JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-015-0411-2 (2015)

Reviewer's report
Title:LDP vs ODP for pancreatic adenocarcinoma: A case matched study from a
single-institution
Version:3Date:23 July 2015
Reviewer: Claudio Ricci
Reviewer's report:
The paper focused on a very important finding. However, some suggestions
could be improve the quality of the manuscript.
Major revisions
1. Lack of the readmission rate. To correctly evaluate the differences in
postoperative course i suggest to consider the readmission rate.
2.Lack of intention to treat analysis. Patients converted in open procedure and
resected must be analyzed in LDP group. If the authors excluded this patients
from the analysis, increased the bias of the study. Please, the authors had to
clarify if 2 patients excluded from LDP group, underwent to pancreatic resection.
In this case, the authors had to be include in the analysis these cases.
3. Lack of information about postoperative management. For example, was the
ERAS protocol applied in both LDP or ODP groups ? Oral intake could be
depend more from the physician choice than a real advantage in mini-invasive
approach ! Please, the authors had to clarify the protocol used in both groups, to
correct interpretation of the results.
4. What is the experience of the surgeon in laparoscopic distal pancreatectomy ?
Have the surgeon completed the learning curve for LDP ? The operative time
and conversion rate is strictly related to this finding. Two recent papers (1.
Updates Surg. 2012 Sep;64(3):179-83. doi: 10.1007/s13304-012-0163-2. Epub
2012 Jul 5; Learning curve for laparoscopic distal pancreatectomy in a
high-volume hospital.Braga M1, Ridolfi C, Balzano G, Castoldi R, Pecorelli N, Di
Carlo V. 2. Surg Today. 2015 Jan;45(1):50-6. doi: 10.1007/s00595-014-0872-x.
Epub 2014 Mar 9.Laparoscopic distal pancreatectomy: what factors are related
to the learning curve?Ricci C1, Casadei R, Buscemi S, Taffurelli G, D'Ambra M,
Pacilio CA, Minni F.)
demonstrated the role of learning curve in LDP. Please, the authors had to
specify the experience of first surgeon, to discuss the role of learning curve in
their experiences and to add in the section "references" the two paper above
mentioned.
5. The conclusions should be "softened". This study is retrospective, with small
sample size. The "oncologic safety" is still un debate. The sentence "the short
oncologic outcomes and long term survival were similar between LDP and ODP
groups" is not supported by the data.
Minor revision
1. Report the median and range instead mean and standard deviation for
continuous variables
2. Include in Cox model: tumor differentiation and tumor stage according AJCC
3. The power of Cox model should be assess calculating Harrell C value
(c-index) in order to verify the robustness of the results.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Review for 10.1186/s12876-015-0409-9 (2015)

Reviewer's report
Title:Deficiency of Endothelial Nitric Oxide Synthase Exacerbates Early-stage
Non-Alcoholic Fatty Liver Disease Pathogenesis by Changing the Fat Distribution
Version:1Date:31 August 2015
Reviewer: Syeda Afroze
Reviewer's report:
In this manuscript entitled “Deficiency of Endothelial Nitric Oxide Synthase
Exacerbates Early-stage Non-Alcoholic Fatty Liver Disease Pathogenesis by
Changing the Fat Distribution” submitted by Nozaki et al, the authors aimed to
demonstrate the role of endothelial nitric oxide synthase (eNOS) derived nitric
oxide (NO) in the pathogenesis od NAFLD / NASH. There are several factors or
molecules are responsible for the pathogenesis of non-alcoholic fatty liver
disease (NAFLD) or non-alcoholic steatohepatitis (NASH), but the role of eNOS
derived NO in the pathogenesis of NAFLD / NASH is not yet well defined.
Therefore to investigate their hypothesis authors performed experiments in
systemic eNOS-knockout mice with high-fat diet. Four groups of mice were used
in this study. Those mice were (a) wild type eNOS+/+ with basal diet (BD), (b)
wild type eNOS-/- with basal diet (BD), (c) wild type eNOS+/+ with High fed Diet
(HFD), (d) wild type eNOS-/- with High fed Diet (HFD). To explore this study the
authors performed measurement of different biochemical markers in plasma and
serum, liver triglyceride content, liver/spleen ratio of CT values and visceral fat
volume as well. The authors determined the insulin tolerance test (ITT), liver
MTP activity assay and hepatic tissue blood flow. CT scan has also been
performed. The authors conducted several experiments as well, like as
histopathological study on liver and immunohistochemical study as well. The
authors also performed qPCR for evaluating at these genes expressions
(SREBP-1c, PPAR-#, nNOS, iNOS). It is an interesting study. As a whole the
expression of this manuscript is well described. So before going for final
submission of this manuscript, it is recommended to take care of this manuscript
in terms of the following minor revision. Minor concerns are mentioned below:
Minor Concerns:
1. The manuscript should be carefully checked and need to follow the manuscript
format criteria for this journal.
2. It is good to revise by Scientific English editor.
3. The Title could be more firm such as “Deficiency of eNOS Exacerbates
Early-stage NAFLD Pathogenesis by Changing the Fat Distribution”
4. Materials and Methods section need to be organized in order of experiment,
for an example all the measurements need to be one after another then all the
assays and then histological study and then qPCR (gene expression study).
5. Figure 4-1 is not clear enough, because all the lines for different groups are
overlapped. Even though the error bar as well. So it is good to use different color
line for each group. So the figure should be clearly visible. Or the figure could be
represented by bar graph either way.
Review for 10.1186/s12876-015-0371-6 (2015)

Reviewer's report
Title:Decreased PCSK9 expression in human Hepatocellular Carcinoma
Version:2Date:19 November 2014
Reviewer: Dayami Lopez
Reviewer's report:
Examining the role of PCSK9 in liver regeneration and tumor progression is
critical not only to determine a screening biomarker for hepatocellular carcinoma
but also to further understand the role of PCSK9 in cholesterol metabolism. The
study was well designed and the results clearly explained. The data shown
support the conclusions of the authors. In my opinion, this manuscript does not
require any major revisions prior to publication.
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/s12876-015-0371-6 (2015)

Reviewer's report
Title:Decreased PCSK9 expression in human Hepatocellular Carcinoma
Version:2Date:20 November 2014
Reviewer: cedric le may
Reviewer's report:
In this study, Bhat M. and colleagues have compared PCSK9 expression levels
in hepatocelular carcinoma (HCC) and adjacent hepatic tissues.
Using immunohistochemistry, they observed that PCSK9 staining was
significantly less expressed in HCC compared to adjacent tissues. Furthermore,
PCSK9 staining was not correlated to the grade of tumor but did significantly
correlate with the stage of fibrosis. Unfortunately, these interesting finding was
poorly validated by quantitative real time PCR. Indeed, the authors only observed
a trend for a decreased PCSK9 expression in HCC compared to adjacent
tissues. Finally they did quantify circulating PCSK9 by ELISA in patients with
HCC and control patients without HCC. They reported that serum PCSK9 levels
were significantly increased among patients with HCC compared to control
patients.
In absence of LDLr staining or LDLr protein quantification in HCC or adjacent
tissues, it is difficult to evaluate and extrapolate the functional and physiological
relevance of these findings.
It is crucial to further explore the putative link between PCSK9 and HCC
regarding the development of PCSK9 inhibitors. However, the data presented in
the actual manuscript are to date insufficent.
Major Compulsory Revisions
1. The strongest data have been obtained from immunohistochemistry, it would
be important to reinforce the quantification by adding representative pictures from
HCC and control tissues stained for PCSK9.
2. A western-blot analysis of PCSK9 in HCC and HCC tissues should be added
to validate the immunostaining experiments.
3. Finally, as PCSK9 expression is reduced in HCC but the circulating PCSK9
levels is increased in HCC patients compared to non HCC control patients, it is
necessary to measure in HCC the real effect on cell surface LDLr. Thus, it is
required to quantified by immunohistochemitry and western blot the LDLr protein
levels in HCC and ajdjacent tissues.
Minor Essential Revisions
1. The authors should precise whether patients included in the study received
any pharmacological treatment.
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/s12876-015-0371-6 (2015)

Reviewer's report
Title:Decreased PCSK9 expression in human Hepatocellular Carcinoma
Version:2Date:25 November 2014
Reviewer: Rosa Maria M Pascale
Reviewer's report:
The author must respond to these before a decision on publication can be
reached. For example, additional necessary experiments or controls, statistical
mistakes
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.
Declaration of competing interests:
No, I have not in the past five years received reimbursements, fees, funding
No, I do not hold or and I am not currently applying for any patents relating to the
content of the manuscript
Review for 10.1186/s12876-015-0371-6 (2015)

Reviewer's report
Title:Decreased PCSK9 expression in human Hepatocellular Carcinoma
Version:2Date:30 November 2014
Reviewer: Bertrand Cariou
Reviewer's report:
In this article, Bhat et al adressed an important question concerning the potential
link between PCSK9 and liver carcinogenesis. Some preclinical data in mouse
suggest that PCSK9 could play a role in liver regeneration and potentially
carcinogenesis. However, there is no data available in humans yet.
Unfortunately, the data presented here don't support the extensive conclusions
drawn by the authors.
Major Revisions:
1. Concerning the immunohistochemistry data, some controls are lacking.
Indeed, the authors only compared PCSK9 expression in HCC and in adjacent
cirrhotic liver. What is the expression of PCSK9 in normal liver? At this time, it
remains unclear whether PCSK9 is downregulated in HCC or overexpressed in
fibrotic liver?
2. The patients are heterogeneous with a mix of hepatitis B & C, NASH, alcoholic
cirrhosis, etc...It should be remind here that it has been suggested that PCSK9
can play a role in the pathophysiology of hepatitis C by controlling the expression
of some specific receptors involved in the uptake of the viruses (LDL-R, CD81).
The authors shoudl perfomed a regression analysis to determine whteher the
etiology of liver disease alters the results of PCSK9 expression in HCC.
3. It's a pity that plasma PCSK9 levels were not measured in the same
population than those for PCSK9 expression in HCC. The number of controls is
very small...What are the clincial characteristics (etiology of liver disease) of the
patients?
4. Since it has been demonstrated that the effect of PCSK9 in liver regeneration
is dependent of cholesterol intake in mice, the plasma lipid parameters of the
studied patients for PCSK9 expression analyses must be described.
Minor points:
1. The quality of the figure 2 is poor
2. For Q-PCR analyses, more than only 1 house-keeping (18S) gene must be
used.
3. The discussion is very speculative (notably concerning the link between
PCSK9 and LDL-R expression, in the absence of LDL-R expression data....)
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests below.
Review for 10.1186/s12876-015-0371-6 (2015)

Reviewer's report
Title:Decreased PCSK9 expression in human Hepatocellular Carcinoma
Version:3Date:25 March 2015
Reviewer: cedric le may
Reviewer's report:
Minor Essential Revisions
The authors have answered to my main concerns.
The manuscrit will gain by adding a representative picture of the LDLR staining
quantification (Figure 3).
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/s12876-015-0371-6 (2015)

Reviewer's report
Title:Decreased PCSK9 expression in human Hepatocellular Carcinoma
Version:3Date:30 March 2015
Reviewer: Bertrand Cariou
Reviewer's report:
The revised version has been improved by adding the expression data of LDL-R
that correlates with those of PCSK9. However, some questions remain, to my
opinion, unanswered. This is notably the case concerning the relationship
between HCC, fibrosis and plasma PCSK9 concentrations.
Additional comments:
- to validate the hypothesis that PCSK9 in HCC downregulates LDL-R expression
at a post-transcriptional level, LDL-R mRNA should be measured in HCC.
- abstract (conclusions): conversely increased LDL-R expression rather than
decreased...
- the discussion is too long.
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/s12876-015-0407-y (2015)

Reviewer's report
Title:Risk of De Novo Post-Transplant Type 2 Diabetes in Patients Undergoing
Liver Transplant for Non-Alcoholic Steatohepatitis
Version:2Date:26 July 2015
Reviewer: Shahid Malik
Reviewer's report:
none
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/s12876-015-0407-y (2015)

Reviewer's report
Title:Risk of De Novo Post-Transplant Type 2 Diabetes in Patients Undergoing
Liver Transplant for Non-Alcoholic Steatohepatitis
Version:2Date:9 August 2015
Reviewer: Kalyan Bhamidimarri
Reviewer's report:
Major:
1) I think there is an unintentional inclusion of HCV related transplants due to
inclusion of primary liver malignancy (27.5%). It is known that a significant
proportion of the HCC patients are probably due to HCV and thus the control
group might not truly represent non HCV controls. This would skew the
calculations and would need to be adjusted.
Rahimi RS, Trotter JF. Liver transplantation for hepatocellular carcinoma:
outcomes and treatment options for recurrence. Annals of gastro 2015.
2) The authors themselves published recently regarding certain donor
characteristics: donor age, donor h/o DM, DCD to have a significant impact on
PTDM (p< 0.0001) in the recipient. The authors include DCD risk in table 2 but it
would be pertinent to include the adjusted hazard ratio (aHR) of donor age and
donor h/o DM for PTDM in this paper as well.
Younossi ZM et al; The impact of type 2 diabetes and obesity on the long-term
outcomes of more than 85 000 liver transplant recipients in the US. Aliment
pharmacol ther 2014.
Minor:
Line 51, 53, 54: Need to rephrase that the etiology is cryptogenic cirrhosis (it can
be clarified later that a majority of them are most likely related to NASH).
Line 56: clarify the sentence “atleast one onset of de novo diabetes”. Do the
authors mean one episode of hyperglycemia?
Line 58: How was diabetes diagnosed? Was ADA criteria used to diagnose DM?
Please use diabetes mellitus or DM or PTDM consistently through out the paper.
Line 107: simplify the sentence.
Line 289: epidemic
Table 2: 2nd group is controls not ALD. Please correct
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/s12876-015-0321-3 (2015)

Reviewer's report
Title:Associations of Coffee Consumption with Markers of Liver Injury in the
Insulin Resistance Atherosclerosis Study
Version:2Date:24 February 2015
Reviewer: Guglielmo Trovato
Reviewer's report:
please, justify better this statement or delete it
Non-alcoholic fatty liver disease (NAFLD) characterizes and predicts T2DM
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
no competing interest is present
Review for 10.1186/s12876-015-0321-3 (2015)

Reviewer's report
Title:Associations of Coffee Consumption with Markers of Liver Injury in the
Insulin Resistance Atherosclerosis Study
Version:2Date:27 February 2015
Reviewer: Ran Jin
Reviewer's report:
Dickson et al. identified significant inverse associations of caffeinated coffee
consumption with ALT, AST, and the NAFLD liver fat score, suggesting a
beneficial impact of caffeinated coffee consumption on liver-related outcomes.
Generally, this is a well-organized and well-written manuscript of important
interest in the related research field. The authors have clearly stated the current
knowledge gaps and posed their research questions, also the methods are
sufficiently provided to support their findings. I am very pleased to review this
work and following are my comments and suggestions. The authors have
adjusted several clusters of potential confounds in the linear regression models
aiming to analyze an independent relationship between coffee consumption and
the liver health. I am not surprised that the observed associations were
attenuated by controlling for insulin sensitivity given the fact that fatty liver and
impaired insulin sensitivity are highly correlated. It is very critical to adjust dietary
factors as the authors did in model 3, but my major concern is sugar
consumption (primarily fructose) should be also controlled as a confounder. Tons
of evidence has proposed fructose (e.g. from sugar-sweetened beverages) as a
culprit of NAFLD. It could be that habitually higher coffee consumers are more
likely to have less sugar-sweetened drinks which could be an underlying link for
the authors’ reported inverse associations in this study. It will be more convincing
to me if the sugar adjustment could be performed, so I will take this as a request
for major compulsory revisions. In addition, a minor concern is although the
reported inverse associations are statistically significant, correlation coefficients
are small numbers (almost > - 0.1 for all) thus how important it will be in the
biological nature?
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/s12876-015-0297-z (2015)

Reviewer's report
Title:vasopressin V2-receptor antagonists in cirrhosis patients with ascites: A
systemic review of randomized controlled trials
Version:4Date:13 April 2015
Reviewer: Elliot B Tapper
Reviewer's report:
COMPULSORY REVISIONS
1. English: The prose must be completely rewritten but is sufficiently clear for
review.
2. The outcomes must be specified and narrowed.
3. The adverse events must be defined
4. Several graphs must be deleted
By section
Introduction:
The authors cite rapid correction of hyponatremia as the complication of vaptans.
In practice, this is more of a theoretical risk. While careful monitoring for speed of
correction is needed/obligatory, it is a given and thus cerebral injury is rare; the
true limits of the vaptan’s clinical application are thirst, hyperglycemia and cost
precluding discharge on the medication. This, of course, is aside from the fact
that vaptans have a black box warning for liver injury (as seen in the trials of
vaptans for PCKD). These are the contemporary concerns that the introduction
must address.
Methods
The start date for the search is not given
The outcome of the study is not specified. Yet, 5 papers were excluded for this
reason (did not report outcome of interest). The authors mention several primary
outcomes in a later paragraph (at least one of which would be discussed in any
RCT of vaptans). The authors should specify a primary outcome and which
outcomes were secondary. The specific serious adverse events are not
explained in the methods or the results section.
Results:
What is the focus? The reader will be overwhelmed by graph after graph and the
authors have not articulated the reason for this volume of data. For example,
abdominal girth (fig 2b) is of limited value when weight is presented; the
difference between figure 3a and 3b is not explained and 3c appears to show
changes in the first 7 days while 3b shows days 1-14; serious adverse events are
ok but it is not clear why hypernatremia is singled out - is it not, by itself, a
serious adverse event. Most outcomes are vague. Essentially, the authors have
performed the steps of meta-analysis without defining the terms they are
analyzing.
The prose in the results section is at times very difficult to understand and must
be rewritten.
Discussion
Unfortunately the english precludes a thorough review of this section. The
authors should rewrite every paragraph save for the first.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Not suitable for publication unless extensively edited
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/s12876-015-0288-0 (2015)

Reviewer's report
Title:Testosterone-receptor positive hepatocellular carcinoma in a 29-year old
bodybuilder with a history of anabolic androgenic steroid abuse: a case report
Version:2Date:27 February 2015
Reviewer: Matias A Avila
Reviewer's report:
This is a very interesting case report. The case is well described and discussed. I
believe it is important to make this information available to the medical
community to provide adequate guidance and avoid similar situations.
I only have one Major Compulsory Revision (according to the journal's
instructions for reviewers):
It would be very helpful to determine the existence of b-catenin mutations and or
deletions in the liver lesions from this patient. It would help to relate the
use/abuse of AAS to the mechanisms that may underlie hepatic tumorigenesis.
Minor essential revisions:
Page 6, line 159: "glutamine syntahtasis" should be glutamine synthetase
Page 8, line 189: The authors state that "b-catenin is not expressed in normal
hepatocytes". This is not correct, b-catenin is expressed in normal hepatocytes.
The authors may refer to the fact that b-catenin is overexpressed in the tumoral
tissues. This should be corrected.
Page 12, line 301: "glutamin-synthetasis" should be glutamine synthetase.
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/s12876-015-0288-0 (2015)

Reviewer's report
Title:Testosterone-receptor positive hepatocellular carcinoma in a 29-year old
bodybuilder with a history of anabolic androgenic steroid abuse: a case report
Version:2Date:1 March 2015
Reviewer: Xueying Sun
Reviewer's report:
Minor Essential Revisions
This is a case report of hepatocellular adenoma (HCA) with literature review.
HCA is an uncommon benign liver tumor. 90% of HCAs arise in women aged
20-40, and most of them have a history of using oral contraceptives. The authors
reported a case of 29-year old male bodybuilder with a history of anabolic
androgenic steroid abuse. It is interesting and the report was well written and
could be accepted for publication. There are only two minor comments: 1. In the
second paragraph of Introduction section (line 72-76), the authors should cite
several references to support these statements. 2. Line 124,125: two typos, 25.6
and 30.1 cm.
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/s12876-015-0315-1 (2015)

Reviewer's report
Title:Multicenter study about hemorrhagic risk of heparin bridging therapy for
periendoscopic thromboprophylaxis
Version:2Date:21 February 2015
Reviewer: Hung Hung-Hsu
Reviewer's report:
Major comments:
1. In the material and methods, the inclusion and exclusion criteria should be
clarified. If you can make a study flow chart to demonstrate how you enrolled and
exclude the patients, it would be better and clearer for the article.
2. In Table 3, factors with a p value < 0.5 in the univariate analysis were further
assessed in multivariate analysis. However, the factors usually < 0.05 were
enrolled in the multivariate analysis. Please clarify it.
3. In page 11, the limitation and strength of the article may be re-written. The
limitations included retrospective study, study by questionnaire, and not all
endoscopic interventions enrolled (For example, no ERCP and PEG). The
strengths of the study included large scale, nationwide, combine upper and low
gastrointestinal scopes, and new idea emphasized on bleeding risk of HBT.
Minor comments
1. In page 6 , line 3, “ undergo therapeutic endoscopyFinally,” should be
“undergo therapeutic endoscopy. Finally,”
2. The title of Table 1 may be revised as “Demographic data in the study”.
3. In table 1, the words in the 2nd, 3rd, and 4th, columns , like anticoagulants ,
antiplatelets, should be moved in the 1st column.
4. All the vertical lines in the tables should be removed. Only three horizontal
lines in the table , 1st, 2nd and last, should be remained and removed all the
others.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/s12876-015-0316-0 (2015)

Reviewer's report
Title:A novel mutation within the lactase gene (LCT): the first case report of
congenital lactase deficiency diagnosed in Central Europe
Version:1Date:16 June 2015
Reviewer: Mamata Sivagnanam
Reviewer's report:
Minor Essential Revisions:
1. This manuscript would be enhanced by putting this mutation in the context of
other mutations. For example- are other mutations deletions, missense or
nonsense mutations? Is there any other deletion mutation leading to a premature
stop?
2. Please include Family history (other children affected?). Depending on the
nature of the consanguineous relation in the family/inclusion of a pedigree would
be of interest.
3. The authors state that biopsy testing should replaced by genetic testing. This
is a strong statement and should be qualified. Genetic testing AND clinical
improvement (including growth improvement) must take place for endoscopy to
be bypassed.
Discretionary Revisions
1. Line 134 gastroscopy should be esophagogastroduodenoscopy or at least
gastroduodenoscopy.
2. Line 146 add gastroenterologists
3. Line 113 Please define colics.
4. In addition to the genetics leading to easier diagnosis, it also aids in the ability
to guide the family with genetic counseling and for family planning. Addition of
these sentiments would improve the discussion.
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 interest
Review for 10.1186/s12876-015-0316-0 (2015)

Reviewer's report
Title:A novel mutation within the lactase gene (LCT): the first case report of
congenital lactase deficiency diagnosed in Central Europe
Version:1Date:19 June 2015
Reviewer: Daniel Agardh
Reviewer's report:
Minor Essential Revisions:
This case report demonstrates a novel mutation in the lactase gene (LCT). The
report is of importance for physicians taking care of these patients. The case
report is well written and clearly presented. I do however think the authors should
consider to rephrase in their conclusion that intestinal biopsies are obsolete and
should be replaced by genetic testing. This is true if the genetic testing is
positive, as in this particular case, but there are also other rare congenital
conditions affecting the intestinal tract that needs to be confirmed by an intestinal
biopsy. I would suggest to phrase it: b) intestinal biopsies can be avoided in
typical cases that are confirmed by genetic testing.
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/s12876-015-0296-0 (2015)

Reviewer's report
Title:The relationship between irritable bowel syndrome, functional dyspepsia,
chronic fatigue and overactive bladder syndrome: A controlled study 6 years after
acute gastrointestinal infection.
Version:1Date:12 March 2015
Reviewer: Antonina Mikocka-Walus
Reviewer's report:
This well designed observational study examined the prevalence of overactive
bladder syndrome (OAB), and its association with three other functional
disorders; irritable bowel syndrome (IBS), functional dyspepsia (FD) and chronic
fatigue (CF). The strong points are the novelty of the study, a large sample and a
well-matched control group. The paper is also well and succinctly written. Its
weak point is a low response rate in controls, though this is not unusual in this
type of studies. The authors also acknowledge it in the discussion. I have very
few comments as the paper is very well written, critical and comprehensive,
without any methodological problems. I can recommend it for publication without
reservations.
Discretionary Revisions
In the introduction, could the authors change ‘Functional disorders include’ to
‘Examples of functional disorders include’ as their list is not comprehensive.
When they mention ‘several infections’ could the authors give examples.
In the sentence ‘One study similarly suggests that a comparable association
exists between OAB and FD’ could the sample size of this study be provided to
enable the reader to judge its importance.
Methods are comprehensive but to improve readability could the authors
consider including subheadings.
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/s12876-015-0296-0 (2015)

Reviewer's report
Title:The relationship between irritable bowel syndrome, functional dyspepsia,
chronic fatigue and overactive bladder syndrome: A controlled study 6 years after
acute gastrointestinal infection.
Version:1Date:18 March 2015
Reviewer: Francesco Luzza
Reviewer's report:
In this study authors reported an higher prevalence of overactive bladder
syndrome (OBS) in a cohort of 724 individuals with laboratory confirmed
giardiasis six years earlier compared with 847 controls matched by gender and
sex (18.7% vs 13.6%). However, this association disappeared when other
comorbid disorders, such as irritable bowel syndrome (IBS), chronic fatigue
syndrome (CFS), and functional dyspepsia (FD), were controlled for. Indeed, the
prevalence of OAB among individuals with no comorbid IBS, CFS, and FD was
quite similar in Giardia exposed and controls (12.4% vs 10.9%). Nevertheless,
the proportion of OAB in the Giardia cohort that could have been prevented had
not individuals been exposed to Giardia was considerably lower than that for any
of the other functional disorders (27.5% vs 70.3, 64%, and 68.6% in IBS, CFS,
and FD, respectively). Authors also found that CFS and sporadic, but not
post-infectious, IBS were associated with increased risk of OAB.
The study is well written, methods are appropriate, and data well presented and
discussed. The limitations of the study are raised and adequately discussed.
Findings (i.e., associations between the explored diseases) may help to advance
understanding and clinical management in the field.
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/s12876-015-0295-1 (2015)

Reviewer's report
Title:Gene Expression Profiling of Laterally Spreading Tumors
Version:2Date:3 March 2015
Reviewer: Jordi Camps
Reviewer's report:
In the present manuscript, Minemura and colleagues attempted to generate the
trancriptional profiling of colorectal laterally spreading tumors (LST) using
PCR-based array analysis by comparing 17 adenomas, 12 carcinomas and 12
pedunculated adenomas as a control. Immunohistochemistry results confirmed
and validated that overexpression of BCL2L1 is associated with laterally
spreading tumors, and potentially indicate worse prognosis. Functionally, the
authors attempted to inversely correlate the expression of the anti-tumor BCL2L1
with the presence of apoptosis in tissue sections. Thus the authors conclude that
BCL2L1 is upregulated and blocks apoptosis in laterally spreading tumors.
The manuscript is well structured and very straightforward; however, there are
some suggestions this reviewer would like to make in order to give some strength
to the author's conclusions.
Major revisions:
1. Some of the conclusions the authors make are only observational so there are
some statements that there should be downsized.
2. The inverse correlation between expression of BCL2L1 and apoptosis is highly
speculative unless some functional assays are performed. There is no biological
rationality to claim that the inverse relation between expression of BCL2L1 and
apoptosis happens specifically in LTS.
3. If possible, the correlation between mRNA and the protein should be
performed in the same set of samples.
4. The methodological description of the immunohistochemistry should include
each dilution factor utilized for each antibody.
5. In Figure 1, some L-Can cluster within the groups of adenomas, both LTS and
non-LTS. Given the fact that cancers should actually be the most well separated
entities in the hierarchical clustering, the authors should attempt to find an
explanation about their results.
6. Is the overexpression of BCL2L1 a marker of high-grade dysplasia in LTS only
or it is also true for other tumor subtypes?
7. The results of the qRT-PCR would be much easier to follow by the reader if
they are presented in a plot (e.g. box plot).
8. Although it is mentioned by the authors in the Discussion, it would be
informative to know whether BCL2L1 upregulated cells are Ki-67 positive. This
could give some insights in the mechanism of action.
9. The rationale as to why the authors dropped off the follow-up of TNFRSF25 is
not clear.
Minor revisions:
1. The name of the genes must be in italics.
2. Last paragraph in the abstract needs to be rewritten.
3. In Line 251 "claim" should "replace" declare.
4. In Line 258 "to" should replace "with".
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 do not have competing interests.
Review for 10.1186/s12876-015-0295-1 (2015)

Reviewer's report
Title:Gene Expression Profiling of Laterally Spreading Tumors
Version:2Date:16 March 2015
Reviewer: Masanobu Takahashi
Reviewer's report:
Major Compulsory Revisions
Minemura et al. have analyzed the gene expression profiling of 41 colorectal
tumors including 17 laterally spreading tumor-type (LST-type) adenomas, 12
LST-carcinomas, and 12 Ip adenomas, and have found that the five genes,
AKT1, BCL2L1, ERBB2, MTA2, and TNFRSF25, were significantly up-regulated
in LST adenomas compared to Ip adenomas. They have also confirmed that
BCL2L1 proteins were significantly up-regulated in another small cohort of 38
patients with LST adenoma. The study may provide additional data that could
help to clarify molecular mechanisms underlying the oncogenesis of this specific
tumor type, LST. However, I feel that the paper shows only preliminary results for
the expressions of some genes and proteins using a quite small number of
patients, and lacks mechanistic experiments to support their hypothesis.
Level of interest: An article of insufficient interest to warrant publication in a
scientific/medical journal
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.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/s12876-015-0295-1 (2015)

Reviewer's report
Title:Gene Expression Profiling of Laterally Spreading Tumors
Version:3Date:7 May 2015
Reviewer: Masanobu Takahashi
Reviewer's report:
The authors have appropriately added the statements about limitations of their
study.
Minor Essential Revisions
The quality of written English still needs some language corrections before being
published.
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/s12876-015-0293-3 (2015)

Reviewer's report
Title:Intrahepatic Biliary Mucinous Cystic Neoplasms: Clinicoradiological
Characteristics and Surgical Results
Version:2Date:5 December 2014
Reviewer: Debolina Ray
Reviewer's report:
The authors sugget that surgical resection is the treatment of choice for tumors
giving rise to high serum and cystic fluid CA 19-9 levels together with loculated
and septated cystic lesions.
In case the lesion is not cancerous (the limitation of pre-operative false negative
diagnosis), then liver resection can call for unnecessary surgical intervention
which can have other side effects on the health of the patient as well as could be
financial burden.
Thus it is essentially important to confirm a diagnostic method to distinguish
between biliary cysts (adenomas/carcinomas).
Discretionary Revision: Thus it would be appropriate to conclude that complete
tumor resection should be the treatment of choice in confirmed cases of
carcinoma. So the interpretation could be a little clear.
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/s12876-015-0293-3 (2015)

Reviewer's report
Title:Intrahepatic Biliary Mucinous Cystic Neoplasms: Clinicoradiological
Characteristics and Surgical Results
Version:2Date:8 February 2015
Reviewer: Terry Lairmore
Reviewer's report:
The manuscript was reviewed for clarity, organization, appropriate grammar,
appropriateness of results/conclusions based on data presented, and scientific
impact/interest. The following comments/criticisms are made:
Minor Essential Revisions:
1. While it is understood that English is not the author's first language, there are
some language/grammatical errors. These are minor but too numerous to list.
The manuscript should be read and corrected by a primary English speaking
author/editor.
2. This is a retrospective review of the clinicopathilogic features of patients with
intrahepatic biliary cystic mucinous neoplasms at a single high volume HPB
center over a 25 year period. This is a rare clinical entity and the current data
review does provide important features of the presentation and imaging features
of these tumors. This manuscript reports one of the largest series of such
patients and therefore adds to the current literature.
3. The clinical and radiographic features are described effectively and in
adequate detail, and the imaging features are illustrated will by the figures. The
typical features of presentation are also well described and useful. There are
inherent limitations to this type of retrospective analysis, specifically the fact that
the study period encompasses a long period with differing surgical approaches,
technology, imaging capabiliites , and pathologic understanding or classification
of the neoplasms described. These limitations cannot be avoided due to the rare
nature of these tumors and the nature of retrospective collection of data.
4. The report of results regarding the usefulness of tumor markers as measured
in cyst fluid or serum is also useful and is reported for a significant percentage of
the tumors in this large collected series. This data is useful and adds to the
current literature.
5. One of the most significant results of the current study is the authors'
conclusion that less than radical resection results in a higher recurrence rate, and
therefore a statement that radical resection is preferred whenever possible. The
manuscipt states that patients included in the study had their extent of hepatic
resection determined by individual factors and surgeon preference. The author's
should state the factors that should be considered in choosing the extent of
surgery. For example, magnitude of comorbid conditions, hepatic reserve or
underlying function, positivity for Hepatitic B or C, etc.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/s12876-015-0404-1 (2015)

Reviewer's report
Title:Prevalence of Non-Alcoholic Fatty Pancreas Disease (NAFPD) and Its Risk
Factors among Adult Medical Check-Up Patients in a Private Hospital: A Large
Cross Sectional Study
Version:4Date:2 November 2015
Reviewer: Gabor Firneisz
Reviewer's report:
I still suggest to correct the following 2 sentences on page 9 Line 209-210 in the
final text as a minor correction:
“The beta cell dysfunction will cause insulin resistance condition. Long-term
hyperglycemia condition will also cause beta cell dysfunction due to
hyperinsulinemia.” (?)
due to that Beta cell dysfunction is rather a medical expression that is used to
describe the reduced relative capacity of beta cells to secrete insulin compared
to as it would be needed to maintain optimal glycemic control.
Therefore I suggest to replace these two sentences in the final text with a
sentence reflecting a better understanding of beta cell dysfunction, similarly to
e.g. as follows:
'The beta cell dsyfunction results in an unmet relative insulin need to maintain
optimal glycemic control and in combination with insulin resistance at the
periphery synergistically contributes to the long-term hyperglycemia.'
Otherwise all the requested changes were made with satisfaction.
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.
Review for 10.1186/s12876-015-0253-y (2015)

Reviewer's report
Title:The Prevalence of Gastro-Esophageal Reflux Disease and Esophageal
Dysmotility in Chinese Patients with Idiopathic Pulmonary Fibrosis
Version:2Date:1 October 2014
Reviewer: fernando Herbella
Reviewer's report:
Gao et al. present a prospective case series of esophageal function tests in 69
patients with IPF.
There are other studies showing the high prevalence of GERD in these patients.
The authors could fill some blanks in the literature by discussing their findings
from the point of view of an esophageal physiologist.
Major Compulsory Revisions
1) According to the findings, the esophagogastric barrier is normal in patients
with GERD +. In consequence, Is GERD secondary to an increased
transdiphragmatic pressure gradient and not the primary cause for IPF? Please
discuss.
2) What was the contribution of MII-pH in the study? How many patients had
abnormal non-acid reflux and normal acid reflux?
Minor Essential Revisions
1) Figures are not contributory.
2) Table 4 is not clear
3) et al., not et al
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 conflict of interest.