Reviewer's report
Title:Pancreatic Adenocarcinoma in Type 2 Progressive Familial Intrahepatic
Cholestasis
Version: 1Date:23 December 2009
Reviewer: Victor Ling
Reviewer's report:
Overall Comment:
This case report is noteworthy as it is the first to show a possible association of
PFIC-2 and pancreatic cancer. This is novel since PFIC-2 is normally associated
with a greatly increased risk for liver cancer. It considers the possibility that the
observed pancreatic cancer results from mere coincidence(family history, and
unlikelihood of bile acid getting to the pancreas). It speculates also on an
interesting new possibility that BSEP may act as a tumor suppresor along with
some erudite embryology.
Minor Essential Revisions:
1) Figure legends and labeling of figures need to be significantly more
comprehensive. Current explanations are far too sketchy and labeling in the
figures is next to none. Major histological features described in the manuscript
should be labeled. Also, rulers should be added in the figures.
2) Page numbering is missing in the manuscript.
3) Beginning in the fifth paragraph in Discussion, the authors should clarify the
meaning of the statement “Exposure to toxic bile acids may offer another
explanation for development of pancreatic adenocarcinoma in this patient”. Bile
acids are all toxic at some level. The so called "toxic bile acids" usually refer to
lithocholic acid, deoxycholic acid and some hydrophobic bile acids. Are the
authors implicating these bile acids as having some more specific role in
pancreatic cancer? I am not aware of any reports suggesting such "toxic" bile
acids are increased in PFIC2 patients. Perhaps the authors mean the
accumulated bile acids are toxic?
Discretionary Revisions:
1) From a clinical perspective, it would be of value to estimate how many people
are currently living with BSEP disease and potentially at risk for pancreatic
cancer. Having that number would make it easier to assess the risk.
2) If pancreatic tissues (normal and malignant)from this patient were available, it
would be of interest to determine if BSEP is expressed and if further mutations
have occurred.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
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. Victor Ling
Reviewer's report
Title:Pancreatic Adenocarcinoma in Type 2 Progressive Familial Intrahepatic
Cholestasis
Version: 1Date:23 December 2009
Reviewer: Victor Ling
Reviewer's report:
Overall Comment:
This case report is noteworthy as it is the first to show a possible association of
PFIC-2 and pancreatic cancer. This is novel since PFIC-2 is normally associated
with a greatly increased risk for liver cancer. It considers the possibility that the
observed pancreatic cancer results from mere coincidence(family history, and
unlikelihood of bile acid getting to the pancreas). It speculates also on an
interesting new possibility that BSEP may act as a tumor suppresor along with
some erudite embryology.
Minor Essential Revisions:
1) Figure legends and labeling of figures need to be significantly more
comprehensive. Current explanations are far too sketchy and labeling in the
figures is next to none. Major histological features described in the manuscript
should be labeled. Also, rulers should be added in the figures.
2) Page numbering is missing in the manuscript.
3) Beginning in the fifth paragraph in Discussion, the authors should clarify the
meaning of the statement “Exposure to toxic bile acids may offer another
explanation for development of pancreatic adenocarcinoma in this patient”. Bile
acids are all toxic at some level. The so called "toxic bile acids" usually refer to
lithocholic acid, deoxycholic acid and some hydrophobic bile acids. Are the
authors implicating these bile acids as having some more specific role in
pancreatic cancer? I am not aware of any reports suggesting such "toxic" bile
acids are increased in PFIC2 patients. Perhaps the authors mean the
accumulated bile acids are toxic?
Discretionary Revisions:
1) From a clinical perspective, it would be of value to estimate how many people
are currently living with BSEP disease and potentially at risk for pancreatic
cancer. Having that number would make it easier to assess the risk.
2) If pancreatic tissues (normal and malignant)from this patient were available, it
would be of interest to determine if BSEP is expressed and if further mutations
have occurred.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
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. Victor Ling
Please review this paper.
user
Reviewer's report
Title:Pancreatic Adenocarcinoma in Type 2 Progressive Familial Intrahepatic
Cholestasis
Version: 1Date:23 December 2009
Reviewer: Victor Ling
Reviewer's report:
Overall Comment:
This case report is noteworthy as it is the first to show a possible association of
PFIC-2 and pancreatic cancer. This is novel since PFIC-2 is normally associated
with a greatly increased risk for liver cancer. It considers the possibility that the
observed pancreatic cancer results from mere coincidence(family history, and
unlikelihood of bile acid getting to the pancreas). It speculates also on an
interesting new possibility that BSEP may act as a tumor suppresor along with
some erudite embryology.
Minor Essential Revisions:
1) Figure legends and labeling of figures need to be significantly more
comprehensive. Current explanations are far too sketchy and labeling in the
figures is next to none. Major histological features described in the manuscript
should be labeled. Also, rulers should be added in the figures.
2) Page numbering is missing in the manuscript.
3) Beginning in the fifth paragraph in Discussion, the authors should clarify the
meaning of the statement “Exposure to toxic bile acids may offer another
explanation for development of pancreatic adenocarcinoma in this patient”. Bile
acids are all toxic at some level. The so called "toxic bile acids" usually refer to
lithocholic acid, deoxycholic acid and some hydrophobic bile acids. Are the
authors implicating these bile acids as having some more specific role in
pancreatic cancer? I am not aware of any reports suggesting such "toxic" bile
acids are increased in PFIC2 patients. Perhaps the authors mean the
accumulated bile acids are toxic?
Discretionary Revisions:
1) From a clinical perspective, it would be of value to estimate how many people
are currently living with BSEP disease and potentially at risk for pancreatic
cancer. Having that number would make it easier to assess the risk.
2) If pancreatic tissues (normal and malignant)from this patient were available, it
would be of interest to determine if BSEP is expressed and if further mutations
have occurred.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
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. Victor Ling
assistant