE ALL C0NSRUCTIVE
1. In the future, Please either number 
your pages or number the lines
progressively across all pages 
this will make any correspondence with the
journal or the peer reviewers easier for everyone
2. 
Page 1 abstract( I will refer to the pages after this 
order) 
Line 13 ( your
numbers) delete "manifested" change to "who presents with a "
3.page 1 line 22 best to explain what endoscopic treatment you did 
4. Page 1 line 26 add at the end of the sentence. "in an appropriate clinical
situation related to pancreatic pathology" 
5. Page 1 lines 17 and 29 when you say "conservative treatment" what do you
mean? Just observation or TPN, NPO, etc 
6. Page 1 conclusions. 
This is too long, shorten some of this- you have already
said above
7. Page 2 line 7 add also "acute necrotizing pancreatitis" as a potential cause
8 page 2 line 18 why not refer to the specific pediatric 
cases in the literature refs
8,9,11, and 15?
9. Page 2 lines 14 and 32 and page 3 line 21 
delete the word "scan" 
tomography
is a "scan"
10. Page 3 line 1 add the word "chain of lakes" after the word 
" dilatations" also
"dilations" would be more correct than dilatations
11. Page 3 line 12 is there any evidence that antioxidants have any role on
treatment? If so I would add a reference to support this treatment; I know of no
good data on this! 
Also was he sent home in oral feeding or was the TPN and the
octreotide continued ? Were there any restrictions on types of food intake? Did
you consider enteral feeding distal to duodenum? 
Need to explain all this
12 page 3 line 23 was he also put on TPN?
13. page 3 line 24 and 28 change to "ERP" 
no need to inject the bile duct
14 figure 2 need to label a and b, 
15. Figure 3. Need to label the panels. 
I cannot be convinced that the arrow
shows the PPF track-- it does show a mediastinal fluid collection 
but this
collection is nowhere near the pancreas on this scan. The track to this posterior
mediastinal pseudocyst 
is further caudal I suggest that you consider this fluid
collection as a mediastinal pseudocyst that ruptured into the right pleural space. 
16. 
Figure 4 I do not see a stricture 
in the PD just after the neck of the gland on
the duodenal side even though that is where it usually is and should be in this
patient 
17. Page3 Lines26 and 27 did you have to dilate the PD structure?
18. Page 4 line 2 I do not understand the sentence. What do you mean by a
discrepancy? Do you mean that only 4 to 40% of families of a patient with a
SPINK 1 mutation have an identifiable family history?
19. Page 4 line 6 the disruption is not always "posterior" 
Delete the word 
20. Page 4 line 14. Liver cirrhosis ? Really? That is unlikely and especially when
the increase in amylase activity 
is so great! I would delete that reference to liver
cirrhosis in fact I would delete the rest of the entire sentence starting 
on line 12
these other causes are really really rare
21 page 4 lines 19 and 29. Quite frankly I think that you mean not "the fistula"
but rather the "pseudocyst"-- in truth most PPFs are small in diameter
22. Page 4 line 29 please add the references
23. Page 4 line 30 what type of complications? Add them briefly so anyone
planning this can be aware of these complications 
24. Page 4 line 31 I would add after the word "management" the following
phrase "such as pancreatic resection or formal operative pancreatic ductal
drainage procedures"
ADDITIONAL REQUESTS/SUGGESTIONS: 
see above
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
No
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.
This reviewer has been recruited by a partner organization, Research Square.
Reviewers with declared or apparent competing interests are not utilized for
these reviews. This reviewer has agreed to publication of their comments online
under a Creative Commons Attribution License attributed to Research Square
and was paid a small honorarium for completing the review within a specified
timeframe. Honoraria for reviews such as this are paid regardless of the reviewer
recommendation.
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?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
assistant