JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-022-02634-x (2022)

Title: Common laboratory blood test immune panel markers are useful for grading ulcerative
colitis endoscopic severity
Version: 1 Date: 04 Nov 2022
Reviewer's report:
Dear Editor, Authors
Thank you for sending manuscript entitled’ Common laboratory blood test immune panel
markers are useful for grading ulcerative colitis endoscopic severity: a case control study’ for
revision, kindly accept the following comments
- Frist, authors  ignore the presence of specific validated markers like calprotectin which actually
included in international guidelines
-  Authors mentioned it is a  retrospective study and in same time they mentioned in methodology
‘The blood samples were obtained on an empty stomach in the morning. Laboratory investigators
were blinded to the patient clinical data’ usually this is done in prospective studies.
- Also how can authors such details in retrospective study’  , visible blood in the stool (percentage
of movements), fecal incontinence, abdominal pain or cramping, general well-being, abdominal
tenderness, and a need for anti-diarrheal drugs.’
- Other systemic infections should be within exclusion criteria.
- Long sentences , frequent grammatical mistakes
- Finally, it is a good idea searching for inflammatory markers , but such markers included in
the study could be sensitive not specific . data mentioned in methodology should be sure trusted
as it obtained only from patient files, while authors gave specific details or instructions for lab
study like blind investigations done without background about patient information, HOW SUCH
DETAILS WRITTEN IN RETROSPECTIVE STUDY.
- Thanks
Review for 10.1186/s12876-022-02634-x (2022)

Title: Common laboratory blood test immune panel markers are useful for grading ulcerative
colitis endoscopic severity
Version: 1 Date: 18 Nov 2022
Reviewer's report:
This paper is a case-control study evaluating several blood biochemical markers that associate
endoscopic activity in UC patients. A variety of recently reported markers, including those for
other diseases, have been evaluated, however, it is not clear what kinds of messages the authors
wanted to tell us in this study.
Major points
1. Are there situations where either Hs-CRP or CAR would be more useful in this study?
Dr. Furukawa’s study in BMC Gastroenterology 2022 reported that CAR is particularly effective
in patients with long disease duration. And/or is it possible to compare the characteristics of
each marker (NLR, MPV, LMR, etc.)?
2. Did the authors apply to the Research Ethics Committee for this study? This paper appears
not to contain the approval from the Ethics Committee.
Minor points
1. Details used for Hs-CRP and IL-6 measurements are not described - please add descriptions
such as detailed products and measurement range.
2. Please clarify the explanation of the significant difference in the a, b and c letters in tables
3 and 4.
Review for 10.1186/s12876-022-02613-2 (2022)

Title: Markers of immune dysregulation in response to the ageing gut: insights from aged murine
gut microbiota transplants
Version: 1 Date: 20 May 2022
Reviewer's report:
1. The manuscript is well conceptualized and well written
2. The analysis is effective and easy to comprehend.
3. It would be nice if the name of the groups being compared using DEG and the sample number
within each group is clearly mentioned in the methods. I do feel that the number of sample count
used within the manuscript (4 vs 5) is very low. Is there a reason for such low sample count
considering these are mice samples.
4. I did not see the Log2 FC threshold being used to filter out upregulated and downregulated
genes. If there isnt any threshold, please mention the base means within each group as well. A
threshold allows the reader to understand that low abundance genes were removed.
5. Line 230 - How many down-regulated genes can be classified as membrane proteins?
6. Considering the dataset has access to Log2 fold change data and q values, it would also be
nice to visualize and depict up regulated and down-regulated genes using volcano plots. That
allows to see how many genes (that are q value significant) are not low abundant.
Review for 10.1186/s12876-022-02613-2 (2022)

Title: Markers of immune dysregulation in response to the ageing gut: insights from aged murine
gut microbiota transplants
Version: 1 Date: 29 Jul 2022
Reviewer's report:
The manuscript “Markers of immune dysregulation in response to the ageing gut: insights
from aged murine gut microbiota transplants” by Prokopidis et al. describes the analysis of
transcriptomic data of another published study by Kundu and colleagues from 2019 (DOI:
10.1126/scitranslmed.aau4760) that colonized young germ-free mice with microbiomes of
either old or young mice to identify immune-associated differentially expressed genes. The
entire manuscript is based on minor analyses (DEGs, GO enrichment, network) of published
transcriptional data. The authors did not perform any validation experiments. The findings do
not significantly extend current knowledge as an increased “inflammatory” response by an
aged microbiome was already known, e.g. DOI 10.1016/j.chom.2017.03.002. The association
analyses between DEG expression and abundance of immune infiltrates based on another
published dataset (TCGA and GTEx projects) is more original, yet there is no validation of any
of these potential associations and thus it remains speculative. Therefore, in its current form the
manuscript does not warrant publication.
Review for 10.1186/s12876-022-02624-z (2022)

Title: Risk Factors for the Poor Prognosis of Benign Esophageal Perforation: 8-year experience
Version: 1 Date: 03 Nov 2022
Reviewer:  Tayfun Kermenli
Reviewer's report:
Thanks to all the authors for the successful study. The retrospective nature of the study is a
limitation.  Data of 135 patients with esophageal perforation were analyzed. It would be helpful
if you include the number of patients admitted to your hospital with esophageal foreign body to
the study. In this way, we can reach the information of how many patients presenting with foreign
body have esophageal perforation. Also, esophageal perforations often result in mediastinitis.
What is the rate of mediastinitis in your patients?
Review for 10.1186/s12876-022-02624-z (2022)

Title: Risk Factors for the Poor Prognosis of Benign Esophageal Perforation: 8-year experience
Version: 1 Date: 28 Nov 2022
Reviewer's report:
Thank you for your study about benign esophageal perforation. Although it is a retrospective
study from single center, the number of cases is relatively large. However, there seems to be
several problems to be improved.
1. The quality of English is poor. Misspelling and grammatical errors are seen in many parts.
2. Introduction is too long.
3. Results and conclusions are similar to previous studies. Therefore, this study seems to lack
of impact.
Review for 10.1186/s12876-022-02620-3 (2022)

Title: Prevalence of frailty among patients with inflammatory bowel disease and its association
with clinical outcomes: a systematic review and meta-analysis.
Version: 1 Date: 31 Jul 2022
Reviewer's report:
The impact of frailty on clinical outcomes and prevalence in patients with inflammatory bowel
disease: a systematic review and meta-analysis. Frailty is a pertinent question in management
of IBD patients. Frail phenotype needs dedicated management. The authors have tried to work
in this area. However they need to work on various aspects of the manuscript.
It's better to define clearly: adverse clinical outcomes in methods.
Was any data available on high versus low risk of frailty in IBD patients?
What was the prevalence of frailty in elderly as compared to young IBD patients?
The subgroup analysis on age and comorbidities would have a relevant impact on outcomes of
frailty in IBD patients. This needs to be shown in results systematically.
The outcomes were two only as mentioned in the abstract. It's better to have primary and
secondary outcomes here. In methods it was mentioned this study included data on frailty in
IBD patients with at least one clinical outcome.
The search has been nearly a year now. Explain 56 incompatible literature as i couldnt find it
in exclusion criteria. Were RCTs and conference abstracts decided to be excluded a priori?It
should be mentioned in methods clearly.
The impact of frailty on the clinical prognosis of IBD patients needs to be redefined more
objectively. Is it just adverse outcomes as mentioned in the abstract ? Hospitalization, need of
surgery, readmission or mortality give better meaning than just adverse outcomes. It needs to
be emphasized in the abstract also under the results section.
There were only 2 studies for each analysis of hospitalization, surgery and complication. This
could have been presented as descriptive data only.
One table should be added in results with each study main outcome and prevalence for easy
interpretation.
The manuscript needs a good grammar check. Minor spelling mistakes at places would need
a check.
Review for 10.1186/s12876-022-02620-3 (2022)

Title: Prevalence of frailty among patients with inflammatory bowel disease and its association
with clinical outcomes: a systematic review and meta-analysis.
Version: 1 Date: 18 Aug 2022
Reviewer:  Suprabhat Giri
Reviewer's report:
ABSTRACT
-The sentence “Two researchers and then data independently then checked it for conformance.”
Seems incorrect. Please check.
INTRODUCTION
-The sentence “Adults at any age may occur frailty, but frailty occurs more often in the elderly”
needs modification.
METHODS
-Outcomes of interest need to be defined
RESULTS
-Table 2 can be moved to supplementary material
-The study by Qian et al. and Singh et al. used HR, the study by Bharati et al. and Wolf et al.
used OR and Fayes et al. used RR for effect size. Combining three different measures of effect
size is statistically incorrect.
-Fayes et al. considered 30-days readmission while Qian et al. analyzed 6-months readmission.
Hence, combining data of two different time frames is incorrect.
-Try reducing the sections of sensitivity analysis, publication bias and meta-regression.
DISCUSSION
-The sentence “About 18.6% of IBD patients have frailty, a high prevalence of frailty in the
general population.” needs modification.
-The sentence “We know that inflammatory bowel disease is an inflammatory disease.” needs
modification.
-Due to difference in the measures of effect size and difference in duration, meta-analysis should
not be performed for the outcomes. A systematic review would be apt for that.
-The authors should discuss how are their findings different from this systematic review,
“Katherine Bedard, Naheed Rajabali, Puneeta Tandon, Juan G. Abraldes, Farhad Peerani,
Association Between Frailty or Sarcopenia and Adverse Outcomes in Inflammatory Bowel
Disease: A Systematic Review, Gastro Hep Advances, Volume 1, Issue 2, 2022, Pages 241-250.”
-Apart the above corrections, the manuscript can benefit from English editing as there are
multiple grammatical errors.
Review for 10.1186/s12876-022-02620-3 (2022)

Title: Prevalence of frailty among patients with inflammatory bowel disease and its association
with clinical outcomes: a systematic review and meta-analysis.
Version: 5 Date: 25 Nov 2022
Reviewer's report:
The authors have revised the manuscript well. The abstract should denote the  hazard rates of
outcomes like mortality and hospitalisation as they were the outcomes of this meta-analysis  .
It would be better if the primary and secondary outcomes are depicted in clear subheadings.
Review for 10.1186/s12876-022-02620-3 (2022)

Title: Prevalence of frailty among patients with inflammatory bowel disease and its association
with clinical outcomes: a systematic review and meta-analysis.
Version: 5 Date: 27 Nov 2022
Reviewer:  Suprabhat Giri
Reviewer's report:
The authors have addressed all the issues raised in the previous review.
Review for 10.1186/s12876-022-02616-z (2022)

Title: Hepatic venous pressure gradient after balloon-occluded retrograde transvenous
obliteration and liver stiffness measurement predict the prognosis of patients with gastric varices
Version: 1 Date: 18 Nov 2022
Reviewer's report:
Thank you for inviting me to evaluate the article titled "Hepatic venous pressure gradient
after balloon-occluded retrograde transvenous obliteration and liver stiff measurement predict
the prognosis of the patients with gastric varices". In this paper, the authors investigated the
influences of HVPG and LSM on patients with GVs. However, it may be more excellent for
readers to understand the manuscript after revision. The following are the questions and some
mistakes in this manuscript.
1.  On page 5, Gastric varices are abbreviated "GV", however, in the manuscript, it seems not
unified, such as "GVs are less prevalent than esophageal varices and are present in 5-33% of the
patients with portal hypertension...". It may be more excellent to polish the manuscript.
2.  According to Baveno VII, BRTO is regarded as efficient secondary prophylactic treatment
technique management. In the present study, B-RTO was performed for preventive treatment
in 29 patients. Why?
3. Roc curves related to HVPG and LSM should be added if possible.
4. How to deal with coexisting EVs in the current study? And on Page 13, on lines 257-259,
“co-existence rates were similar to those- observed in previous reports (63.9 vs. 45.6–68.0%)”,
where does the literature come from?
5. It seems to be unclear to the reader about the inclusion and exclusion criteria.
Review for 10.1186/s12876-022-02616-z (2022)

Title: Hepatic venous pressure gradient after balloon-occluded retrograde transvenous
obliteration and liver stiffness measurement predict the prognosis of patients with gastric varices
Version: 1 Date: 20 Nov 2022
Reviewer's report:
In this manuscript, Yuki Shirane et al. showed that post-HVPG of #13 mmHg and high level of
serum aspartate aminotransferase were significant independent risk factors for EV exacerbation
after B-RTO. They also showed that elevated liver stiffness measurement (LSM) of #21 kPa
was a significant independent risk factor for poor prognosis after B-RTO.
There is no disputing that this study is a very interesting. However, as noted in the limitation,
the biggest concern in this study is the small sample size and the very large number of cases
that deviated during the observation period, especially with regards to the EV exacerbation rate.
Since the rate decreased to 22.2% (8/36) of all cases within 2 years of observation, the results
cannot be said to be supported by definite evidence. Therefore, unfortunately, we consider it
difficult to accept about this manuscript.
In addition, please refer to the following three points.
1. Table 1: Existence of large portosystemic shunt was 23.5%, which is low in this cohort
that underwent B-RTO in this study. Therefore, the explanation of the definition of large
portosystemic shunt is necessary.
2. The stage of hepatocellular carcinoma and the presence or absence of portal vein tumor
thrombosis should be evaluated as they may influence the results of this study.
3. Are there any cases in which partial splenic embolization (PSE) was performed along with
B-RTO? Since the number of cases treated with the two therapies in combination has been
increasing recently, it is recommended that if there are any cases of combined PSE, they should
be analyzed, and if there are no PSE cases, it is recommended that they be noted.
Review for 10.1186/s12876-022-02616-z (2022)

Title: Hepatic venous pressure gradient after balloon-occluded retrograde transvenous
obliteration and liver stiffness measurement predict the prognosis of patients with gastric varices
Version: 2 Date: 10 Dec 2022
Reviewer's report:
Thank you for inviting me to evaluate the article again. I appreciated the efforts of the author
and the co-authors point-by-point responses to the comments. After the polishment of the
manuscript, It is appropriate to accept.
Review for 10.1186/s12876-022-02606-1 (2022)

Title: Usefulness of the combined orthodontic rubber band and clip method for gastric
endoscopic submucosal dissection
Version: 1 Date: 31 Oct 2022
Reviewer's report:
This paper shows the usefulness of a combined orthodontic rubber band and clip technique in
ESD of early gastric neoplasms. It offers good results, but there are a few things I would like
to confirm or question.
1 )  The traction method can reduce the time for submucosal dissection. If you have data only
on the time and speed of submucosal dissection, please include them in the report.
2 )  The subanalysis shows no significant difference in the lower region or lesions larger than 2
cm. Still, if only data on the time of submucosal dissection were used, there could be a significant
difference.
3 )  There are ring traction devices for endoscopic treatment, such as MLTD (Boston Scientific)
and Traction band (Micro-tech), but what makes them particularly useful for ORBs compared
to those?
4 )  Because the stomach has a wider lumen than the large intestine, one small ring is likely to
result in more clip dropouts due to air delivery. In this paper, clips dropped out in two cases.
What were the sites of those lesions? Is there a difference in the ease of clip dropout depending
on the location of the lesion?
5 )  Please include a photograph of an orthodontic rubber band (not attached to the lesion) in
the figure.
Review for 10.1186/s12876-022-02606-1 (2022)

Title: Usefulness of the combined orthodontic rubber band and clip method for gastric
endoscopic submucosal dissection
Version: 1 Date: 31 Oct 2022
Reviewer's report:
#Please add the standardized difference in table3 (in order to evaluate propensity score matching)
#Table4:   Is Median Procedure time, min (IQR)  Correct? (>2cm, Conventional ESD)
you wrote the maxim time as 107.0min, but you wrote the maxim time as 70min (in table3)
Review for 10.1186/s12876-022-02606-1 (2022)

Title: Usefulness of the combined orthodontic rubber band and clip method for gastric
endoscopic submucosal dissection
Version: 1 Date: 02 Nov 2022
Reviewer's report:
The authors described the usefulness of orthodontic rubber band (ORB)-assisted ESD compared
with the conventional method based on the detailed clinical data. Most of the data in this
manuscript are convincing and presented by well-designed analysis. This manuscript provides
an important contribution to the rapidly growing field of ESD. However, I have some questions
about this study to strengthen the manuscript.
Major issues
#1 The ORB may slip off when the stomach was over-insufflated due to the lack of elasticity
or extensibility compared with other internal traction methods (e.g., S-O clip, multiloop). As
the authors mentioned, slip-off seems to have occurred in cases where the stomach was over-
insufflated by the trainee. Was the ORB attached after the stomach had been significantly
degassed?
#2 If the retroflexed endoscopic position was selected for submucosal dissection, there is a
possibility of contact between the endoscope and ORB, which may result in a slip-off of the
ORB. How did authors avoid this problem? Did the authors perform all cases with the forward
endoscopic position?
#3 As the authors described, the ORB was attached to the contralateral normal mucosa, which
may provide traction vertical to the gastric wall in most cases. What traction direction against
the gastric wall or endoscope tip did this procedure provide actually?
#4 Authors stated that "We set the caliper value to 0.2 for a 1:1 match to select patients."
Please clarify the specific method of PSM (e.g., Nearest Neighbor Matching) and the presence
or absence of replacement.
#5 Please provide statistical evidence regarding the validity and multicollinearity of the PSM
analysis (e.g., Hosmer-Lemeshow test, C statistic, standard difference score, variance inflation
factors of explanatory variables).
Minor issues
#1 Please add not only specimen size but also tumor size to the table before and after matching.
#2 For lesions that develop in anatomically narrow areas, such as those near the esophagogastric
junction or pyloric ring, it may be sometimes difficult to achieve the appropriate distance
between the anchor point of the gastric wall and the lesion to gain sufficient traction force. How
did the authors address this problem?
Review for 10.1186/s12876-022-02606-1 (2022)

Title: Usefulness of the combined orthodontic rubber band and clip method for gastric
endoscopic submucosal dissection
Version: 2 Date: 16 Nov 2022
Reviewer's report:
Thank you for giving me the opportunity to read the revised manuscript. The authors have
addressed issues reviewers raised, but I would still like to confirm two points as below.
Major issues #2
Thank you for addressing major issue #2 I raised. Please consider adding your explanation to
“The ESD procedure” in MATERIALS AND METHODS. In addition, I would suggest adding
Fig. 3 (Schematic illustration of retroflexed endoscopic position for submucosal dissection)
described in your Response letter to the revised manuscript to help readers understand the ORB-
ESD procedure.
Minor issue #2
Thank you for addressing minor issue #2 I raised. You have clarified the specific situations
where the ORB traction may not work well. This is a crucial point, so I would appreciate it if
you could add your explanation to the Discussion of the revised manuscript.
Review for 10.1186/s12876-022-02606-1 (2022)

Title: Usefulness of the combined orthodontic rubber band and clip method for gastric
endoscopic submucosal dissection
Version: 2 Date: 18 Nov 2022
Reviewer's report:
Thank you very much for your revision. I understand your traction method and efficacy well.
ORB seems to be useful for ESD, especially in shorten of procedure time.
Review for 10.1186/s12876-022-02627-w (2022)

Title: Clinical significance and long-term prognosis of ulcerative colitis patients with
appendiceal orifice inflammation
Version: 1 Date: 23 Oct 2022
Reviewer's report:
The authors conducted a long-term study of the association between ulcerative colitis(UC) and
appendiceal orifice inflammation(AOI). They concluded that the long-term prognosis of UC
patients with AOI was not different from that of patients without AOI, and that there was no
difference in outcome between patients with and without resolution of AOI.
The authors' study is interesting because AOI is a lesion that is occasionally encountered, but its
significance is still unclear. There are a few items we would like to confirm before publication.
1) AOI was associated with 5ASA use. how many cases of 5ASA intolerance were included
in this study?
2) What was the percentage of Pancolitis among Extensive colitis?
3) How many cases requiring hospitalization were present with or without AOI?
Review for 10.1186/s12876-022-02627-w (2022)

Title: Clinical significance and long-term prognosis of ulcerative colitis patients with
appendiceal orifice inflammation
Version: 1 Date: 15 Nov 2022
Reviewer's report:
The manuscript entitled ‘Clinical significance and long-term prognosis of ulcerative colitis
patients with appendiceal orifice inflammation‘ studies the role of AOI in patients with UC,
which is an important topic in this field. This article was interesting in trying to explain the
clinical course of UC patients with AOI. However, several questions arose while reading this
manuscript.
1. Mild disease activity at the diagnosis of UC was more included in patients with AOI than
others. Does it influence the long-term outcomes of patients with AOI compared to those without
AOI?
2. The patients with AOI were less included in the group treated with high-dose 5-ASA than
those without AOI (13.3% vs. 24.8%, P = 0.016). Does the treatment with high-dose 5-ASA
induce the occurrence of AOI, resulting in outcomes of them?
3. This study included patients with proximal involvement. How can you differentiate them from
patients with lesions responding to pharmacotherapy?
Review for 10.1186/s12876-022-02627-w (2022)

Title: Clinical significance and long-term prognosis of ulcerative colitis patients with
appendiceal orifice inflammation
Version: 1 Date: 18 Nov 2022
Reviewer's report:
This manuscript analyzed the clinical significance of AOI in UC by cross-sectionally comparing
the clinical outcomes between patients with AOI and those without. The authors did not find any
difference between them and concluded that AOI might have no prognostic implication in distal
UC patients. The manuscript is well-structured, and the focus is very clear. However, there are
several shortcomings that should be addressed prior to publication.
Major
1) The authors compared the clinical outcomes between patients with AOI and those without
only cross-sectionally. Since this work was performed retrospectively and the follow-up period
varies dependent on patients, longitudinal data including time to disease extension and treatment
intensification (i.e., use of corticosteroids or anti-TNF agents etc.) should be analyzed using a
Kaplan-Meier method.
2) A significantly higher proportion of patients with AOI took high doses of 5-ASA than
those without. In contrast, AOI negative patients were more likely to have treatment with
corticosteroids, thiopurines, or anti-TNF agents than AOI positive patients (Table2). These
data seem to imply that AOI negative patients are more refractory to 5-ASA and thus required
treatment intensification than AOI positive patients. Indeed, a total proctocolectomy was
performed only in AOI negative patients (Line 1-2 of Page 8). The author should discuss this
point in the manuscript.
Minor
1) The mean values of continuous variables are shown frequently with ranges in the manuscript.
The authors should think about their distribution to determine whether they use mean or median
value. The mean values are usually accompanied by standard deviations and the median values
are by ranges. If the continuous variables are not normally distributed, the authors should avoid
to use Student’s t-test.
Review for 10.1186/s12876-022-02627-w (2022)

Title: Clinical significance and long-term prognosis of ulcerative colitis patients with
appendiceal orifice inflammation
Version: 2 Date: 19 Dec 2022
Reviewer's report:
The authors satisfactorily responded to all my questions and made necessary changes in the
revised manuscript. I would like to recommend this manuscript to be published.
Review for 10.1186/s12876-022-02617-y (2022)

Title: A novel missense mutation of the STK11 gene in a Chinese family with Peutz-Jeghers
syndrome
Version: 1 Date: 09 Nov 2022
Reviewer's report:
• This paper presents the first missense mutation of STK11 gene in c.521A > C, p.H174
• The images of the clinical findings and the radiologic images are satisfactory.
• In the introduction section, could you share the epidemiologic data on this condition in Chinese,
linked as in the title? Also all the mutations of STK11 in chinese
• In Line 186, "However, other researchers reported that there was no statistically significant
difference in the phenotype between patients who had PJS with truncating and missense variant
types", could you specify more about the reason for this statement?
• Is there any missense STK11 mutation of c.521A > C, p.H174 ever mentioned in any references
before?
•
Review for 10.1186/s12876-022-02617-y (2022)

Title: A novel missense mutation of the STK11 gene in a Chinese family with Peutz-Jeghers
syndrome
Version: 1 Date: 19 Nov 2022
Reviewer:  Zi-ye Zhao
Reviewer's report:
The purpose of this study is to report a novel missense mutation of the STK11 gene in a Chinese
family with Peutz-Jeghers syndrome. The design of this study is comprehensive, but there are
a few problems. So it is suggested to be re-submitted after revision. The main problems are as
follows:
1. The description of the proband's medical history is somewhat tedious, especially the section
on bile duct cancer.
2. Please add a scale to the image and improve the resolution of pathological images.
3. The authors should carefully check the full text, including grammar mistakes. The manuscript
should be corrected by a native English speaker who is a specialist.
Review for 10.1186/s12876-022-02564-8 (2022)

Title: Long-standing Diabetes Mellitus Increases Concomitant Pancreatic Cancer Risk in
Patients with Intraductal Papillary Mucinous Neoplasms
Version: 1 Date: 06 Jul 2022
Reviewer's report:
Yamaguchi et al retrospectively analyzed risk factors for concomitant PDAC in a cohort of
IPMN patients.  A total of 547 pancreatic cyst patients (initial visit 2005-2019) were selected and
underwent imaging (CT, MRCP, EUS) followed by surveillance.  Of these, 439 patients with
IPMN were identified of which 14 had distinct concomitant PDAC and 5 had high grade/invasive
IPMN.  Upon data analysis, longstanding diabetes mellitus was identified as a significant risk
factor for concomitant PDAC.
General Comment:  It is not clear how many patients underwent surgery with confirmed
pathological diagnosis for this study versus preoperative diagnosis only.  Final numbers of
patients with either high-grade/invasive IPMN or IPMN with concomitant PDAC were relatively
low.  To confirm and validate findings, larger patient numbers would be required.
Specific Comments:
1. Abstract wording:  In their concluding statement regarding the monitoring of IPMN, authors
write “…rather than…” but both concomitant PDAC and IPMN-derived carcinoma should be
considered.
2. Page 5: authors state that IPMN patients had “high” frequencies of concomitant PDAC.  What
is “high”?
3. Page 7-8: Patients were divided into IPMN, SCN and non-IPMN/SCN (P-cyst) groups for the
study based upon 2017 International Guidelines, but preoperative diagnosis by these criteria/
imaging may not be accurate.  Please clarify the two sentences describing IPMN/P-cysts as being
“nearly equal” to “suspected” or “presumed” IPMN, respectively.
4. Of the initial 547 patients, how many were resected?  Were the 14 concomitant PDAC and
5 high grade/invasive IPMN diagnosed on final pathology following surgery?  It appears only
a subset from Supplementary tables (12 of 14 and 3 of 5, respectively).  If not resected, how
are authors confident of diagnosis?
5. Page 9: Authors should provide more detail about how IPMN-derived carcinoma was
distinguished from concomitant PDAC by imaging and/or pathology.  For Figure 1, authors
should indicate regions of interest with arrows.
6. Why are the number of patients different between Tables 1 (initial) and 2 (follow-up)?
Authors should use current terminology for IPMN.  “IPMA” is no longer commonly used and
IPMC should refer to IPMN with associated invasive carcinoma.  Carcinoma in situ is high-grade
IPMN, not IPMC as written.  Patients with a final diagnosis and concomitant PDAC in Table
2 all underwent surgery (see question 4)?  “Final Diagnosis” implies pathological confirmation
following surgery.
7. Page 12: Authors state that “this difference was not statistically significant (P = 0.08), but
we presumed that IPMN diagnosed with 2017 international guidelines carried a higher risk of
concomitant PDAC than other cysts.”  If not significant, this statement cannot be made.
8. Paper, especially Discussion section, should be corrected for grammar.
Review for 10.1186/s12876-022-02564-8 (2022)

Title: Long-standing Diabetes Mellitus Increases Concomitant Pancreatic Cancer Risk in
Patients with Intraductal Papillary Mucinous Neoplasms
Version: 1 Date: 11 Jul 2022
Reviewer's report:
This paper described a retrospective cohort analysis of patients with pancreatic cysts, which
reported the finding of Long-standing Diabetes Mellitus Increases Concomitant Pancreatic
Cancer Risk in Intraductal Papillary Mucinous Neoplasms. The design of analysis of this study
was fairly straightforward with relatively large number of patients, 547 patients, although cases
with event, concomitant carcinoma, were just 14 cases. Statistical examinations seem to be
acceptable. There are some concerns as follows:
1. Classification of IPMN should follow WHO classification. IPMA may correspond to IPMN
with low-grade dysplasia, IPMC, carcinoma in situ may correspond to IPMN with high-grade
dysplasia, IPMC, invasive may correspond to IPMN with associated invasive carcinoma.
2. Describing cysts other than IPMN or SCN as “P-cyst” sounds peculiar. The classification may
be described as IPMN, SCN, and Others.
Review for 10.1186/s12876-022-02564-8 (2022)

Title: Long-standing Diabetes Mellitus Increases Concomitant Pancreatic Cancer Risk in
Patients with Intraductal Papillary Mucinous Neoplasms
Version: 3 Date: 10 Aug 2022
Reviewer's report:
General comment:  Authors revised according to comments and paper is improved; however,
see points below that should be addressed.
Specific comments:
1. Abstract: “Five intraductal papillary mucinous adenocarcinomas were encountered.”  There
appears to be only one IPMN with associated invasive carcinoma (not resected).  There are 5
high-grade IPMN, but these would not be adenocarcinoma.
2. Reliance on imaging alone to classify the pancreatic cysts should be considered a limitation
of the study since different cyst types may mimic each other on imaging.  If cyst type is
misclassified during surveillance (IPMN vs SCN vs other) or diagnosed incorrectly (low vs high
vs invasive), this may affect the study’s results/conclusions since only a small subset of patients
had surgery with definitive diagnosis.  As an example, in Supplementary Figure 1, two patients
were initially classified as “other” but were actually IPMN upon resection; similarly, a pre-
operative diagnosis of IPMN was actually SCN on final pathology.
3. Page 8, sentence: “If those 3 cysts were not IPMNs…” based on what criteria - imaging?  If
there were other IPMNs present, then you assumed that these 3 were in fact IPMNs?  Please
clarify.
4. Page 9: Criteria used for IPMN associated with invasive carcinoma vs concomitant PDAC
still not very detailed.  What exactly does “assessment of continuity” mean?  For example,
Ohtsuka et al (Pancreapedia, 2014) state that “PDAC concomitant with IPMN is usually defined
as occurring when the lesion is separated from the IPMN by an uninvolved segment of pancreatic
duct, and there is no transition area from adenoma to carcinoma in the distinct PDAC.”
5. Page 10 seems to have some missing words.
6. Page 11 seems to be duplication of prior text.
7. Page 16: “In 6 IPMN-derived carcinomas…” – high-grade IPMN are not considered
carcinoma (see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814593/).  There is only one
invasive IPMN.  The high-grade and invasive IPMNs can be grouped together as ‘high-risk”
versus “low-risk” IPMN (low-grade).
8. Figure 1 legend: Provide arrows for IPMN in A and C as well to clearly show difference
between concomitant vs IPMN-derived PDAC
Review for 10.1186/s12876-022-02493-6 (2022)

Title: Study on the effectiveness of modified colonoscopy nursing pads in colonoscopy
Version: 0 Date: 31 May 2022
Reviewer:  Miroslaw Szura
Reviewer's report:
I read your manuscript with great interest. I have no significant reservations regarding the
planning and execution of the study and the statistical analysis performed. However, my doubts
are raised by the course of the procedure itself, where the quality of patient care and the devotion
to the patient is not important. The use of a modified nursing pad, in accordance with the
conducted analysis, shortened the steps related to patient positioning by 9-13 seconds. Is it such
an important time and is the lack of verbal contact between the nurse and the patient good? What
is the importance of the degree of environmental contamination, since the stand must be fully
cleaned after each test? Did the reduction in overall study time allow more colonoscopy per day?
Despite the analysis and the conclusions resulting from it, I believe that the practical value of
the research is negligible.
Review for 10.1186/s12876-022-02493-6 (2022)

Title: Study on the effectiveness of modified colonoscopy nursing pads in colonoscopy
Version: 0 Date: 12 Jun 2022
Reviewer's report:
Interesting research on materials to essentially improve endoscopy unit efficiency by using an
instructional drape to help with patient positioning.
The time difference is less than one minute which may or may not have clinically significant
effect in terms of caseload. The mat may ease workload of staff however.
It would be useful to have a cost analysis with this. It may be useful as a widespread tool but
it would have to be cost effective.
Thank you for the opportunity to review your work.
Review for 10.1186/s12876-022-02493-6 (2022)

Title: Study on the effectiveness of modified colonoscopy nursing pads in colonoscopy
Version: 0 Date: 15 Jul 2022
Reviewer's report:
Dear Authors.
thanks for the opportunity to review your article. The issue is very interesting and of practical
impact.
Your colonoscopy pad helps personnel to ease patient positioning without frequent explanations,
avoiding misunderstanding  for language barriers.
Time spared is not much and probably not significant. Could you provide statistic? Please do.
Cost analysis may be relevant. Have you made such evaluation? This should be done if possible.
Contamination is reported to be dimished by using this pad. How could you rate this? Please
explain since  subjective  evaluation may be biased.
Patient's satisfaction has been evaluated by a questionnaire. Please provide a graph showing
results and the questionnaire as appendix to the article.
Review for 10.1186/s12876-022-02622-1 (2022)

Title: The hsa_circ_0039857/miR-338-3p/RAB32 axis promotes the malignant progression of
colorectal cancer
Version: 1 Date: 21 Jun 2022
Reviewer's report:
This study demonstrated that hsa_circ_0039857/miR-338-3p/RAB32 axis promotes the
malignant progression of colorectal cancer. The research content is too small, and the intrduction
and abstract are not well.
Review for 10.1186/s12876-022-02622-1 (2022)

Title: The hsa_circ_0039857/miR-338-3p/RAB32 axis promotes the malignant progression of
colorectal cancer
Version: 1 Date: 21 Jun 2022
Reviewer's report:
• In  the sentence " The targeting relationship between molecules was then analyzed by
bioinformatics." And " Surprisingly, bioinformatics analysis revealed that circ_0039857 binds
to miR-338-3p (Fig. 5A)." the authors mentioned the bioinformatics analysis. Unfortunately, I
couldn't find in detail material and method and results for bioinformatics analysis. Please provide
the related sections .
• In the introduction section, the authors didn't describe how they select circ_0039857 ,
miR-338-3p, RAB32  for evaluation in detail.   The authors provide general information about
circ-RNAs, miRNAs, and mRNAs . please mention more detail about selected circ-RNA,
miRNA, and mRNA.
• The country of each product should be mentioned in addition to the company name for example:
"The cells were cultured in RPMI-1640 medium (Gibco, USA) with 10% FBS (Gibco,USA),
1% penicillin and streptomycin (Gibco, USA) solution."
• in the sentence "GAPDH and U6 were set as the internal parameters for mRNA and miRNA."
please declare that for normalization of circ-RNA , miRNA, and mRNA which internal was used
separately.  Was the GAPDH used for circ-RNA normalization?
• In table 2 please provide the accession number of circ-RNA, miRNA, and mRNA.
• In the sentence "Each group of cells (300 cells) was added to a 6-well plate and cultured two
weeks" please declare that if all used cell lines were seeded in equal density and evaluated at
equal times (two weeks).
Review for 10.1186/s12876-022-02622-1 (2022)

Title: The hsa_circ_0039857/miR-338-3p/RAB32 axis promotes the malignant progression of
colorectal cancer
Version: 4 Date: 16 Nov 2022
Reviewer's report:
The sequence of siRNAs for circRNA was not provided.  Please provide the sequence in the
material and method section.
The real-time PCR  method for miRNA was so ambiguous. Did the authors use stem-loop
method? Please provide the RT primer for U6 and miRNA.
in the sentence "Interaction of circRNA-miRNA was predicted by the StarBase and circBase
online databases. " please mention the web page addresses.
The sentence "Target regions of miRNA-mRNA were predicted by StarBase and miRBase
bioinformatics tools. RAB32 was a predicted target of miR-338-3p." should be checked did you
mean mirdb instead of miRBase. please mention the related web page dresses.
There was some grammatical and writing error that should be revised.
In table 2 please provide the annealing temperature of primers
Review for 10.1186/s12876-022-02523-3 (2022)

Title: Title# Defibrotide improved outcome of monocrotaline induced rat hepatic sinusoidal
obstruction syndrome
Version: 2 Date: 20 Jun 2022
Reviewer's report:
The authors reported  their experimental study regarding the effect of defibrotide for treatment
for monocrotaline-induced sinusoidal obstruction syndrome. However, defibrotide was already
approved for medical use to treat veno-occlussive disease of the liver in the European Union
in October 2013, in the United States in March 2016, and in Australia in July 2020. Of course,
it was approved by FDA.
Review for 10.1186/s12876-022-02523-3 (2022)

Title: Title# Defibrotide improved outcome of monocrotaline induced rat hepatic sinusoidal
obstruction syndrome
Version: 2 Date: 21 Jun 2022
Reviewer:  Shohei Yamamoto
Reviewer's report:
The authors described defibrotide improved new rat HSOS model using monocrotaline.
Although the paper was well written and organized experiment, some date were obscure.
1. The authors described the survival rate were significantly lower in defibrotide group (81.9%)
than model group (43.7%). Is that correct?  I think "higher" instead on "lower".   Defibrotide
improved the cure rate.
2. Group A, B,  C, D, E were described in Fig3. But, figure legends were Group1, 2,3,4,5.
Which was correct?
3. Did you analyze the combined group which was including LMWH and defibrotide?
4. We want to know what is the advantages this rat model than that of actual SCT model rat?
Would you please mention that in discussion part?
Review for 10.1186/s12876-022-02523-3 (2022)

Title: Title# Defibrotide improved outcome of monocrotaline induced rat hepatic sinusoidal
obstruction syndrome
Version: 2 Date: 05 Jul 2022
Reviewer's report:
The authors attempt to test therapeutic effect of Defibrotide on amending liver injury with
hepatic sinusoidal obstruction syndrome in rat. Well, Sinusoidal obstruction syndrome is a veno-
occlusive disease arises in liver. Therapeutic strategies to ameliorate HSOS remain to develop. In
this study, monocrotaline (MCT) administration to rat was applied to establish hepatic sinusoidal
obstruction syndrome (HSOS) diseased rat model to test the therapeutic effect of Defibrotide
on treating HSOS.
Description is insufficient and unclear in the text. Linkage of data to explanation is inadequate.
For examples, The Fig 1. is not adapted to text and subtitle 3.1 narrated gross anatomy. Anatomic
pictures did not display in this manuscript. Also English writing is not good enough. English
proofreading is required.
Line 38-39 Defibrotide was efficient for HSOS followed hematopoietic stem cell
transplantation.
HSOS being caused by hematopoietic stem cell transplantation did not have the equivalent cell
damages in liver with HSOS by MCT administration.
Line 42-47
The method paragraph abstract
Should drop more ward to describe what methods the authors applied to biochemical analysis.
In second paragraph in abstract, the authors did only write the animal grouping
Line 185
The subtitle 3.1 “The gross anatomy and pathology characteristics of MCT induced HSOS”
The authors showed only histochemical staining but none of data for gross anatomy
Line 187-193 none of data are available for those words.
Line 282
“We created an MCT induced HSOS rat model………….”
The way that MCT induced HSOS rat was reported previous studies. The authors are not the
first one who established this animal model.
Line 301 “Defibrotide has been proved to stabilize and protect endothelial cells against
activation”
The mean of this sentence is not clear. What is therapeutic effect of Defibrotide on stabilizing
and protecting endothelial cells against activation. What kind of activation that endothelial cells
do against?
Review for 10.1186/s12876-022-02523-3 (2022)

Title: Title# Defibrotide improved outcome of monocrotaline induced rat hepatic sinusoidal
obstruction syndrome
Version: 3 Date: 28 Jul 2022
Reviewer's report:
This revision is much better. Still, several typo errors, improper descriptions, and grammatical
errors were present in this manuscripts. This manuscript may require professional editing to
eliminate possible grammatical  errors.
Line 476 typo error
bibrin
Line 513, please, use sentence, instead of symbol description.
Line 607 error,
Each groups?
Line 694/ Line 696/ Line 700
What means “Plasma levels of TNF-# and PAI-1 n different groups”
Do the authors meant “TNF-# and PAI-1 levels I in plasmas from animals in different
experimental groups.
Line 821-823 please, add literature to reference
Line 828-829 This description is inappropriate.
In the past, several drugs have been attempted to treat or prevent HSOS following HSCT.
Line 850-853
The description is improper. None of mechanisms were characterized in that literature “reference
15”. That is kind of pheromonal observation.
Review for 10.1186/s12876-022-02602-5 (2022)

Title: Safety and Efficacy Analysis of Chemoradiotherapy/Radiotherapy Combined with
Nimotuzumab for Treating Advanced Unresectable Oesophageal Squamous Cell Carcinoma in
Elderly Patients: A Retrospective Analysis
Version: 0 Date: 13 Jun 2022
Reviewer:  Madhup Rastogi
Reviewer's report:
Esophageal cancers are a challenge for any oncologist and it becomes more difficult when
patient is of geriatric age group. Your option of adding Nimotuzumab along with chemotherapy
and also as single modality with radiotherapy seems to be pretty beneficial for such patients.
Nimotuzumab has already shown benefit to Head and neck cancer patients as concurrent
chemoradiotherapy. Well conducted study. I will suggest prospective evaluation of adding
nimotuzumab along with concurrent chemotherapy in all the esophageal cancer patients
undergoing upfront radiotherapy to evaluate the outcome and comparison with the available
modality of treatment in the form of Concurrent Chemoradiotherapy.
Review for 10.1186/s12876-022-02602-5 (2022)

Title: Safety and Efficacy Analysis of Chemoradiotherapy/Radiotherapy Combined with
Nimotuzumab for Treating Advanced Unresectable Oesophageal Squamous Cell Carcinoma in
Elderly Patients: A Retrospective Analysis
Version: 0 Date: 15 Sep 2022
Reviewer's report:
This retrospective analysis is not suited to estimate efficacy and toxicity of a treatment, since
confounding factors cannot be ruled out. The purpose of the invetigation is not quite clear. Why
did the authors compare radiotherapy and Nimotuzumab with radiotherapy and chemotherapy
and Nimotuzumab. It has been known for many years that simultaneaous chemotherapy would
improve the outcome of radiotherapy. This has been confirmed by this study. The real question
is whether the addition of Nimotuzumab is improving the outcome in these patients compared to
radio-chemotherapy alone. All randomized studies which compared radio-chemotherapy with
or without anti-EGFR-antibodies have been negative. So it is hard to see a rationale to use
Nimotuzumab at all in esophageal cancer.
Table 1 should show patient characteristics in comparison of the two treatment arms. Similarly
the toxic effects shown in Table 2 should be given for each treatment arm separately.Quality of
life should be displayed for both treatment arms (Table 3) as well. Treatment allocation to the
patients has not been described clearly. Therefore the risk for a bias by patient selection might
be a problem in this study.
Review for 10.1186/s12876-022-02602-5 (2022)

Title: Safety and Efficacy Analysis of Chemoradiotherapy/Radiotherapy Combined with
Nimotuzumab for Treating Advanced Unresectable Oesophageal Squamous Cell Carcinoma in
Elderly Patients: A Retrospective Analysis
Version: 3 Date: 28 Nov 2022
Reviewer:  Hironaga Satake
Reviewer's report:
Thank you for the revisions.