JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/1471-230X-9-3 (2009)

Reviewer's report
Title:Paraoxonase-1 is related to inflammation, fibrosis and PPAR delta in
experimental liver disease
Version: 2Date:2 December 2008
Reviewer: Fabio Marra
Reviewer's report:
The revised version of this manuscript is markedly improved by the addition of
sentences that better explain the findings and allow to put forward some
hypotheses for their interpretation.
Yet, this Reviewer feels that some additional efforts could be made to support the
hypotheses and speculation made in the Discussion. Specifically, and in relation
to point#1 of the previous review:
1. I wonder whether the Authors could run a simple Western blot analysis with
PON1 antibodies, as they have already done in other studies (e.g. J Gastrointest
Surg 2008;12:891). Apparently, this would also allow the Authors to establish
whether PON1 proteolysis is indeed reduced, as hypothesized.
2. Another piece of information could derive from analysis of HDL levels, that are
said to be decreased, but no experimental indication of this fact is provided.
At least one of these approaches would make the study stronger.
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
Review for 10.1186/1471-230X-9-3 (2009)

Reviewer's report
Title:Paraoxonase-1 is related to inflammation, fibrosis and PPAR delta in
experimental liver disease
Version: 3Date:7 January 2009
Reviewer: Fabio Marra
Reviewer's report:
No further comments
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
Review for 10.1186/1471-230X-9-2 (2009)

Reviewer's report
Title:Selenoprotein S (SEPS1) gene -105G>A promoter polymorphism
influences the susceptibility of Japanese to gastric cancer
Version: 2Date:23 September 2008
Reviewer: caspar grond-ginsbach
Reviewer's report:
This manuscript presents the findings of a genetic association study with
case/control design. A known promoter polymorphism (rs28665122) of candidate
gene SEPS1 was genotyped in 268 Japanes patients with gastric cancer (GC)
and in 306 Japanese control patients from the same center. Th A-allele of the
promoter polymorphism was found more frequently in GC patients than in control
subjects, but the difference was not significant. However, in some subgroups of
patients (patients with intestinal type of GC, patients with tumors located in the
middle third) the A-allele of rs28665122 was significantly more frequently than in
the control series. This observation suggests, as the authors express in the title
of their study, that the SEPS1 promoter polymorphism influences the
susceptibility of Japanese to gastric cancer.
This is an interesting study of a gene, that was only recently described as
pro-inflammatory, and that is an interesting candidate for the study of
inflammation and cancer development in relation with Helicobacter pylori.
Major compulsory revisions
1. The authors did not compare a study group of GC patients with a study group
of healthy normal subjects, but analyzed two different patient groups: patients
with CG and patients without GC, but with other disease of the digestive system
that are also associated with Helicobacter pylori infections (gastric ulcer,
duodenal ulcer or gastritis). The conclusion of the study therefore must be that
the SEPS1 promoter variant is associated with some differences between GC
and gastritis or other infectious diseases of the stomach. The suggestion of the
authors that the genetic variant of SEPS1 is related to the risk for GC in the
Japanese population requires the analysis of a control group from the healthy
population. The authors must either recruite a third study group of healthy control
subjects or they must change the interpretation of the results of their study and
consider the role of SEPS1 in two study groups, both Helicobacter pylori positive,
with different diseases of the stomach.
2. The recruitment of the study populations must be described in more detail.
Was the series of patients consecutive? Which were exclusion criteria?
3. The test results in Table 4 reach for some of the different subgroups of
patients nominal p-values <0.05. However, the authors did not use any correction
for multiple testing. The data are interesting and promising, but their preliminary
nature should be underlined.
Minor Essential Revisions
1. The language needs editing.
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: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests.
Caspar Grond-Ginsbach
Review for 10.1186/1471-230X-9-2 (2009)

Reviewer's report
Title:Selenoprotein S (SEPS1) gene -105G>A promoter polymorphism
influences the susceptibility of Japanese to gastric cancer
Version: 2Date:25 September 2008
Reviewer: Bing Xia
Reviewer's report:
1. Is the question posed by the authors well defined?
Yes, well defined.
2. Are the methods appropriate and well described?
Yes,
3. Are the data sound?
a little big
4. Does the manuscript adhere to the relevant standards for reporting and data
deposition?
yes,
5. Are the discussion and conclusions well balanced and adequately supported
by the data?
yes,
6. Are limitations of the work clearly stated?
no
7. Do the authors clearly acknowledge any work upon which they are building,
both published and unpublished?
yes
8. Do the title and abstract accurately convey what has been found?
yes
9. Is the writing acceptable?
Yes, acceptable
Comments:
The manuscript written by Dr. Tomoyuki Shibata et al entitled selenoprotein S
(SEPS1) gene -105G>A promoter polymorphism influences the susceptibility of
Japanese to gastric cancer is very interesting. The authors found that the A allele
of SEPS1 -105G>A promoter polymorphism was associated with intestinal type
of gastric cancer and gastric cancer located in middle third part in Japanese
population. However, there are several questions raised for the manuscript:
1. Since a border significance for the association of SEPS1 -105G>A promoter
polymorphism with gastric cancer, how to prevent bias for this small significance,
at least has to mention in discussion part.
2. H. pylori infection was determined only by one positive of microscopic
examination, urea breath test or serum anti-H pylori antibody titer. Disparity of
the methods may also exist for the explanation. So at least two methods used to
define Hp infection could be better than one method.
3. The control groups are not well defined.
I suggest to revise the manuscript.
Review for 10.1186/1471-230X-9-2 (2009)

Reviewer's report
Title:Selenoprotein S (SEPS1) gene -105G>A promoter polymorphism
influences the susceptibility to gastric cancer in the Japanese population
Version: 3Date:17 November 2008
Reviewer: Charles Foster
Reviewer's report:
Major Compulsory Revisions:
None
Minor Essential Revisions:
page 8. "Enrolled subjects were undergone upper gastrointestinal endoscopy to
check for gastric cancer followed by a barium X-ray examination as a health
check or for the complaint of abdominal symptoms."
Consider: "Enrolled subjects were screened for gastric cancer by upper
gastrointestinal endoscopy followed by a barium X-ray examination."
page 14. "In previous reports, it was suggested that the decreased
concentrations of selenium was the gastric cancer risk. And in experimental
study, high selenium diet inhibited the H. pylori growth in Guinea pig. Nutrition
effect of selenium, however, has not been defined for prevention of the
development of precancerous lesions of gastric cancer so far."
Consider: "Although low selenium status has been associated with risk of human
gastric cancer, and high selenium diets inhibit the growth of H. pylori in Guinea
pigs, human clinical trials have failed to demonstrate a benefit for selenium
supplements in the prevention of precancerous gastric lesions."
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.
Review for 10.1186/1471-230X-9-2 (2009)

Reviewer's report
Title:Selenoprotein S (SEPS1) gene -105G>A promoter polymorphism
influences the susceptibility to gastric cancer in the Japanese population
Version: 3Date:18 November 2008
Reviewer: Bing Xia
Reviewer's report:
Discretionary Revisions
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
Review for 10.1186/1471-230X-9-2 (2009)

Reviewer's report
Title:Selenoprotein S (SEPS1) gene -105G>A promoter polymorphism
influences the susceptibility to gastric cancer in the Japanese population
Version: 3Date:17 December 2008
Reviewer: caspar grond-ginsbach
Reviewer's report:
Minor revisions:
1. The suggestion of the authors that the genetic variant of SEPS1 is related to
the risk for GC in the Japanese population requires the analysis of a control
group from the healthy population. The authors explained in their answer to this
comment that they analyzed a series of volunteers and their the findings in this
healthy control group suggested them that the comparison between the two
patients groups permitted the analysis of the association between SEPS1 and
the risk of GC. Perhaps the authors can mention the findings in their small control
group of volunteers (as data not shown) and discuss this point shortly in the text.
2. Methods section, page 8. Please change:
....Hospital in Japan. Enrolled subjects were undergone upper .....
into
....Hospital in Japan. Consecutively enrolled subjects underwent upper
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Review for 10.1186/1471-230X-9-1 (2009)

Reviewer's report
Title:Usefulness and safety of 0.4 percent sodium hyaluronate solution as a
submucosal fluid acushiona for endoscopic resection of colorectal mucosal
neoplasms: A prospective multi-center open-label trial
Version: 1Date:16 March 2008
Reviewer: Hans Herfarth
Reviewer's report:
The authors report the first experience with 0.4% sodium hyaluronate (SH)
injections prior to endoscopic resections of colonic mucosal neoplasms in a
prospective multi-center study.
Comments:
Overall the paper is well written and might provide a basis for a prospective trial
comparing the clinical usefulness of SH injections to saline injections.
The authors should clarify the final concentration of the 0.4% SH, since
epinephrine and indigo carmine were added to the solution at the discretion of
the endoscopist. They should at least be able to give a range of the final
concentration of SH (or an estimate).
Figure 1: What happened to the 6 incomplete resections described in figure 1 but
not in the result section?
Figure 2 does not add additional information. The numbers are already presented
in table 4.
Table 1 and Table 6 are difficult to comprehend (even with the table description).
The tables should be better presented. Table 6: What does variable (n=41) stand
for. Since only 40 patients were evaluated, (1 patient was excluded due to
exclusion criteria as presented in figure 1)
Minor:
The English grammar and the wording are sometimes wrong or awkward.
What next?: Unable to decide on acceptance or rejection until the authors have
responded to the major compulsory revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
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
Review for 10.1186/1471-230X-9-1 (2009)

Reviewer's report
Title:Usefulness and safety of 0.4 percent sodium hyaluronate solution as a
submucosal fluid cushion for endoscopic resection of colorectal mucosal
neoplasms: A prospective multi-center open-label trial
Version: 1Date:7 May 2008
Reviewer: Todd Baron
Reviewer's report:
1. Why were drugs contraindicated in the treatment of peptic ulcer prohibited?
2. Most of the polyps were small and one could have removed without injection.
3. The usefulness rate is arbitrary, subjective, and has not been validated.
4. Steepness is also subjective.
5. This is a single-arm, non-blinded study.
6. I don’t see how the sample size calculation was of any benefit. The numbers
are not large enough to show a difference – at best would be an equivalency to
data published on saline.
7. The types of EMR differed amongst endoscopists making it difficult to tell what
the true benefit of the HS is.
8. Adverse events occurred in almost half the patients.
9. Healing at 8 weeks would be expected regardless of whether HS was used or
not.
Level of interest: An article of insufficient interest to warrant publication in a
scientific/medical journal
Quality of written English: Needs some language corrections before being
published
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
Review for 10.1186/1471-230X-9-1 (2009)

Reviewer's report
Title:Usefulness and safety of 0.4 percent sodium hyaluronate solution as a
submucosal fluid cushion for endoscopic resection of colorectal mucosal
neoplasms: A prospective multi-center open-label trial
Version: 1Date:7 May 2008
Reviewer: P Draganov
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'
Review for 10.1186/1471-230X-9-1 (2009)

Reviewer's report
Title:Usefulness and safety of 0.4 percent sodium hyaluronate solution as a
submucosal fluid cushion for endoscopic resection of colorectal mucosal
neoplasms: A prospective multi-center open-label trial
Version: 2Date:10 September 2008
Reviewer: Greger Lindberg
Reviewer's report:
I think the authors have adequately responded to all my comments and
questions. I also think this is an important contribution in the area of colonoscopic
interventions that I wish that all my colleagues would read. I would however
recommend linquistc revision by someone native to the English language.
Minor essential revision: Linguistic
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
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
Review for 10.1186/1471-230X-9-1 (2009)

Reviewer's report
Title:Usefulness and safety of 0.4 percent sodium hyaluronate solution as a
submucosal fluid cushion for endoscopic resection of colorectal mucosal
neoplasms: A prospective multi-center open-label trial
Version: 2Date:13 September 2008
Reviewer: Hans Herfarth
Reviewer's report:
The authors addressed all of my concerns.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Review for 10.1186/1471-230X-9-1 (2009)

Reviewer's report
Title:Usefulness and safety of 0.4 percent sodium hyaluronate solution as a
submucosal fluid cushion for endoscopic resection of colorectal mucosal
neoplasms: A prospective multi-center open-label trial
Version: 2Date:24 September 2008
Reviewer: Todd Baron
Reviewer's report:
No comments
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.
Review for 10.1186/1471-230X-9-1 (2009)

Reviewer's report
Title:Usefulness and safety of 0.4 percent sodium hyaluronate solution as a
submucosal fluid cushion for endoscopic resection of colorectal mucosal
neoplasms: A prospective multi-center open-label trial
Version: 2Date:15 October 2008
Reviewer: alessandro A repici
Reviewer's report:
Despite the revision made by the authors and the extensive explanations
reported in the point-by-point response, the limitations and the bias of the study
remain unchanged with relatively high impact on the scientific or technical value
of the paper.
The study design, the small sample size, the different dilution of HA used (please
see response to reviewer 1 in which the authors declare that a subgroup of
patients was treated with HA diluted with indigo carmine and another subgroup
with epinephrine), the different techniques of polyp resection used as well as the
subjective evaluation score of the HA performance make the results of the study
still too weak and hard to translate in significant meaningful value.
To my opinion and according to the comments and doubts raised by the other
reviewers this study is not completely appropriate to be published on the journal
Level of interest: An article of insufficient interest to warrant publication in a
scientific/medical journal
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
no competing interests
Review for 10.1186/1471-230X-8-59 (2008)

Reviewer's report
Title:Outcomes in Culture Positive and Culture Negative Ascitic Fluid Infection in
Patients with Viral Cirrhosis: Cohort Study
Version: 2Date:14 September 2008
Reviewer: Sang Hoon Ahn
Reviewer's report:
This retrospective study examined the outcome and predictors for the survival in
cirrhotic patients with ascitic fluid infection. The authors found that the patients
with culture positive (SBP) had a higher in-hospital mortality compared to those
culture negative (CNNA), and independent predictors for the survival included
lower serum creatinine level and blood culture negativity.
This study addressed an interesting issue that has not been confirmed
previously. The supplement for the following points would improve the
manuscript.
Comments
1. The author should show the survival curve depicting the difference of
in-hospital mortality between SBP and CNNA group. In addition, please add the
table that shows the list of predictors for the survival and statistical results on
uni/multi-variate analysis described on page 10.
2. Describe the cause of death. How many patients died of ascitic fluid infection
rather than of other cirrhotic complications?
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-8-59 (2008)

Reviewer's report
Title:Outcomes in Culture Positive and Culture Negative Ascitic Fluid Infection in
Patients with Viral Cirrhosis: Cohort Study
Version: 3Date:25 November 2008
Reviewer: Sang Hoon Ahn
Reviewer's report:
The manuscript have been revised as per reviewer's comments.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
'I declare that I have no competing interests'
Review for 10.1186/1471-230X-8-58 (2008)

Reviewer's report
Title:Alcohol consumption is associated with an increased risk of erosive
esophagitis and Barrett's epithelium in Japanese men
Version: 1Date:14 June 2008
Reviewer: Yoshihisa URITA
Reviewer's report:
Dear Dr. Tomoyuki Akiyama,
Your manuscript entitled “Alcohol consumption is associated with an increased
risk of erosive esophagitis and Barrett's epithelium in Japanese men” has been
reviewed. The authors conclude that alcohol consumption plays an important role
in the etiology of erosive esophagitis and Barrett's epithelium in Japanese men.
This manuscript is of enough interest and describes original work that merits its
publication in the Journal of MBC Gastroenterology . Although the work was of
good quality, the manuscript required some revisions as below;
1. There was no description of the reason that patients attended to the hospital
and underwent an upper endoscopic examination. In Japan, most of patients with
reflux esophagitis do not complain of typical GERD symptoms, including
heartburn and regurgitation, whereas some patients without erosive gastritis
have persistent heartburn. It is possible that heavy drinkers may be insensitive to
gastroesophageal reflex of gastric acid, resulting in taking a greater amount of
ethanol.
2. Authors should describe the mean value of age, and BMI, and the rate of
subjects with smoking habit in each group of regular drinkers (<25.0g,
25.0-50.0g, and >50.0g).
3. Based on the results that alcohol consumption in Japanese men is associated
with a statistically significant increased risk of erosive esophagitis and Barrett’s
epithelium regardless of the presence of hiatal hernia, is alcohol consumption
more likely to contribute to developing erosive esophagitis? The author had
better describe this in the Discussion Section.
4. In Table 2, p-value is unwritten. The author should fill in a blank.
I believe that you can modify your paper by considering the above-mentioned
comments to make this paper into better form.
Yours sincerely,
Yoshihisa Urita,MD, FACG
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-8-58 (2008)

Reviewer's report
Title:Alcohol consumption is associated with an increased risk of erosive
esophagitis and Barrett's epithelium in Japanese men
Version: 2Date:31 October 2008
Reviewer: Piers Gatenby
Reviewer's report:
Thank-you for making the amendments, which have been undertaken diligently
and the manuscript has been considerably strengthenned.
1. Is the question posed by the authors well defined?
Yes
2. Are the methods appropriate and well described?
Yes
3. Are the data sound?
Yes
4. Does the manuscript adhere to the relevant standards for reporting and data
deposition?
Yes
5. Are the discussion and conclusions well balanced and adequately supported
by the data?
Yes
6. Are limitations of the work clearly stated?
Yes
7. Do the authors clearly acknowledge any work upon which they are building,
both published and unpublished?
Not applicable
8. Do the title and abstract accurately convey what has been found?
Yes
9. Is the writing acceptable?
Yes
Recommend 1 minor amendment: Reference 21 should be Guidelines for the
diagnosis and management of Barrett's columnar-lined oesophagus A Report of
the Working Party of the British Society of Gastroenterology, principal authors: A
Watson, RC Heading, NA Shepherd. Published by British Society of
Gastroenterology, London, UK 2005. http://www.bsg.org.uk
Recommend accept following this minor revision.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-8-57 (2008)

Reviewer's report
Title:Wnt-reporter expression pattern in the mouse intestine during homeostasis
Version: 2Date:20 October 2008
Reviewer: Ramesh Shivdasani
Reviewer's report:
The authors have addressed the issues I raised in my original review of this
manuscript.
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.
Review for 10.1186/1471-230X-8-55 (2008)

Reviewer's report
Title:Imbalance of tissue inhibitors of metalloproteinases (TIMP) - 1 and - 4
serum levels, in patients with inflammatory bowel disease
Version: 1Date:7 March 2008
Reviewer: Ioannis Koutroubakis
Reviewer's report:
The authors present an important, nicely conceived and analyzed study. This
paper builds on the current literature documenting the role of tissue inhibitors of
metalloproteinases (TIMPs) in IBD. Only minor changes are needed.
Major Compulsory Revisions:
None
Minor Essential Revisions:
1.TIMPs are important markers of fibrosis. Although the number of CD patients is
rather small for subgroup analysis, the results in relation to the disease type and
especially in stenotic vs non-stenotic disease should be provided in more detail.
2.Possible differences in TIMPs levels between pre-and post-menopausal
women should be examined and reported.
3.Figure 3 could be better depicted using smaller scale since values higher than
10.000 pg/ml are not included.
What next?: Accept after minor essential revisions
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
Review for 10.1186/1471-230X-8-55 (2008)

Reviewer's report
Title:Imbalance of tissue inhibitors of metalloproteinases (TIMP) - 1 and - 4
serum levels, in patients with inflammatory bowel disease
Version: 1Date:22 March 2008
Reviewer: Klaus Fellermann
Reviewer's report:
Major compulsory revisions
The submitted manuscript presents serum levels of TIMP1, 2 and 4 in
inflammatory bowel disease. Sera from more than 150 patients were
investigated. TIMP1 showed a marked increase during inflammation whereas
TIMP2 was almost unchanged. Conversely, serum TIMP4 was downregulated
during the inflammatory process.
TIMP´s are inhibitors of MMP´s and an imbalance of this system may favor ECM
degradation. It is of crucial importance whether this occurs at the tissue or
systemic level. What is the meaning of systemic TIMP levels in inflammatory
bowel disease at all? Do TIMP´s originate from blood cells or rather reflect a
spillover from local inflammation into sera. This is open to question and the report
does not provide an answer.
Mucosal TIMP1 has been shown to be correlated with proinflammatory cytokine
responses as well as endoscopic grading in inflammatory bowel disease. On the
other hand TIMP2 is known to be constitutive and no change has been
demonstrated in mucosal biopsies from inflammatory bowel disease compared to
controls. In both situations the ratio of TIMP/MMP may be affected in the same
manner if the corresponding MMP levels do increase. Thus, serum levels of
TIMP with unknown MMP levels are of limited value. I am concerned and
critically recommend a consecutive determination of serum MMP´s (e.g. MMP-1,
2 and 9) in the same set of patients. This will help to clarify this issue.
However, the observations of TIMP1 and 2 are in line with previous reports while
the findings regarding TIMP4 are novel.
Nevertheless, the paper is well written and concise.
What next?: Unable to decide on acceptance or rejection until the authors have
responded to the major compulsory revisions
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
Review for 10.1186/1471-230X-8-55 (2008)

Reviewer's report
Title:Imbalance of tissue inhibitors of metalloproteinases (TIMP) - 1 and - 4
serum levels, in patients with inflammatory bowel disease
Version: 1Date:31 March 2008
Reviewer: N Yoshida
Reviewer's report:
In this study, authors demonstrate the importance of serum levels of TMP-1 and
–4 in the patients with IBD. In the clinical field, it is very important to detect the
marker of the activity in IBD patients. As the authors conclude that the TIMP-1
serum levels may be a useful marker of disease activity in IBD, this paper
includes very important and interesting points.
Major points
1. In this study, serum TIMP-2 levels have no statistically significant difference
between IBD patients and HC. So the authors do not have to show “figure 2”;
serum TIMP-2 data.
2. In this study, the author should show the importance of serum TIMP-1 levels
which is correlated with the activity of IBD. They determined that TIMP-1 levels
are significantly higher in patients with active IBD as compared with patients with
inactive disease. This data should be much more important than figure 2; serum
TIMP-2 data.
No minor points are detected.
Review for 10.1186/1471-230X-8-55 (2008)

Reviewer's report
Title:Imbalance of tissue inhibitors of metalloproteinases (TIMP) - 1 and - 4
serum levels, in patients with inflammatory bowel disease
Version: 2Date:2 June 2008
Reviewer: Ioannis Koutroubakis
Reviewer's report:
I think that the authors covered the majority of the queries of the reviewers and
the manuscript has been singnificantly improved
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
Review for 10.1186/1471-230X-8-55 (2008)

Reviewer's report
Title:Imbalance of tissue inhibitors of metalloproteinases (TIMP) - 1 and - 4
serum levels, in patients with inflammatory bowel disease
Version: 2Date:10 June 2008
Reviewer: andrew S Day
Reviewer's report:
Specific comments:
1. The Results section of the Abstract now includes details of TIMP-2 data.
Whilst I agree it is important to mention TIMP-2 in the results, it may be sufficient
to comment that TIMP-2 levels did not differ between groups (and to remove the
detail of the actual numbers).
2. The ratio between TIMP-1 and TIMP-4 may have relevance to our
understanding of the roles of these proteins: the relationship to disease activity
(such as it is) should not alter this.
3. The fact that the TIMP-4 positively correlates with two markers of
inflammation, yet is less in patients with IBD than in controls has not yet been
explained adequately.
4. Furthermore the relationship between these proteins and a disease activity
index needs to be considered carefully: it is clear that activity indices, which
contain various clinical and historical aspects, do not always indicate the amount
of mucosal (and systemic) inflammation.
5. The Abstract and the final conclusion of the Discussion section mention that
TIMP-1 levels can be used as indicators of disease activity. Given that there was
a numerical difference of only approximately 33 ng/ml between the mean TIMP-1
level in active and that in the inactive group, I am not convinced that this would
be useful in clinical practice.
6. The Background section refers on page 4 to plasma levels of TIMP-1, whereas
it is stated on the next page that serum levels of TIMPs have not been evaluated.
This is conflicting, given that these measurements both refer to circulating levels
of the protein (as contrasted to mucosal levels).
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
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'
Review for 10.1186/1471-230X-8-55 (2008)

Reviewer's report
Title:Imbalance of tissue inhibitors of metalloproteinases (TIMP) - 1 and - 4
serum levels, in patients with inflammatory bowel disease
Version: 2Date:13 June 2008
Reviewer: N Yoshida
Reviewer's report:
This paper is corrected according to my comment.
Review for 10.1186/1471-230X-8-55 (2008)

Reviewer's report
Title:Imbalance of tissue inhibitors of metalloproteinases (TIMP) - 1 and - 4
serum levels, in patients with inflammatory bowel disease
Version: 2Date:20 June 2008
Reviewer: Klaus Fellermann
Reviewer's report:
As I stated in my first review I do not understand the significance of isolated
TIMP serum levels in IBD. In order to improve the manuscript I recommended
additional investigations, at leats MMP serum levels. However, this seems to be
impossible and my final conclusion is that I cannot accept this paper for
publication in its present form.
Level of interest: An article of limited interest
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.
Review for 10.1186/1471-230X-8-56 (2008)

Reviewer's report
Title:Loss of PTEN expression is associated with colorectal cancer liver
metastasis and poor patient survival
Version: 1Date:1 June 2008
Reviewer: John Mariadason
Reviewer's report:
Loss of PTEN expression is associated with colorectal cancer liver metastasis
and poor survival.
Sawai et al.
The authors report a potentially important finding that downregulation of PTEN
may be linked to the onset of metastasis in colon cancer. However, there are
several concerns with the study as presented.
First, on multiple occasions the authors present the findings of this study as a
comparison of PTEN expression in primary colorectal cancer and colorectal
cancer liver metastases. However, no evidence of PTEN expression in
metastatic colorectal tumor tissue is presented. Rather, the analysis appears to
be a comparison of PTEN expression in primary colon tumors in patients with
and without metastatic disease. Presentation of the manuscript is therefore highly
confusing.
For patients with liver metastases the authors compare survival time in patients
with high versus low PTEN expression. However, not all patients in this analysis
are stage IV. The validity of the 5 year survival analysis is therefore questionable.
Expression of PTEN in stage matched patients should be performed.
A single “representative” image of PTEN expression from the 2 groups is
presented. This is inadequate as it fails to demonstrate the range of staining
intensities reported. Also, the PTEN expression appears nuclear which based
upon the literature is potentially important. This is not referred to or addressed.
The method of data presentation of data in Tables 1 and 2 is highly confusing
and should be reconsidered.
Discussion: PTEN does not function by dephosphorylating PI3K.
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
'I declare that I have no competing interests'
Review for 10.1186/1471-230X-8-56 (2008)

Reviewer's report
Title:Loss of PTEN expression is associated with colorectal cancer liver
metastasis and poor patient survival
Version: 3Date:17 July 2008
Reviewer: Milo Frattini
Reviewer's report:
the authors answered correctly to reviewers' questions and comments. I
recommend the publication (not high priority, however).
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-8-56 (2008)

Reviewer's report
Title:Loss of PTEN expression is associated with colorectal cancer liver
metastasis and poor patient survival
Version: 3Date:29 July 2008
Reviewer: John Mariadason
Reviewer's report:
The author’s continue to conclude that PTEN is downregulated in liver
metastases, however PTEN staining in only a single liver met is shown in Figure
1. It is not clear how many paired samples were examined and how the authors
arrived at this conclusion. Statistical analyses to support this conclusion are not
provided.
In response to the previous comment the authors state that strong cytoplasmic
PTEN expression and weak nuclear expression was observed. However, as
pointed out in the original critique, the image shown in Figure 1 shows exactly the
opposite.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
'I declare that I have no competing interests'
Review for 10.1186/1471-230X-8-53 (2008)

Reviewer's report
Title:Plasma Pentraxin3 is a Novel Marker for Nonalcoholic Steatohepatitis
(NASH)
Version: 2Date:19 October 2008
Reviewer: Anna Baranova
Reviewer's report:
I am satisfied with reply of the authors. The paper can be accepted in its present
form.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-8-54 (2008)

Reviewer's report
Title:Commonly used bowel preparations have significant and different effects
upon cell proliferation in the colon: a pilot study
Version: 1Date:16 June 2008
Reviewer: Pascal Bucher
Reviewer's report:
Interesting paper evaluating a new aspect of the effect of mechanical bowel
preparation, which will be taken into account in future research
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'
Review for 10.1186/1471-230X-8-54 (2008)

Reviewer's report
Title:Commonly used bowel preparations have significant and different effects
upon cell proliferation in the colon: a pilot study
Version: 1Date:19 June 2008
Reviewer: Robert A Goodlad
Reviewer's report:
The authors describe some changes in cell proliferation following preparation
with Picolax [actively draw water into the bowel lumen] – and Prep, a lavage
solution with some osmotic activity
The Number of subjects is rather low but nevertheless some significant
differences were observed. The results have some relevance and are worth
publishing.
Other points
(p=0.0192) and pHH3 (p=0.0170) suggest round up
“floor-to-ceiling” please elaborate
No effect in HNPCC – there have been reports of much increased crypt fission in
FAP see Wasan h et al.
Value of methods and applicability to biopsy samples should be elaborated i.e.
PCNA is of dubious value as it has anomalous results and is difficult to
standardize and micro dissection allows many crypts to be studied. – See Hall P
and see Alferez and Goodlad in Cell Proliferation
Were effects of food intake [or lack of it] the same? I.e. were the unpreped
starved in a similar manner. Should discuss the concepts of luminal
nutrition/luminal workload.
Review for 10.1186/1471-230X-8-54 (2008)

Reviewer's report
Title:Commonly used bowel preparations have significant and different effects
upon cell proliferation in the colon: a pilot study
Version: 1Date:29 July 2008
Reviewer: Frank Simmen
Reviewer's report:
The authors have provided an interesting manuscript that suggests a potential
caveat in studies of biopsied colonic mucosa for proliferative status. Namely,
their results suggest that type of laxative used to purge the bowel may itself
affect proliferative status of colonic epithelium.
Major Compulsory Revisions
In general, the results that suggest differences between Klean-Prep and Picolax
are the most convincing; however, it is unclear why either group does not differ
from unprepared controls? One wonders if there was some sort of random bias
introduced during allocation of indviduals to each laxative group that might
explain the results.
Secondly, the manuscript would be strengthened by greater numbers of
individuals per group, greater numbers of crypts per individual, and an
examination of effects of laxatives on a second distinct region of the colon.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-8-54 (2008)

Reviewer's report
Title:Commonly used bowel preparations have significant and different effects
upon cell proliferation in the colon: a pilot study
Version: 2Date:3 October 2008
Reviewer: Frank Simmen
Reviewer's report:
The authors have suitably addressed my previous concerns. The MS is
well-written and in my view, the data are appropriately interpreted.
The MS points to the need for controlled bowel cleansing procedures to be used
prior to colonoscopy for tissue collection from humans.
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'
Review for 10.1186/1471-230X-8-52 (2008)

Reviewer's report
Title:Predictors Of Gastrointestinal Lesions On Endoscopy In Iron Deficiency
Anemia Without Gastrointestinal Symptoms
Version: 1Date:22 November 2007
Reviewer: bruno annibale
Reviewer's report:
General comment
This paper investigates, in a group of asymptomatic IDA patients ( n=95), the
frequency of upper and lower potential GI causes able to justify their anemia and
evaluate potential predictors for the GI diagnosis .
I think the study and its results are interesting, however there are important
methodological aspects that should be better addressed
a) Criteria for IDA definition are questionable, since both WHO criteria and the
previous literature data are different than those used in this paper ( Hb levels in
man > 13,5 g/dl or 14 g/dl; women < 12 g/dl ). Why the author choosed this low
cut off values ?
b) The population investigated refer to both patients referred and admitted for
urgency , this represents two completely different population with different
prevalence of IDA causes. Authors should to consider them separately.
C) Portal hypertensive gastropathy and esophagastric varices are conditions
related to the cirrosis that is a chronic condition that per se’ justify the IDA and
should be considered criteria of exclusion from the study . Are these patients
really asymptomatic from GI point of view ?
d) How authors classified heavy menstrual flow : on the basis of self-reported
patients’ opinion or on the basis of gynecological evaluation ?
e) Erosive esophagitis is not sufficient to be considered a causes of IDA .
f) In table 3 authors include patients with oesophageal mass, gastric mass ,
colonic mass please specify are neoplatic lesions or what else ?
g) It’s interesting to kown the results of GI endoscopical investigation in patients
with FOB positive
h) It is surprisingly low the percentage of patients with both upper and lower GI
lesion just one
All the literature data observe more robust prevalence ( 15-20%). Moreover the
concomitant IDA causes are usually observed e.g. Hp gastritis and large hiatal
hernia, atrohic gastritis and colon cancer and so on . This aspect is not covered
What next?: Unable to decide on acceptance or rejection until the authors have
responded to the major compulsory revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
'I declare that I have no competing interests'
Review for 10.1186/1471-230X-8-52 (2008)

Reviewer's report
Title:Predictors Of Gastrointestinal Lesions On Endoscopy In Iron Deficiency
Anemia Without Gastrointestinal Symptoms
Version: 1Date:15 December 2007
Reviewer: Patrick G Brady
Reviewer's report:
This is an interesting manuscript dealing with endoscopic findings and the
causes of iron deficiency anemia in patients without gastrointestinal symptoms.
The study population is Asian and the findings differ from those expected in a
Western population providing additional data useful to those evaluating similar
populations.
Minor Essential Revisions:
1. The manuscript is well written but contains numerous inappropriate
capitalizations which need to be corrected prior to publication.
Some of the terminology used is unclear. The authors need to specify exactly
what is meant by a bleeding related lesion as opposed to a cause of iron
deficiency anemia.
2. Atrophic gastritis is listed as a non-bleeding cause of iron deficiency anemia.
This is not generally accepted and atrophic gastritis should be termed a possible
cause of iron deficiency anemia (page five, paragraph 1).
3. Helicobacter pylori related chronic gastritis was listed as a possible cause of
iron deficiency anemia. The authors need to specificy if this included only
patients with gastric erosions, or if any H. pylori related chronic gastritis
diagnosed by biopsy was included in this category regardless of endoscopic
findings (page 5, paragraph 1). This is especially important since 14.7% of
patients had H, pylori gastritis identified as the etiology of their iron deficiency
anemia.
What next?: Accept after minor essential revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.