JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/1471-230X-13-149 (2013)

Reviewer's report
Title:Penile metastasis from primary cholangiocarcinoma: the first case report
Version: 1Date:5 August 2013
Reviewer: Alcides Chaux
Reviewer's report:
In this study authors report the clinicopathologic and immunohistochemical
features of a cholangiocarcinoma metastatic to the penis. According to the
authors’ review this is the first case of such instance. Recommendations for
improving the manuscript are provided below.
MAJOR COMPULSORY REVISIONS
- Keep in mind that case reports submitted to the journal should make a
contribution to medical knowledge and must have educational value or highlight
the need for a change in clinical practice or diagnostic/prognostic approaches. In
this regard, please expand the Discussion to include how the case was handled
until the final diagnosis was reached, including all the steps taken for ruling out
other more common malignancies that might have similar clinical and pathologic
features. For example, considering gender and age, prostatic and bladder
carcinomas, which may have glandular features as well and are more common
as penile secondary tumors, should also be taken into account. Instead of plainly
stating that this is the first case report of a cholangiocarcinoma metastatic to the
penis (which indeed is interesting but has limited value per se), please discuss
the finding in the context of other penile secondary tumors. Considering the rarity
of such clinical scenario other diagnosis must be discussed to offer the readers a
broader perspective of the clinical situation. Keep the focus on the case and build
the Discussion around it.
MINOR ESSENTIAL REVISIONS
- Figures are of great quality. Nevertheless, I don’t think showing the primary
tumor (Figure 3A and B) is necessary, considering that the diagnosis of the
primary lesion is not under discussion. I also feel that Figure 3C is at loo low
power to be of any help. Please consider keeping only Figure 3D and create a
panel of immunohistochemical stains showing the same microscopic field. Also,
for the same reason, please consider dropping Figures 4A to F and showing only
the immunohistochemical findings of the secondary lesion. As mentioned before,
it would be more impressive if H&E and immunohistochemistry show the same
microscopic field.
DISCRETIONARY REVISIONS
- Please follow the author guidelines regarding reference style.
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-13-149 (2013)

Reviewer's report
Title:Penile metastasis from primary cholangiocarcinoma: the first case report
Version: 1Date:11 September 2013
Reviewer: Zsófia Küronya
Reviewer's report:
Accepted without comment.
Good luck ! :)
... looking forward to further publications on the progress of treatment of this
particular case.
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-13-147 (2013)

Reviewer's report
Title:Predicting native papilla biliary cannulation success using a multinational
Endoscopic Retrograde Cholangiopancreatography (ERCP) Quality Network
Version: 1Date:9 July 2013
Reviewer: lars aabakken
Reviewer's report:
This is an excellent piece of work eluciding the factors contributing to successful
ERCP.
I have the following minor comments:
- The issue of selection bias must be commented upon. While the control for
total/expected volumes is useful for selection within the doctors (probably), it is
highly likely that those volunteering to this network are not your average doctor.
Thus, the problematic situations of lower competence may not have been
properly addressed by a volunteer system. This may limit generalizability of the
findings.
- Some of the factors involved, e.g. case complexity, are based on issues related
to the entire procedure, while this is a cannulation- focused study. Better
gradings may be lacking, but it should be commented on that complex procedure
may not translate to complex cannulation per se.
- The issue of trainees is unclear to me – what does 100% involvement mean?
Involvement in 100% of cases, or cases done 100% by the trainee? If the latter is
the case, then no wonder the success was 100%, by circular definition… To be
clarified. Otherwise, the issue if trainee involvement is inherently difficult to
interpret, to the extent that it might be better avoided.
- A lot of the discussion is related to training and competence, - somewhat in the
outskirts of this study, may be shortened.
- Also, somewhat surprising, cannulation seems related to anything BUT
training-associated factors. This challenges current thinking on training, volumes
etc, but may be merely a result of the selection bias touched upon above.
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-13-147 (2013)

Reviewer's report
Title:Predicting native papilla biliary cannulation success using a multinational
Endoscopic Retrograde Cholangiopancreatography (ERCP) Quality Network
Version: 1Date:20 August 2013
Reviewer: Jorma Halttunen
Reviewer's report:
Discretionary Revisions
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-13-146 (2013)

Reviewer's report
Title:A case of rectal tumor in which the shape altered with regression in short
period
Version: 1Date:15 June 2013
Reviewer: Ulrich Keilholz
Reviewer's report:
Nakamura and colleagues present an exciting case of an almost complete
spontaneous regression of a biopsy-verified rectal carcinoma. The case is
impressibly well documented and very well described. It is a singular unusual
case, but because of the precise clinical and histological documentation the case
is of high interest. The description od this case provides food for thought to
develop hypotheses on potential mechanisms of spontaneous cancer regression.
The manuscript reads well, although minor linguistic corrections by a native
English speaker would be helpful.
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:
no competing interests
Review for 10.1186/1471-230X-13-146 (2013)

Reviewer's report
Title:A case of rectal tumor in which the shape altered with regression in short
period
Version: 1Date:26 June 2013
Reviewer: Charles LeVea
Reviewer's report:
The paper describes a 10 mm well differentiated adenocarcinoma that
"spontaneously" regressed after biopsy to a 1 mm lesion. An endoscopic
submucosal resection with a ligation device was performed a month after
diagnosis to resect the tumor from an area that the endoscopist had difficulty
identifying as tumor. This may have been from the same area as the initial
biopsy; however, tattoo ink was not used at the time of initial biopsy to mark the
site of the tumor. From the submitted photomicrographs, this resection specimen
contained submucosal fibrosis, intramucosal hemorrhage, and a single gland
with high grade glandular dysplasia. I could not identify residual
adeonocarcinoma in the photos in the submitted figure. Additionally, the initial
biopsy that carried a diagnosis of a well differentiated adenocarcinoma was not
submitted as a figure. Therefore, this case report is based on an uncomfirmed
diagnosis of adenocarcinoma. Without an ability to confirm that an
adenocarcinoma was present, this case report should not be accepted for
publication. Please see Major Compulsory Revisions below.
Major Compulsory Revisions
1. Figure of the initial biopsy specimen clearly showing an adenocarcinoma
2. Diagnosis for Figure 6 - high grade glandular dysplasia - not invasive
adenocarcinoma or show picture proving invasion
Minor Essential Revision
"further" is misspelled page 5 line 3
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:
No competing interests to declare.
Review for 10.1186/1471-230X-13-144 (2013)

Reviewer's report
Title:Online follow-up of individuals with gastroesophageal reflux disease using
a patient-reported outcomes instrument: results of an observational study
Version: 2Date:21 June 2013
Reviewer: Jan Gunnar JH Hatlebakk
Reviewer's report:
This is a study that documents to some extent the concept of defining groups of
dyspeptic patients by internet surveys, and following up by repeated symptom
questionnaires.
A main problem is selection bias, since particularly the PPI user group is likely to
consist of PPI partial or non-responders, furthermore the study is for practical
reasons open only to internet users. It can be argued that more people are
internet users than are consulters for GERD (supported by the finding that only
37-45% actually visited their PCP). It must be emphasized that symtoms
compatible with GERD is not a diagnosis, although GerdQ is designed to exclude
dyspeptic symptoms of epigastric pain and nausea to some extent by weighting
the negatively.
The two patients groups can not be compared, as all assessment variables and
endpoints are different. In non-PPI users, the definitions do not make sense,
since small or larger changes in GerdQ score crossing (or not) the cutoff of "8"
are all classified the same.
In the PPI users group, endpoints are more in line with whatr is used in clinical
studies.
All this leaves us with a pure feasibility study.
In the "Statistical analysis" section, we are presented with more variables which
should have been in the Outcomes section, or elsewhere in a separate section.
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-13-144 (2013)

Reviewer's report
Title:Online follow-up of individuals with gastroesophageal reflux disease using
a patient-reported outcomes instrument: results of an observational study
Version: 2Date:11 August 2013
Reviewer: ALEKSANDAR M NAGORNI
Reviewer's report:
Some Minor Essential Revisions have to be done:
1. Second page-At the beginning of new sentence in the 6th line of results
authors have to correct 55% in Fifty-five percent.
2. Citation of references 3 and 12, need correction and true citation as The New
England Journal of Medicine.
3.Correct citation of references 6,10,15,16,17,21,22,23,24,25 is Alimentary
Pharmacology&Therapeutics or shorten Aliment Pharmacol&Ther.
4. In relation of policy of citation of BMC Gastroenterology for multiple authors, if
the number of citated authors is 10, then authors of article are correctly do that.
In the case the number of authors are 4 or 6 than authors need to change
corrections in a few references.
5. In reference number 4 authors citated French name of Canadian Journal of
Gastroenterology as English. English name is sufficient.
6. In reference 2, after Melton LJ, 3rd need to delete.
7. In references 7 and 19 after volume there are only first page of article.
8. In reference 7 After BMC G in gastroenterology need to be in blocj letter.
9.Citation of reference 18 is not complete. Fail number of pages.
10. Reference number 28 is not complete and need to be changed with addition
of netherlands as language of reference.
11. In references 8 and 19, first block letter in the name of references need to be
done.
12. The same corrections should be done in references 9,14, and 26.
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-13-145 (2013)

Reviewer's report
Title:Possible etiology of improvements in both quality of life and overlapping
gastroesophageal reflux disease by proton pump inhibitor treatment in a
prospective randomized controlled trial
Version: 1Date:16 July 2013
Reviewer: Yeong Yeh Lee
Reviewer's report:
The current clinical trial indicates that the PPI, pantoprazole 40 mg daily is
effective in relieving symptoms and sustaining improvement in quality of life for at
least 6 mo in patients with GERD overlapping with functional upper and lower GI
symptoms. This study addresses a rather common scenario of patients that GI
clinicians often encounter.
Major compulsory revisions
1. A section in methods should be created for data and statistical analysis.
Descriptions of analysis and statistics mentioned in the assessment of GI
symptoms and HRQOL are to be moved into this section. Please clarify whether
the ReQuest™ scores in the results were reported in mean or median (mean
mentioned in Figure 2).
2. Results; are there any differences in symptoms and HRQoL improvement
between different grades of esophagitis?
3. Discussion; the authors proposed the sustained improvement of functional
symptoms with PPI over time could be immune-mediated but evidence were
lacking and remain largely speculative. Likewise, current data on genetic
polymorphisms being useful in such circumstances is also speculative and
should be tone down in the conclusion in the abstract. The improvement seen is
likely to be multifactorial.
4. Discussion; limitations of study were not mentioned. One would be a small
number of patients in subgroups of FD and IBS. This study did not address
patients with the more prevalent endoscopy-negative GERD, who are more
resistant to PPI. Lack of a control group with purely functional symptoms
Minor Essential Revisions
1. Page 6, Methods, study design and patients, line 3 – need to rephrase the
sentence “In brief, this randomized, multicenter……” and clarify treatment
intensity comparison and diagnosis of GERD which was based on the presence
of erosive esophagitis (LA classification) and symptoms.
2. Page 6, Methods, study design and patients, line 7 – is it treatment “endpoints”
or “concepts”?
3. Page 7, Methods, study design and patients, line 18 – functional missing from
“dyspepsia”, FD was used in quoted reference 16. Also maintain consistency of
use for the term FD throughout the manuscript.
4. Page 9, Results, therapy-associated change in GI symptoms, para 2, last
sentence – there is no need to mention “highly” and it is appropriate to report p
value for each comparison.
5. Page 12, Discussion, para 1, line 10 – remove “e” from the sentence.
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-13-143 (2013)

Reviewer's report
Title:Association between obesity and Barrett's esophagus in a Japanese
population: a hospital-based, prospective pilot study
Version: 1Date:22 April 2013
Reviewer: Aaron Thrift
Reviewer's report:
Please refer to the attached document.
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-13-143 (2013)

Reviewer's report
Title:Association between obesity and Barrett's esophagus in a Japanese
population: a hospital-based, prospective pilot study
Version: 1Date:11 July 2013
Reviewer: Jennifer Kramer
Reviewer's report:
Minor essential revision.
I think it would be of interest to conduct a sensitivity analysis that examines the
effect of obesity markers on those with definitive SIM to see if the results are
similar to that of ESBE.
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-13-143 (2013)

Reviewer's report
Title:Association between obesity and Barrett's esophagus in a Japanese
population: a hospital-based, prospective pilot study
Version: 1Date:14 July 2013
Reviewer: Anna Mokrowiecka
Reviewer's report:
Major Compulsory Revisions
1. Please, check if the definition of large WC as "more than 85 cm for men and
more than 90 cm for women" is correct? I am not sure what is Japanese
definition but in western countries these measures are usually lower in women.
Is it a mistake or it was use wrong in the statistical assessment?
Minor Essential Reviosions
2. I could not agree with the conclusions that visceral obesity were not risk factor
for ESBE, because the main measure of central obesity - WC - was higher in BE
in patients taking PPIs. It is even more important because patients with GERD
and BE are usually on PPIs.
It would be interesting to try to answer in discussion section why this association
is seen in patients on PPIs? Any practical conclusions?
2. It is very difficult to diagnose BE in patients with RE. Particularly, the
histopathological assessment of BE is impossible during esophageal
inflammation. Thus did You assess the histopahology after treatment in RE
patients, because they could not be BE any more?
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-13-142 (2013)

Reviewer's report
Title:Efficacy and tolerability of alpha galactosidase in treating gas-related
symptoms in children: a randomized, double-blind, placebo controlled trial.
Version: 3Date:1 February 2013
Reviewer: Anshu Srivastava
Reviewer's report:
Abstract:
In results or conclusion it should be mentioned ---“short term treatment “ with
#-galactosidase. This is because therapy was given only for 2weeks and we do
not if the patients will continue to show the same response with continued
therapy at this point of time.
Results and discussion
II paragraph discussion
The significant decrease of FPS-R score occurring in the active group and the
marginal change in the placebo group provides the evidence of the efficacy of
#-galactosidase. “The similar score values at end of treatment should be
evaluated taking into account the apparent imbalance in the baseline FPS-R”.
This statement is not clear as this suggests that children in the #-galactosidase
arm had higher baseline FPS-R score than those in the placebo arm. This is not
expected in a RCT, so the authors should modify the table1—characterstics of
2groups of patients, include baseline symptoms apart from demography and
check the p value between the two groups for all the demographic or symptom
intensity or frequency data. If it is present, then it should be mentioned in the
results.
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:
None
Review for 10.1186/1471-230X-13-142 (2013)

Reviewer's report
Title:Efficacy and tolerability of alpha galactosidase in treating gas-related
symptoms in children: a randomized, double-blind, placebo controlled trial.
Version: 3Date:4 February 2013
Reviewer: Bridget Southwell
Reviewer's report:
see attached document. I have added my comments to the authors revision
letter.
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-13-142 (2013)

Reviewer's report
Title:Efficacy and tolerability of alpha galactosidase in treating gas-related
symptoms in children: a randomized, double-blind, placebo controlled trial.
Version: 4Date:29 April 2013
Reviewer: Anshu Srivastava
Reviewer's report:
Minor essential revisions:
• Abstract: Age needs to be added as shown in red. “Fifty-two pediatric patients
(32 female, age range 4-17) with chronic or recurrent gas-related symptoms were
randomized to receive placebo (n = 25) or #-galactosidase (n = 27)”.
• It is adequate to give the p value as 2 digits after decimal i.e 0.02 rather than
0.023
• Table 2, 3 and 4 can be put together as one table. And baseline symptom
section can be removed from table 1 as the same data will be shown in the
combined table of 2/3 and 4. Add the baseline data for number of days with
moderately to severe bloating also in the same table. So total FPS-R score, no of
days with severe bloating and individual symptoms baseline and end of treatment
will be shown in one table.
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:
no competing interest
Review for 10.1186/1471-230X-13-142 (2013)

Reviewer's report
Title:Efficacy and tolerability of alpha galactosidase in treating gas-related
symptoms in children: a randomized, double-blind, placebo controlled trial.
Version: 4Date:9 May 2013
Reviewer: Bridget Southwell
Reviewer's report:
Major Compulsory Revisions
the authors have responded to most of the questions from the reviewers well,
however I would still like a little more detail added to the manuscript.
The results of the study are very borderline for significance. I think it is worth
publishing but only if the data are clearly shown so that people can decide if they
think it is worth pursuing.
The authors have modified table 1 and included ns for the p value. Please
change this to list each p value.
Please add bloating to table 1 to give a context for table 3.
In the answer to question 3 reviewer 1, you have included a graph. please
suppply a figure legend to make it possible to understand the graph, please
explain the symbols- which is pre and which is post. then it would be useful to
add this to the manuscript.
Please add to the results section of the manuscript- how many patients in each
group improved pain by more than 0.5 units, how many had pain worsen by more
than 0.5 units. Then relate this to the improvement reported by the clinician at
followup.
on page 4 line 21 and 22 - 'The primary endpoint was reduction......Secondary
endpoints were.....'. The endpoint is when will the trial/study be considered to be
finished. I think a reduction in FPS_R at the end of treatment compared to
baseline is the 'primary outcome measure', The reduction in proportion of
patients with relevant symptoms is the 'secondary outcome measure'.
Minor Essential Revisions
page 8 line 7 insert 'of'- ...identify groups 'of' patients who are more likely to
respond.....
page 8 line 8, change 'in which' to 'in whom'.
page 8 line 8, add commas- .....recgonise children in whom, based on the
medical history, food appears......
page 9 line 7 add 's' after 'tend'
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-13-142 (2013)

Reviewer's report
Title:Efficacy and tolerability of alpha galactosidase in treating gas-related
symptoms in children: a randomized, double-blind, placebo controlled trial.
Version: 5Date:19 August 2013
Reviewer: Bridget Southwell
Reviewer's report:
This paper is now much improved from the original version. It is much clearer to
follow. The reader can now judge for themselves if they wish to try the treatment.
Minor essential revisions
p4 line 6, add hyphen between out and patients- to create single word
'out-patients'.
p4 join paragraph 5 to 6. .....patient flow. After...............
table 3: insert new column 1, containing the words 'improved' and 'worse' . this
will help the reader to know if a higher score is better or worse.
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-13-141 (2013)

Reviewer's report
Title:MYC, FBXW7 and TP53 copy number variation and expression in Gastric
Cancer
Version: 2Date:21 March 2013
Reviewer: Yueyong Liu
Reviewer's report:
This manuscript is a revised version of previous submission. The authors
improved the results, discussion and added zymography data to this manuscript.
Due to the complexity of oncogene and tumor suppressor in the tumorigenesis,
it’s hard to straighten out the relationship of MYC, FBXW7 and TP53 under
several parameters including copy number, mRNA level and protein expression
level. Even so this manuscript still brings to us lots of interesting information
including the firstly reported deregulation of MYC (amplification) and FBXW7
(LOH) associated with lymph node metastasis and stage III-IV disease. The
authors made great efforts in investigating gene status of MYC, FBXW7 and
TP53 in three different levels in GC tumors and cancer cell lines which is
potentially useful for the researchers in this related field. Based on the data
presented, it is worthy of being published in BMC gastroenterology journal.
Minor concerns:
1. The authors added and showed the increased active MMP9 form in ACP02
cell line which is more invasive as compared to ACP02. Increased MMP9 and
reduced FBXW7 level can promote cell motility. However, ACP2 showed
impaired migration capability instead, please specify.
2. Typos: a. line 2 in results: deletion instead of delection.
b. line 2 in subtitle 2 of results: non-neoplastic instead of non-tissue
c.line 10 in subtitle 4 of results: punctiform instead of puntiform
d. the symbol in table2: age 50.
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.
Review for 10.1186/1471-230X-13-140 (2013)

Reviewer's report
Title:The role of ursodeoxycholic acid in nonalcoholic steatohepatitis-a
systematic review
Version: 1Date:3 February 2013
Reviewer: Raluca Pais
Reviewer's report:
The present systematic review analyzed the impact of UDCA as derived from
randomized control trials on liver biology and histology in patients with NAFLD.
Major comments:
1. No critical interpretation of the results of included studies is provided. As you
mentioned, there is an important heterogeneity of the different trials and there are
discrepancies in the reported outcomes. However, when looking attentively to the
design, inclusion criteria and primary outcomes (in placebo and treatment arms)
of these studies, these discrepancies may be easily explained. For example, in
Leuschner’s study, transaminases levels decreased with a similar magnitude in
placebo and in UDCA group, which might explain the lack of statistical
significance when the two groups were compared. Also provide comments on the
inclusion criteria regarding elevated transaminases levels used in the two
studies.
2. Footnote table 3- fibrosis at follow-up in Ratziu’s study was assessed by
FibroTest not by Fibroscan
3. Please comment on the effect of UDCA on metabolic parameters (when this
end point was assessed).
4. Please focus the discussion section of the methodological design of the main
UDCA trials.
Because the lack of a critical analysis of the outcomes reported by the different
trials, I consider that the message derived from this systematic review is not
pertinent enough to be published in its actual from unless major revisions.
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-13-140 (2013)

Reviewer's report
Title:The role of ursodeoxycholic acid in nonalcoholic steatohepatitis-a
systematic review
Version: 1Date:22 March 2013
Reviewer: John Dillon
Reviewer's report:
This is a useful systematic review that has been conducted to a good standard,
in topic that is highly relevant. The removal of the usual language restictions is
particlarly valuable.
Major revisions
Tables 1-3 are useful, but the formatting of the tables needs to be improved to
make them clearer, the use of boxes and landscape layout wold be helpful.
minor revisions
There are a few typos and one or two sentences that do not read well in english
that should be reviewed again by the authors, but there meaning remains clear.
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:
none
Review for 10.1186/1471-230X-13-140 (2013)

Reviewer's report
Title:The role of ursodeoxycholic acid in nonalcoholic steatohepatitis-a
systematic review
Version: 2Date:10 June 2013
Reviewer: Raluca Pais
Reviewer's report:
The authors properly responded to reviewer suggestions and considerably
ameliorated the quality of the manuscript.
Minor comment
There is a need to revise english language throughout the manuscript.
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:
No conflict of interest to declare
Review for 10.1186/1471-230X-13-139 (2013)

Reviewer's report
Title:Klebsiella pneumoniae bacteremia and renosplenic abscesses, without
intestinal symptoms, as the initial manifestations of non-steroidal
anti-inflammatory drug-induced colitis: a case report and literature review
Version: 5Date:7 June 2013
Reviewer: Giovanni Di Nardo
Reviewer's report:
This manuscript is an interesting and well-written manuscript reporting the first
case of disseminated abscess formation caused by community-acquired K.
pneumoniae in kidney and spleen without liver involvement in an NSAID-induced
colitis patient.
Major comments:
1. I think that this manuscript can’t be considered a literature review. I suggest to
cut this affirmation in the title.
2. Specify type of NSAID, dose and duration of the therapy.
3. Speculate in the discussion on the different risk of colitis related to the type of
NSAID.
4. “….wall thickening of sigmoid colon, descending colon, and terminal ileum….”
we need more detail on this TC finding (i.e parietal stratification loss, calibre of
the lumen, contrast enhancement).
5. “…..A colonoscopy revealed diffuse ulceration with exudation at the distal
terminal ileum, segmental ulceration at the colon, with stenotic lumen at the
sigmoid…..”. If the endoscopist was able to pass the stenosis, it’s better to define
reduction in the lumen calibre and not stenosis.
6. “…She led an uneventful course at the OPD, and the follow-up colonoscopy
two years later revealed no ulcer or stenosis over the entire colon...” Why so late,
what about biopsies during this follow-up colonoscopy. This point is crucial to
exclude that we are observing an IBD during a period of endoscopic remission
but with histological signs of quiescent disease.
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 conflict of interest to declare
Review for 10.1186/1471-230X-13-139 (2013)

Reviewer's report
Title:Klebsiella pneumoniae bacteremia and renosplenic abscesses, without
intestinal symptoms, as the initial manifestations of non-steroidal
anti-inflammatory drug-induced colitis: a case report and literature review
Version: 5Date:25 June 2013
Reviewer: Giovanni Carini
Reviewer's report:
This is a case report of a disseminated infection by K.pneumoniae in a diabetic
patient with a supposed NSAID colitis.
- Major compulsory revisions: none.
- Minor essential revisions:
There is a typo error in the discussion (e.g. second paragraph: “The infection rate
increased…” instead of “increases”).
Some sentences in the discussion also need to be written in a better English (3rd
paragraph: “Intra-abdominal abscess…as in this case”; 6th paragraph
“Prostaglandins…immune system”).
-Discretionary revisions:
1) The authors could add some information about the clinical history of the
patient, such as the eventual concomitant use of other drugs than NSAIDs.
2) Have other forms of infectious colitis been ruled out, for instance by fecal
culture or colonic bioptic specimen culture/molecular biology exams? If yes,
authors could better clarify this point.
3) The lack of liver involvement is quite unusual given the hypothesis of bacterial
translocation from the colon as in this case. Have the authors considered the
possibility of other sources of infection (e.g. urinary tract) and, if not, what is their
opinion on the localization of the abscesses?
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-13-138 (2013)

Reviewer's report
Title:Long-term Follow up Helicobacter Pylori Reinfection Rate After
Second-Line Treatment: Bismuth-Containing Quadruple Therapy versus
Moxifloxacin-Based Triple Therapy
Version: 2Date:10 June 2013
Reviewer: Gian luigi de' Angelis
Reviewer's report:
Minor Essential Revisions
This study is well conducted and shows very interesting results, but:
- why patients were subjected to endoscopy after 1 year from diagnosis, if in
Korea the governement national health insurance program recommends biannual
endoscopy? If these patients needed endoscopy because of their clinical or
histological features, this have to be specified.
- in page 10, row 12: numbers used at the beginning of the sentences, should be
written in letter and not in digit (...show in table 3. 1 patient...).
- It would have been important to know among the reinfected patients, how many
subjects belonged at the same household: this data could give an idea about the
intrafamilial transmission rate, one of the most important transmission routes of
the H. pylori infection.
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-13-138 (2013)

Reviewer's report
Title:Long-term Follow up Helicobacter Pylori Reinfection Rate After
Second-Line Treatment: Bismuth-Containing Quadruple Therapy versus
Moxifloxacin-Based Triple Therapy
Version: 2Date:14 June 2013
Reviewer: Arne Kandulski
Reviewer's report:
SUMMARY
This is a prospective trial that randomized patients after failed first line H. pylori
eradication to receive either bismuth containing quadruple therapy (EBMT) or
moxifloxacin-based second line regimen (MEA).
After initial successful eradication within the first year, patients´ H. pylori status
was followed every other using UBT or invasive tests.
The authors defined a recurrent positive H. pylori diagnosis within the first year
as “reappearance”. The rate was calculated at 1.7% for the EBMT group and
3.3% for the MEA group.
A recurrent positive test for H. pylori in the further follow-up was defined as
reinfection. The mean duration of Follow-up was 31.9 months for EBMT and 30.4
months for MEA regimen.
11.9% of the patients in the EBMT group were tested positive and 16.54% in the
MEA group.
Only 3-1 patients were followed for the period of 7 years. Therefore a really
long-term analysis is impossible.
Major remarks
Though missing deeper experience in the field of H. pylori transmission and the
nature of possible re-infection, it seems unlikely that a positive H. pylori test in
the follow-up of approximately 30 months is a true re-infection rather. Therefore it
would be worth to re-edit the manuscript to entitle “recurrent” H. pylori infection.
40% of the patients were included with gastric cancer. It needs to be stated if
these patients were in advanced tumor stages and were probably lost in follow
up. The data needs reanalyzing after exclusion of the gastric cancer cases.
Atrophic gastritis is well known to interfere with test accuracy of UBT as well as
invasive tests.
- Table 1 leeds to misunderstandings as atrophic changes and intestinal
metaplasia are much more prevalent in the MEA group which can also explain
differences between the two regimen. Data definitely needs a careful revision in
this issue.
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-13-137 (2013)

Reviewer's report
Title:Requirement of epithelial integrin-linked kinase for facilitation of Citrobacter
rodentium-induced colitis.
Version: 1Date:7 February 2013
Reviewer: Chihiro Sasakawa
Reviewer's report:
Assi et al. describe that integrin-linked kinase (ILK)-knockout (ko) mice shows
reduced inflammation and attenuated hyperplastic cryptal response to
Citrobacter rodentium infection. In the authors’ recent studies (2008 Gut and
2011 BMC Immunology), they have shown that ILK-ko mice also exhibited less
wasting disease or attenuated carcinogenesis in response to dextran sodium
sulfate (DSS) treatment. Their findings are intriguing, since ILK potentiates
colonic inflammation through perhaps indirect effect on chemokine expression,
epithelial cell proliferation, and extracellular matrix protein expression induced by
both DSS treatment and C. rodentium infection. However, it is not clear that the
changes are caused by bacterial infection or ILK-loss. Though the present study
finds potential significance, additional evidence is required to draw any
conclusion.
Major comments;
1) The authors showed the reduction of cell proliferation (Ki-67 positive cell
number), crypt heights and the level of cyclinD1 at both 6 and 15 days post
infection in the ILK-ko mice (figure 8, 9). However, they have already reported
that the reduction of proliferating cell number, crypt heights, and cyclinD1
expression level in non-infected ILK-ko mice compared to WT mice (Gut 2008,
figure 2C, D, G, E, H). It is not clear the results that are shown here are due to
the ILK-loss per se or bacterial infection. They should compare the infected colon
with non-infected control in both WT and ILK-ko mice.
2) In the GUT paper (2008), the ILK-KO mice colon architecture is different from
that of wild type. They did not show non-infected control in both WT and ILK-ko
mice throughout the paper. Therefore it is difficult to judge the results. They
should show non-infected control in both WT and ILK-KO mice as following
figures; figure 2E, 3C, 9, 10.
3) The authors showed that bacteria cannot migrate downwards along the lateral
aspect of crypts in ILK-ko mice colon (figure 6D) in compared with WT mice
colon (figure6C). However the difference is not evident in these figures, because
ILK-ko mice colon crypts are cut latitudinally in figure 6D, while WT colon crypts
are cut longitudinally.
4) The authors said the bacterial colonization is not change between WT and
ILK-ko mice.
However, LPS and TIR positive signal shows big difference between these two
groups. Please give some comments.
5) The authors said that the colon stem cell compartment is stained positive for
cyclinD1 in figure 9. CyclinD1 is not a proper stem cell marker of colon. They
need to stain with the proper stem cell marker protein such as Lgr5.
Minor comments:
1) Figure 5A is not clear. Therefore it is difficult to judge the results mentioned for
this experiment.
2) C. rodentium and CyclinD are not properly labeled.
3) Figures are not properly labeled.
4) Many critical literatures through the text are missing.
5) Many references need to put published year.
Review for 10.1186/1471-230X-13-137 (2013)

Reviewer's report
Title:Requirement of epithelial integrin-linked kinase for facilitation of Citrobacter
rodentium-induced colitis.
Version: 1Date:7 April 2013
Reviewer: Shahid Umar
Reviewer's report:
Integrin-linked kinases (ILK) have been shown previously to be involved in
bacterial infection-induced stabilization of focal adhesion and cell attachment. In
the study presented here, the authors examine ILK's role in the pathogenesis of
Citrobacter rodentium infection and provide a possible therapeutic target for
studying diseases with infectious etiology. The manuscript is well written for the
most part and provides significant amount of data to justify ILK's role in bacterial
infection-induced hyperplastic and/or inflammatory responses. The manuscript
may be further improved if following modifications are made:
1. It will be helpful if half-life of ILK in various cell lines is atleast discussed if not
experimentally proven.
2. The way the results are interpreted for Figure 1 suggests that somehow total
Akt has to be affected in response to ILK activation, giving less significance to
the phosphorylated form of the protein which is more important.
3. Please provide ILK levels in Figure 1B to show its knockdown following siRNA
treatment.
4. Likewise, ILK levels should be shown for comparison in Figure 5. It may be
beyond the scope of this paper but the manuscript will improve significantly if
epithelial cells instead of whole tissue lysate is utilized for protein measurement
as doing this will confirm ILK expression in the crypt given that the IHC shown for
ILK in Figure 2E is not very conclusive.
Level of interest: An article of outstanding merit and interest 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-13-137 (2013)

Reviewer's report
Title:Requirement of epithelial integrin-linked kinase for facilitation of Citrobacter
rodentium-induced colitis.
Version: 2Date:17 June 2013
Reviewer: Chihiro Sasakawa
Reviewer's report:
The authors provide additional data and comments in response to my concern in
full.
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' below. If your reply is yes to any .
Review for 10.1186/1471-230X-13-136 (2013)

Reviewer's report
Title:Risk factors and management strategy for ulcer hemorrhage following
gastric endoscopic submucosal dissection in patients on antithrombotic therapy
Version: 4Date:20 February 2013
Reviewer: MASAMI OMAE
Reviewer's report:
This manuscript is well arranged. If there are no similar papers published before,
I recommend to the editor to accept for the Journal, BMC Gastroenterology.
Major
1. The author described that odds ratios of ESD duration is 1.04 (95%CI
1.10-1.08, p=0.025). However, there is no description of the reason that a long
time of ESD duration is a risk factor for postoperative bleedings. For example,
you spend more times to stop bleeding in Bleeding group than Non-bleeding
group during ESD.
2. In the Table2, are there significant differences in the lesion with ulcerative
scars or not, histology, and standard or expanded indications?
Minor
1.All patients who had postoperative bleeding were perfomed only EGD to stop
bleedings. Are there patients who needed operation to stop bleeding?
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.
Review for 10.1186/1471-230X-13-136 (2013)

Reviewer's report
Title:Risk factors and management strategy for ulcer hemorrhage following
gastric endoscopic submucosal dissection in patients on antithrombotic therapy
Version: 4Date:8 May 2013
Reviewer: Osamu Goto
Reviewer's report:
This is a retrospective study regarding influential factors in patients taking
antithrombotic agents (A group) on bleeding after gastric endoscopic submucosal
dissection (ESD). Although the purpose of this study would be important, it
seems that the composition of this manuscript may make readers confused and
the results are overestimated. The followings should be taken into consideration.
Major Compulsory Revisions
1. This study seems to be mainly aimed not to compare post-ESD bleeding rate
between the A group and the non-antithrombotic (NA) group, but to elucidate the
causal factors on post-ESD bleeding in the A group by comparing the bleeding
patients to the non-bleeding patients. Accordingly, Table 2 and 3 would be more
relevant than Table 1. To avoid the confusion, the authors should focus on the
main purpose, and clearly describe the main aim in the Background section and
the main outcome measure in the Methods section.
2. The abbreviated terms, “the A group” and “the NA group” are unnecessary. If
the authors create groups in this study, the patients having antithrombotic agents
should be divided into 2 groups, Bleeding group and Non-bleeding group.
3. The study design should be clearly stated. If my interpretation is right, this
should be a retrospective case-control study with consecutive data.
4. In the multivariate analysis, PPI with gastroprotective agent was not a
statistically-significant influential factor on post-ESD bleeding in the
antithrombotic users (p = 0.054). Therefore, the authors cannot conclude that it is
useful to prevent post-ESD bleeding.
5. Similarly, duration of ESD was a statistically-significant influential factor in the
analysis. The authors should mention it at least in the Discussion section.
6. Gastroprotective agent varies. The authors did not mention the details of
gastroprotective agents which had been administered to the patients. It is
overestimated to insist on its efficacy only by this study.
7. I wonder why post-ESD bleeding within Day 2 was not taken into consideration
in the analysis. The authors should make a comment of that reason.
Minor Essential Revisions
1. The number of references is inaccurate.
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.