JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/1471-230X-13-44 (2013)

Reviewer's report
Title:Linear Echoendoscope-Guided ERCP for the Diagnosis of Occult Common
Bile Duct Stone
Version: 1Date:9 September 2012
Reviewer: Werner Hartwig
Reviewer's report:
The study by Hoi-Hung Chan et al. is a prospective observational study in that
linear endoscopic ultrasound was assessed in 30 patients with clinical suspicion
of common bile duct stones. Sensitivity and specificity rates as well as adverse
effects of linear EUS are provided. The issue of the study is not new, and the
study has some flaws which need clarification:
Major Compulsory Revisions:
1. As it has been demonstrated by several studies before, EUS is well
established in several centers in the evaluation of patients with suspected bile
duct stones. This is true for radial (several randomized studies that compared
EUS with ERCP for detection of CBD stones) as well as linear EUS (e.g. Kohut
et al, World J Gastroenterol 2003 or Endoscopy 2002). It is unclear to the
reviewer: what are the real new findings of the study? Please discuss.
2. There is no “gold standard” for the detection of CBD stones in the study. Since
ERCP has been only performed in EUS CBD-stone positive patients and
follow-up of patients has in parts been done by telephone only, the rate of false
negative findings may be underestimated. Another shortcoming of the study is
that EUS and ERCP have been performed by the same investigator and no
blinding has been performed. The authors should include a paragraph in the
discussion where the shortcomings of the study are detailed.
3. Diagnostic studies should also provide data about positive and negative
predicted values. Please provide data.
4. In the discussion, the authors tend to neglect possible disadvantages of EUS,
e.g. the invasiveness of EUS compared to MRCP. Why do the authors think that
MRCP needs more manpower as compared to invasive EUS?
5. No abstract has been available to the reviewer. Please provide.
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:
no cometing interests
Review for 10.1186/1471-230X-13-44 (2013)

Reviewer's report
Title:Linear Echoendoscope-Guided ERCP for the Diagnosis of Occult Common
Bile Duct Stone
Version: 1Date:25 September 2012
Reviewer: Martin Freeman
Reviewer's report:
Important study
Minor points
In introducion, It has been shown that the rate of post-ERCP pancreatitis may be
as high as 15.1%, which
includes 1% of patients graded as severe in degree.[9] (THIS IS IN HIGH RISK
PATIENTS WITH SUSPECTED SPHINCTER OF ODDI DYSFUNCTION, NOT
BILE DUCT STONES. SHOULD ADD STATEMENT TO THAT EFFECT
Moreover, the diagnostic rate is
dramatically reduced for smaller CBD stones (#5 mm). [13] PLEASE STATE THE
RATE.
In Methods section, need to state "GOLD STANDARD" for TRUTH STANDARD
for definition of bile duct stone. What was considered true positive, true negative,
false positive and false negative? Was ERCP truth standard? If so what?
Need to calculate positive and negative predictive values in addition to sensitivity
and specificity
Is this appropriate? Stones seen at EUS can easily be missed by
cholangiography and even balloon extraction.
Otherwise worthwhile paper.
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 have no competing interests
Review for 10.1186/1471-230X-13-44 (2013)

Reviewer's report
Title:Linear Echoendoscope-Guided ERCP for the Diagnosis of Occult Common
Bile Duct Stones
Version: 4Date:28 November 2012
Reviewer: Werner Hartwig
Reviewer's report:
The authors adequately adressed the comments of the reviewer and changed
the manuscript accordingly.
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-13-44 (2013)

Reviewer's report
Title:Linear Echoendoscope-Guided ERCP for the Diagnosis of Occult Common
Bile Duct Stones
Version: 4Date:21 December 2012
Reviewer: Hjalmar van Santvoort
Reviewer's report:
The authors have provided good answers to the points raised in my previous
review. However, not all answers (especially when requesting additional data)
have also been added in some form to the revised paper. Please go through your
rebuttal once more and revise the paper accordingly, so the future reader will not
have the same questions as I did.
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-13-42 (2013)

Reviewer's report
Title:Microscopic polyangiitis complicated with ileal involvement detected by
double-balloon endoscopy: a case report
Version: 1Date:23 November 2012
Reviewer: Chrong-Reen Wang
Reviewer's report:
The authors reported on ileal involvement detected by double-balloon endoscopy
in microscopic polyangiitis, and they concluded that this disease should be
considered as a differential diagnosis when small intestinal changes observed by
the endoscopy such as various form of ulcers with redness and edema. This
case report is interesting and, in general, the manuscript is well written in
English. It reflects the rare presentation of small intestinal involvement in
anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and is
worthwhile to be published in BMC Gastroenterology.
However, four minor issues needed to be clarified as follows.
1.On the page 8 of Conclusion section, the authors pointed out that treatment
should be performed when the ANCA-associated vasculitis is strongly suspected
clinically even if no histological evidence of necrotizing vasculitis, and repeated
biopsy should be avoided because it can result in delayed initiation of treatment
and adverse sequelae. Therefore, the authors could consider to revise their
statement on the lines 3 to 4 of page 3 in Abstract section “Although histological
evidence of microscopic polyangiitis is important, the treatment should not be
delayed by repeating the biopsy”.
2.Since the authors performed the renal biopsy to confirm the kidney involvement
in microscopic polyangiitis, the amount of proteinuria could be expressed
quantitatively rather than ‘slight” proteinuria on the lines 17 to 18 of page 5.
3.The authors might precise their examination on ANCA on the line 16 of page 6.
The test used for the measurement of ANCA could be anti-myeloperoxidase
antibodies with 42.5 U/ml by using the enzyme-linked immunosorbent assay.
4.Wegener’s granulomatosis should be replaced with another name
“Granulomatosis with polyangiitis” in this report on the line 4 of page 4 and line 7
of page 9 (Arthritis Rheum 2011; 63: 863-4).
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:
The rewiewer declares no competing interests.
Review for 10.1186/1471-230X-13-42 (2013)

Reviewer's report
Title:Microscopic polyangiitis complicated with ileal involvement detected by
double-balloon endoscopy: a case report
Version: 2Date:24 January 2013
Reviewer: Chrong-Reen Wang
Reviewer's report:
The authors have revised their manuscript according to the suggestions and all
of the raised issues have been clarified. The reviewer has no further comment on
the revised manuscript.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
The reviewer declares no competing interests.
Review for 10.1186/1471-230X-13-42 (2013)

Reviewer's report
Title:Microscopic polyangiitis complicated with ileal involvement detected by
double-balloon endoscopy: a case report
Version: 2Date:8 February 2013
Reviewer: Jorgen Agnholt
Reviewer's report:
The questions raised in the first review have been commented relevantly.
However, I think the authors should make a short comment in the discussíon
where they outline what the advantage of the DBE is in the present case
(stenosis would probably has been without reach of the colonoscope and capsule
endoscopy has been associated with a significant risk of capsule retention).
New nice artmaterial!
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:
none
Review for 10.1186/1471-230X-13-41 (2013)

Reviewer's report
Title:Efficacy, Safety and Cost Analyses in Ulcerative Colitis Patients
Undergoing Granulocyte and Monocyte Adsorption or Receiving Prednisolone
Version: 2Date:17 January 2013
Reviewer: Takafumi Dr Tabuchi
Reviewer's report:
In this article, the authors report on the analyses of efficacy, safety and cost of
treatment for patients with intractable ulcerative colitis who were treated with a
conventional corticosteroid vs therapeutic granulocyte and monocyte adsorption
(GMA) which is an extracorporeal intervention. The efficacy and safety of GMA
therapy has been reported, with GMA having a very favourable safety profile vs a
glucocorticosteroid. However, the strength of the study on the clinical efficacy vs
economic burden is not very strong. However, it is an important and new point of
view that the authors have focused on the analyses of medical-economic
pertained to the treatment of patients with ulcerative colitis. From this viewpoint,
the manuscript should find interest in clinical settings.
Some references do not numbered in square brackets.
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 have no competing interests'
Review for 10.1186/1471-230X-13-41 (2013)

Reviewer's report
Title:Efficacy, Safety and Cost Analyses in Ulcerative Colitis Patients
Undergoing Granulocyte and Monocyte Adsorption or Receiving Prednisolone
Version: 2Date:21 January 2013
Reviewer: yasuo suzuki
Reviewer's report:
Fortunatly thereis no improvement.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
'I declare that I have no competing interests'
Review for 10.1186/1471-230X-13-39 (2013)

Reviewer's report
Title:Cost and burden of gastroesophageal reflux disease among patients with
persistent symptoms despite proton pump inhibitor therapy: an observational
study in France
Version: 1Date:7 October 2012
Reviewer: Fermin Mearin
Reviewer's report:
This study was aimed to provide information on the treatment pathways,
resource utilization, costs, symptoms and HRQL in European patients (France)
with GERD who were newly identified as partial responders to optimized PPI
therapy.
He paper is interesting and is well written. I just have some concerns about some
of the definitions, but this does not hamper the value of the study. I do
understand that this is an observational study and some variables are difficult to
control but, then, the conclusions (and methods related to these conclusions)
should be putted in a more clinical practice context.
Specifically I have some concerns about how GERD diagnosis was made, and
how “optimized PPI therapy” and “partial response to PPI therapy” were defined.
GERD was diagnosed when “#6 month history of GERD symptoms” but this is
not much to say. This is important because, as cited by the authors in the
Discussion section, possibility of incorrect diagnosis is one of the main reasons
of therapeutic failure.
There is neither clear definition of “partial response”, when several guidelines
have defined it (8 weeks double doses? Need of pHmetric response?)
The same for “optimized treatment with a PPI”: double doses? Triple doses?
Under pHmetric control?
I do not mind that pHmetry had to be done in this study, just that this
observational study (and its conclusions) should be putted in a more
clinical/practical context.
Other comments
Results. “the maximum dose had been reached in 86% of patients”. Please
explain what the authors mind by maximum dose.
Results. “A total of 6 patients (2%) were reported as being hospitalized during the
study”. Related to GERD? Please specify causes of admission.
I miss a practical conclusion. It is clear that partial response to PPI therapy for
GERD is associated with a high costs and burden. I suggest including, not in the
abstract but at the end of the Discussion section, the need of better diagnosis
and new therapies.
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-13-39 (2013)

Reviewer's report
Title:Cost and burden of gastroesophageal reflux disease among patients with
persistent symptoms despite proton pump inhibitor therapy: an observational
study in France
Version: 1Date:14 October 2012
Reviewer: Tomohiko Shimatani
Reviewer's report:
In this manuscript, the authors presented the results of the REMAIN France
study, i.e., the treatment pathways, resource utilization, costs, symptoms and
HRQL in European patients with GERD who were newly identified as partial
responders to optimized PPI therapy. The study was uniquely performed and the
results were well discussed. The reviewer considered that no serious problems
were found, however, it contains some questions as follows.
1) Were the results of this study different between proton pump inhibitor users
and other drug users?
2) Do the doses of proton pump inhibitors, i.e., half dose or full dose, affect these
results?
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
None declared.
Review for 10.1186/1471-230X-13-39 (2013)

Reviewer's report
Title:Cost and burden of gastroesophageal reflux disease among patients with
persistent symptoms despite proton pump inhibitor therapy: an observational
study in France
Version: 2Date:25 January 2013
Reviewer: Wieslaw Bochenek
Reviewer's report:
Authors' replies and proposed revisions to the manuscript and the expanations
are accepted
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
'I declare that I have no competing interests'
Review for 10.1186/1471-230X-13-40 (2013)

Reviewer's report
Title:Successful modified dietary treatment of non-responsive celiac disease:
Not all resistance to a strict gluten-free diet is refractory sprue.
Version: 3Date:3 January 2013
Reviewer: PAOLA IOVINO
Reviewer's report:
Summary
This is a retrospective study. From 2005 through 2011, a total of 29 patients all
gluten free diet-adherent non-responsive celiac disease (NRCD patients) who
attended the University of Maryland Center for Celiac Research in Baltimore
were instructed on the Gluten Contamination Elimination Diet (GCED) i.e. a 3-6
month diet of whole, unprocessed foods. Of the 17 compliant patients, 82%
responded to the GCED and 79% successfully returned to a traditional gluten
free diet (GFD) without resurgence of symptoms.
The Authors concluded that the GCED is an effective therapeutic option for
GFD-adherent NRCD patients. Furthermore, this diet can prevent an inaccurate
diagnosis of refractory celiac disease (RCD1) and avoid immunotherapy.
I have the following comments:
This is an interesting study because it gives another therapeutic option for
GFD-adherent NRCD patients and, moreover identifies a subgroup of patients,
previously classified as RCD1, that is not truly refractory to dietary treatment.
I have some concerns about the methodological approach.
Firstly, the retrospective design represents the main limitation because it reduces
the accuracy of information that prospective investigations permit to obtain.
Secondly, the detailed description of all symptoms referred for a clear definition
of symptom resolution should be mandatory. In fact, NRCD is defined as failure
of symptomatic or histological improvement with a presumed GFD. Then, the
Authors stated that EGDS with biopsies should be performed as the first
investigation in GFD adherent NRCD patients to differentiate those with celiac
enteropathy, and therefore possibly RCD, from those without persistent mucosal
disease. But, in this study the data collected are few because only 5 patients
being biopsied after completing the GCED.
Lastly, I found very intriguing the belief that the majority of such patients are
continuing to react to miniscule amounts of gluten cross-contamination, however
I have a concern about the lack of a systematic approach to diagnose GFD
adherent NRCD patients as recently described (Mooney PD et al J Gastrointestin
Liver Dis 2012, 2(2):197-203) and, also about the influence of other dietary
compounds (for example the quality and the quantity of grains, the fruits and
vegetable, the dairy products) on symptoms resolution.
Further studies especially multicenter studies that allow to include a larger
number of GFD adherent NRCD patients should be 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:
no competing interests
Review for 10.1186/1471-230X-13-40 (2013)

Reviewer's report
Title:Successful modified dietary treatment of non-responsive celiac disease:
Not all resistance to a strict gluten-free diet is refractory sprue.
Version: 3Date:15 January 2013
Reviewer: Geoffrey Holmes
Reviewer's report:
Patients with non-responsive coeliac disease (NRCD) present a challenge to
carers. The commonest cause is the ingestion of gluten either accidentally or by
design. In some co-morbidity is responsible. The remainder have been labelled
refractory coeliac (RCD). This group can be sudivided into RCD I and II
depending on the clonality of intraepithelial lymphocytes. Those with RCD I have
a good prognosis and I behave little differently from other coeliacs while those
with RCD II have a poor prognosis with a propensity to develop lymphoma.
The authors, in this interesting paper, address the question whether those
labelled RCD I who are are taking a gluten free diet (GFD) remain unwell
because they are in fact ingesting small amount of gluten in a conventional GFD
so are not suffering from RCD 1 at all. This turns out to be true for some cases of
NRCD and RCD1 because when given a gluten contamination elimination diet
(GCED) they get better and once over the hill some could return to a GFD.
I have suspected that those with RCD I might be very sensitive to gluten and so
are ill and this paper documents evidence for this. It will be of value to those
managing CD
Abstract. Fine
Backgound. This is a good summary.
Minor essential revisions
1. In the second paragraph conventional histology does not really separate RCD
I and II and it would be better to mention immunological techiques that are in use.
2. In this section I would add somewhere that elimination of co-morbidities in
those with NRCD is necessary before a diagnosis of RCD can be given. The
legend of Fig 1 aludes to this.
Methods
Minor esential revisions
1. The authors define RCD as persistent or relapse of symptoms and villous
atrophy. They have not used other lab tests as far as I can see so in the second
paragraph the sentence beginning, If polymerase chain reaction .... is out of
place. This is more of a comment.
Results
These are well laid out in text and tables.
Minor essenatial revisions
1. At the beginning of the Histology section villous blunting is an odd description.
Marsh 3 is more than blunting. Atrophy would be a better term and this also
applies to the 4th paragraph of the Discussion.
Discussion
This is well laid out.
Table 3. RCD1 is mentioned in the legend but in the body of the Table is only
RCD.
On my copy the Table headings were out of alignment.
Satisfactory reference list
Did the authors ancounter any patients with RCD II?
Have the authors considered that those who did not respond might have had
other food intolerances such as eggs and soy protein, elimination of which can
improve the symptoms of some CD patients?
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-13-40 (2013)

Reviewer's report
Title:Trace gluten contamination may play a role in mucosal and clinical
recovery in a subgroup of diet-adherent non-responsive celiac disease patients.
Version: 4Date:4 February 2013
Reviewer: Kamran Rostami
Reviewer's report:
This is a very interesting study with a very important message thoroughly written.
Despite the small number of patients recruited I like the concept of GCED and I
think this will be very usefull to many clinicians and nutritionists as a guide in how
to manage NRCD.
Minor comments:
Page 6 most of paragraph 2 should be in conclusion and discussion instead of
introduction.
Page 7 line 10 methods: Response to GCED defined as normal villous
architecture: as far as the current literature suggest, histological recovery is very
slow, unrelated to symptoms and hardly ever completeld in coeliac patients. The
definition of GCED therefore should be revised. Did some patients in this study
truly completely normalised in their histology? i would suggest the authors to
discuss their findings on histology correlated with the existence literature on
mucosal recovery.
Page 15 line 10: tTG serology does (should be doesn't)
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Review for 10.1186/1471-230X-13-37 (2013)

Reviewer's report
Title:Attenuated antigen-specific T cell responses in cirrhosis are accompanied
by elevated serum interleukin-10 levels and down-regulation of HLA-DR on
monocytes
Version: 2Date:2 December 2012
Reviewer: Robert Thimme
Reviewer's report:
In this well performed an clinical relevant study, Peter et al performed a
comprehensive phenotypical and functional analysis of T cell function, phenotype
and cytokine profiles in patients with liver cirrhosis and patients with liver
cirrhosis and inflammation (as indicated by CRP levels). Especially in patients
with liver cirrhosis and inflammation, they found higher levels of IL-10, an
expansion of CD14+ monocytes with a low HLA-DR expression and an increased
expression and an increased proportion of CD25+ CD4+ and CD8+ T cells. While
in these patients, TNFa production of CD4+ and CD8+ T cells was reduced after
stimulation with SEB, this was not significant when comparing the overall group
of cirrhotic patients and healthy controls. Also, no significant difference in the
antigen-specific T cell response against Ebstein Barr virus was observed.
However, patients without any virus-specific T cell response showed higher IL-10
levels. In sum, this study is well performed with adequate controls and comes to
clear conclusions.
I have the following comments:
Major:
1. In Figures 2, 3 and 4 original data should be displayed to allow the reader/
reviewer to judge the data quality.
2. The increase expression of CD25+ on CD4+ T cells suggests that these cells
may indeed be regulatory T cells as the authors discuss themselves. Why have
they not stained for Foxp3 or have performed suppression assays? This should
be stated.
3. The possible source of elevated IL-10 should be discussed in more detail.
4. HLA-Dr is also an activating marker. Its down-regulation might suggest that
cells are less activated during inflammation in cirrhosis. Why have the authors
not used other activation markers such as CD69 or CD38 to address activation?
Minor:
1. In the abstract, the authors state three pre-defined groups with defining those.
That should be done more clearly.
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:
no competing interest
Review for 10.1186/1471-230X-13-37 (2013)

Reviewer's report
Title:Attenuated antigen-specific T cell responses in cirrhosis are accompanied
by elevated serum interleukin-10 levels and down-regulation of HLA-DR on
monocytes
Version: 3Date:2 February 2013
Reviewer: Robert Thimme
Reviewer's report:
My concerns have all been addressed.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
'I declare that I have no competing interests'
Review for 10.1186/1471-230X-13-37 (2013)

Reviewer's report
Title:Attenuated antigen-specific T cell responses in cirrhosis are accompanied
by elevated serum interleukin-10 levels and down-regulation of HLA-DR on
monocytes
Version: 3Date:7 February 2013
Reviewer: Pilar Garcia-Peñarrubia
Reviewer's report:
Comment of the Reviewer: Pilar García Peñarrubia
The manuscript by Jack Peter and colleagues entitled: “Attenuated
antigen-specific responses in cirrhosis are accompanied by elevated serum
interleukin-10 levels and down-regulation of HLA-DR on monocytes” aims to
evaluate the cellular immune status in cirrhotic patients related with the presence
or absence of inflammatory processes. To accomplish this goal they determined
antigen-specific T cell response towards EBV derived peptides EBNA1 and
BZLF1 from two groups of cirrhotic patients (without inflammation vs
inflammation, according to CRP lower or higher than 10 mg/ml, respectively). As
control group they used peripheral blood leukocytes from healthy donors.
I stated in the first revision, that although the topic is potentially interesting, it was
suffering from a non-very coherent analysis and presentation of the results
according to the proposed aims and the discussion section.
The manuscript has been now thoroughly revised, and the data are presented in
a more understandable way, and more accordingly with the negative results
found in this study as regards to the proposed hypothesis.
I agree that publication of negative results is not very exciting, but it can avoid
others expending their time searching in the same hypothesis.
I now recommend its publication in BMC Gastroenterology.
Minor essential revision: Figure 3C, y-axis must say CD8 instead of CD4.
Level of interest: An article of sufficient interest to warrant publication in a
scientific/medical journal
Quality of written English: Still needs minor typographic corrections before being
published
Statistical review: No
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-13-34 (2013)

Reviewer's report
Title:Consumption of Coffee Reduces Risk for Liver Cancer: A Meta-Analysis
Version: 2Date:9 October 2012
Reviewer: Naping Tang
Reviewer's report:
In this study, Sang et al. evaluated the association between coffee consumption
and liver cancer risk with a meta-analysis. Medline, Embase, ISI Web of Science
and Cochrane library were searched for the studies on this topic, and a total of
16 studies with 9 retrospective studies and 7 prospective studies were included
in this meta-analysis. Their data suggested that coffee consumption may be
associated with reduced risk of liver cancer.
The following are the comments on the study:
Major Compulsory Revisions
1. This is an updated meta-analysis of previous two studies (Hepatology.
2007;46:430-5. Gastroenterology. 2007;132:1740-5.), however, the author did
not provide any comments/discussion on these two studies.
2. For study by Tanaka (ref. 22), three different control groups were used, why
this study was only stratified into HCCS?
Minor Essential Revisions
3. The outcomes (liver cancer incidence, liver cancer mortality, etc) of the
prospective studies were different in the included studies. It will be better to
specify the outcomes of the studies included in the meta-analysis.
4. All abbreviations in the table should be expanded under the table, such as
HCCS, CS1, CS2, NCCS in table 3, etc.
5. English writing should be improved.
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-13-34 (2013)

Reviewer's report
Title:Consumption of Coffee Reduces Risk for Liver Cancer: A Meta-Analysis
Version: 2Date:16 October 2012
Reviewer: Susan Stewart
Reviewer's report:
This is well-conducted study of some interest, and the methods and interpretation
of the results are appropriate. I have only a few comments.
Minor essential revisions: Please address the following issues.
1. Materials and methods: statistical analysis
a. How were random effects models used? Were any of the pooled ORs shown
in the results section computed from random effects models?
b. The next to last sentence in the section states that p<0.05 was considered
statistically significant; however, the 4th sentence of the section states that
p<0.10 was considered statistically significant for the evaluation of heterogeneity.
For which analyses was a significance level of 0.05 used?
2. Results
a. Study characteristics: The second sentence states that there were 15 articles
(should be 16).
b. Subgroup analysis: Table 4 shows that I2 was > 50% for two of the subgroup
analyses (hospital-based case-control studies and studies unadjusted for main
confounders), indicating heterogeneity. Were the pooled ORs for these
subgroups computed using random effects models?
3. Discussion: The authors note that their results are consistent with those of a
previously published meta-analysis (Bravi et al., 2007). This is not surprising,
since the authors’ meta-analysis includes all of the studies in the previous
meta-analysis; this overlap should be noted.
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, 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-13-34 (2013)

Reviewer's report
Title:Consumption of Coffee Reduces Risk for Liver Cancer: A Meta-Analysis
Version: 3Date:10 December 2012
Reviewer: Naping Tang
Reviewer's report:
The authors have addressed all the comments. I have no further comments for
the revised manuscript.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-13-34 (2013)

Reviewer's report
Title:Consumption of Coffee Reduces Risk for Liver Cancer: A Meta-Analysis
Version: 3Date:24 December 2012
Reviewer: Susan Stewart
Reviewer's report:
The authors have responded to the reviews and made several improvements,
resulting in a much more polished manuscript.
Major compulsory revisions: Unfortunately, they have added two sentences to
their conclusions that are unwarranted. 1) A negative association between coffee
consumption and liver cancer incidence found in observational studies is
insufficient basis for suggesting that coffee could be used as an adjunct in liver
cancer management. 2) Although additional cohort studies could provide a more
precise estimate of relative risk, and extend the geographical area covered,
conducting more observational studies is likely to be of limited value in
understanding this association and elucidating the biological mechanisms by
which coffee may reduce the risk of liver cancer.
Minor essential revisions:
1. The authors revised their analysis to include the most extreme comparison in
the Inoue (2005) study, overall (figure 2) and in the analyses stratified by study
type (figure 4). However, it appears that the analyses by study region (figure 5)
were not updated. Also, the results given in the abstract were not updated. The
authors need to update all places in the manuscript affected by the risk estimate
for the Inoue (2005) study (and to verify that the most extreme comparisons for
this study were used in the gender-specific analyses).
2. Materials and methods
a. Search strategy: A key word is missing at the end of the first list of key words:
“lifestyle OR)”.
b. Statistical analysis: The text should say, “Otherwise” (rather than “In addition”)
“a random effects model was used.”
3. Discussion: Regarding the meta-analyses of Bravi et al. and Larsson & Wolk
(“Susanna” should be changed to “Larsson”), the authors do not go far enough in
describing the overlap: it should be noted that all of the studies in these two
articles are included in the authors’ analysis. Also the statements about the
results of the two articles are not quite correct. Bravi et al. found a relative risk of
0.45 (55% reduction) for high consumption vs. non-drinkers. Larsson & Wolk
found a risk reduction of 43% per 2 cups of coffee per day increment.
4. The format for references 29-31 should be made consistent with that of the
other references.
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-13-35 (2013)

Reviewer's report
Title:A re-evaluation of the scratch test for locating the liver edge: a reliable
physical sign
Version: 1Date:28 December 2012
Reviewer: Michael A.J Moser
Reviewer's report:
Major Revisions:
1. Would like to see more discussion of how this paper differs from the papers in
J Clin Gastro and Lancet, which both seemed to put the nail in the coffin of the
scratch test. I enjoy studies such as these, but given what has been published
already, the arguments will need to be quite convincing to swing my opinion the
other way.
2. Comment more on diaphragm height and how this will influence the distance
of the liver below the CM.
3. You chose a number of tests for looking at agreement and would like to hear
more justification of why these particular tests were chosen and not just a single
test. Introducing so many tests introduces the bias of repeated tests; with enough
tests, one will often become significant.
Minor revisions:
1. Why was Kappa not used (takes into account agreement beyond that which
would be obtained by chance alone)?
I did like the way you tested for the possibility of skin transmission vs liver
transmission and documented this well.
2. It would be good to document what should be considered a clinically significant
distance below the RCM; I was taught that palpating or percussing the liver edge
more than 3 cm below the CM meant we could call this liver 'hepatomegally' and
apply a standard set of differentials to this. Yet the scratch test is within 3 cm of
the US measurment (different 3 cm, I know) only just over half the time. To me
this might call into question the utility of the test altogether- would need to justifiy
this to me or explain it (in case I am misinterpreting your data).
Thanks for the opportunity to review this paper.
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 delare that I have no competing interests.
Review for 10.1186/1471-230X-13-35 (2013)

Reviewer's report
Title:A re-evaluation of the scratch test for locating the liver edge: a reliable
physical sign
Version: 2Date:2 February 2013
Reviewer: Michael A.J Moser
Reviewer's report:
The authors have satisfactorily adressed all of my concerns.
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-13-35 (2013)

Reviewer's report
Title:A re-evaluation of the scratch test for locating the liver edge: a reliable
physical sign
Version: 2Date:16 February 2013
Reviewer: Jochen Schuld
Reviewer's report:
no comments.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Review for 10.1186/1471-230X-13-33 (2013)

Reviewer's report
Title:Low Rate of recurrence of Helicobacter Pylori infection in spite of high
clarithromycin resistance in Pakistan
Version: 1Date:23 November 2012
Reviewer: Barbara Schneider
Reviewer's report:
Yakoob et al describes a study involving treatment of symptomatic patients for H.
pylori infection, and follow-up of 1 year, to see if eradication was persistent. This
is a second review of the manuscript, following its revision. Although most of the
textual problems have been corrected, the larger problem remains that the paper
continues to discuss reinfection vs recrudescence determined by an insensitive
method of establishing whether the strains are the same or different. This
language is confusing to the unwary reader. This problem could be solved with
more conservative language, as was detailed in the first review.
Textual issues:
On page 12, line 3 from bottom, the meaning of “could not follow” is not clear. Do
the authors mean “could not be done”?
Review for 10.1186/1471-230X-13-33 (2013)

Reviewer's report
Title:Low Rate of recurrence of Helicobacter Pylori infection in spite of high
clarithromycin resistance in Pakistan
Version: 1Date:5 December 2012
Reviewer: Daniel P Barry
Reviewer's report:
The authors have satisfactorily addressed most of my previous comments except
for one: The Materials and Methods contains stratification of various "levels" of
antibiotic resistance defined by MIC breakpoints. As there is no discussion of
these categories in the rest of the paper, such discussion should be removed.
A few other issues have also been identified and listed below. Most are minor
problems with editing and language of the text.
Minor Essential Revisions
1) There is inconsistent abbreviation of H. pylori.
2) There are multiple punctuation problems, especially spacing following the
period/full stop (.).
3) Strange underlining appears at various spots in the text.
4) Abbreviation use is still inconsistent (e.g. PCR and RUT are defined in more
than one place, BD is not defined).
5) There is inconsistent capitalization of section headers.
6) The degree symbol (#) changes size throughout the paper.
7) Actual p values resulting from Fisher's Exact Test should be given, rather than
p > 0.05.
8) The last sentence in the "Patients" section of the M&M needs to be rewritten
("... those with negative returned 14C-UBT were administered every 3
months...").
9) Rewrite the "Rapid urea test" section ("The tissue specimens were used for
the rapid urease test consists of a dry filter paper containing...).
10) The description of restriction sites in the "PCR-RFLP" section in the M&M is
confusing. The restriction enzymes recognize and cut at a palindromic sites.
Since HhaI digestion resulted in two fragments, there must be a single site of
digestion. Similarly, if Sau3A1 produces 3 fragments there must be two
restriction sites. This section should be rewritten.
11) In the "PCR-based RFLP Analysis" section of the Results, the meaning of the
sentence, "Five of these 6 patients were previously documented to have different
RFLP patterns in antrum and body and same on both biopsy sites." is not
understandable.
12) The authors' additional description of Table 2 in the body of the text is
beneficial. However, the p values within the Table are still confusing as it is
unclear what is being compared. Perhaps they should be removed from the
Table.
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, 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-13-32 (2013)

Reviewer's report
Title:Genetic polymorphisms of epidermal growth factor in relation to risk of
hepatocellular carcinoma: two case-control studies
Version: 1Date:27 August 2012
Reviewer: Manal Hassan
Reviewer's report:
This is a very well-written article from a well-established researchers in the field
of cancer epidemiology specially liver cancer. The strength of the article is the
comparison between high risk population form China vs Low risk population from
USA. Given the importance of the HCC in USA, shedding the light on genetic
variation of EGF gene and its relation with HCC among USA population is very
important. Analysis and results are very appropriate and tables are very clear.
Discussion is very detailed.
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-13-32 (2013)

Reviewer's report
Title:Genetic polymorphisms of epidermal growth factor in relation to risk of
hepatocellular carcinoma: two case-control studies
Version: 4Date:2 January 2013
Reviewer: Pierre Nahon
Reviewer's report:
The authors have manged to provide sufficient answers to my previous
comments.
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.
Review for 10.1186/1471-230X-13-31 (2013)

Reviewer's report
Title:Threaded biliary inside stents are a safe and effective therapeutic option in
cases of malignant hilar obstruction.
Version: 2Date:12 October 2012
Reviewer: Joseph Kim
Reviewer's report:
Major Compulsory Revisions
1. TIS is a poor acronym and should be changed.
2. The authors indicate that, "when the patient was intolerant to reintervention,
increasing jaundice and/or emergence of cholangitis was assumed to indicate
stent occlusion." This is an assumption that is wrong under several
circumstances, e.g., intrahepatic disease progression. Please revise.
3. The authors indicate that, "Three patients who initially received MS underwent
TIS placement because of stent obstruction caused by tumor ingrowth." How
long was the overall survival of these 3 patients? What are the recommendations
for type of stents in such patients?
4. The authors contend that the advantage of TIS is that they can be easily
removed and replaced with occlusion. How often were the TIS replaced because
of occlusion?
5. It appears that there may have been a low rate of occlusion and replacement.
If so, then what is the advantage of the thread in this cohort of patients? Was the
theoretical advantage of the thread realized in this group of patients?
6. The authors reported a stent patency of approximately 30 days for PS. Is this
short period of patency consistent with published reports?
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-13-31 (2013)

Reviewer's report
Title:Threaded biliary inside stents are a safe and effective therapeutic option in
cases of malignant hilar obstruction.
Version: 2Date:26 October 2012
Reviewer: Rishi Pawa
Reviewer's report:
For distal biliary stricture (malignant), a fully covered metal stent is clearly
superior to a plastic stent or an uncovered metal stent due to higher patency
rates (requiring fewer interventions) and comparable rates of cholecystitis
(between covered and uncovered metal stents).
For malignant hilar strictures, covered metal stent is not an option. Numerous
studies have quoted better outcomes with uncovered metal stents as compared
to plastic stents. The idea of using a "Threaded Inside Stent" for malignant hilar
strictures appears very intriguing. The results published in this study are
promising, as these stents (TIS) not only have a comparable patency rate as
compared to metal stents, but also have significantly lower cost. However, larger
prospective trials need to be done before their (TIS) use becomes widely
accepted in clinical practice.
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.