Reviewer's report
Title:Alpha-Fetoprotein-Producing Neuroendocrine Carcinoma of the Pancreas:
a Case Report
Version:1Date:17 December 2014
Reviewer: Gianluca Tamagno
Reviewer's report:
The authors have described an interesting case of alpha-fetoprotein
(AFP)-producing pancreatic neuroendocrine tumor (pNET). This clinical case has
some interesting aspects, especially with regard to the histopathological
characterization of the pNET, but a number of points need to be carefully
addressed and reviewed.
Major compulsory revisions:
1) The grammar needs a very careful revision and improvement;
2) The case described clearly appears to presents with metastatic disease and
the fact that AFP did not normalize after surgery, together with the quick
detection of mets and a number of other signs, might confirm the same.
Unfortunately the mets were not radiologically evident initially but the suspicion
was indeed really high and the case evolution confirmed that. I think that maybe
the authors have a bit emphasized the issue with the goal of highlighting as much
as possible the rarity / exceptionality of the case. I suggest to review the case
presentation and discussion keeping in mind this comment and maybe focus
mostly on the histopathological aspects, which im my opinion are the strongest
and better characterized aspects of this case report;
3) Is this case report indeed a "first time" ever report? I am not fully convinced.
The fact the mets were missed, though very likely already present, etc... makes
this report to be a bit more similar to other previous cases described in the
literature. I suggest to revise this manuscript also with this regard;
4) There is no mention of chromogranin A circulating levels in the manuscript,
though this is the most important circulating tumor marker in non-functioning
pNETs. Why?
5) A post-mortem examination would have been extremely useful for
characterizing the picture and also very interesting from a scientific point of view.
Maybe the mets could present with some features of hepatic differentiation which
could be consistent with the raised AFP level (on the top of the AFP
immunoreactivity in the primary tumor). Was the post-mortem examination done?
If not, why? the lack of post-mortem examination here might represent a relevant
limit of this case study;
6) At the best of my knowledge, the anti-proliferative effects of somatostatin
analogs in pNETs are still not clearly and definitely proven. I suggest to refer to
the recent CLARINET study, for example.
Minor essential revisions:
1) Case presentation: I suggest to report in this section the reason for carrying
out the AFP check and explain why the pancreas was radiologically investigated;
I suggest to review and describe the past medical history of the patient in a
clearer way; were circulating chromogranin A levels (and maybe NSE levels)
checked? If not, why? Why not carrying out a triphasic liver CT scan, which is a
sensitive investigation for detecting liver mets in NETs?
Endoscopic ultrasound is a sensitive method for studying pNETs, including the
assessment of locoregional disease. Was an endoscopic ultrasound carried out?
If not, why? Was an intra-operative ultrasound carried out? If not, why?
2) Histopathologic findings: Any description of the enlarged peri-pancreatic lymph
nodes, which I suppose have been removed and analysed?
3) Follow-up: why following-up with CEA and CA19.9 though these markers were
normal at baseline and never check chromogranin A, though the tumor was
diagnosed as pNET?
4) Discussion: Page 8, pNETs are not only sporadic tumors; pNEts can be not
diagnosed for a long time also because lack of a syndrome in the case of
non-functioning tumors; Page 9, was there any evidence of sst receptor
expression in this pNET? Was an octreoscan carried out or maybe the sst
receptors assessed at immunohistochemistry?
5) Please include PNETs in the abbreviation list.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Alpha-Fetoprotein-Producing Neuroendocrine Carcinoma of the Pancreas:
a Case Report
Version:1Date:17 December 2014
Reviewer: Gianluca Tamagno
Reviewer's report:
The authors have described an interesting case of alpha-fetoprotein
(AFP)-producing pancreatic neuroendocrine tumor (pNET). This clinical case has
some interesting aspects, especially with regard to the histopathological
characterization of the pNET, but a number of points need to be carefully
addressed and reviewed.
Major compulsory revisions:
1) The grammar needs a very careful revision and improvement;
2) The case described clearly appears to presents with metastatic disease and
the fact that AFP did not normalize after surgery, together with the quick
detection of mets and a number of other signs, might confirm the same.
Unfortunately the mets were not radiologically evident initially but the suspicion
was indeed really high and the case evolution confirmed that. I think that maybe
the authors have a bit emphasized the issue with the goal of highlighting as much
as possible the rarity / exceptionality of the case. I suggest to review the case
presentation and discussion keeping in mind this comment and maybe focus
mostly on the histopathological aspects, which im my opinion are the strongest
and better characterized aspects of this case report;
3) Is this case report indeed a "first time" ever report? I am not fully convinced.
The fact the mets were missed, though very likely already present, etc... makes
this report to be a bit more similar to other previous cases described in the
literature. I suggest to revise this manuscript also with this regard;
4) There is no mention of chromogranin A circulating levels in the manuscript,
though this is the most important circulating tumor marker in non-functioning
pNETs. Why?
5) A post-mortem examination would have been extremely useful for
characterizing the picture and also very interesting from a scientific point of view.
Maybe the mets could present with some features of hepatic differentiation which
could be consistent with the raised AFP level (on the top of the AFP
immunoreactivity in the primary tumor). Was the post-mortem examination done?
If not, why? the lack of post-mortem examination here might represent a relevant
limit of this case study;
6) At the best of my knowledge, the anti-proliferative effects of somatostatin
analogs in pNETs are still not clearly and definitely proven. I suggest to refer to
the recent CLARINET study, for example.
Minor essential revisions:
1) Case presentation: I suggest to report in this section the reason for carrying
out the AFP check and explain why the pancreas was radiologically investigated;
I suggest to review and describe the past medical history of the patient in a
clearer way; were circulating chromogranin A levels (and maybe NSE levels)
checked? If not, why? Why not carrying out a triphasic liver CT scan, which is a
sensitive investigation for detecting liver mets in NETs?
Endoscopic ultrasound is a sensitive method for studying pNETs, including the
assessment of locoregional disease. Was an endoscopic ultrasound carried out?
If not, why? Was an intra-operative ultrasound carried out? If not, why?
2) Histopathologic findings: Any description of the enlarged peri-pancreatic lymph
nodes, which I suppose have been removed and analysed?
3) Follow-up: why following-up with CEA and CA19.9 though these markers were
normal at baseline and never check chromogranin A, though the tumor was
diagnosed as pNET?
4) Discussion: Page 8, pNETs are not only sporadic tumors; pNEts can be not
diagnosed for a long time also because lack of a syndrome in the case of
non-functioning tumors; Page 9, was there any evidence of sst receptor
expression in this pNET? Was an octreoscan carried out or maybe the sst
receptors assessed at immunohistochemistry?
5) Please include PNETs in the abbreviation list.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:Alpha-Fetoprotein-Producing Neuroendocrine Carcinoma of the Pancreas:
a Case Report
Version:1Date:17 December 2014
Reviewer: Gianluca Tamagno
Reviewer's report:
The authors have described an interesting case of alpha-fetoprotein
(AFP)-producing pancreatic neuroendocrine tumor (pNET). This clinical case has
some interesting aspects, especially with regard to the histopathological
characterization of the pNET, but a number of points need to be carefully
addressed and reviewed.
Major compulsory revisions:
1) The grammar needs a very careful revision and improvement;
2) The case described clearly appears to presents with metastatic disease and
the fact that AFP did not normalize after surgery, together with the quick
detection of mets and a number of other signs, might confirm the same.
Unfortunately the mets were not radiologically evident initially but the suspicion
was indeed really high and the case evolution confirmed that. I think that maybe
the authors have a bit emphasized the issue with the goal of highlighting as much
as possible the rarity / exceptionality of the case. I suggest to review the case
presentation and discussion keeping in mind this comment and maybe focus
mostly on the histopathological aspects, which im my opinion are the strongest
and better characterized aspects of this case report;
3) Is this case report indeed a "first time" ever report? I am not fully convinced.
The fact the mets were missed, though very likely already present, etc... makes
this report to be a bit more similar to other previous cases described in the
literature. I suggest to revise this manuscript also with this regard;
4) There is no mention of chromogranin A circulating levels in the manuscript,
though this is the most important circulating tumor marker in non-functioning
pNETs. Why?
5) A post-mortem examination would have been extremely useful for
characterizing the picture and also very interesting from a scientific point of view.
Maybe the mets could present with some features of hepatic differentiation which
could be consistent with the raised AFP level (on the top of the AFP
immunoreactivity in the primary tumor). Was the post-mortem examination done?
If not, why? the lack of post-mortem examination here might represent a relevant
limit of this case study;
6) At the best of my knowledge, the anti-proliferative effects of somatostatin
analogs in pNETs are still not clearly and definitely proven. I suggest to refer to
the recent CLARINET study, for example.
Minor essential revisions:
1) Case presentation: I suggest to report in this section the reason for carrying
out the AFP check and explain why the pancreas was radiologically investigated;
I suggest to review and describe the past medical history of the patient in a
clearer way; were circulating chromogranin A levels (and maybe NSE levels)
checked? If not, why? Why not carrying out a triphasic liver CT scan, which is a
sensitive investigation for detecting liver mets in NETs?
Endoscopic ultrasound is a sensitive method for studying pNETs, including the
assessment of locoregional disease. Was an endoscopic ultrasound carried out?
If not, why? Was an intra-operative ultrasound carried out? If not, why?
2) Histopathologic findings: Any description of the enlarged peri-pancreatic lymph
nodes, which I suppose have been removed and analysed?
3) Follow-up: why following-up with CEA and CA19.9 though these markers were
normal at baseline and never check chromogranin A, though the tumor was
diagnosed as pNET?
4) Discussion: Page 8, pNETs are not only sporadic tumors; pNEts can be not
diagnosed for a long time also because lack of a syndrome in the case of
non-functioning tumors; Page 9, was there any evidence of sst receptor
expression in this pNET? Was an octreoscan carried out or maybe the sst
receptors assessed at immunohistochemistry?
5) Please include PNETs in the abbreviation list.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
assistant