Reviewer ’s report  
 
Title:  Clinicopathological features and surgical outcomes of neuroendocrine tumors of ampulla 
of Vater  
 
Version: 0 Date: 03 Jan 2017 
 
Reviewer:  Katarzyna  Kusnierz  
 
Reviewer’s report:  
 
The study "Clinicopathological features and surgical outcomes of neuroendocrine tumors of 
ampulla of Vater" refers to rare neuroendocrine tumors of ampulla of Vater. It presents 5 cases, 
is properly written; however, it requires certain clarifications and additions.  
 
 
Notes to Methods  
 
In the Methods the authors report tha t they used the WHO, ENETS and UICC classifications. 
For the correct interpretation, please specify the year of issuing the classifications.  
 
 
Notes to Results  
 
Clinical findings and preoperative evaluation  
 
Please indicate whether either in CT or MRI occurred  the signs of amputation or dilatation of 
Wirsung 's duct.  
 
 
Notes to Treatment  
 
The authors report they performed pancreaticoduodenectomy. Please specify what decided about 
the type of surgery performed (conventional or PPPD) and what was the extent of lymph  nodes 
removal (standard?). Additionally, define the type of pancreatic anastomosis performed.  
 
"Three minor complications"  - specify what scale of complications was applied (Accordion 
Severity Grading System, Clavien -Dindo ?)  
 
"Recurrence of NETAoVs occurr ed in 2 patients" - it may be more accurate to use the term 
"distant recurrence", since it is a metastasis in the liver.  
 
 
Pathologic findings  
 
Please indicate how many lymph nodes were removed and state the LNR (Lymph node ratio). 
Information on how many nod es were affected by metastases is insufficient. Please indicate 
whether the resections were R0 and give the definition of R which was used.  
 
The authors wrote:"In case 3, the histological result was collision tumor accompanied with 
neuroendocrine tumor and adenocarcinoma (pT1). In this patient, liver metastases was 
confirmed…" It is unclear whether the tumor was diagnosed as MANEC, or there was an extra 
tumor - adenocarcinoma? According to the above quoted sentence, patient No. 3 (3case) had 
metastases to th e liver, why was this not included in the table, according to which only patients 
No. 2 and No. 5 had metastases?  
 
 
Survival  
 
Please specify what tests constituted the follow -up, and how often they were performed.  
 
 
Notes to Discussion  
 
It is difficult to fully agree with the statement: "But, the prognostic role of the Ki -67 index is not 
clear and more research is needed." Certainly, the prognostic significance of both Ki67 and 
removed lymph nodes requires further study, it is difficult to downplay the importance  of the Ki 
67 index  in neuroendocrine tumors. According to the authors themselves, patients with the 
highest Ki67% (5 and 70%) had liver metastases.  
 
 
Notes to Conclusion  
 
It is worth noting that in 80% of patients cancer was asymptomatic and despite the 
implementation of radical resection in the form of pancreatoduodenectomy, two patients 
developed metastases within 10 and 11 months after surgery, which proves high aggressiveness 
of this group of cancers.  
 
The statement: "Radical resection for NETAoVs can pr ovide the information of the status of 
lymph node metastasis after surgery" is well known and very general. It will be more reliable 
after taking into account the above -mentioned details (the exact scope of the removal of lymph 
nodes, the number of removed  ones and the number of affected ones).  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
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 your comments to the authors.  
 
No 
 
Are 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 further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
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 t he 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 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 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 comments 
to the editors, which will not be published . 
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title:  Clinicopathological features and surgical outcomes of neuroendocrine tumors of ampulla 
of Vater  
 
Version: 0 Date: 03 Jan 2017 
 
Reviewer:  Katarzyna  Kusnierz  
 
Reviewer’s report:  
 
The study "Clinicopathological features and surgical outcomes of neuroendocrine tumors of 
ampulla of Vater" refers to rare neuroendocrine tumors of ampulla of Vater. It presents 5 cases, 
is properly written; however, it requires certain clarifications and additions.  
 
 
Notes to Methods  
 
In the Methods the authors report tha t they used the WHO, ENETS and UICC classifications. 
For the correct interpretation, please specify the year of issuing the classifications.  
 
 
Notes to Results  
 
Clinical findings and preoperative evaluation  
 
Please indicate whether either in CT or MRI occurred  the signs of amputation or dilatation of 
Wirsung 's duct.  
 
 
Notes to Treatment  
 
The authors report they performed pancreaticoduodenectomy. Please specify what decided about 
the type of surgery performed (conventional or PPPD) and what was the extent of lymph  nodes 
removal (standard?). Additionally, define the type of pancreatic anastomosis performed.  
 
"Three minor complications"  - specify what scale of complications was applied (Accordion 
Severity Grading System, Clavien -Dindo ?)  
 
"Recurrence of NETAoVs occurr ed in 2 patients" - it may be more accurate to use the term 
"distant recurrence", since it is a metastasis in the liver.  
 
 
Pathologic findings  
 
Please indicate how many lymph nodes were removed and state the LNR (Lymph node ratio). 
Information on how many nod es were affected by metastases is insufficient. Please indicate 
whether the resections were R0 and give the definition of R which was used.  
 
The authors wrote:"In case 3, the histological result was collision tumor accompanied with 
neuroendocrine tumor and adenocarcinoma (pT1). In this patient, liver metastases was 
confirmed…" It is unclear whether the tumor was diagnosed as MANEC, or there was an extra 
tumor - adenocarcinoma? According to the above quoted sentence, patient No. 3 (3case) had 
metastases to th e liver, why was this not included in the table, according to which only patients 
No. 2 and No. 5 had metastases?  
 
 
Survival  
 
Please specify what tests constituted the follow -up, and how often they were performed.  
 
 
Notes to Discussion  
 
It is difficult to fully agree with the statement: "But, the prognostic role of the Ki -67 index is not 
clear and more research is needed." Certainly, the prognostic significance of both Ki67 and 
removed lymph nodes requires further study, it is difficult to downplay the importance  of the Ki 
67 index  in neuroendocrine tumors. According to the authors themselves, patients with the 
highest Ki67% (5 and 70%) had liver metastases.  
 
 
Notes to Conclusion  
 
It is worth noting that in 80% of patients cancer was asymptomatic and despite the 
implementation of radical resection in the form of pancreatoduodenectomy, two patients 
developed metastases within 10 and 11 months after surgery, which proves high aggressiveness 
of this group of cancers.  
 
The statement: "Radical resection for NETAoVs can pr ovide the information of the status of 
lymph node metastasis after surgery" is well known and very general. It will be more reliable 
after taking into account the above -mentioned details (the exact scope of the removal of lymph 
nodes, the number of removed  ones and the number of affected ones).  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
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 your comments to the authors.  
 
No 
 
Are 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 further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
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 t he 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 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 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 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:  Clinicopathological features and surgical outcomes of neuroendocrine tumors of ampulla 
of Vater  
 
Version: 0 Date: 03 Jan 2017 
 
Reviewer:  Katarzyna  Kusnierz  
 
Reviewer’s report:  
 
The study "Clinicopathological features and surgical outcomes of neuroendocrine tumors of 
ampulla of Vater" refers to rare neuroendocrine tumors of ampulla of Vater. It presents 5 cases, 
is properly written; however, it requires certain clarifications and additions.  
 
 
Notes to Methods  
 
In the Methods the authors report tha t they used the WHO, ENETS and UICC classifications. 
For the correct interpretation, please specify the year of issuing the classifications.  
 
 
Notes to Results  
 
Clinical findings and preoperative evaluation  
 
Please indicate whether either in CT or MRI occurred  the signs of amputation or dilatation of 
Wirsung 's duct.  
 
 
Notes to Treatment  
 
The authors report they performed pancreaticoduodenectomy. Please specify what decided about 
the type of surgery performed (conventional or PPPD) and what was the extent of lymph  nodes 
removal (standard?). Additionally, define the type of pancreatic anastomosis performed.  
 
"Three minor complications"  - specify what scale of complications was applied (Accordion 
Severity Grading System, Clavien -Dindo ?)  
 
"Recurrence of NETAoVs occurr ed in 2 patients" - it may be more accurate to use the term 
"distant recurrence", since it is a metastasis in the liver.  
 
 
Pathologic findings  
 
Please indicate how many lymph nodes were removed and state the LNR (Lymph node ratio). 
Information on how many nod es were affected by metastases is insufficient. Please indicate 
whether the resections were R0 and give the definition of R which was used.  
 
The authors wrote:"In case 3, the histological result was collision tumor accompanied with 
neuroendocrine tumor and adenocarcinoma (pT1). In this patient, liver metastases was 
confirmed…" It is unclear whether the tumor was diagnosed as MANEC, or there was an extra 
tumor - adenocarcinoma? According to the above quoted sentence, patient No. 3 (3case) had 
metastases to th e liver, why was this not included in the table, according to which only patients 
No. 2 and No. 5 had metastases?  
 
 
Survival  
 
Please specify what tests constituted the follow -up, and how often they were performed.  
 
 
Notes to Discussion  
 
It is difficult to fully agree with the statement: "But, the prognostic role of the Ki -67 index is not 
clear and more research is needed." Certainly, the prognostic significance of both Ki67 and 
removed lymph nodes requires further study, it is difficult to downplay the importance  of the Ki 
67 index  in neuroendocrine tumors. According to the authors themselves, patients with the 
highest Ki67% (5 and 70%) had liver metastases.  
 
 
Notes to Conclusion  
 
It is worth noting that in 80% of patients cancer was asymptomatic and despite the 
implementation of radical resection in the form of pancreatoduodenectomy, two patients 
developed metastases within 10 and 11 months after surgery, which proves high aggressiveness 
of this group of cancers.  
 
The statement: "Radical resection for NETAoVs can pr ovide the information of the status of 
lymph node metastasis after surgery" is well known and very general. It will be more reliable 
after taking into account the above -mentioned details (the exact scope of the removal of lymph 
nodes, the number of removed  ones and the number of affected ones).  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
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 your comments to the authors.  
 
No 
 
Are 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 further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
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 t he 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 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 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 comments 
to the editors, which will not be published . 
 
I agree to the open peer review policy of the journal  
assistant