JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/1471-230X-12-92 (2012)

Reviewer's report
Title:Pediatric Primary Biliary Cirrhosis and Type 2 Autoimmune Hepatitis
Overlapping Features In A 3-Year-Old Girl: A Case Study And Review of the
Literature on AMA Positivity in Pediatric Age
Version: 2Date:30 April 2012
Reviewer: Gideon Hirschfield
Reviewer's report:
Interesting patient with interesting issues that help inform the debate on aetiology
of autoimmune liver disease. Helpful overview broadly.
My major issue is that I do not see evidence for PBC; I see evidence for
immunoserologic overlap. I would interpret the presentation as serologic overlap
with AMA in the context of severe acute autoimmune hepatitis, with biliary
overlap features. I do not see classic PBC and the AMA titre falls in keeping with
resolving acute liver injury. The images provided do not show convincing PBC
lesions.
Therefore I think this paper is useful and the review component helpful, but I
would favour that the title, abstract and emphasis is adjusted very clearly to
discuss the findings in the context as above. This is still interesting because Type
2 AIH is distinct precisely because of its recognised antigen specificity. Hence
the observation of AMA here is intriguing, although my personal opinion is that
this is serologic overlap in the context of severe liver injury and not true PBC.
The family history suggests certain shared risk across AIH/PBC/AMA production.
Do the authors have AMA-MIT3 results and gp210 or sp100 titres? Can they
stain tissue for AMA (biliary phenotype).
I would be happy to trust the authors to make the necessary changes without
re-review.
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:
No relevant disclosures; I have no competing interests.
Review for 10.1186/1471-230X-12-92 (2012)

Reviewer's report
Title:Pediatric Primary Biliary Cirrhosis and Type 2 Autoimmune Hepatitis
Overlapping Features In A 3-Year-Old Girl: A Case Study And Review of the
Literature on AMA Positivity in Pediatric Age
Version: 2Date:8 June 2012
Reviewer: fernando alvarez
Reviewer's report:
Dr Invernizzi et al. described a case of a 3 years old girl with autoimmune
hepatitis type 2, and circulating anti-mitochondrial autoantibodies.
The patient presented as an acute severe hepatitis (hepatic failure),
hyperammoniemia and neurological deterioration. It is not clear why ultrasound
examination showed signs of “chronic” parenchymal damage only in the liver
left-lobe.
An increase of serum IgG levels, but normal IgM levels were recorded at onset of
the liver disease. High serum IgG levels with normal IgM levels is a particular
sign of AIH. Increase of serum IgM, absent in this patient (see table 1), is
generally observed in patients with PBC.
Histological findings described were compatible with an AIH under treatment,
however, no signs to believe that this girl had a PBC were found (“only hepatic
lesion diagnostic of PBC is the granulomatous destruction of septal of interlobular
bile ducts”, Oxford Textbook of Clinical Hepatology). Figure 3 does not allow to
propose a possible PBC.
Initial response to treatment and further evolution were typical of an AIH, without
any sign in favour of PBC in the long term follow-up. As the authors mentioned in
the description of the case: “the cholangiopatic component “of PBC” does not
respond to immunosuppressive treatment.
This case report does not justify the title of the article : “Primary Biliary cirrhosis...
overlaping...” The title may be change to : “AIH type 2 associated with an
unexpected and transient presence of AMA”.
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:
I declare that I have not competing interests'.
Review for 10.1186/1471-230X-12-90 (2012)

Reviewer's report
Title:Diagnosing celiac disease by video capsule endoscopy (VCE) when
esophogastroduodenoscopy (EGD) and biopsy is unable to provide a diagnosis:
A case series
Version: 2Date:17 March 2012
Reviewer: Osman Ersoy
Reviewer's report:
The argument in this article is very interesting. It is an article that sees to safety
using of capsule endoscopy in difficulty diagnosis for patients with celiac disease
(serology positive but endoscopy and/or biopsy negative).
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Review for 10.1186/1471-230X-12-90 (2012)

Reviewer's report
Title:Diagnosing celiac disease by video capsule endoscopy (VCE) when
esophogastroduodenoscopy (EGD) and biopsy is unable to provide a diagnosis:
A case series
Version: 2Date:6 May 2012
Reviewer: Georgia G Malamut
Reviewer's report:
M. Chang et al report an interesting case series of eight patients investigated for
celiac disease and treated by a gluten free diet basing on capsule endoscopy
reports without histological proof. Some points should be precised and other
possible causes of villous atrophy need to be discussed.
Major Points
• Patients & Methods: how many patients with a possible celiac disease did the
authors screen? Please precise the time period of recording. How many these 8
patients represent among all the suspected celiac patients investigated in this
tertiary care center in USA?
• Please precise the type of autoantidodies: anti-gliadin IgA or IgG? Anti-TTG IgA
or IgG?
• Was the dosage of total and subtypes of immunoglobulins (IgA, IgG, IgM)
performed, particularly in patients 3 and 4?
• Were the other causes of villous atrophy excluded such as autoimmune
enteropathy with the dosage of anti-enterocytes or anti-AIE 75KD antibodies?
Indeed positive celiac antibodies may be observed in patients with autoimmune
enteropathy (Akram S, Murray JA, Pardi DS, et al. Adult autoimmune
enteropathy: Mayo Clinic Rochester experience. Clin Gastroenterol Hepatol
2007;5:1282-90).
• Please, indicate the HLA-type II for each patient. Had all the patients the
celiac-susceptibility HLA DQ2/DQ8 genotype?
• How many duodenal biopsies have been performed in each case?
• Have been some patients investigated by a second endoscopy with biopsy, 6
months or 1 year later to check histology before beginning the gluten free diet?
• Did some patients have a control capsule endoscopy under gluten free diet to
check villous recovery?
Minor points
* Please precise the delay of gluten free diet and the time of evaluation for each
patient. These data including possible changes in celiac antibodies levels, control
capsule endoscopy and biopsy could be included in a second Table "Response
to a Gluten free diet"
* Capsule endoscopy images of the eight patients should be given in a composite
figure.
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 am co-author of a review on refractory celiac disease in a chapter book treating
of celiac disease coordinated by Peter H. Green. This review is not yet published.
I have no financial competing interest.
Review for 10.1186/1471-230X-12-88 (2012)

Reviewer's report
Title:Systemic administration of a novel human umbilical cord mesenchymal
stem cells population accelerate the resolution of acute liver injury
Version: 2Date:22 February 2012
Reviewer: Laurent Dollé
Reviewer's report:
The authors have definitively answered to all comments. I have no additional
comments on the resumitted paper.
Regards,
Laurent Dollé
Level of interest: An article of outstanding merit and interest in its field
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-12-88 (2012)

Reviewer's report
Title:Systemic administration of a novel human umbilical cord mesenchymal
stem cells population accelerate the resolution of acute liver injury
Version: 2Date:27 February 2012
Reviewer: Claus Kordes
Reviewer's report:
Major Compulsory Revision:
The authors improved their manuscript substantially. However, the TGF-beta
isoform measured by qPCR is still not mentioned in the manuscript. A detailed
analysis of the primer sequences of mice used by the authors revealed that a
target gene of TGF-beta 1 (i.e. transforming growth factor beta 1 induced
transcript 1 or Tgfb1i1; NM_009365.2), but not TGF-beta 1 was measured.
Moreover, the primers for IL-5 and beta-actin of mice are barely homologous to
the mRNA reference sequences NM_010558 and NM_007393. In addition, it is
surprising that the authors are not able to show the basal expression of albumin
and alpha-fetoprotein by RT-PCR in a normal agarose gel, which is also a very
sensitive method. If the “no template control” is not included, the qPCR can also
provide false positive data through measuring for example primer dimers. This
should be excluded.
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-12-88 (2012)

Reviewer's report
Title:Systemic administration of a novel human umbilical cord mesenchymal
stem cells population accelerates the resolution of acute liver injury
Version: 3Date:7 May 2012
Reviewer: Claus Kordes
Reviewer's report:
The primer sequences are now correct.
Best regards,
Claus Kordes
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.
Review for 10.1186/1471-230X-12-89 (2012)

Reviewer's report
Title:Association of polymorphism of PTPN 11 encoding SHP-2 with gastric
atrophy but not gastric cancer in Helicobacter pylori seropositive Chinese
population
Version: 1Date:9 May 2012
Reviewer: Asahi Hishida
Reviewer's report:
The authors investigated the association of htSNPs in the PTPN11 gene with
gastric atrophy (GA) and gastric cancer (GC) in Chinese population, and found
the novel association that rs12423190 was associated with GA. Although the
sample size for gastric atrophy is relatively small, this reviewer thinks it is worth
being published in this journal after the following minor revisions, considering the
importance of the present finding in the field of genetic epidemiology of H.
pylori-induced gastric precancerous lesions.
Minor Essential Revisions:
1) In the Methods section: I wonder whether the PG criteria used for GA
screening (<82.3 for PG I and <6.05 for PG I/II) are really appropriate; is the
reference [23] raised by the authors the only report that confirmed these criteria?
If so, the number confirmatory studies may be insufficient to draw a reliable
diagnosis, which thus should be described as the limitation.
2) Please spell out "CVs".
3) "Selection of Tagging SNPs": the LD data (D' and r2) should be moved into the
Results section.
4) If possible, please describe briefly the rationale used in the HAPSTAT
software.
5) Cray would be "Cary".
6) Near the end part of the Discussion: "In addition, we demonstrated that gastric
cancer patients had high prevalence of both HP seropositivity and GA... ,
implying the connection of genetic factors..." sounds rather ambiguous. The
authors should clearly describe to which step of gastric pathogenesis (i.e., HP
infection, GA, GC) which genetic factor may contribute to, etc.
7) This reviewer wonders why the prevalence of HP(+) GA is relatively low in
Chinese population. Is there any other reports that compared its prevalence
among different East Asian populations? How are the genotype frequencies of
PTPN11 SNPs among the races/ethnicities?
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-12-89 (2012)

Reviewer's report
Title:Association of polymorphism of PTPN 11 encoding SHP-2 with gastric
atrophy but not gastric cancer in Helicobacter pylori seropositive Chinese
population
Version: 1Date:11 May 2012
Reviewer: Kazuhiro Tsukamoto
Reviewer's report:
BMC Gastroenterology
To editor:
This manuscript by Jiang J, et al. entitled “Association of polymorphism of
PTPN11 encoding SHP-2 with gastric atrophy but not gastric cancer in
Helicobacter pylori seropositive Chinese population“ reports that a new gastric
atrophy-susceptibility SNP in PTPN11 was confirmed by a single candidate
gene-based association study for 109 patients with gastric atrophy and 923
healthy control subjects in the Chinese population.
This is concise, easily readable, and has accurately statistical analyses.
Furthermore, this study is one of the replication studies, indicating that a new
SNP in PTPN11 is associated with susceptibility to H. pylori-seropositive gastric
atrophy in the Chinese population. However, PTPN11 is already known as a
disease-susceptibility gene related to gastric atrophy in the Japanese population
in several reports, although the associated SNP in this manuscript is different
from that associated in the Japanese population. This manuscript is involved in
the same manner of the leading studies. There are no new idea, study design,
suggestions, and attractive prospects on the molecular mechanisms, which are
related to the predisposition to the onset of gastric atrophy, but not gastric
cancer. Therefore, the study design with SNP analysis of 6 tag SNPs of one
gene, results, and explanation of a pathophysiological perspective are not
enough for publication. My recommendation is to reject this manuscript and to
publish it to another journal.
My minor comments are following below.
1. The total number of the healthy control subjects is described as 932 in Table
1. However, 923 was subject to the following analysis.
2. The authors suggest that an intronic enhancer may be located within or around
the rs12423190 SNP site in PTPN11 as shown in the Discussion section (Lines
20-21 in page 12). This putative enhance may induce the overexpression of
PTPN11, thereby resulting in the gain-of-function of SHP-2. As another
mechanism, the gain-of-function of SNP-2 may accelerate the downregulation of
T-cell and B-cell activation through CTLA-4/PD-1 as well as IL-6/STAT3
signalings, eventually leading to a decrease in inflammation. This point shows a
discrepancy in the suggestion of this manuscript.
I declare that I have no competing interests.
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-12-89 (2012)

Reviewer's report
Title:Association of polymorphism of PTPN 11 encoding SHP-2 with gastric
atrophy but not gastric cancer in Helicobacter pylori seropositive Chinese
population
Version: 2Date:18 June 2012
Reviewer: Asahi Hishida
Reviewer's report:
(Minor Essential Revisions:)
The authors have satisfactorily addressed all the comments provided by the
reviewers; however, as several (- quite a few) awkward English expressions or
mis-spellings are found here and there in the draft, I recommend the authors to
have this draft re-checked by the native English speakers before publication.
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-12-87 (2012)

Reviewer's report
Title:Association of an NF-kappaB1 intron SNP (rs4648068) with gastric cancer
patients in Chinese Han population
Version: 2Date:21 December 2011
Reviewer: Joanne M Bowen
Reviewer's report:
I am grateful for the opportunity to review this manuscript. The authors describe a
case control study investigating the relationship between an NFKB1
polymorphism and risk of gastric cancer. In addition, the association between this
polymorphism and clinicopathologic variables was assessed.
Major Compulsory Revisions
Results: Patient characteristics of the cancer vs control patients are not shown.
Please include a table of age and sex demographics, and an evaluation of
balance between groups.
Minor Essential Revisions
Throughout the manuscript (including the title) the authors refer to their gene of
interest using the protein name, NF-#B 1. All references to the gene should be as
NFKB1 (italicised).
The manuscript contains editing errors related to; spacing, gene names not
shown in italics and inconsistent presentation of protein names.
Background section, paragraph 3. Please remove the results of the pilot
genotyping study from this section, since this is repetitive of what is covered in
the results section.
Methods section, paragraph 2. MJ Research have “Opticon” thermal cyclers, not
“Option”. Please check correct name of instrumentation.
Methods section, paragraph 3. The statistical analysis description lacks sufficient
detail to determine which measures were applied to each analysis.
Results section, paragraph 2. Change extron to exon
Results section, paragraph 4. Change from (Table 4) to (Table 3)
Discretionary Revisions
Include 3 – 10 keywords
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
Review for 10.1186/1471-230X-12-87 (2012)

Reviewer's report
Title:Association of an NF-kappaB1 intron SNP (rs4648068) with gastric cancer
patients in Chinese Han population
Version: 2Date:20 January 2012
Reviewer: Jyotsna Batra
Reviewer's report:
The current study has been conducted on a very small no of samples, so doesn't
have adequate power to reach to a conclusion, thus is unacceptable unless is
replicated in another cohort. please see my response to the editorial Q's below;
1. Is the question posed by the authors well defined? Yes 2. Are the methods
appropriate and well described? No, small sample size and inadequate power.
3. Are the data sound? NO, lack of power.
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? partly 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, but the conclusion is not
imperative due to lack of the power 9. Is the writing acceptable? Yes
Review for 10.1186/1471-230X-12-87 (2012)

Reviewer's report
Title:Association of an NFKB1 intron SNP (rs4648068) with gastric cancer
patients in the Han Chinese population
Version: 6Date:24 May 2012
Reviewer: Megan Hitchins
Reviewer's report:
The authors have adequately taken the Reviewer's recommendations into
consideration and included them in manuscript appropriately. I believe this has
improved the overall quality of the paper, so that it now provides a report of an
interesting SNP association with gastric cancer, as well as some ideas in terms
of its functionality, which will impact on future directions. The authors are to be
commended on the quality of their revised paper.
I have only one Minor Essential Revision that I think is required:
The following sentence in the Abstract has been written in such a way it is
factually incorrect:
"Furthermore, stratified by lymph node status and serosa invasion, the effect of
the rs4648068 GG genotype was larger in gastric cancer patients (AORs.....)."
This needs to be corrected, eg suggestion that might fit with word count:
"Furthermore, among the gastric cancer cases, the rs4648068 GG genotype was
associated with high clinical stage (AOR), lymph node involvement (AOR) and
serosa invasion (AOR).
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-12-86 (2012)

Reviewer's report
Title:Ferritin for the diagnosis of gastrointestinal cancer in patients with
involuntary weight loss
Version: 1Date:20 January 2012
Reviewer: Stefan Lindgren
Reviewer's report:
Major compulsory revisions
1. The ferritin level is influenced also by inflammation and alcohol. CPR has been
measured according to the Methods section, but the results are not presented or
discussed in relation to ferritin data. This must be done, particularly in relation to
inflammation. How many patients had elevated CRP? What was the situtation in
those patients with Ferritin >100? Are the conclusions still valid if the
contributions from inflammation and alcohol are included or if patients with active
inflammation are excluded?
2. The number of patients that had both upper and lower endoscopy should be
clearly stated also in the text - can be concluded from Fig 1.
3, The titel could be more informative. Maybe "Ferritin above 100 mcg/L rule out
colon cancer in patients with involuntary weight loss."
Minor essential revisions
1. Explain the meaning of "hospital work-up" Under "Patient inclusion," paragraph
2.
2. Figure 2 may not be needed
Level of interest: An article of importance in its field
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-12-86 (2012)

Reviewer's report
Title:Ferritin for the diagnosis of gastrointestinal cancer in patients with
involuntary weight loss
Version: 1Date:10 May 2012
Reviewer: Neve Vendt
Reviewer's report:
Major Compulsory Revisions
Level of interest: An article of limited interest
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-12-86 (2012)

Reviewer's report
Title:Ferritin above 100 mcg/L could rule out colon cancer, but not gastric or
rectal cancer in patients with involuntary weight loss
Version: 3Date:4 June 2012
Reviewer: Stefan Lindgren
Reviewer's report:
I have read the letter from the authors with their comments to my previous
remarks and their actions.
I ahve also checked the changes made in the manuscript.
I find that the authors have responed in a satisfactory way to my remarks and
revised the paper accordingly.
I am happy with the outcome and have no further remarks. I believe that the
paper now is acceptable for publication.
Review for 10.1186/1471-230X-12-86 (2012)

Reviewer's report
Title:Ferritin above 100 mcg/L could rule out colon cancer, but not gastric or
rectal cancer in patients with involuntary weight loss
Version: 3Date:8 June 2012
Reviewer: Neve Vendt
Reviewer's report:
Discretionary 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.
Review for 10.1186/1471-230X-12-85 (2012)

Reviewer's report
Title:hTERT, MYC and TP53 deregulation in gastric preneoplastic lesions
Version: 1Date:15 May 2012
Reviewer: Reginald V. Lord
Reviewer's report:
Review of “hTERT, MYC and TP53 deregulation in gastric preneoplastic lesions”
by Tanielly Cristina Raiol Silva et al. for BMC Gastroenterology
This manuscript reports on a straightforward study by a group who have
investigated these genes in detail in previous studies, including in non-human
primate gastric cancer models. The study is well conducted, the results and
analysis are very clear, and the paper is well written. The overall importance of
the findings is only moderately high but the difference in positive
immunoreactivity, in particular, in IM compared to gastritis, may be clinically
valuable.
My only major suggestion is that the importance of the findings has been
overstated. In the Discussion the authors claim that “Therefore, taking our results
together with those from the literature, we hypothesize that patients presenting
intestinal metaplasia with immunoreactivity of hTERT, MYC, and p53 –
alterations common described in gastric neoplasia – must be included in a risk
group for gastric cancer and should be monitored at regular intervals with
endoscopy and histopathology analysis.” This implies that these three markers
are valid biomarkers of progression to cancer in patients with IM. The data have
not shown this and references to others’ work to support this statement is also
lacking. I believe this statement should be modified to indicate that the proteins
should be investigated further for roles as markers of disease progression, for
which a much larger patient cohort(s) will be needed, ideally with sequential
biopsies from the same individuals.
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-12-85 (2012)

Reviewer's report
Title:hTERT, MYC and TP53 deregulation in gastric preneoplastic lesions
Version: 1Date:10 June 2012
Reviewer: Rodney J. Scott
Reviewer's report:
The small correlative study describes the relationship between mRNA gene
expression of key proteins and their immuno-histochemical expression involved
in gastric carcinoma sequence. It is a small, well defined study.
Major compulsory Revisions: The authors should include in the patient
description the smoking status of their study subjects. This is an important point
and one that must be included due to the significant relationship between
smoking and tumour likelihood.
Minor essential revisions: None
Discretionary revisions: Since the results are certainly very interesting, it would
be useful to know if larger studies are planned.
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-12-85 (2012)

Reviewer's report
Title:hTERT, MYC and TP53 deregulation in gastric preneoplastic lesions
Version: 2Date:15 June 2012
Reviewer: Rodney J. Scott
Reviewer's report:
2nd Review
Nothing to add
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-12-85 (2012)

Reviewer's report
Title:hTERT, MYC and TP53 deregulation in gastric preneoplastic lesions
Version: 2Date:17 June 2012
Reviewer: Reginald V. Lord
Reviewer's report:
The revisions are sufficient for publication
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-12-84 (2012)

Reviewer's report
Title:Predicting incident fatty liver at 4.37 year follow up, using simple
cardio-metabolic risk factors at baseline
Version: 1Date:18 May 2012
Reviewer: JUDE OBEN
Reviewer's report:
This is an interesting study describing the utility of easily measurable liver and
laboratory parameters in the diagnosis of NAFLD. The study is of importance
give the rising rates of obesity and in parallel rates of NAFLD. The study
deserves to be read by the general hepatology and gastroenterology
communities.
I am however, sceptical as to its utility given the ready availability and reasonable
cost of first line imaging modalities – ie USS in most healthcare systems where
NAFLD is a burgeoning problem, although the sensitivity of USS is an issue. A
more clinically useful study would have been the comparison of factors with a
more sensitive imaging modality such as MRS, but as the authors acknowledge
such a study would have been prohibitively expensive. An even more useful
study would have been the comparison of factors that allowed avoidance of a
staging liver biopsy.
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.
Review for 10.1186/1471-230X-12-83 (2012)

Reviewer's report
Title:Capsule endoscopy with flexible spectral imaging color enhancement
reduces the bile-pigments effect and improves the detectability of small bowel
lesions.
Version: 1Date:3 April 2012
Reviewer: Daniel Urbain
Reviewer's report:
I do not understand the rational of testing a technique by trainees in this study. If
a system improves the quality of a technique, it should be demonstrated in
practitioners with more experience. This makes the message of the study very
limited.
The study is not correctly designed to give an appropriate judgment on the
usefulness of the small bowel preparation or not.
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.
Review for 10.1186/1471-230X-12-83 (2012)

Reviewer's report
Title:Capsule endoscopy with flexible spectral imaging color enhancement
reduces the bile-pigments effect and improves the detectability of small bowel
lesions.
Version: 1Date:29 April 2012
Reviewer: Peter Green
Reviewer's report:
1. the authors use the term “flexible spectral imaging color enhancement (FICE)”
yet the references they use are titled virtual chromoendoscopy.(ref 16-19). Is this
the same? This is the basis of their paper. This needs to be explained why their
references are different to the title and content of their manuscript..
2. The results of the two expert VCE readers is shown in Table 1. I cannot see
the results of any of the trainees’ readings. This is confusing. Does Table 1 show
the trainees results?
3. I find the results section difficult to interpret
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 have no competing interests
Review for 10.1186/1471-230X-12-83 (2012)

Reviewer's report
Title:Capsule endoscopy with flexible spectral imaging color enhancement
reduces the bile-pigments effect and improves the detectability of small bowel
lesions.
Version: 2Date:8 June 2012
Reviewer: Edward Ciaccio
Reviewer's report:
Capsule endoscopy with flexible spectral imaging color enhancement reduces
the bile pigment effect and improves the detectability of small bowel lesions.
Sakai et al.
The authors have satisfactorily answered all of my queries.
Please note that although ‘detectability’ (see title) is used in some science
articles, it is not defined as a word in most dictionaries.
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-12-83 (2012)

Reviewer's report
Title:Capsule endoscopy with flexible spectral imaging color enhancement
reduces the bile-pigments effect and improves the detectability of small bowel
lesions.
Version: 2Date:11 June 2012
Reviewer: Peter Green
Reviewer's report:
thebauthors have answered my queries
the paper is clearer
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 have no competing interests
Review for 10.1186/1471-230X-12-80 (2012)

Reviewer's report
Title:Capsule Colonoscopy Increases Uptake of Colorectal Cancer Screening
Version: 2Date:29 February 2012
Reviewer: Marty M Meyer
Reviewer's report:
Minor essential revisions: misspellings on p 4
Discretionary revisions:
1.) Make a comment about any possible bias introduced by focusing only on one
group covered by a single insurance carrier (economic diversity, tendency to
utilize health care resources, etc.)
2.) Comment on possible impact of free capsule on opportunity to participate in
screening as this would not reflect real world circumstances of screening
3.) p 8, Revise comment speculating sensitivity of capsule colonoscopy. do not
state an estimated percentage, simply state that under routine conditions the
sensitivity may be expected to be lower.
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-12-80 (2012)

Reviewer's report
Title:Capsule Colonoscopy Increases Uptake of Colorectal Cancer Screening
Version: 2Date:7 March 2012
Reviewer: Pat M Lynch
Reviewer's report:
Summary:
Investigators in Germany tested the hypothesis that an offer of capsule
endoscopy through a major regional insurer, would increase the uptake of CRC
screening. Enrollees were offered description of pros and cons of capsule
colonoscopy (CC) and conventional optical colonoscopy (OC), with an offer to
undergo either test. Capsule was preferred by a 3:1 margin over OC. A large
number of invitees evidently underwent OC outside the scope of the program, so
the effect of the invitation was uncertain in this group. Adenoma detection rate
(by patient) was 26% in OC group and 9% in CC group. A survey was used to
identify bases for user preferences and post hoc satisfaction..
Critique:
This study marks an interesting addition to the armamentarium of approaches
taken to foster CRC screening, and likely the first to compare patient uptake of
CC when offered as an alternative to OC. The greater preference for CC in men
is perhaps not surprising and a consideration that could be used to leverage
greater screening participation, especially in men.
Limitations of the study are several, but nonfatal. There was an overall rather low
overall response rate, though likely not much lower than observed in other similar
trials. An effort to reach nonresponders to assess their reasons for
nonparticipation would have been helpful. Of the 15 with technically
unsatisfactory CC (“incomplete”), 6 underwent OC. The difference in adenoma
rate of 26% vs 9% in the OC vs CC groups was described as nonsignificant. This
is actually a fairly dramatic difference, with a nonsignificant outcome likely due to
sample size. Authors might wish to comment on this. A high proportion of polyps
found on CC were >1cm, whereas the OC-detected tended to be smaller. One
tends to assume this discrepancy may be due to relative insensitivity of CC for
subcentimeter polps. A comment about this would be worthwhile.
The authors do comment on the logistic challenges of following a CC positive
screen with OC in a timely enough way as to avoid reprepping the patient. It
would be helpful if the authors could comment on how explicitly this need to
reprep was explained to subjects, including the fact that this would be a needed
undertaking in about 5-20% of cases that would be positive or incomplete. The
combination of (apparent) insensitivity for polyps <1cm with CC and relatively
high rate of repeat CC would be thought to have accounted for a lower proportion
of CC uptake. Authors may wish to comment on this as well.
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-12-80 (2012)

Reviewer's report
Title:Capsule Colonoscopy Increases Uptake of Colorectal Cancer Screening
Version: 3Date:17 May 2012
Reviewer: Marty M Meyer
Reviewer's report:
I am satisfied with the revisions.
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-12-78 (2012)

Reviewer's report
Title:Transporter function and cyclic AMP turnover in normal colonic mucosa
from patients with and without colorectal neoplasia
Version: 1Date:9 February 2012
Reviewer: Theresia Thalhammer
Reviewer's report:
The study is an important contribution in the field of physiology/pathophysiology
of cyclic nucleotide transport in colon.
Studies were done on biopsies from patients with and without neoplasia (CRN).
By measuring electrogenic ion transport parameters in a Using chamber, the
authors demonstrate transport of cAMP. Together with data on the expression of
influx and efflux transporters (known to transport cAMP and prostaglandins), they
propose a model for the turnover of cAMP in different colon cell types.
The findings are important to understand cAMP turnover in the colon.
- The methods are appropriate, the concept explained in the Discussion is
pausibel, and it is based on the data given.
- However, there are number of open questions, but to answer them, would
require extenisive investigations. This is beyond the scope of the study and
would be better done in a subsequent study in appropriate cell lines.
(also with respec to the limited amount of material obtained by biopsies).
However, other major points must be clarified before publication.
Major points:
1. By immunohistochemistry, the authors show that OATP1C1, OATP2B1,
OATP4A1, and OATP4C1 as well as ABC transporters (ABCC5, ABCC4 and
ABCC3 are located in different colon cell types.
Double immunofluorecence staining of transporters with cell specific marker (e.g
chromogranin for endocrine cells, cytokeratin 7 for goblet cells) would allow a
valid identification of these cell types in selected samples. It would also help to
dicriminate between similar appearing cell types, e.g. endocrine cells vs. B-cells.
This is important, because OATP2B1 immunoreactivity restricted to endocrine
cells has not been observed so far.
2. Question: Is the localization of transports different in normal vs. CRN samples.
Do the PCR data relate to the staining intensity?
3. Results: probing the excretory system … the description OATP4C1 function (
Fig. 5D).. the authors should discuss that it OATP4C1 is regarded as a “kidney
specific” transporter implicated in the removal of uremic toxins, drugs etc.
(Toyohara et al. 2009)
4. No explanation for OATP1C1, known as thyroid transporter, is given.
.
Minor points:
1. Results, paragraph: Cox enzymes… second paragraph…….. higher levels of
OATP4A1 in colon cancer were first shown by Ancona et al. (add citation)
2. Conclusion:
3rd line. ABCC4 in the periphery of Goblet cells ?
3. Figures:
The same magnification should be applied in all images. Details could be shown
as Inserts. Show negative controls (non-immunogenic IgG staining).
Level of interest: An article of outstanding merit and interest 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-12-78 (2012)

Reviewer's report
Title:Transporter function and cyclic AMP turnover in normal colonic mucosa
from patients with and without colorectal neoplasia
Version: 1Date:20 February 2012
Reviewer: Kacper Wojtal
Reviewer's report:
Major Compulsory Revisions:
1. In my opinion the fact that db-cAMP is a membrane permeable analog puts the
working hypothesis of transport of this molecule into question. Hence, the extent
of the passive uptake in the generation of SCC by this molecule must be
somehow considered and possibly verified. cAMP did not give rise to a strong
signal, possibly due to either lower influx rate as compared to db-cAMP or
hydrolysis by PDEs. These issues could be approached by using either another
cAMP analog or the experiment with cAMP should be performed in combination
with any of the phosphodiesterase inhibitors, such as IBMX.
2. The proposed involvement of PKA and PDEs (Discussion; page 8-9) in the
generation of SCC could provide the support for the observed differences
between control and neoplastic tissues. If not approached experimentally, this
aspect should be more elaborated in the discussion section of the manuscript.
Discretionary Revisions:
1. Despite determining mRNA levels and localization in the colonic tissues, one
would still consider checking the protein levels of implicated transporters in both
control and neoplastic specimens by Western blot.
2. Concerning the other transporters which could be possibly involved in the
uptake of cNTs: were ENTs and/or CNTs tested? Do they transport cAMP?
Minor Essential Revisions:
Microscopic images in figures 5 and 6 appear to have different optical settings,
which should be adjusted. Also, in my opinion instead of providing the info about
the objectives used in the figure legends, placing the appropriate size bars
directly on the images would be more informative.
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-12-78 (2012)

Reviewer's report
Title:Transporter function and cyclic AMP turnover in normal colonic mucosa
from patients with and without colorectal neoplasia
Version: 1Date:27 February 2012
Reviewer: J.J. Eloranta
Reviewer's report:
In this manuscript the authors Kleberg et al have investigated the colonic
transport of cyclic nucleotides using electrophysiological measurements in
mini-Ussing air suction chamber set-up, using human colonic biopsy tissue. They
show that colorectal neoplasia seems interestingly to be associated with lower
transport of or sensitivity to the cyclic nucleotide dibuturyl-cAMP. In the second
part, the authors study the expression of selectecd ABC and OATP transporters
in colonic tissue material by real-time PCR and immunohistochemistry.
Major compulsory revisions:
1. The range of OATP transporters, the expression levels of which in CRN vs.
non-CRN tissue have been studied is not comprehensive enough. Based on the
past study by Hilgendorf et al (DMD 2007; 35:1333-1340), in which the
expression of eight SLCO genes in human colon tissue was studied, the authors
have selected OATP1C1, OATP2B1, OATP4A1, and OATP4C1 to be measured.
Please see the recent review by Obaidat et al. (Annu. Rev. Pharmacol. Toxicol.
2012; 52:135-151) for further members of the SLCO gene superfamily that would
be of interest to study in colorectal neoplasia, as well as relevant literature
references therein. For example:
• OATP2A1 has been detected in the colon.
• Normally liver-specific OATP1B1 and OATP1B3 have been found expressed in
colon cancer cell lines and colon cancer tissue.
• OATP3A1 has been detected in colon adenocarcinoma cell lines.
In fact, the best approach would be to include all 11 human OATPs in the study.
2. The authors have not sufficiently described the method of calculating relative
expression levels in real-time PCR experiments. Have they used the comparative
threshold cycle method?
Discretionary revisions:
1. It is regrettable that the authors have used the non-specifically intercalating
dye SYBR Green in real-time PCR experiments, instead of the TaqMan probe
technology, superior in its specificity. At least they have performed the
dissociation curve analysis to control this - perhaps these data could be provided
to the reviewers?
Minor essential revisions:
1. Page 8, line six from bottom: “dictoystelium” should be “Dictyostelium”.
2. Page 10, bottom line: “OAT2B1” should be “OATP2B1”.
3. Methods: The exact details of the antibodies used for immunohistochemistry
should be provided (ie. catalogue numbers, final concentrations used etc.).
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-12-78 (2012)

Reviewer's report
Title:Transporter function and cyclic AMP turnover in normal colonic mucosa
from patients with and without colorectal neoplasia
Version: 2Date:23 April 2012
Reviewer: Theresia Thalhammer
Reviewer's report:
The authors have revised the paper as suggested by the reviewer.
They have answered the questions and have added appropriate statements in
the manuscript.
These revisions improved the clearity (and quality) of the manuscript.
The paper, which is an important contribution in the field of uptake and
efflux-transporter expression and function in colon cancer, is now ready for
publication.
Level of interest: An article of outstanding merit and interest 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-12-78 (2012)

Reviewer's report
Title:Transporter function and cyclic AMP turnover in normal colonic mucosa
from patients with and without colorectal neoplasia
Version: 2Date:1 May 2012
Reviewer: Kacper Wojtal
Reviewer's report:
Minor Essential Revisions:
The fact that db-cAMP had no effect on SCC when applied to the apical side
does not directly disprove the fact that it is cell-permeable analog, which is in my
opinion still the case. The lack of effect may be simply due to specific mucosal
barrier properties, which create limited diffusion barrer for these compounds as
compared to basolateral side. Nevertheless, I understand the rationale of the
authors when trying to correlate the effect of cAMPs and the presence of cNTs at
the basal surface, which is in my opinon difficult to disprove afterall.
Hence, I suggest to modify the existing statement (Page 8, Section: 'Functional
characterization of transport'; line 9) into the following:
...indicating db-cAMP as a non-permeable analog in our experimental setting and
implying the transport mechanism at the balolateral membrane.
Level of interest: An article of outstanding merit and interest 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