Reviewer's report
Title:Prostaglandin E2-induced colonic secretion in patients with colorectal
neoplasia
Version: 1Date:15 October 2009
Reviewer: Markus Sjöblom
Reviewer's report:
General
This paper describes the effects of prostaglandins on colonic secretion in biopsy
specimens of patients with or without colorectal neoplasia. The authors are using
a modified Ussing air-suction chamber in which they are enabling to study ion
secretion (e.g. short circuit current and slope conductance). In this chamber, the
secretion is investigated upon adding a number of different prostaglandin
agonists, an unselective COX inhibitor as well as various stimulators of epithelial
ion transport.
No differences between the groups are observed in the stimulated secretion.
However, when adding indomethacin to the Ussing chamber the secretion
decreases significantly more in neoplasia-patients than in control-patients.
The data presented are novel and the manuscript is well written.
Major Compulsory Revisions
Major
1. The cyclooxygenase-2 enzyme is suggested to be involved in the development
of neoplasia. The aim of the present study is to establish possible differences in
COX-2/PGE2 levels and the functional expression/response of PGE2
EP-receptor subtypes by the use of indomethacin and EP receptor agonists. The
authors only use indomethacin, an unspecific COX inhibitor. Experimental data
need to be strengthening by investigating the effects of a specific COX-2
inhibitor. Additional experimental work is needed.
2. The authors express their data as mean ± SEM. In several groups the n
(number of biopsy specimens) is large. With large samples the SEM should
always be small, and this is not the case in the present study. When n is large
SEM should be avoided. Interpretation of the data would be easier if expressed
as mean ± SD or as median and range (minimum-maximum).
Specific comments
Abstract.
p.2. Conclusions. Data only supports that ion transport is altered during
indomethacin treatment. The authors should consider re-wording the conclusion.
Introduction,
p.5. Last paragraph. The authors have neither measured COX-2 levels/activity
nor used a selective COX-2 inhibitor in the present study and should therefore
avoid this conclusion. Consider re-wording the paragraph.
Results
p.9. Basal levels. The SCC baseline values in both C-patients and N-patients
have a very large variation. For example, the SCC baseline for C-patients is 38.1
± 75 µA/cm2 (mean ± SD). Are these great variations from edge-damage? The
results indicate that at basal condition the epithelium can be either secreting or
absorbing, although the tissue is treated the same way. How can this be
explained?
Since the exposed tissue area is only 3.4 mm2 to what extent does the
edge-damage in the MUAS chamber contribute to the large variation of the data?
p.9. Inhibition. The N-patients are more sensitive to indomethacin than the
C-patients, but no differences in halftimes for the inhibition of SCC. How can this
be explained?
p.10. Histological examination. The authors state that “In particular, no signs of
inflammation or neoplasia were detected in the biopsies from N-patients”. If this
is true how was the tissue divided into the two groups? This requires
explanation/clarification from the authors.
Level of interest: An article whose findings are important to those with closely
related research interests
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'
Reviewer's report
Title:Prostaglandin E2-induced colonic secretion in patients with colorectal
neoplasia
Version: 1Date:15 October 2009
Reviewer: Markus Sjöblom
Reviewer's report:
General
This paper describes the effects of prostaglandins on colonic secretion in biopsy
specimens of patients with or without colorectal neoplasia. The authors are using
a modified Ussing air-suction chamber in which they are enabling to study ion
secretion (e.g. short circuit current and slope conductance). In this chamber, the
secretion is investigated upon adding a number of different prostaglandin
agonists, an unselective COX inhibitor as well as various stimulators of epithelial
ion transport.
No differences between the groups are observed in the stimulated secretion.
However, when adding indomethacin to the Ussing chamber the secretion
decreases significantly more in neoplasia-patients than in control-patients.
The data presented are novel and the manuscript is well written.
Major Compulsory Revisions
Major
1. The cyclooxygenase-2 enzyme is suggested to be involved in the development
of neoplasia. The aim of the present study is to establish possible differences in
COX-2/PGE2 levels and the functional expression/response of PGE2
EP-receptor subtypes by the use of indomethacin and EP receptor agonists. The
authors only use indomethacin, an unspecific COX inhibitor. Experimental data
need to be strengthening by investigating the effects of a specific COX-2
inhibitor. Additional experimental work is needed.
2. The authors express their data as mean ± SEM. In several groups the n
(number of biopsy specimens) is large. With large samples the SEM should
always be small, and this is not the case in the present study. When n is large
SEM should be avoided. Interpretation of the data would be easier if expressed
as mean ± SD or as median and range (minimum-maximum).
Specific comments
Abstract.
p.2. Conclusions. Data only supports that ion transport is altered during
indomethacin treatment. The authors should consider re-wording the conclusion.
Introduction,
p.5. Last paragraph. The authors have neither measured COX-2 levels/activity
nor used a selective COX-2 inhibitor in the present study and should therefore
avoid this conclusion. Consider re-wording the paragraph.
Results
p.9. Basal levels. The SCC baseline values in both C-patients and N-patients
have a very large variation. For example, the SCC baseline for C-patients is 38.1
± 75 µA/cm2 (mean ± SD). Are these great variations from edge-damage? The
results indicate that at basal condition the epithelium can be either secreting or
absorbing, although the tissue is treated the same way. How can this be
explained?
Since the exposed tissue area is only 3.4 mm2 to what extent does the
edge-damage in the MUAS chamber contribute to the large variation of the data?
p.9. Inhibition. The N-patients are more sensitive to indomethacin than the
C-patients, but no differences in halftimes for the inhibition of SCC. How can this
be explained?
p.10. Histological examination. The authors state that “In particular, no signs of
inflammation or neoplasia were detected in the biopsies from N-patients”. If this
is true how was the tissue divided into the two groups? This requires
explanation/clarification from the authors.
Level of interest: An article whose findings are important to those with closely
related research interests
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'
Please review this paper.
user
Reviewer's report
Title:Prostaglandin E2-induced colonic secretion in patients with colorectal
neoplasia
Version: 1Date:15 October 2009
Reviewer: Markus Sjöblom
Reviewer's report:
General
This paper describes the effects of prostaglandins on colonic secretion in biopsy
specimens of patients with or without colorectal neoplasia. The authors are using
a modified Ussing air-suction chamber in which they are enabling to study ion
secretion (e.g. short circuit current and slope conductance). In this chamber, the
secretion is investigated upon adding a number of different prostaglandin
agonists, an unselective COX inhibitor as well as various stimulators of epithelial
ion transport.
No differences between the groups are observed in the stimulated secretion.
However, when adding indomethacin to the Ussing chamber the secretion
decreases significantly more in neoplasia-patients than in control-patients.
The data presented are novel and the manuscript is well written.
Major Compulsory Revisions
Major
1. The cyclooxygenase-2 enzyme is suggested to be involved in the development
of neoplasia. The aim of the present study is to establish possible differences in
COX-2/PGE2 levels and the functional expression/response of PGE2
EP-receptor subtypes by the use of indomethacin and EP receptor agonists. The
authors only use indomethacin, an unspecific COX inhibitor. Experimental data
need to be strengthening by investigating the effects of a specific COX-2
inhibitor. Additional experimental work is needed.
2. The authors express their data as mean ± SEM. In several groups the n
(number of biopsy specimens) is large. With large samples the SEM should
always be small, and this is not the case in the present study. When n is large
SEM should be avoided. Interpretation of the data would be easier if expressed
as mean ± SD or as median and range (minimum-maximum).
Specific comments
Abstract.
p.2. Conclusions. Data only supports that ion transport is altered during
indomethacin treatment. The authors should consider re-wording the conclusion.
Introduction,
p.5. Last paragraph. The authors have neither measured COX-2 levels/activity
nor used a selective COX-2 inhibitor in the present study and should therefore
avoid this conclusion. Consider re-wording the paragraph.
Results
p.9. Basal levels. The SCC baseline values in both C-patients and N-patients
have a very large variation. For example, the SCC baseline for C-patients is 38.1
± 75 µA/cm2 (mean ± SD). Are these great variations from edge-damage? The
results indicate that at basal condition the epithelium can be either secreting or
absorbing, although the tissue is treated the same way. How can this be
explained?
Since the exposed tissue area is only 3.4 mm2 to what extent does the
edge-damage in the MUAS chamber contribute to the large variation of the data?
p.9. Inhibition. The N-patients are more sensitive to indomethacin than the
C-patients, but no differences in halftimes for the inhibition of SCC. How can this
be explained?
p.10. Histological examination. The authors state that “In particular, no signs of
inflammation or neoplasia were detected in the biopsies from N-patients”. If this
is true how was the tissue divided into the two groups? This requires
explanation/clarification from the authors.
Level of interest: An article whose findings are important to those with closely
related research interests
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'
assistant