JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/1471-230X-12-30 (2012)

Reviewer's report
Title:Glucagon-like peptides 1 and 2 and vasoactive intestinal peptide are
neuroprotective on cultured and mast cell co-cultured rat myenteric neurons
Version: 1Date:19 December 2011
Reviewer: Marcin Arciszewski
Reviewer's report:
The study of E. Ekblad group is well designed and the manuscript is written in
understandable manner. The aims, methods and the results are clearly
described. The discussion is broad and adequate.
Discretionary Revisions
The authors declared that two neuronal markers (PGP 9.5 and Hu C/D) were
used in the study. However, Fig 1 presents cultured myenteric neurons stained
with PGP 9.5 anti-sera only (no Hu C/D-positive cultured perikarya were
presented) which makes an impression that PGP 9.5 neuronal marker was
predominantly used. If the latter is true it is not clear in which circumstances the
authors decided to use Hu C/D antibodies. Moreover, it is not clear whether any
changes in percentages of survived neurons were noted when analogous
neuronal cultures were stained with different neuronal markers (Hu C/D vs. PGP
9.5). This aspect may be of importance since PGP 9.5 was found to be
expressed in cultured fibroblast (Olerud et al.; J Inv. Derm, 1998). Therefore,
there is a low risk that a few PGP-positive cultured fibroblast (which are known to
be present in myenteric neuronal cultures) could be counted as cultured neurons.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-12-30 (2012)

Reviewer's report
Title:Glucagon-like peptides 1 and 2 and vasoactive intestinal peptide are
neuroprotective on cultured and mast cell co-cultured rat myenteric neurons
Version: 1Date:20 December 2011
Reviewer: Tanya Little
Reviewer's report:
This is a novel study. The authors aimed to determine whether the gut peptides
GLP-1, GLP-1 and VIP had neuroprotective effects on rat cultured myenteric
neurons. The series of experiments performed using previously established
techniques provide a solid answer to the question posed.
The authors have demonstrated protective effects of the gut peptides GLP-1 and
GLP-2 and VIP, on cultured myenteric neurons. These protective effects were
also demonstrated in myenteric neurons that were co-cultured with mast cells.
These observations were significantly strengthened by the demonstration that
these effects were reversed in the presence of specific antagonists of the GLP-1
and VIP receptors.
The discussion and conclusions are well balanced and supported by the data.
The authors clearly acknowledge previous work in the area, and discuss in
context with the current results. Limitations of the work are discussed.
Minor Essential Revisions
-Abstract, rephrase sentence referring to common super family of peptides.
-Methods, page 10, paragraph 2. The statement ‘followed by exposure of GLP-1,
GLP-2, or VIP” should read “followed by exposure to GLP-1, GLP-2, or VIP.”
Methods - comment on how the doses of GLP-1 GLP-2 and VIP used would
relate to concentrations found in vivo.
Results: page 10, please provide units after values for Emax.
-Figure 1 legend: Final line, the legend refers to G, instead of F.
-Please check the tense used throughout.
-Please consistently refer to hypbVIP as a VIP-receptor antagonist rather than a
VIP antagonist.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-12-30 (2012)

Reviewer's report
Title:Glucagon-like peptides 1 and 2 and vasoactive intestinal peptide are
neuroprotective on cultured and mast cell co-cultured rat myenteric neurons
Version: 1Date:21 December 2011
Reviewer: Dorit Samocha-Bonet
Reviewer's report:
This is a well-performed and written study of the effect of GLP1, GLP2 and VIP
on cultured rat myenteric neurons.
There is evidence that diabetes is associated with neurodegenerative processes
in the enteric nervous system that eventually lead to the neuropathy and
intestinal dysfunction, including delayed gastric emptying, that is well-established
in diabetes.
The rationale of the study is well-explained and the authors build on previous
knowledge to answer yet unanswered questions in the field.
The authors present their data in a clear way and they are not over-interpreting
their data.
Minor essential revision:
What were the diluting agents used with the different pharmacological agents
and were the control cells treated with the diluent? This should be added to the
'Methods' section.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-12-30 (2012)

Reviewer's report
Title:Glucagon-like peptides 1 and 2 and vasoactive intestinal peptide are
neuroprotective on cultured and mast cell co-cultured rat myenteric neurons
Version: 1Date:21 December 2011
Reviewer: Axel Brehmer
Reviewer's report:
This study demonstrates neuroprotective effects of glucagon-like peptides and
VIP on rat myenteric neurons in culture. The peptides counteracted mast
cell-induced cytotoxicity and this effect was reversed by addition of appropriate
receptor antagonists. Generally, experiments and results were described
adequately. Some minor comments should be considered before publication.
(1) Background and Discussion sections could be shortened (20% each) without
loss of information. Additionally, for the general reader, subheadings in the
Discussion would be helpful.
(2) Page 8/Histochemistry: Mast cell estimation by toluidine blue staining should
be documented or, if already published, should be referred to.
(3) Page 8/Immunocytochemistry and page 9/Cell counting: The authors report
on HuC/HuD-staining, without documentation. Since PGP9.5 is not a real
pan-neuronal marker (among others: Phillips, J Neurosci Methods, 133, 2004,
99-107), the authors should re-check and discuss their neuron count strategy.
Furthermore, in the Results section/page 9, the authors note that HuC/D-stained
neurons “displayed rich networks of arborizing fibres”. Generally, HuC/D displays
only neuronal nuclei and perikarya. Supposedly, this observation was made by
PGP-staining only?
(4) Page 9: Please, specify data on the “synthetic histamine antiserum”.
(5) Legend to Fig 1: What are “anatomical contacts” between neurons and mast
cells?
(6) Fig 1 and legend: I suppose that the reason for visualizing both PGP and
histamine by using the same secondary antibody is rather the fact that both
primary antibodies derived from rabbit, not “to percieve the anatomical
relationship” between cells. Although I realize that “neurons and mast cells are
simply distinguished” by their morphologies, a differential visualization would be
both more objective and elegant.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Review for 10.1186/1471-230X-12-30 (2012)

Reviewer's report
Title:Glucagon-like peptides 1 and 2 and vasoactive intestinal peptide are
neuroprotective on cultured and mast cell co-cultured rat myenteric neurons
Version: 2Date:20 February 2012
Reviewer: Axel Brehmer
Reviewer's report:
No further comments
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Review for 10.1186/1471-230X-12-27 (2012)

Reviewer's report
Title:Assessment of liver fibrosis and associated risk factors in HIV-infected
individuals using transient elastography and biomarkers (Fibrotest)
Version: 1Date:18 December 2011
Reviewer: Patrick Ingiliz
Reviewer's report:
Vermehren et al. have conducted a study on liver fibrosis in a typical central
European HIV collective with 17% coinfected with HCV and 9% with HBV.
The paper is clearly written, the language is good and the study is of major
importance as the impact of HIV infection, cART and metabolic factors on liver
fibrosis in HIV positive individuals is not entirely understood.
Liver fibrosis was measured by non-invasive tools, namely Fibroscan and
Fibrotest, and the cut-offs to define significant fibrosis/cirrhosis used here are
those defined in HCV and HIV/HCV positive individuals.
In my opinion, the major finding is the percentage of significant fibrosis in HIV
monoinfected individuals (4%), because patients were apparently randomly
chosen and not for signs of liver disease.
Major comments:
1) As no liver biopsy has been performed, it is not possible to say which test
would perform better to detect fibrosis in HIV patients. The Bordeaux algorithm
(Castera et al., combination FS/FT) has been validated in patients with HCV
infection and has proven it´s potential to avoid liver biopsy. However, one of the
main findings here is the presence of significant fibrosis/cirrhosis in HIV
monoinfected patients. I would suggest to consider instead the presence of
fibrosis if one of the tests indicates it and analyse the data accordingly.
2) The number of patients with elevated GGT levels is high. As GGT is an
independent marker of liver fibrosis, but may also indicate
steatosis/steatohepatitis and, more importantly, nevirapine use, the authors
should comment on the number of patients taking nevirapine at the time of blood
draw. This is even more important as GGT is part of the Fibrotest algorithm
which may explain the higher rates of significant fibrosis found in this analysis by
Fibrotest compared to Fibroscan.
Minor comments
1) Table 2: "Factors associated with significant fibrosis..." or "Factors associated
with liver stiffness values >= 7.1kPa and/or Fibrotest values >0.48..."
2) In my opinion, the viral hepatitis coinfected patients do not contribute positively
to the quality of the manuscript: The group is small, longer infected, had more
d-drugs and the duration of HCV infection is not indicated.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-12-26 (2012)

Reviewer's report
Title:Quantitative Modeling of the Physiology of Ascites in Portal Hypertension
Version: 3Date:9 February 2012
Reviewer: Beate Appenrodt
Reviewer's report:
Levitt et al. describes a new, quantitative model for the pathomechanism of
ascites in portal hypertension. The authors explain in detail the two common
theories of evolving ascites, the underfill and the overflow theory.
They conclude that the mechanism of developuing ascites is only poorly
understood beside both theories.
Furthemore, they remark that the pathophysiology of the known plasma-ascitic
gradient of albumin is also poorly understood.
The manuscript is structured in three sections. In section III, a new quantitative
physical model describing ascites accumulation is discussed.
It is a very interesting and new attempt to explain the pathomechanism of
ascites.
However, there are some comments:
1) One main pathomechansim is the activation of the RAAS in portal
hypertension. Please discuss this mechanism more detailed.
1) On page 14 (E), SAAG as differential diagnostic marker between different
causes of ascites is discussed. “A SAAG of > 1.1 gm% is ... indicative of portal
hypertension (either cirrhotic or cardiac ascites).” The authors should explain the
pathophysiology of cardiac ascites in comparison to cirrhotic ascites. Portal
hypertension is not the common cause for cardiac ascites.
2) Please give references for a) “…administration of spironolactone or furosemid
decreases P(HVPG) by about 20%” and b) decrease in cardiac output with
corresponding fall in hepatic blood flow and P(HVPG) in the main text..
3) On page 17, the authors explain that clonidine produces a significant decrease
in P (HVPG).
Please explain the effect in more detail and add references.
It is not common that clonidine is used for treatment of varices. The authors
should comment on this and add references in the main text (not only in the
attachement).
5) The authors should also discuss the effect of terlipressin and vasopressin-2
antagonists in the treatment of ascites in the main text.
Minor comments:
1) Page 8, line 22 (section II, A.): please change ascetic in ascitic (or
contrariwise)
2) typing error: Page 20, 2 mmHg instead of 2 mm
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 do not have anything to declare.
Review for 10.1186/1471-230X-12-26 (2012)

Reviewer's report
Title:Quantitative Modeling of the Physiology of Ascites in Portal Hypertension
Version: 3Date:15 February 2012
Reviewer: Tony Bruns
Reviewer's report:
In this communication, the authors provide a qualitative and quantitative
pathophysiological model for the development of ascites due to portal
hypertension. Notably, this model only considers the difference of liver pressure
and abdominal pressure and the rate of lymph drainage from the abdominal
cavity but does not include systemic changes due to renal sodium retention,
mesenteric vasodilatation and hyperdynamic changes.
The model bases on certain assumptions:
1) There is a critical difference of liver pressure and abdominal pressure that
allows leaking of protein from the liver to the abdominal cavity via the (ruptured)
liver capsule or (ruptured) lymphatics.
2) The mesothelium has similiary properties as capillaries and is not highly
permeable for protein.
3) The lymphatic flow from the peritoneal cavity (linearly) increases with
increasing abdominal pressure/ascitic fluid volume.
Although some of the assumptions are controversial, the model provided here is
consistent in itself and offers a recently neglected perspective on the
development of ascites. Furthermore, it allows to estimate effects of
pharmaceutical interventions on ascitic fluid (AF) volume.
Minor Essential Revisions:
1) Transfer some of the evidence from the literature for weeping from liver
surface (Add. File 1D) to the main manuscript to support this concept without
looking into the supplementary files.
2) In their model, diuretics decrease ascites volume by lower central venous
pressure. Please provide evidence that ascitic fluid reduces in patients with
ascites that are refractory to diuretics or anuric (body weight would not be a
sufficient measure, since AF should be redistributed to the venous
compartiment). How much ascites could be mobilized in an anuric patient with
gross ascites without a change in HPVG?
3) The model and Figure 1 does not consider hepato-venous shunts in patients
with decompensated cirrhosis. Please discuss how the presence of a certain
shunt volume would change the critical pressure for protein weeping from the
liver (PL-PA).
4) Figure 2 provides AF protein as a function of HPVG. Ascitic protein
concentration is provided as colloid-osmotic pressure (COP) and varies between
7 and 11 mmHg. In clinical practice AF protein concentrations between 5 and 20
g/l are ususally found. Please provide the corresponding concentrations (g/l) of
AF protein COP (mmHg) in Figure 2 and discuss the narrow range observed by
the quantitative model.
Discretionary Revisions
1) Please insert a step in eq. 15 to allow easier understanding, i.e.
PL-PA=(Phv+Ppv)/2-Phv=(Pwedge-Pfree)/2
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-12-25 (2012)

Reviewer's report
Title:Early effect of oral administration of omeprazole with mosapride as
compared with those of omeprazole alone on the intragastric pH
Version: 1Date:14 December 2011
Reviewer: Kazuma Fujimoto
Reviewer's report:
The purpose of this study is not clear.
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 have no major criticisms in this study, but I have one big question.
I wonder why they tried to examine an effect of mosapride on gastric acid
secretion suppressed by PPI. What is an clinical advantage of this effect of
mosapride?
Review for 10.1186/1471-230X-12-25 (2012)

Reviewer's report
Title:Early effect of oral administration of omeprazole with mosapride as
compared with those of omeprazole alone on the intragastric pH
Version: 1Date:19 December 2011
Reviewer: Yoshihisa URITA
Reviewer's report:
Dear Dr. Hiroshi Iida,
Your manuscript entitled “Early effect of oral administration of omeprazole with
mosapride as compared with those of omeprazole alone on the intragastric pH.”
has been reviewed. The authors conclude that an oral dose of omeprazole 20 mg
plus mosapride 5 mg increased the intragastric pH more rapidly than omeprazole
20 mg alone. This manuscript is of enough interest and describes original work
that merits its publication in the journal of BMC Gastroenterol. Although the work
was of good quality, the manuscript required some revisions as below;
1. I cannot understand the mechanism by which administration of mosapride
enhances inhibitory effects of gastric acid secretion. Although the authors
described that mosapride accelerates the absorption of omeprazole, is this a true
theory? Furthermore, if enhanced gastric emptying is associated with enhanced
absorption from the small intestine, should administration of omeprazole plus
mosapride provide higher pH during earlier time? Contrary to this hypothesis, the
gastric pH was not higher during 0-1, 1-2, or 2-3-hour period, but significantly
higher during 3-5-hour study period in the present study. These results did not
accord with your description. The author should describe the mechanism of
inhibitory effect of gastric acid during ingestion of PPI plus mosapride.
2. In Figure 2, intragastric pH during 3-4-hour study period was fallen from 4.0 to
3.3. Why this transient decrease of intragastric pH observed in this study? Did
this reflect reduced blood concentration of omeprazole? If this speculation was
correct, why was the intragastric pH during 4-5-hour syudy period increased
again?
3. The big problem of the study was the absence of discussion on relationship
between enhanced absorption of omeprazole and unchanged pH in the early
time. Ordinary, enhanced absorption results in enhanced excretion, suggesting
that the effect of acid secretion should not be last for a long time. Why did
additional ingestion of mosapride avoid fall in intragastric pH during 3-4-hour
study period?
4. The authors should describe the kind of EIA kit used for H.pylori infection.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
declare that I have no competing interests
Review for 10.1186/1471-230X-12-24 (2012)

Reviewer's report
Title:Metachronous metastases- and survival-analysis show prognostic
importance of lymphadenectomy for colon carcinomas
Version: 2Date:21 December 2011
Reviewer: Oliver Schwandner
Reviewer's report:
This is a very clear and detailed analysis focussing on the importance of
lymphadenectomy for colon cancer. Statistiscs, study design, exclusion/inclusion
criteria are clear. Results and discussion are well documented.
Major Compulsory Revisions:
None
Minor Essential Revisions:
None
Discretionary Revisions:
None
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I have no competing interests
Review for 10.1186/1471-230X-12-24 (2012)

Reviewer's report
Title:Metachronous metastases- and survival-analysis show prognostic
importance of lymphadenectomy for colon carcinomas
Version: 2Date:14 January 2012
Reviewer: Dieter Hoelzel
Reviewer's report:
This is a well written paper with a well defined question and adequately
described, sound data. The background is a large, prospective, well documented,
patient cohort from a university hospital. A specific feature is the consequent
selection with clearly defined criteria, which results in a homogenous cohort.
Nonetheless, the conclusion is only partially comprehensible. The lymph node
involvement – that is the number of positive lymph nodes – is the most important,
classical, prognostic factor. This is shown by the multivariate Cox regression. But
a correlation is not causation or “post hoc ergo propter hoc” would be a logical
fallacy. Therefore, the prognostic relevance of positive lymph nodes is not a
justification for the lymphadenectomy. If positive lymph nodes are not the cause
of distant metastases then the reliable identification of a positive lymph node
status would be sufficient for the indication of an adjuvant treatment comparable
to the sentinel lymph node procedure in other cancers. Therefore, the last
sentence in the conclusion and the last chapter of the discussion should be
specified, perhaps with an additional paper e.g. Yachida Nature 2010 and PA04.
In addition, the following improvements are recommended:
The term stage is a defined term. Therefore, the term N-stage, T-stage should be
replaced by N-category and T-category, also in the figures.
Table 1: A line with the number of deaths in both groups should be added. The
differences in the Cox models are in part dependent on the different numbers of
each event, metastases or cancer related death or all dependent and in Table 3
all deaths, also the cancer independent cases.
Fig.1: The reduction of the cohort is reasonable but the numbers of the excluded
patients are not reproducible. The groups are not disjunctive. Therefore, the sum
must be greater then the number of the excluded 645 or 329 patients.
It would be very informative for interested readers, if the selection process would
be described with tables with the T-category pT1, pT2, pT3, pT4 and others listed
as columns and as lines R1/R2, previous second non-CRC, synchronous
metastases, with further grouped criteria such as age <50y, or positive family
history . These tables should replace the two boxes.
The exclusion criteria primary surgery is actual unnecessary because
Kaplan-Meier curves and Cox models can use cases with shorter follow-up. But a
new evaluation would not change the conclusion and is therefore not necessary.
Fig.2 d should describe the grade dependent survival instead of N-category N0
or N2
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Review for 10.1186/1471-230X-12-22 (2012)

Reviewer's report
Title:Do gastrointestinal and respiratory signs and symptoms correlate with the
severity of gastroesophageal reflux?
Version: 1Date:8 December 2011
Reviewer: P. Marco Fisichella
Reviewer's report:
Nice paper. It would be interesting to see what is the specificity and sensitivity of
the pH monitorning in this patient papulation. The Authors have all the
information to perform the calculations.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Review for 10.1186/1471-230X-12-22 (2012)

Reviewer's report
Title:Do gastrointestinal and respiratory signs and symptoms correlate with the
severity of gastroesophageal reflux?
Version: 1Date:17 January 2012
Reviewer: Maciej Kaczmarski
Reviewer's report:
Minor Essential Revisions
1. The paper is interesting from the clinical point of view, because
gastroesophageal reflux is a common cause of various clinical symptoms (typical
and atypical) in developmental age and adult patients what is also confirmed by
the results obtained by authors who have established the incidence of GER in
Turkish children.
2. Examined group of 70 patients was divided into 3 subgroups of patients having
gastrointestinal complaints, respiratory complaints, and mixed symptoms
(gastrointestinal and respiratory symptoms both).
3. The diagnostic method for GER detection was 24 hour esophageal pH-metry
4. An important conclusion drawn from the study is that coexistence of
gastrointestinal and respiratory symptoms in the patients with GER confirm the
severity of reflux.
5. The statistics, discussion and referrences are satisfactory.
5. Remarks:
a. The established incidence of GER in examined subgrups of patients is limited
only to those with the acidic GER (pH-metry detected).
b. In the in the remaining examined subjects who did not show the occurrence of
acid reflux the presence of alkaline refluks should be suspected. Combined
mulitichannel intraluminal impedance and pH measurement should be used.
c. The main conclusion is probably true, although the examined group with mixed
GER symptoms is numerically small (6patients). „The severity of GER” should be
confirmed by application of diagnostic methods of pHmetry, gastroscopy
(eosaphagitis?) and nature of the clinical symptoms observed in the patients
d. The study should be continued in the future, according to the above remarks,
with MI Impedance and pH-metry application.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
'I declare that I have no competing interests.
Review for 10.1186/1471-230X-12-23 (2012)

Reviewer's report
Title:Colorectal cancer screening services in family medicine vs. internal
medicine practices: a cross-sectional study
Version: 2Date:17 January 2012
Reviewer: Alexander Link
Reviewer's report:
In the present study, authors compare the CRC screening rates or screening
awareness based on the patients self-report in US-national study. The authors
show that those patients that usually visit “internal” doctors are potentially less
likely to be aware of the screening colonoscopy, but at the same time do undergo
CRC screening with either methods more frequently than those from “familial”
doctors. I believe that this well-written report may be helpful for future
improvement of cancer preventive strategies.
Minor Essential Revisions:
1. Please revise the conclusion statement in the abstract. Since the study was
designed to evaluate the self-reported awareness and personal adherence to the
recommendations, I believe that there is not enough data to support the “failure”
statement.
2. This is U.S. national-based study and the results may not be applicable to
other countries. Please state this in the limitations.
3. I would strongly recommend adding following descriptions to the title of the
paper: in United States and self-report.
4. According to the Figure 1, the patients were asked about the recent
colonoscopy time point (<1, 1-2, 2-3 etc). The authors may wish to complete the
information in the table.
5. Please include the characteristics and adherence to CRC screening for the
disabled patients. What is the percentage of the disabled patients in this study?
Discretionary Revisions:
6. One of the main limitations of the study is the defined normal screening
variable within five years and not as usually recommended 10 years. The authors
may wish to elaborate more on that in discussion.
7. To simplify the understanding of the Table 1, this may be splitted into two
tables separating characteristics and results.
8. The identification of the specialty of the usual care primary care physician may
have strong biased overlap because of the self-reported context. The authors
may wish to provide the numerical distribution of particular subjects regarding
“greater number” of services prior to the assignment to FPs or internist.
9. To simplify the understanding of the Table 1, this may be splitted into two
tables separating characteristics and results.
10. The authors state in the discussion part that the CRC screening rate was
lower than the national goal of 70%. Since CRC screening was defined within a
5-year time period and not as recommended within 10-year period, this
statement may be misleading.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-12-23 (2012)

Reviewer's report
Title:Colorectal cancer screening services in family medicine vs. internal
medicine practices: a cross-sectional study
Version: 2Date:18 January 2012
Reviewer: Montserrat Andreu
Reviewer's report:
The article by Higgins et al. describes lower rates of acceptance of cancer
screening by either FIBT or endoscopy in patients from family medicine
physicians compared to internal medicine physicians, based on data obtained
from Medicare.
The following points deserve consideration:
1. Information and conclusions of the study is only relevant for the health system
from which data was obtained, and cannot be generalized to other systems.
2. Reliability of the questionnaire on having been offered a CRC screening
methodology (FOBT or colonoscopy) has not been tested, and is potentially
exposed to considerable recall bias, which in its turn may be dependent on some
of the demographic factors analyzed (e.g. level of education, income).
3. As the authors acknowledge in the discussion, recommendation to undergo
sigmoidoscopy every 5 years is acceptable, but colonoscopy is recommended at
10 years interval.
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Review for 10.1186/1471-230X-12-21 (2012)

Reviewer's report
Title:Dome-type Carcinoma of the Colon; A Rare Variant of Adenocarcinoma
Resembling a Submucosal Tumor: a case report
Version: 3Date:8 November 2011
Reviewer: Colin Stewart
Reviewer's report:
The authors present a case of dome carcinoma of the colon including endoscopic
images. As the authors note, their case is unusual in that it showed advanced
local spread (to the subserosa) while apparently maintaining its dome phenotype.
The paper is well written and the histological illustrations are convincing.
There are no major revisions required.
Minor essential revisions
1. In the pathological description (p5) the authors state that the tumor was
associated with ‘a dense lymphocytic infiltration’. I think they should include a
comment that reactive germinal centres were also present (illustrated in their
Figures 5 & 6) since the association with germinal centres was a key feature that
led Jass and colleagues to postulate that these tumors were arising from (or
differentiating towards) dome-type epithelium.
2. The authors appear to use microsatellite instability and mismatch repair
protein immunohistochemistry interchangeably. These are related but different
techniques and they do not always provide identical results. Thus, it is not strictly
accurate to state that the normal MMR protein staining in their case indicated a
microsatellite stable phenotype (p5) although, of course, this is likely to be true.
Equally, some of the previously recorded cases (p6) were examined using either
molecular or immunohistochemical techniques.
3. In the Conclusion (p6) the authors suggest that the terminology used by Jass
and colleagues in their initial description of this tumor was ‘Adenocarcinoma of
colon associated with gut-associated lymphoid tissue’ (their parenthesis). In fact,
and as is clear in References 1 and 2 in this article, the term used by Jass et al
was ‘ Adenocarcinoma of colon differentiating as dome epithelium of
gut-associated lymphoid tissue’. It seems odd that the current authors have
omitted ‘dome epithelium’ since they themselves use the term ‘dome-type
carcinoma’ as have others previously.
4. The standard Journal abbreviation for Reference 7 should be ‘J Clin Pathol’.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-12-21 (2012)

Reviewer's report
Title:Dome-type Carcinoma of the Colon; A Rare Variant of Adenocarcinoma
Resembling a Submucosal Tumor: a case report
Version: 3Date:15 December 2011
Reviewer: Susanne Holck
Reviewer's report:
Yamada et al provide a beautifully illustrated example of dome carcinoma. Its
publication can be recommended as a reminder to the GI-pathologists of the
existence of this unique variant of colorectal carcinoma. Dome carcinoma has
been the subject of merely a handful of case reports since its introduction to the
literature in 2000. Noteworthy, this tumour was not included in the most recent
edition of the WHO Classification of Tumours of the Digestive System.
At variance with the few previously reported cases, the present one has retained
the unique histological attributes, including the prominent lymphoid tissue,
despite its high pT-stage. Since this is not always the case, its correct
classification relies on a high diagnostic acumen on the part of the pathologist.
With the advent of screening for colorectal neoplasms that implies the
identification of lower cancer stages, more likely to retain the characteristic
qualities, more such cases may be identified.
Thereby, data on the molecular pathology aspects and issues concerning
carcinogenesis, specifically the role of M-cells and the accompanying lymphoid
component may be provided.
Declaration of competing interests:
'I declare that I have no competing interests'
Review for 10.1186/1471-230X-12-20 (2012)

Reviewer's report
Title:Effect of intracellular lipid accumulation in a new model of non-alcoholic
fatty liver disease
Version: 1Date:2 November 2011
Reviewer: Ali Canbay
Reviewer's report:
The manuscript of Chavez-Tapia et al. deals with the effects of intracellular lipid
accumulation in a cell culture model of non-alcoholic fatty liver disease (NAFLD).
HuH7 cells were incubated with different concentrations of free fatty acids
(palmitic and oleic acid at a molar ratio of 1:2) for 24h. After the incubation period
fatty acid uptake, cytotoxic effects, apoptosis, oxidative stress and the release of
inflammatory and fibrogenic cytokines as interleukin-6 and -8, TNF#, TGF-#,
A2M, VEGFA, CTGF, IGF2, NGF and THBS1 were measured. The experiments
could show that free fatty acids play a primary role within the pathogenesis of
NAFLD and NASH by affecting the expression and release of pro-inflammatory
and profibrotic cytokines, enhancing oxidative stress and apoptosis.
The results are reported in a clear and well-organized manner with established
and adequate methods and exactness.
Major Compusory Revisions:
1. As the authors already mentioned using HuH7 cell line demonstrates a limiting
factor. Further experiments with additional hepatic cell lines or ideally with
primary hepatocytes could emphasize and upgrade this study.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-12-19 (2012)

Reviewer's report
Title:Fully covered self-expandable metal stents (SEMS), partially covered
SEMS and self-expandable plastic stents for the treatment of benign esophageal
ruptures and anastomotic leaks
Version: 2Date:16 November 2011
Reviewer: Manon Spaander
Reviewer's report:
van Boeckel et al review their experience on fully covered self-expandable metal
stents (SEMS), partial covered SEMS and plastic stent for the treatment of
benign esophageal rupture and anastomotic leakage. The authors evaluated the
efficacy of these different stents and found no significant differences between
them.
Minor comment:
- Stents were placed for different indications, namely anastomotic leak, iatrogenic
rupture, Boerhaave's syndrome and other causes. Were the different stents
(equally) divided for the different indications or did the attending physician prefer
one of these stents in a specific indication?
-How many days- months after stent removal were patients in follow up. What
was the follow-up time?
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-12-19 (2012)

Reviewer's report
Title:Fully covered self-expandable metal stents (SEMS), partially covered
SEMS and self-expandable plastic stents for the treatment of benign esophageal
ruptures and anastomotic leaks
Version: 3Date:21 January 2012
Reviewer: Bas P Wijnhoven
Reviewer's report:
No major compulsory comments, essential revision or discretionary revisions.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Review for 10.1186/1471-230X-12-19 (2012)

Reviewer's report
Title:Fully covered self-expandable metal stents (SEMS), partially covered
SEMS and self-expandable plastic stents for the treatment of benign esophageal
ruptures and anastomotic leaks
Version: 3Date:29 January 2012
Reviewer: Manon Spaander
Reviewer's report:
My comments are answere with satisfaction
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Review for 10.1186/1471-230X-12-18 (2012)

Reviewer's report
Title:Gaviscon(R) vs. omeprazole in symptomatic treatment of moderate
gastroesophageal reflux. A direct comparative randomised trial
Version: 3Date:2 December 2011
Reviewer: Guido Tytgat
Reviewer's report:
major:interesting study,long overdue.The endpoint:24h heartburn free day at d7
is confusing.It is not at d7.This should be rephrased.Surprisingly no mention is
made of the acid pocket,related to gaviscon
minor
p5:what is beas resistance?
p7:exact composition of gaviscon and of the placebo should be given.The
precise instructions regarding the precise timing of intake of the study drugs
should be given.
p12>at which time did syptoms recur in the gaviscon arm?What is
úlcerative'esophagitis?
p13:what is 'moderate'gerd? what is 'raft of beads'?
p14:what are 'moderate'sumptoms?...ackward sentence:...reduce excessive use
of curative or preventive RATHER THAN PPIs.
Tables:What is the precise 'heartburn intensity score'.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Review for 10.1186/1471-230X-12-18 (2012)

Reviewer's report
Title:Gaviscon(R) vs. omeprazole in symptomatic treatment of moderate
gastroesophageal reflux. A direct comparative randomised trial
Version: 4Date:30 January 2012
Reviewer: Vicki Strugala
Reviewer's report:
Thank you for allowing me to check the revision of this manuscript. I am happy
with the comments addressing my concerns in the cover letter and the changes
to the manuscript. I recommend that this manuscript is published without further
changes.
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 am a consultant for Reckitt Benckiser
Review for 10.1186/1471-230X-12-18 (2012)

Reviewer's report
Title:Gaviscon(R) vs. omeprazole in symptomatic treatment of moderate
gastroesophageal reflux. A direct comparative randomised trial
Version: 4Date:3 February 2012
Reviewer: Guido Tytgat
Reviewer's report:
I have already answered quite some time ago to ACCEPT the paper as it is now.
No further revisions or changes are necessary
Review for 10.1186/1471-230X-12-17 (2012)

Reviewer's report
Title:Correlation between magnifying narrow band imaging and histopathology
in gastric protruding/ or polypoid lesions: a pilot feasibility trial
Version: 1Date:11 August 2011
Reviewer: Hsiu-Po Wang
Reviewer's report:
Comments to the authors:
In this study, authors have investigated the usefulness of magnifying endoscopy
with narrow band imaging (ME-NBI) system in the evaluation of gastric polypoid
lesions. Although few studies have addressed this issue, however, there are
some questions that need considerations.
1) The classifications of gastric lesions by ME-NBI have been studied by several
investigators previously, such as Yao et al, Nakayoshi et al, Goto et al, Kaise et
al, etc.; however, the clinical implication is still limited due to complicated
classification system. In this study, by using four “fine mucosal structures” and
five “micro vascular patterns”, there will be “20” combined patterns for
interpretations. Therefore, the complexity hampered the clinical usefulness of this
study.
2) Because the interpretation of ME-NBI imaging is subjective if the classification
is complicated, the variations of endoscopist’s opinions may exist. Although the
endoscopic diagnoses of this study were confirmed by consensus with the
members, there were no “inter-observer” or “intra-observer” evaluation for the
classification system.
3) In this study, because not all the polypoid lesions were removed in en-bloc
pattern (some of them ,especially for endoscopic suspicious non-neoplastic
lesions, were biopsied for pathological examination), bias exist for the
histopathological results of the polypoid lesions.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-12-17 (2012)

Reviewer's report
Title:Correlation between magnifying narrow band imaging and histopathology
in gastric protruding/ or polypoid lesions: a pilot feasibility trial
Version: 1Date:19 September 2011
Reviewer: Helmut Neumann
Reviewer's report:
Omori and coworkers present an interesting article on the correlation between
magnification endoscopy with NBI and histology in gastric protruding or polypoid
lesions. Overall, 95 lesions from 76 patients were included and the authors
described that microvascular patterns as identified by magnification endoscopy
with NBI may provide meaningful information for prediction of histology of gastric
protruding or polypoid lesions.
The manuscript needs some revisions.
1. Abstract:
- Please describe the abbreviations used within the abstract (FGP, HP).
2. Introduction:
- Please describe the technique of NBI in more detail.
3. Patients:
- Please provide the magnification used in your study.
- Did you really perform EMR in gastric neoplasia or ESD? Please check this
sentence.
- Please add if the endoscopists were blinded to histological data.
Results:
- The sensitivity for unclear pattern given in this section for GN is very low
(14.2%) Is this correct? If yes, than please discuss this results.
Discussion:
- The discussion is a little bit confusing and there are numerous spelling
mistakes. I recommend to rewrite this section with more emphasis given to the
results.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-12-17 (2012)

Reviewer's report
Title:Correlation between magnifying narrow band imaging and histopathology
in gastric protruding/ or polypoid lesions: a pilot feasibility trial
Version: 2Date:29 January 2012
Reviewer: Hsiu-Po Wang
Reviewer's report:
The authors have had correct & add the discussion of the considerations of
reviewer.
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' below
Review for 10.1186/1471-230X-12-16 (2012)

Reviewer's report
Title:Involvement of a periodontal pathogen, Porphyromonas gingivalis on the
pathogenesis of non-alcoholic fatty liver disease.
Version: 2Date:7 September 2011
Reviewer: Richard Blumberg
Reviewer's report:
Yoneda and colleagues provide a very interesting study wherein they show
increased prevalence of P. gingivalis in patients with NAFLD, that P. gingivalis
worsened NAFLD in rodents and periodontal treatment improved LFTs in NAFLD
patients suggesting a biologically important role of this colonization in humans.
The studies are well-performed, presented and interpreted. It is an important
study. There is only one significant concern that deserves consideration. The
authors need to show that the periodontal treatments affected the quantities of P.
gingivalis in order to conclude that there may be an association in relationship to
the latter finding. In the absence of changes in P. gingivalis, the findings remain
interesting. They should also make sure that the emphasize though the
preliminary nature of the clinical findings but based upon this a randomized
clinical trial is in order to show the clinical benefit as it has important practical
implications for 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.
Review for 10.1186/1471-230X-12-16 (2012)

Reviewer's report
Title:Involvement of a periodontal pathogen, Porphyromonas gingivalis on the
pathogenesis of non-alcoholic fatty liver disease.
Version: 2Date:19 September 2011
Reviewer: Lawrence J Saubermann
Reviewer's report:
Major Compulsory Revisions:
1. In Figure 4, was there a change in weight or other medical treatments in the 10
subjects with NAFLD?
2. In Table 3, the ALT and gGTP levels were higher in the P. gingivalis (-) group.
Although these were not significantly different than the PG (+) group, it raises
concern with the hypothesis the authors are proposing. How do they explain this?
3. The authors mention that other oral bacteria did not affect the HFD NAFLD
mouse model (data not shown). It would strengthen their paper if they did include
the data.
Minor essential revisions:
1. The discussion mentions the same statement twice. At the top of page 20, the
sentence is almost the same as the one at the bottom of the page and top of
page 21. It discusses how PG may be involved in both the first and second
stages of NAFL.
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.