JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/1471-230X-11-143 (2011)

Reviewer's report
Title:Comparison of percutaneous radiofrequency thermal ablation and surgical
resection for small hepatocellular carcinoma
Version: 2Date:5 October 2011
Reviewer: Alfredo Guglielmi
Reviewer's report:
This is a retrospective analysis of 231 patients with small HCC treated by either
liver resection (SR) or percutaneous radiofrequency thermal ablation therapy
(PRFA).
The study addresses an important topic that is particularly relevant in the context
of the increasing incidence of viral hepatitis, cirrhosis and HCC. Several
retrospective study had been already published in this field and importantly three
RCT had been recently published.
Several criticism must be underline:
1. In the methods the two groups of patients have significant differences in
sample size.
The Authors had to specify the criteria to assign patients to the two different
treatments.
and why they excluded to PRFA 35 patients with chronic hepatitis and without
cirrhosis and included in the analysis three patients with Child Pugh C cirrhosis.
The Authors should revise the selection criteria for this study selecting more
precisely the two groups of patients .
2. In the methods the diagnosis of HCC should be done according to the
international guidelines.
Why they use the angiography, that is not recommended in all recent guidelines?
3. In the methods the assessment of complete necrosis after PRFA is made after
1 week. Several clinical and experimental studies demonstrated that this
assessment should be done after 4 weeks to avoid inflammatory perilesional
alterations that can alter the accuracy of CT evaluation. Why they do not apply
this recommendations ?
5. In the results survival and DFS should be reported also as median values. We
suggest performing, if possible, subgroup analysis according to the different
Child Pugh classes or the presence of LC.
6. In the DFS analysis the Authors should specify the local recurrence rate in the
two different groups
Level of interest: An article of limited interest
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-11-143 (2011)

Reviewer's report
Title:Comparison of percutaneous radiofrequency thermal ablation and surgical
resection for small hepatocellular carcinoma
Version: 3Date:25 November 2011
Reviewer: Martin Bodingbauer
Reviewer's report:
The manuscript is fully reviewed and good for publication now.
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-11-143 (2011)

Reviewer's report
Title:Comparison of percutaneous radiofrequency thermal ablation and surgical
resection for small hepatocellular carcinoma
Version: 3Date:13 December 2011
Reviewer: Alfredo Guglielmi
Reviewer's report:
Even if the main bias of the paper remains the retrospective non randomized
study design that can alter the results statistical analysis . The Authors answered
to all the major issue that had been raised and significantly improved the quality
of the manuscript.
Level of interest: An article of limited interest
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-11-142 (2011)

Reviewer's report
Title:Arsenic, vinyl chloride, viral hepatitis, and hepatic angiosarcoma: A
hospital-based study and review of literature in Taiwan
Version: 3Date:12 August 2011
Reviewer: Steven Lamm
Reviewer's report:
Review:
This paper is worthy of publication. It succeeds in doubling the detailed case
report numbers for HAS from Taiwan and thus makes a contribution. Major
interest in HAS was thirty years ago and subsequently case series have been
infrequent. This paper is of importance since the authors have sought histories of
the three causes of HAS was demonstrated thirty years ago and have found
none for either arsenic or VCM. This suggests that the exposure controls that
have been subsequently introduced have been effective. This is important
information. The quality of written English is quite satisfactory.
There are a few errors in the statistical presentation that should be corrected.
>0.95 should be reported as 1.00 in Tables 2 and 3. In Table 2, the p-value for
pathology and for hepatitis should be 1.00. The statistical comparison is between
the 6 male and the 3 female cases, which allows statistical significance only in
the extremes (exposures of 5 or 6 vs 0). I would suggest a comparison between
these
9 cases and the previously published 9 cases. The one potentially causal
exposure that is noted here is HCV as 2 of the 9 cases have such a history. It
may be feasible to compare whether the frequencies of the viral hepatitis and of
the medical conditions are greater than would be age expected. These rates
could also be compared with the rest of the literature.
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-11-142 (2011)

Reviewer's report
Title:Arsenic, vinyl chloride, viral hepatitis, and hepatic angiosarcoma: A
hospital-based study and review of literature in Taiwan
Version: 3Date:22 August 2011
Reviewer: laura rozek
Reviewer's report:
This manuscript is a description of cases of hepatic angiosarcoma in Taiwan.
Cases at a single hospital were reviewed to evaluate the roles of vinyl chloride
monomer, arsenic and viral hepatitis. A literature review was conducted and
included all patients of hepatic angiosarcoma reported in Taiwan. Cases
descriptions were provided for nine cases over a ten year period from the
hospital, and an additional nine cases identified in the literature. The conclusions
are that hepatic angiosarcoma are rare and not explained by exposure to
hepatitis, arsenic or vinyl choloride monomer. This manuscript is limited in that
the exposure history was collected through evaluation of medical records and
through literature case report, with no information provided on completeness of
records or comparativeness of data between hospital records and published
reports. The number of cases is too small to draw any epidemiologic conclusions.
Thus, the findings are inconclusive at best.
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 no competing interests
Review for 10.1186/1471-230X-11-142 (2011)

Reviewer's report
Title:Arsenic, vinyl chloride, viral hepatitis, and hepatic angiosarcoma: A
hospital-based study and review of literature in Taiwan
Version: 5Date:2 November 2011
Reviewer: Steven Lamm
Reviewer's report:
There are a few errors in the references that should be corrected.
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, although I do have a long
professional career in assessing cancer risk from arsenic exposure.
Review for 10.1186/1471-230X-11-141 (2011)

Reviewer's report
Title:Association between Helicobacter pylori cagA-related genes and clinical
outcomes in Colombia and Japan
Version: 2Date:15 August 2011
Reviewer: Hossein Dabiri
Reviewer's report:
- Major Compulsory Revisions
There is no need to major revision.
- Minor Essential Revisions
1- Page 6, line 6: each deoxynucleotide concentration must be written in
millimolar not Micro liter (µL)
2- Page 6, line 8: regarding the product size of used primers are short ( table 1),
thereby the PCR program as 30 cycles; 5 min at 94°C, 30 sec and 5 min at 72°C
seems uncommon and must be checked.
3-page 6 and 7: In some cases, the standard material sources addressing
(company, county) is not considered as the name of country is missed.
4- In case of table 2, since the references of selected genes have given in the
context, the table2 is no longer mandatory.
5- In case of the table 4 and 5, P value should be calculated for each row.
6- Page 9, paragraph2, in result section under subtitle of “The association
between candidate genes and clinical outcomes” only two genes (jhp0045,
jhp0046) of four studied genes (hp0967, jhp0045, jhp0046 and jhp0951) have
been considered.
7- Page 9, under subtitle of “The association between candidate genes and
clinical outcomes”: it is better to present each country result separately and more
clearly.
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.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-11-141 (2011)

Reviewer's report
Title:Association between Helicobacter pylori cagA-related genes and clinical
outcomes in Colombia and Japan
Version: 2Date:1 September 2011
Reviewer: Alex Boussioutas
Reviewer's report:
This is a correlation study that reports an association between certain H. pylori
genes and Gastric Cancer in a subpopulation of Columbian patients. The authors
selected genes from previous microarray experiments that were correlated with
cagA status and used a subgroup of these genes to assess expression of those
genes in different patient pathologies in Columbian and Japanese cohorts.
I have a number of questions regarding the manuscript.
Major compulsory revisions
1. This addresses virulence factors in the bacteria but the complex interplay
between host and pathogen are not really addressed in this analysis. Were the
populations studied tested for established host polymorphisms that increase the
risk of GC (eg IL-1R)?
2. I have an issue with the methodology used for selection of genes. Microarray
analyses involving correlations require correction for multiple testing. The p
values reported here do not appear to be corrected for multiple testing. This
would reduce some of the significance of the genes reported as correlated to
cagA status. If you perform appropriate multiple testing correction do these
genes still reach significance?
3. I think it is insufficient to perform a multivariate analysis of age and gender for
risk of GC in these populations. There are other risk factors that could be
incorporated that are more relevant for risk of GC (see question 1).
4. It would be relevant to ascertain whether other established H. pylori genetic
markers of risk as mentioned in the manuscript are also relevant to risk in these
cohorts. The results would serve as a positive control if they indeed correlated as
the authors suggest they would.
5. This study seems to investigate presence of genes, however gene expression
would be more relevant. Does the level of expression of the genes being studied
have biologically significant expression differences? There is no data presented
about fold change of gene expression only that there was negative or positive
association with cagA status. Whereas a correlation may be statistically
significant between genes the expression difference may be marginally different
and hence have little biological meaning.
Minor essential revisions
6. There are a number of grammatical errors throughout the manuscript that
would need to be addressed
Level of interest: An article of limited interest
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-11-141 (2011)

Reviewer's report
Title:Association between Helicobacter pylori cagA-related genes and clinical
outcomes in Colombia and Japan
Version: 2Date:1 September 2011
Reviewer: Elina Spina
Reviewer's report:
No comments
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-11-141 (2011)

Reviewer's report
Title:Association between Helicobacter pylori cagA-related genes and clinical
outcomes in Colombia and Japan
Version: 2Date:4 October 2011
Reviewer: Richard Ferrero
Reviewer's report:
General comments:
Watada and colleagues have investigated correlations between novel candidate
virulence genes with cagA, a marker of more virulent Helicobacter pylori strains,
and the association of these novel genes with clinical outcomes in Columbian
and Japanese populations. From previous microarray studies, the authors
identified nine genes as being significantly correlated with the presence of cagA;
they selected four of these for examination in 177 Colombian and 169 Japanese
H. pylori strains. The key finding of the work was the identification of two genes
(jhp0045 and jhp0046) as markers for gastric cancer in cagA-positive cases in
Colombia, but not for cases of gastric cancer in Japan. Although this is a
relatively modest observation it does illustrate the limitations of using
cagA-positivity alone as a predictor for more severe forms of H. pylori-associated
disease. Furthermore, the work identifies additional bacterial factors that may be
important as promoters of gastric carcinogenesis and also demonstrates how the
etiology of this disease may vary between different human populations. The
authors need to address the specific comments below.
Major compulsory revisions:
None
Minor essential revisions:
1) (Throughout) The manuscript needs to be edited by a native English speaker.
2) (pg 8) The authors should give as much information as possible on the
different genes/ORFs i.e. Are these conserved hypothetical genes? In which of
the sequenced H. pylori genomes are these genes found? The authors also need
to address why they investigated two of the ORFs (jhp0967 and jhp0951), which
are associated with duodenal ulcer (DU) disease, when it is commonly accepted
that DU and gastric cancer are mutually exclusive diseases.
3) (pg 23) From “eye balling” of the numbers, it seems surprising that there is a
significant association between the carriage of jhp0045 and jhp0046 in H. pylori
strains and gastric cancer development (32.6% and 37%, respectively) when
compared with gastritis (11.4% and 18.2%, respectively), yet there is no
association with duodenal ulcer disease (28.6% and 28.6%, respectively).
Discretionary revisions:
4) (pg 20) What are PZ1 and PZ2?
5) (Tables 3 and 4) For consistency, the data in the two tables should be
presented in the same order. i. e. Japanese strains then those from Columbia.
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-11-140 (2011)

Reviewer's report
Title:Postprandial fullness correlates with gastric barium excretion but not with
chronic gastritis.
Version: 2Date:30 September 2011
Reviewer: Hiroaki Zai
Reviewer's report:
Comments:
The description of study design and methodology has generally been improved in
this resubmitted manuscript. The central finding of the paper remains intriguing,
but the point of an argument still remain to be clarified.
Major Compulsory Revisions
1 The opening two paragraphs of the background (p. 5) are not directly relevant
to the study, and could be edited considerably. Because this study was
performed in healthy subjects.
2 The title of manuscript is inappropriate. It is ambiguous which result of “gastric
barium excretion” correlates with postprandial fullness.
3 The methodology of this study could not describe the gastrointestinal motor
function. This study merely shows that some category of X-ray imaging after
injection of spasmolytic agent correlate with postprandial fullness. The 2nd and
3rd paragraph (p. 12-13) of discussion could be edited considerably.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Review for 10.1186/1471-230X-11-140 (2011)

Reviewer's report
Title:Postprandial fullness correlates with gastric barium excretion but not with
chronic gastritis.
Version: 2Date:18 November 2011
Reviewer: Greger Lindberg
Reviewer's report:
The authors have studied barium meal findings and their relation to reported
symptoms from a group of apparently healthy persons who have undergone a
routine medical check-up at a Japanese steel company. In order to understand
the merits of this study it is necessary to think a little about the experimental
set-up. Barium meal with a spasmolytic agent is presumably done to increase the
likelihood of detecting gastric cancer. This is how I interpret the multitude of
projections for the barium meal. I don't think that this technique has been applied
for the study of functional disturbances in the upper gut before. However, it does
allow the radiologist to determine with good sensitivity and specificity the
presence or absence of chronic gastritis (refs 9 & 10). The position of the head of
a barium meal is more difficult to interpret and I don't think there is data to show
that the head of barium has any clear relation with gastric emptying as assessed
by scintigraphy or breath testing. However, I think the position of the head of
barium during a barium meal examination might be an indicator of an underlying
mechanism that could be involved in the pathogenesis, or be an indicator of
post-prandial fullness. This is highly speculative but for example an
open-standing pylorus might represent a corresponding endoscopic finding or the
group with rapid filling of the duodenum could be similar to those with an early
rapid gastric emptying reported by Delgado-Aros et al. (ref 23). In all, I think this
study reports new information about a symptom that is quite common but still
puzzles us as to its underlying pathophysiology. If I were to give an advice to the
authors it would be to try to avoid mirroring their findings with findings from other
techniques, i.e. the head of the barium meal does not mirror gastric emptying at
least not that of solid food. I think this confuses the reader.
Now to the points raised by dr Sadik in his primary verdict on this manuscript.
#1. Not met, but the authors should not report the position of the head of barium
as a measure of gastric emptying, as long as the latter term has universal
acceptance for another finding using another technique.
#2 Adequately met (refs 9 & 10)
#3 Adequately met (builds on a validated questionnaire)
#4 Adequately explained, could be amended by informing the reader about the
reason for including barium meal using this technique in a routine medical
check-up.
#5 Adequately met.
Level of interest: An article whose findings are important to those with closely
related research interests
Review for 10.1186/1471-230X-11-139 (2011)

Reviewer's report
Title:Cerebral Air Embolism as a Complication of Peptic Ulcer in the Gastric
Tube: Case report
Version: 1Date:18 September 2011
Reviewer: Patrick Yachimski
Reviewer's report:
The authors present a case report of cerebral air embolism due to a perforated
gastric conduit ulcer into the pulmonary vein. This is an unusual presentation of a
devastating (and ultimately fatal) clinical problem in a patient with surgically
altered anatomy.
The report is described in clear and concise fashion, and the manuscript reads
easily.
I would recommend these minor revisions:
1) Case presentation: not sure how the elevated C-reactive protein is helpful in
diagnosis or management, this detail can be omitted from the manuscript
2) The ulcer is described as a UL-IV ulcer--not all readers may be familiar with
this classification, so this needs to be described in detail.
3) Not sure why the CD34 immunostaining is important--wasn't penetration of the
ulcer into the pulmonary vein already evident?
4) Conclusion: the recommendation of endoscopic surveillance and PPI
treatment for peptic ulcers is certainly reasonable, but I'm not convinced that this
conclusion is supported by your manuscript--a more appropriate conclusion,
based on the presented case, might be something like: "Cerebral air embolism is
a rare complication of penetrating gastric ulcer, but should be considered in
patients with a history of esophagectomy with gastric conduit and who presented
with acute neurologic findings."
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-11-139 (2011)

Reviewer's report
Title:Cerebral Air Embolism as a Complication of Peptic Ulcer in the Gastric
Tube: Case report
Version: 1Date:2 October 2011
Reviewer: Keith L Obstein
Reviewer's report:
This manuscript represents a case report of a cerebral air embolism likely
secondary to an ulcer in the surgically created gastric tube 8 years after subtotal
esophagectomy for squamous cell carcinoma of the esophagus. Background
information was presented, followed by clinical details of the case (including
imaging studies and pathology).
Major Compulsory Revisions:
(1) There have been several reports in the medical literature of cerebral gas
embolism (in patients who have a gastric tube) after esophagetomy. While there
are no apparent reports of this complication being directly secondary to
spontaneous perforation of a gastric tube ulcer, I would recommend that the
reference list in this case report be updated and that more recent publications be
cited (i.e. ter Laan M, Totte E, van Hulst RA, et al. Cerebral gas embolism due to
upper gastrointestinal endoscopy. Eur J Gastroenterol Hepatol. 2009
Jul;21(7):833-5.)
(2) Conclusion, first sentence, "...postoperative endoscopic surveillance should
be conducted regularly." Regular postoperative endoscopic surveillance is
currently being actively debated. If this is not the current standard of care, I would
re-phrase the sentence to state "...postoperative endoscopic surveillance should
be considered based on the risk-benefit profile and clinical symptoms of each
individual patient."
Minor Essential Revisions:
(1) The figures in this .pdf created for the peer-review process are currently
labeled as Figure 1, Figure 2, Figure 3, and Figure 4. Figure 2 includes a "b" in
the lower left hand corner; Figure 3 includes an "a" in the lower left hand corner;
and Figure 4 includes a "b" in the lower left hand corner. While it is clear after
reading the Figure Legends section of the manuscript that Figure 1 is actually
both the current Figure 1 and Figure 2; and that Figure 2 is actually both the
current Figure 3 and Figure 4; this will need to be fixed as appropriate and
confirmed as correct in the edited article proof.
Discretionary Revisions:
(1) Case-presentation, 4th sentence. "Laboratory studies revealed elevated
C-reactive protein..." Would consider deleting "elevated C-reactive protein" and
instead include information on the white blood cell count (WBC) and Lactic Acid
(if performed).
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-11-138 (2011)

Reviewer's report
Title:Transcript levels of Toll-like receptors 5, 8 and 9 correlate with
inflammatory activity in Ulcerative Colitis
Version: 3Date:22 January 2011
Reviewer: Mathias Chamaillard
Reviewer's report:
The manuscript by Sánchez-Muñoz et al showed a significant correlation
between disease activity and colonic expression of TLR5, TLR8 and TLR9
mRNA levels in Ulcerative colitis. The findings are consistent with previous
reports showing an increased expression of the latter pattern recognition
receptors in active disease (Int J Colorectal Dis. 2007 Mar;22(3):293-301; Scand
J Gastroenterol. 2009;44(2):195-204; Inflamm Bowel Dis. 2010
Aug;16(8):1267-8). The manuscript is well written and easy to follow. However, it
lacks an in-depth functional analysis to assess the relevance of the expression
changes of TLR5, TLR8 and TLR9 on disease pathogenesis. Whereas the
methodology used in this study is adequate, here are some suggestions that, I
think, need to be considered :
- Is there any abnormal responsiveness to TLR5, TLR8 and TLR9 agonists of
colonocytes from UC patients with quiescent disease?
- Is there any influence of the therapeutical management of the UC patients on
changes of TLR5, TLR8 and TLR9 transcript levels?
Specific comments:
- In the abstract, the authors wrote that 50 UC patients were included in their
study while in the methods section they mentioned that rectum biospies were
collected from 60 UC patients. This is confusing.
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 no competing interests
Review for 10.1186/1471-230X-11-138 (2011)

Reviewer's report
Title:Transcript levels of Toll-like receptors 5, 8 and 9 correlate with
inflammatory activity in Ulcerative Colitis
Version: 3Date:3 February 2011
Reviewer: Ingrid Arijs
Reviewer's report:
The manuscript by Sanchez-Munoz et al. has investigated the toll-like receptors
(TLRs) mRNA expression in colonic mucosal biopsies from 51 UC patients and
33 controls.
The manuscript is sloppy and not clearly written, e.g.:
- The number of the studied patients are different in the text and the table
- Please put all the p-values between brackets.
- Please write the references according to the instructions of the journal.
- The mentioned authors in the text are not correctly written or are not the same
as in the references (e.g. Steenholdt, Stanislawowski,)
- Written errors: please check the whole text, e.g. Spearman instead of Sperman,
assess instead of assess’, TOLLIP instead of Toll on page 6, chemokines instead
of chemokine’s.
- Check the comma’s and points (the authors forgot a point between Smirnoff
and Differences under the paragraph ‘Analysis’ in the methods section) in the
text, and the construction of some sentences (some are too long and some are
not correct, e.g. first sentence on page 4: ‘demonstrated TO BE important’)
- Human gene symbols need to be written in italic
- The text of the methods is not clearly written, especially the qPCR text and
analysis text
- The figures are not clear: please add what the x-axis and the y-axis are
showing.
- Please give the reason of the endoscopy of the controls
- Please add medication and disease activity (riley scores) in table 1
- In table 1, the values of age are median and interquartile range?
- In the introduction test, the sentence ‘Most studies in IBD have focused only in
TLR2, TLR3 and TLR4, but other TLRs expression has not been extensively
explored in the colonic mucosa form UC patients’ is mentioned twice.
- Disease is missing in Crohn’s disease on page 3 in second alinea.
- In the discussion, the reference of Cario is missing in the text
- Besides the figures, please make a table of the qPCR results showing the
p-values of the comparisons of TLRs between the different groups.
It is a descriptive manuscript that might show interesting data of TLR transcript
expression in UC. It would be a good research manuscript after thorough
rewriting the text. Furthermore, it would be nice to confirm the results on protein
level and in an independent cohort.
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-11-138 (2011)

Reviewer's report
Title:Transcript levels of Toll-like receptors 5, 8 and 9 correlate with
inflammatory activity in Ulcerative Colitis
Version: 4Date:22 March 2011
Reviewer: Mathias Chamaillard
Reviewer's report:
The authors have now adressed most of the minor comments on the text, but a
confirmation at the protein level of any changes in TLR expression is still lacking.
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-11-138 (2011)

Reviewer's report
Title:Transcript levels of Toll-like receptors 5, 8 and 9 correlate with
inflammatory activity in Ulcerative Colitis
Version: 6Date:5 November 2011
Reviewer: Mathias Chamaillard
Reviewer's report:
This version of the manuscript has been greatly improved. The authors have
done a nice job by addressing most of the comments and adding supporting
additional data.
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 have no competing interests to declare.
Review for 10.1186/1471-230X-11-137 (2011)

Reviewer's report
Title:A randomised Controlled Trial on hypnotherapy for Irritable Bowel
Syndrome; design and methodological challenges (The IMAGINE study)
Version: 1Date:7 November 2011
Reviewer: Michael Farthing
Reviewer's report:
1. Will the study design adequately test the hypothesis? Yes
2. Are sufficient details provided to allow replication of the work or comparison
with related analyses: if not, what is missing? Yes
3.Is the planned statistical analysis appropriate? Yes
4.Is the writing acceptable?Yes
Review for 10.1186/1471-230X-11-136 (2011)

Reviewer's report
Title:Clinical benefit of gluten-free diet in screen-detected older celiac disease
patients
Version: 3Date:10 November 2011
Reviewer: Geoffrey Holmes
Reviewer's report:
Coeliac disease is being increasingly diagnosed in the elderly and in this report
the authors provide useful information on 35 coeliac patients uncovered by
screening. They show that this is worthwhile,for the patients benefitted from a
gluten free diet as judged by a number of different parameters.
They also draw attention to the importnat fact that in this group there are pointers
to the presence of coeliac disease e.g. a family history, subtle symptoms,
previous low impact fractures, that are often missed and in this grop 29 of the 35
patients would have been diagnosed if these features had been taken into
account without screening. They do not advocate mass screening which would
entail huge logistical problems but do recommend rigorous case finding in the
elderly who are an at-risk group. Most gastroenterologicsts would concur with
this strategy.
I have some comments.
Minor essential revisions.
1. In the Abstract it is stated dietary complicance was good. This is supported by
statements on page 13 and on page 5 it is said the patients saw a dietician and a
gastroenterologist but there are no details given. This is a crucial aspect of the
study and I think readers would like more information on this aspect of the work.
How was compliance assessed clinically? What were the criteria for good
complicance? how many patients were judged to be strict and how many lax on
the GFD? There is still a view, widely held, that elderly patients cannot manage a
GFD or that dietary habits in the elderly are difficul to change.
2. In the Methods section - stored at 20C; should be stored at -20C.
3. In the Discussion page 13, line 11 - delete which is.
4. The Legend for Table 3 is misleading because some of the patients, as
pointed out in the text on page 10, received not only a GFD but also
supplements. I think the legend should also point this out and refer back to page
10.
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 conflicting interests.
Review for 10.1186/1471-230X-11-135 (2011)

Reviewer's report
Title:Endoscopic diagnosis of early gastric cancer and precancerous lesion
Version: 1Date:7 October 2011
Reviewer: Philip Le Page
Reviewer's report:
Major Comulsory revisions:
- The Method does not address the Aim of the study. The Aim is stated to
"compare the accuracy and sensitivity of magnifying chromoendoscopy, NBI with
conventional endoscopy for diagnosis of precancerous lesions and early gastric
cancer". The Method is for the observers the subjectively score the image
qualities. A Poor or a Good Image quality does not mean the "accuracy or
sensitivity is different". In fact no Data is given on these 2 findings. In this study it
appears all methods, included conventioanl endoscopy, had 100% sensitivity! (as
only those with confirmed lesions on histo were included). So the Method does
not address the Aim and hence detracts from the validity of the Results.
- The only conclusions of the results from the utilised method are that the image
quality is superior for the 2 new technologies. Yet Observer bias in the discussion
is not noted, and should be discussed as a source of bias....One may extrapolate
that these new technologies may improve sensitivity and accuracy, but there is
no evidence in their scientific data for that here.
- The numbers are also inconsistent. The abstract states 142 patients but the
Body states 122 patients.
- A flow chart would be useful here to show what actually happened. It appears
Included patients were those that already had conventional then NBI/Mag
imaging and HAD Histo confirming a lesion. But were there patients that had a
lesion on conventional endoscopy but not on the other 2 methods and no lesion
found on histo??? If so this would address accuracy issues. Also, categorically
did these patients not have any biospies after their inital endoscopy finding a
lesion?
Minor Essential Revisions:
- Labelling on figure 1 - Photos not marked A/B/C/D
- Abstract states is retropective study but main body states is prospective study
(again in Background of main body states is retrospective). This needs to be
clarified.
Discretionary Revisions:
- They could talk about potential problems of over sensitivity (Reduced
specificity)
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-11-134 (2011)

Reviewer's report
Title:A capillary blood ammonia bedside test following glutamine load to improve
the diagnosis of hepatic encephalopathy in cirrhosis
Version: 1Date:2 August 2011
Reviewer: Giovanni Tarantino
Reviewer's report:
Minor Essential Revisions
AA are kindly requested to re-phrase the sentence in Introduction ...Neurologic
alterations observed....in response to liver insufficiency and portosystemic
collaterals... because my research (the 7th reference) has hardly evidenced a
correlation between NH4 and porto-systemic encephalopaty (PSE)..... in the
text......Ammonia levels did not predict severity of PSE measured as W-H grades,
i.e., coefficient = 5.04, beta = 0.088, p = 0.28. Furthermore, AA should
emphasize that high venous concentrations of NH4 are a marker of collaterals
presence and not of PSE presence or severity, according to the previously
quoted sudy.
Results
AA have declared to have studied the NH4 changes over time by ANOVA, so
they are kindly requested to show pertinent data, also in a reduced or partial
population.
They have evidenced only the incidence of further episodes of hepatic
encephalopathy (HE) in their follow-up.
Discussion
AA are kindly requested to add among additional parameters that may influence
the minimal HE also the viral factor ..see and quote...Citro V, Milan G, Tripodi FS,
Gennari A, Sorrentino P, Gallotta G, Postiglione A, Tarantino G.
Mental status impairment in patients with West Haven grade zero hepatic
encephalopathy: the role of HCV infection. J Gastroenterol. 2007
Jan;42(1):79-82.
AA are strongly advised to be more direct in lessening the importance of NH4
determinations as valid tool to diagnose HE
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-11-134 (2011)

Reviewer's report
Title:A capillary blood ammonia bedside test following glutamine load to improve
the diagnosis of hepatic encephalopathy in cirrhosis
Version: 2Date:17 October 2011
Reviewer: Giovanni Tarantino
Reviewer's report:
No comment.
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-11-134 (2011)

Reviewer's report
Title:A capillary blood ammonia bedside test following glutamine load to improve
the diagnosis of hepatic encephalopathy in cirrhosis
Version: 2Date:20 October 2011
Reviewer: Debbie Shawcross
Reviewer's report:
Thank you for taking my comments on board which have improved the quality of
the manuscript.
I have just a couple of very minor suggestions that will further improve the
manuscript quality:
Can you please also add the specific number of controls and patients that Table
2 and Figure 2 pertain to into the table/figure legends as you have done for
Figure 3. For example adding n=... in brackets.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
'I declare that I have no competing interests'
Review for 10.1186/1471-230X-11-133 (2011)

Reviewer's report
Title:The MLH1 2101C>A (Q701K) variation is related to risk of gastric cancer in
Chinese males
Version: 1Date:21 September 2010
Reviewer: Karsten Schulmann
Reviewer's report:
The manuscript entitled „The MLH1 2101C>A (Q701K) variation is related to risk
of gastric cancer in Chinese males“ by Zhi et al. Reports on data of MLH1
germline mutations in unselected 236 gastric cancer patients from two institutions
in China and 240 matched controls.
They found six MLH1 sequence variants among 236 cases. No mutation was an
obvious pathogenic germline mutation (frameshift, nonsense, splice site
mutation, exon deletion). Five sequence variants were not associated with an
increased (or decreased) gastric cancer risk compared to controls.
The 2101C>A mutation was not associated with an increased gastric cancer risk
overall; however in the subgroup of males they identified an increased gastric
cancer risk (OR 8.42 (95% CI 1.04-68.06) with a moderate significance level of
p= 0.041. This correlation was not observed in females. In addition, they reported
a correlation with younger age; however this finding was not significant.
The 2101C>A mutation was scored as tolerant using SIFT score which supports
not an altered protein function.
Major points:
The section regarding the exon splicing of the 2101C>A mutation within the
results is not understandable since the results and terms were not introduced in
the method section. As far as the reviewer was able to conclude findings suggest
an influence on the splicing effect of exon 18.
The study design is adequate. However the conclusion must be drawn very
carefully. The findings regarding 2101C>A should be replicated in an
independent set of gastric cancer samples (perhaps exclusively males). In
addition impaired splicing should be investigated analyzing RNA transcripts.
Third, the cancer of the patient should be analyzed for MSI and MMR protein
expression by immunohistochemistry.
Minor points:
The authors state that the polymorphism c. -28 A>G has been so far reported
exclusively in the Chinese population. However, the InSight database has a total
of five entries of this mutation; one was the referenced paper from China;
however there were 4 more non-Asian entries between 2001 and 2008 of this
mutation.
In addition, the manuscript was written by non-native speakers and a revised
manuscript needs significant editing by a native speaker.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Review for 10.1186/1471-230X-11-133 (2011)

Reviewer's report
Title:The MLH1 2101C>A (Q701K) variation is related to risk of gastric cancer in
Chinese males
Version: 1Date:23 November 2010
Reviewer: TL Chan
Reviewer's report:
Current manuscript described the mutation spectrum of MLH1 in the cohort of
Chinese patients developed gastric cancer. The authors identified six mutations
including 2 in the promoter region and 4 in the coding region. However, none of
them shows direct evidence of pathogenic mutation. The association of MLH1
2101C>A and gastric cancer has been proposed although the authors did not
provide explanation for MLH1 2101 C>A that only affect a specific age group.
Specific comments:
1) The authors did not state clearly why MLH1 gene is selected and examined.
Even MLH1 was selected, it is not clear immunohistochemistry/MSI test, which
are effective screening step in colorectal cancer associated with MMR genes
defect, was not adopted as a preliminary screening strategy.
2) The background of MLH1 methylation should be addressed and it is, in fact,
one of the publication of Yap.
3) The correlation of mutation and family history of gastric cancer of the patient
should be provided.
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-11-133 (2011)

Reviewer's report
Title:The MLH1 2101C>A (Q701K) variation is related to risk of gastric cancer in
Chinese males
Version: 2Date:21 January 2011
Reviewer: Karsten Schulmann
Reviewer's report:
Comment to revised manuscript entitled „The MLH1 2101C>A (Q701K) variation
is related to risk of gastric cancer in Chinese males“ by Zhi et al.
All my issues from the initial review were successfully addressed and I have no
further comments on the text.
However, I am not happy with the added photography of MLH1 staining. As far
as I can recognize smooth muscle cells and lymphocytes are not stained as well
which is quite unusual.
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-11-133 (2011)

Reviewer's report
Title:The MLH1 2101C>A (Q701K) variation is related to risk of gastric cancer in
Chinese males
Version: 2Date:25 February 2011
Reviewer: TL Chan
Reviewer's report:
Can the authors clarify the loss of clinical classification of the 74 cases? It is not
align with the statement in method and materials that the cancers were reviewed
by histological method. It is more appropriate that the author should avoid using
the term "marginally significant/associated". "A trend was observed" is more
appropriate. Overall, the authors have already addressed all questions.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-11-133 (2011)

Reviewer's report
Title:The MLH1 2101C>A (Q701K) variation is related to risk of gastric cancer in
Chinese males
Version: 3Date:4 October 2011
Reviewer: Eugenia Flores
Reviewer's report:
The authors have incorporated the corrections to the original document and
properly justified when it was not possible to make changes. Although I have one
last observation, in the abstract document authors should be more careful when
making the following statement on the results: Compared with the MLH1 2101CC
genotype, the 2101CA genotype was associated with a significantly elevated risk
of gastric cancer (OR=8.42, 95% CI =1.04-68.06) in males. Although the
association is significant, is weak, and there is loss in statistical efficiency by a
decrease of n to gender stratification, and possibly will be a biased estimator. I
suggest removing the term significantly elevated.
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