Reviewer’s report
Title: 
Signet-ring cell carcinoma of the duodenal bulb
presenting with gastrointestinal hemorrhage: a case report and literature review
Version: 
0 
Date: 
31 Dec 2021
Reviewer: 
Thomas Wichelmann
Reviewer's report:
Title: 
Fitting title that captures the main idea of the manuscript. Could consider
changing "presented by" to "presenting with" or "presenting as"
Abstract:
Overall: While the abstract reflects the main points of the case report and
summarizes the case well, many of the sentences are copied and pasted directly
from the main manuscript. Recommend a more unique approach to the writing
styles/language of the abstract rather than copying sentences from the main text. 
Line 14: should outline the endoscopic findings in greater detail
Grammar/writing suggestions:
Line 11: change "presented by" to "presenting with" or "presenting as"
Line 12-13: consider changing sentence to "Physical examination revealed upper
abdominal tenderness but was otherwise unrevealing. Laboratory workup was
significant for anemia." 
Line 14-16: could change to: "Multiple endoscopic attempts along with
interventional embolization were attempted and, unfortunately, adequate
hemostasis was not achieved resulting in distal subtotal gastrectomy."
Lines 16-19: sentences should be rewritten. Additionally, "refused" has negative
implications and should be changed. Could change sentences to: "Post-
operatively, the patient experienced persistent gastrointestinal bleeding. Family
declined further intervention and the patient eventually died of respiratory and
heart failure one month post-resection."
Line 22: change "should be considered as the first choice" to "is considered a
first line option". 
Line 22-23: change to "Early diagnosis and resection has been shown to improve
prognosis."
Introduction:
Overall: introduces the topic well and impresses the rarity of the case upon the
reader. Some grammatical errors and supporting evidence needed as outlined
below.
Line 28: SRCC is extremely rare → this should have a qualifying % if available
from literature
Line 28-29: sentence needs citations to support this statement.
Grammar/writing suggestions:
Line 26: change to "Primary duodenal cancer is rare and accounts for just 0.3-
0.5% of gastrointestinal cancers"
Line 28: change to "It's reported that over 96% of SRCC occur in the stomach."
Line 29-31: citation reference should be at end of sentence and could change
sentence to "Since Sekoguchi et al. first reported SRCC of the duodenal ampulla
in 1979, few cases of duodenal SRCC have been reported [2]." 
Line 31-32: could change sentence to "SRCC within the duodenal bulb is an
even rarer entity with no more than 15 cases reported in English literature to date
[3]."
Line 32: change "Here" to "Herein" and "presented by" to "presenting with"
Case Presentation:
Overall: Needs improvement to the flow of the case with additional details
requested and post-operative case description is confusing. Greater detail is
necessary regarding post-operative decline/complications. 
Pertinent medication history is not included at present and should be noted.
Plavix is mentioned in the discussion and should be included. Were there any
NSAIDs or recent steroid use?
Family history does not seem relevant to the case at hand and could likely be
omitted. 
Was biopsy performed on endoscopy performed two weeks prior to admission?
A statement should include if this was performed and, if so, what the results of
this biopsy were. 
Unfamiliar with the term "niche sign" and this could be
expanded upon. 
Why were tumor markers sent with initial lab work? Was this in fact completed
after endoscopic evaluation? This needs clarification. 
Endoscopic findings and intervention should be described in further detail.
Additional information regarding embolization should be included (ie findings of
procedure and what vessel was embolized).
Line 48: according to the discussion, distal subtotal gastrectomy was performed
under emergency pretences. This should be discussed within the case
presentation. 
Line 51: SRC components should be described in detail, was the 50% SRC
threshold met on pathology report?
How were lymph nodes and metastases investigated? Does line 52-53 refer to
findings from surgical intervention? This should be clarified and TNM staging
should be included.
Was any staining for Mucin completed? Should be addressed if staining was not
completed. 
The post-operative hospital course is very confusing and not written in medical
terms. For instance, terms like "abdominal cavity infection", "pulmonary
infection", "anti-infection", and "pulverization inhalation" are not terms that
would commonly be encountered in English medical journals. This paragraph
needs significant revision both grammatically and from a case report storyline
standpoint. Development of obstruction and intra-abdominal infection are two
important post-operative complications that should be described further. When
did these occur in the post-operative course? What interventions were
performed? Was this a result of expanding tumor? Also, it's very unclear how
the patient progressed to needing a tracheostomy and placement of nutritional J-
tube. 
Grammar/writing suggestions:
Line 36: information should not be included in parenthesis, could change to
"intermittent melena of 2 months duration and hematemesis over the past 10
hours."
Line 37: could include that he had been treated with Plavix
Line 43: could change sentence to "The patient was tachycardic, but vital signs
were otherwise normal."
Line 43-44: could change to "Physical examination revealed tenderness in the
epigastric region, but was otherwise unrevealing." What is meant by anemia on
physical exam? Was the patient pale? This should be clarified.
Line 48: "disappointing results" should be changed to "without hemostasis as
evidence by" then would need to include further information on hospitalization
such as persistent melena, dropping hemoglobin, etc. 
Line 58: would recommend using a different word than "refused" given negative
connotations. 
Line 59-61: not written in medical lingo/context and needs re-writing
Line 61-62: this is confusing and needs more clarification regarding "positive
treatments" and results.
Discussion:
Overall: Significant grammar/linguistic errors distract from the main points in
the discussion. The discussion is thorough, however, additional topics of
discussion including immunohistochemical analysis of SRCC and potential role
of chemotherapy could be considered.
Line 65-66 is repeated from introduction and thus should be omitted from
discussion/conclusions. 
Line 67 is not an entirely accurate statement. Given the limited number of
reported cases, there is limited data to support "typical clinical symptoms",
however, research completed by Dabaja et al. on 217 patients with
adenocarcinoma of the small bowel identified abdominal pain, intestinal
obstruction, and bleeding as the most common presenting symptoms. 
(Dabaja BS, Suki D, Pro B, et al. "Adenocarcinoma of the small bowel:
presentation, prognostic factors, and outcome of 217 patients." Cancer.
2004;101(3):518-26.)
Additional information/citation should be added to support the statement that
early stage cancer may be misdiagnosed as duodenal ulcer. Suspect this is largely
due to the rarity of primary duodenal cancer and frequent diagnosis of benign
peptic ulcer disease. 
What is meant by "no attention was paid" in line 71? This sentence is confusing
and deserves clarification or omission. 
The section on imaging modalities should be re-written given extensive
grammatical issues. Additionally, hypotonic duodenography is a fairly dated
diagnostic tool and not frequently used within the United States. Not sure if this
should be included in discussion. "Diagnostic rate" is frequently mentioned as
"low" throughout this paragraph but not substantiated with any data for
ultrasound, CT, or MRI. This should be supported with objective data or omitted.
Clarification regarding what is meant by "high-degree malignant cancer" is
needed. Additionally, supporting evidence should be used to substantiate the
claim that SRCC does not respond to chemotherapy or radiation. Could consider
further expanding on the role of chemotherapy in this type of malignancy. 
In the discussion section on surgical procedures, it should be noted that
pancreaticoduodenectomy has been considered the preferred surgical option for
primary duodenal malignancy. See: 
Khanal S, Joshi U, Bhattarai A, et al. "Primary Duodenal Adenocarcinoma:
Uncommon Tumor, Uncommon Presentation. A Case Report and Review of the
Literature". Int Medical Case Reports Journal. 2020;13:165-9.
Kawahira H, Miura F, Saigo K, et al. "Survival predictors of patients with
primary duodenal adenocarcinoma." Int Surg. 2011;96(2):111-6. 
Dabaja BS, Suki D, Pro B, et al. "Adenocarcinoma of the small bowel:
presentation, prognostic factors, and outcome of 217 patients." Cancer.
2004;101(3):518-26.
In line 97, "better long-term efficacy" should be substantiated with evidence.
Additionally, #3 Distal gastrectomy was highlighted as a potential surgical
treatment, however, this would not accomplish resection given the duodenum
would remain. The authors should clarify how this is pertinent to discussion of
primary duodenal cancer and likely omit. 
According to Line 107, malignancy was not considered pre-operation. The case
narrative does not reflect this as tumor markers are discussed prior to
gastrectomy. Case presentation should be amended to better reflect flow of
information as it resulted within the case and how this impacted the medical
decisions that were made. 
Line 109: authors should elaborate on what is meant by "the prognosis was
poor". Is this because SRCC was identified?
Line 109-110: this claim is not fully supported by evidence presented earlier in
which the patient developed post-operative abdominal infection and intestinal
obstruction that could be a direct post-operative complication irreflective of
baseline health status. Post-operative complications could be further discussed
given the multitude of complications experienced by the patient. 
Line 113: therapy utilized should have been elaborated on in the case
presentation. "Anti-ulcer therapy" is not a sufficient description nor accepted
medical jargon. 
Line 117-119 
sentence needs evidence to support this claim. 
Line 123-126 needs supporting evidence, consider citing recommendations from
large Gastroenterology organization like ACG or AGA.
Line 132: again there is reference to subtotal gastrectomy, however, this would
not accomplish resection of a duodenal malignancy. 
Grammar/writing suggestions:
Line 71-72: omit this sentence, does not belong in discussion section and does
not add to discussion
Line 72-72: omit the sentence "After the…" as this does not add to the
discussion
Line 79-80: "which can be the main diagnostic method at present" should be
changed to a stronger statement such as "Endoscopy is the diagnostic modality
of choice for evaluation of primary duodenal malignancy."
Line 82: "abdominal flatulence" should be changed to "abdominal gaseous
distension" or "bowel gas patterns". 
Line 82-85 is a run-on sentence and should be edited. 
Line 88 belongs in the case report section. 
Line 89: misspelling of cancer
Line 91: citations belong at end of sentence
Line 93-94: change sentence to "Duodenal bulb SRCC prognosis is largely
impacted by tumor infiltration and lymph node metastasis [4,11]".
Line 94-95: could change to "Surgical resection is accomplished via four main
procedures."
Line 103-105: run-on sentence needs rewriting
Line 116: omit "with SRCs could be seen"
Line 127: sentence is confusing and needs re-writing
Line 127-129 repeats previously stated information and should be omitted
Line 129-130 sentence is confusing and not substantiated with evidence. 
Line 132-133: consider changing to "Prognosis is potentially improved through
early diagnosis and radical surgical resection" - though this statement should be
supported with objective evidence. 
References:
Thorough review of the literature. Additional sources for consideration provided
above. 
Figures:
Recommend obtaining higher quality images as they appeared grainy and
distorted in the PDF. 
Figure Legend:
Fig 1 and Fig 2 after "endoscopy" add the word image
Unclear what is meant by a "delle with active bleeding" in Fig 2 description.
Fig 3 should expand on SRC components in greater description
Manuscript Overall Scientific Quality: 
Rare case that is worthy of publication. Several areas of improvement regarding
the flow and details of case presentation are necessary to improve. Additionally,
there were several scientific phrases/words that were used and are inconsistent
with current English medical literature/jargon. Lastly, I recommend further
discussion on the histopathological findings that define SRCC and how this case
exemplifies these findings. 
See the following citation for additional information regarding SRCC of different
organs:
Chu PG and Weiss LM. "Immunohistochemical Characterizations of Signet-
Ring Cell Carciomas of the Stomach, Breast, and Colon". Am J Clin Pathol.
2004;121:884-92.
Manuscript Overall Language Quality: 
Needs significant improvement as indicated and outlined in detail above. Poor
language quality distracts from this unique case and, from the standpoint of this
reviewer, is not considered publishable in present form. 
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
No competing interests to declare.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please publish my name with my
report.
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
Signet-ring cell carcinoma of the duodenal bulb
presenting with gastrointestinal hemorrhage: a case report and literature review
Version: 
0 
Date: 
31 Dec 2021
Reviewer: 
Thomas Wichelmann
Reviewer's report:
Title: 
Fitting title that captures the main idea of the manuscript. Could consider
changing "presented by" to "presenting with" or "presenting as"
Abstract:
Overall: While the abstract reflects the main points of the case report and
summarizes the case well, many of the sentences are copied and pasted directly
from the main manuscript. Recommend a more unique approach to the writing
styles/language of the abstract rather than copying sentences from the main text. 
Line 14: should outline the endoscopic findings in greater detail
Grammar/writing suggestions:
Line 11: change "presented by" to "presenting with" or "presenting as"
Line 12-13: consider changing sentence to "Physical examination revealed upper
abdominal tenderness but was otherwise unrevealing. Laboratory workup was
significant for anemia." 
Line 14-16: could change to: "Multiple endoscopic attempts along with
interventional embolization were attempted and, unfortunately, adequate
hemostasis was not achieved resulting in distal subtotal gastrectomy."
Lines 16-19: sentences should be rewritten. Additionally, "refused" has negative
implications and should be changed. Could change sentences to: "Post-
operatively, the patient experienced persistent gastrointestinal bleeding. Family
declined further intervention and the patient eventually died of respiratory and
heart failure one month post-resection."
Line 22: change "should be considered as the first choice" to "is considered a
first line option". 
Line 22-23: change to "Early diagnosis and resection has been shown to improve
prognosis."
Introduction:
Overall: introduces the topic well and impresses the rarity of the case upon the
reader. Some grammatical errors and supporting evidence needed as outlined
below.
Line 28: SRCC is extremely rare → this should have a qualifying % if available
from literature
Line 28-29: sentence needs citations to support this statement.
Grammar/writing suggestions:
Line 26: change to "Primary duodenal cancer is rare and accounts for just 0.3-
0.5% of gastrointestinal cancers"
Line 28: change to "It's reported that over 96% of SRCC occur in the stomach."
Line 29-31: citation reference should be at end of sentence and could change
sentence to "Since Sekoguchi et al. first reported SRCC of the duodenal ampulla
in 1979, few cases of duodenal SRCC have been reported [2]." 
Line 31-32: could change sentence to "SRCC within the duodenal bulb is an
even rarer entity with no more than 15 cases reported in English literature to date
[3]."
Line 32: change "Here" to "Herein" and "presented by" to "presenting with"
Case Presentation:
Overall: Needs improvement to the flow of the case with additional details
requested and post-operative case description is confusing. Greater detail is
necessary regarding post-operative decline/complications. 
Pertinent medication history is not included at present and should be noted.
Plavix is mentioned in the discussion and should be included. Were there any
NSAIDs or recent steroid use?
Family history does not seem relevant to the case at hand and could likely be
omitted. 
Was biopsy performed on endoscopy performed two weeks prior to admission?
A statement should include if this was performed and, if so, what the results of
this biopsy were. 
Unfamiliar with the term "niche sign" and this could be
expanded upon. 
Why were tumor markers sent with initial lab work? Was this in fact completed
after endoscopic evaluation? This needs clarification. 
Endoscopic findings and intervention should be described in further detail.
Additional information regarding embolization should be included (ie findings of
procedure and what vessel was embolized).
Line 48: according to the discussion, distal subtotal gastrectomy was performed
under emergency pretences. This should be discussed within the case
presentation. 
Line 51: SRC components should be described in detail, was the 50% SRC
threshold met on pathology report?
How were lymph nodes and metastases investigated? Does line 52-53 refer to
findings from surgical intervention? This should be clarified and TNM staging
should be included.
Was any staining for Mucin completed? Should be addressed if staining was not
completed. 
The post-operative hospital course is very confusing and not written in medical
terms. For instance, terms like "abdominal cavity infection", "pulmonary
infection", "anti-infection", and "pulverization inhalation" are not terms that
would commonly be encountered in English medical journals. This paragraph
needs significant revision both grammatically and from a case report storyline
standpoint. Development of obstruction and intra-abdominal infection are two
important post-operative complications that should be described further. When
did these occur in the post-operative course? What interventions were
performed? Was this a result of expanding tumor? Also, it's very unclear how
the patient progressed to needing a tracheostomy and placement of nutritional J-
tube. 
Grammar/writing suggestions:
Line 36: information should not be included in parenthesis, could change to
"intermittent melena of 2 months duration and hematemesis over the past 10
hours."
Line 37: could include that he had been treated with Plavix
Line 43: could change sentence to "The patient was tachycardic, but vital signs
were otherwise normal."
Line 43-44: could change to "Physical examination revealed tenderness in the
epigastric region, but was otherwise unrevealing." What is meant by anemia on
physical exam? Was the patient pale? This should be clarified.
Line 48: "disappointing results" should be changed to "without hemostasis as
evidence by" then would need to include further information on hospitalization
such as persistent melena, dropping hemoglobin, etc. 
Line 58: would recommend using a different word than "refused" given negative
connotations. 
Line 59-61: not written in medical lingo/context and needs re-writing
Line 61-62: this is confusing and needs more clarification regarding "positive
treatments" and results.
Discussion:
Overall: Significant grammar/linguistic errors distract from the main points in
the discussion. The discussion is thorough, however, additional topics of
discussion including immunohistochemical analysis of SRCC and potential role
of chemotherapy could be considered.
Line 65-66 is repeated from introduction and thus should be omitted from
discussion/conclusions. 
Line 67 is not an entirely accurate statement. Given the limited number of
reported cases, there is limited data to support "typical clinical symptoms",
however, research completed by Dabaja et al. on 217 patients with
adenocarcinoma of the small bowel identified abdominal pain, intestinal
obstruction, and bleeding as the most common presenting symptoms. 
(Dabaja BS, Suki D, Pro B, et al. "Adenocarcinoma of the small bowel:
presentation, prognostic factors, and outcome of 217 patients." Cancer.
2004;101(3):518-26.)
Additional information/citation should be added to support the statement that
early stage cancer may be misdiagnosed as duodenal ulcer. Suspect this is largely
due to the rarity of primary duodenal cancer and frequent diagnosis of benign
peptic ulcer disease. 
What is meant by "no attention was paid" in line 71? This sentence is confusing
and deserves clarification or omission. 
The section on imaging modalities should be re-written given extensive
grammatical issues. Additionally, hypotonic duodenography is a fairly dated
diagnostic tool and not frequently used within the United States. Not sure if this
should be included in discussion. "Diagnostic rate" is frequently mentioned as
"low" throughout this paragraph but not substantiated with any data for
ultrasound, CT, or MRI. This should be supported with objective data or omitted.
Clarification regarding what is meant by "high-degree malignant cancer" is
needed. Additionally, supporting evidence should be used to substantiate the
claim that SRCC does not respond to chemotherapy or radiation. Could consider
further expanding on the role of chemotherapy in this type of malignancy. 
In the discussion section on surgical procedures, it should be noted that
pancreaticoduodenectomy has been considered the preferred surgical option for
primary duodenal malignancy. See: 
Khanal S, Joshi U, Bhattarai A, et al. "Primary Duodenal Adenocarcinoma:
Uncommon Tumor, Uncommon Presentation. A Case Report and Review of the
Literature". Int Medical Case Reports Journal. 2020;13:165-9.
Kawahira H, Miura F, Saigo K, et al. "Survival predictors of patients with
primary duodenal adenocarcinoma." Int Surg. 2011;96(2):111-6. 
Dabaja BS, Suki D, Pro B, et al. "Adenocarcinoma of the small bowel:
presentation, prognostic factors, and outcome of 217 patients." Cancer.
2004;101(3):518-26.
In line 97, "better long-term efficacy" should be substantiated with evidence.
Additionally, #3 Distal gastrectomy was highlighted as a potential surgical
treatment, however, this would not accomplish resection given the duodenum
would remain. The authors should clarify how this is pertinent to discussion of
primary duodenal cancer and likely omit. 
According to Line 107, malignancy was not considered pre-operation. The case
narrative does not reflect this as tumor markers are discussed prior to
gastrectomy. Case presentation should be amended to better reflect flow of
information as it resulted within the case and how this impacted the medical
decisions that were made. 
Line 109: authors should elaborate on what is meant by "the prognosis was
poor". Is this because SRCC was identified?
Line 109-110: this claim is not fully supported by evidence presented earlier in
which the patient developed post-operative abdominal infection and intestinal
obstruction that could be a direct post-operative complication irreflective of
baseline health status. Post-operative complications could be further discussed
given the multitude of complications experienced by the patient. 
Line 113: therapy utilized should have been elaborated on in the case
presentation. "Anti-ulcer therapy" is not a sufficient description nor accepted
medical jargon. 
Line 117-119 
sentence needs evidence to support this claim. 
Line 123-126 needs supporting evidence, consider citing recommendations from
large Gastroenterology organization like ACG or AGA.
Line 132: again there is reference to subtotal gastrectomy, however, this would
not accomplish resection of a duodenal malignancy. 
Grammar/writing suggestions:
Line 71-72: omit this sentence, does not belong in discussion section and does
not add to discussion
Line 72-72: omit the sentence "After the…" as this does not add to the
discussion
Line 79-80: "which can be the main diagnostic method at present" should be
changed to a stronger statement such as "Endoscopy is the diagnostic modality
of choice for evaluation of primary duodenal malignancy."
Line 82: "abdominal flatulence" should be changed to "abdominal gaseous
distension" or "bowel gas patterns". 
Line 82-85 is a run-on sentence and should be edited. 
Line 88 belongs in the case report section. 
Line 89: misspelling of cancer
Line 91: citations belong at end of sentence
Line 93-94: change sentence to "Duodenal bulb SRCC prognosis is largely
impacted by tumor infiltration and lymph node metastasis [4,11]".
Line 94-95: could change to "Surgical resection is accomplished via four main
procedures."
Line 103-105: run-on sentence needs rewriting
Line 116: omit "with SRCs could be seen"
Line 127: sentence is confusing and needs re-writing
Line 127-129 repeats previously stated information and should be omitted
Line 129-130 sentence is confusing and not substantiated with evidence. 
Line 132-133: consider changing to "Prognosis is potentially improved through
early diagnosis and radical surgical resection" - though this statement should be
supported with objective evidence. 
References:
Thorough review of the literature. Additional sources for consideration provided
above. 
Figures:
Recommend obtaining higher quality images as they appeared grainy and
distorted in the PDF. 
Figure Legend:
Fig 1 and Fig 2 after "endoscopy" add the word image
Unclear what is meant by a "delle with active bleeding" in Fig 2 description.
Fig 3 should expand on SRC components in greater description
Manuscript Overall Scientific Quality: 
Rare case that is worthy of publication. Several areas of improvement regarding
the flow and details of case presentation are necessary to improve. Additionally,
there were several scientific phrases/words that were used and are inconsistent
with current English medical literature/jargon. Lastly, I recommend further
discussion on the histopathological findings that define SRCC and how this case
exemplifies these findings. 
See the following citation for additional information regarding SRCC of different
organs:
Chu PG and Weiss LM. "Immunohistochemical Characterizations of Signet-
Ring Cell Carciomas of the Stomach, Breast, and Colon". Am J Clin Pathol.
2004;121:884-92.
Manuscript Overall Language Quality: 
Needs significant improvement as indicated and outlined in detail above. Poor
language quality distracts from this unique case and, from the standpoint of this
reviewer, is not considered publishable in present form. 
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
No competing interests to declare.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please publish my name with my
report.
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Please review this paper.
user
Reviewer’s report
Title: 
Signet-ring cell carcinoma of the duodenal bulb
presenting with gastrointestinal hemorrhage: a case report and literature review
Version: 
0 
Date: 
31 Dec 2021
Reviewer: 
Thomas Wichelmann
Reviewer's report:
Title: 
Fitting title that captures the main idea of the manuscript. Could consider
changing "presented by" to "presenting with" or "presenting as"
Abstract:
Overall: While the abstract reflects the main points of the case report and
summarizes the case well, many of the sentences are copied and pasted directly
from the main manuscript. Recommend a more unique approach to the writing
styles/language of the abstract rather than copying sentences from the main text. 
Line 14: should outline the endoscopic findings in greater detail
Grammar/writing suggestions:
Line 11: change "presented by" to "presenting with" or "presenting as"
Line 12-13: consider changing sentence to "Physical examination revealed upper
abdominal tenderness but was otherwise unrevealing. Laboratory workup was
significant for anemia." 
Line 14-16: could change to: "Multiple endoscopic attempts along with
interventional embolization were attempted and, unfortunately, adequate
hemostasis was not achieved resulting in distal subtotal gastrectomy."
Lines 16-19: sentences should be rewritten. Additionally, "refused" has negative
implications and should be changed. Could change sentences to: "Post-
operatively, the patient experienced persistent gastrointestinal bleeding. Family
declined further intervention and the patient eventually died of respiratory and
heart failure one month post-resection."
Line 22: change "should be considered as the first choice" to "is considered a
first line option". 
Line 22-23: change to "Early diagnosis and resection has been shown to improve
prognosis."
Introduction:
Overall: introduces the topic well and impresses the rarity of the case upon the
reader. Some grammatical errors and supporting evidence needed as outlined
below.
Line 28: SRCC is extremely rare → this should have a qualifying % if available
from literature
Line 28-29: sentence needs citations to support this statement.
Grammar/writing suggestions:
Line 26: change to "Primary duodenal cancer is rare and accounts for just 0.3-
0.5% of gastrointestinal cancers"
Line 28: change to "It's reported that over 96% of SRCC occur in the stomach."
Line 29-31: citation reference should be at end of sentence and could change
sentence to "Since Sekoguchi et al. first reported SRCC of the duodenal ampulla
in 1979, few cases of duodenal SRCC have been reported [2]." 
Line 31-32: could change sentence to "SRCC within the duodenal bulb is an
even rarer entity with no more than 15 cases reported in English literature to date
[3]."
Line 32: change "Here" to "Herein" and "presented by" to "presenting with"
Case Presentation:
Overall: Needs improvement to the flow of the case with additional details
requested and post-operative case description is confusing. Greater detail is
necessary regarding post-operative decline/complications. 
Pertinent medication history is not included at present and should be noted.
Plavix is mentioned in the discussion and should be included. Were there any
NSAIDs or recent steroid use?
Family history does not seem relevant to the case at hand and could likely be
omitted. 
Was biopsy performed on endoscopy performed two weeks prior to admission?
A statement should include if this was performed and, if so, what the results of
this biopsy were. 
Unfamiliar with the term "niche sign" and this could be
expanded upon. 
Why were tumor markers sent with initial lab work? Was this in fact completed
after endoscopic evaluation? This needs clarification. 
Endoscopic findings and intervention should be described in further detail.
Additional information regarding embolization should be included (ie findings of
procedure and what vessel was embolized).
Line 48: according to the discussion, distal subtotal gastrectomy was performed
under emergency pretences. This should be discussed within the case
presentation. 
Line 51: SRC components should be described in detail, was the 50% SRC
threshold met on pathology report?
How were lymph nodes and metastases investigated? Does line 52-53 refer to
findings from surgical intervention? This should be clarified and TNM staging
should be included.
Was any staining for Mucin completed? Should be addressed if staining was not
completed. 
The post-operative hospital course is very confusing and not written in medical
terms. For instance, terms like "abdominal cavity infection", "pulmonary
infection", "anti-infection", and "pulverization inhalation" are not terms that
would commonly be encountered in English medical journals. This paragraph
needs significant revision both grammatically and from a case report storyline
standpoint. Development of obstruction and intra-abdominal infection are two
important post-operative complications that should be described further. When
did these occur in the post-operative course? What interventions were
performed? Was this a result of expanding tumor? Also, it's very unclear how
the patient progressed to needing a tracheostomy and placement of nutritional J-
tube. 
Grammar/writing suggestions:
Line 36: information should not be included in parenthesis, could change to
"intermittent melena of 2 months duration and hematemesis over the past 10
hours."
Line 37: could include that he had been treated with Plavix
Line 43: could change sentence to "The patient was tachycardic, but vital signs
were otherwise normal."
Line 43-44: could change to "Physical examination revealed tenderness in the
epigastric region, but was otherwise unrevealing." What is meant by anemia on
physical exam? Was the patient pale? This should be clarified.
Line 48: "disappointing results" should be changed to "without hemostasis as
evidence by" then would need to include further information on hospitalization
such as persistent melena, dropping hemoglobin, etc. 
Line 58: would recommend using a different word than "refused" given negative
connotations. 
Line 59-61: not written in medical lingo/context and needs re-writing
Line 61-62: this is confusing and needs more clarification regarding "positive
treatments" and results.
Discussion:
Overall: Significant grammar/linguistic errors distract from the main points in
the discussion. The discussion is thorough, however, additional topics of
discussion including immunohistochemical analysis of SRCC and potential role
of chemotherapy could be considered.
Line 65-66 is repeated from introduction and thus should be omitted from
discussion/conclusions. 
Line 67 is not an entirely accurate statement. Given the limited number of
reported cases, there is limited data to support "typical clinical symptoms",
however, research completed by Dabaja et al. on 217 patients with
adenocarcinoma of the small bowel identified abdominal pain, intestinal
obstruction, and bleeding as the most common presenting symptoms. 
(Dabaja BS, Suki D, Pro B, et al. "Adenocarcinoma of the small bowel:
presentation, prognostic factors, and outcome of 217 patients." Cancer.
2004;101(3):518-26.)
Additional information/citation should be added to support the statement that
early stage cancer may be misdiagnosed as duodenal ulcer. Suspect this is largely
due to the rarity of primary duodenal cancer and frequent diagnosis of benign
peptic ulcer disease. 
What is meant by "no attention was paid" in line 71? This sentence is confusing
and deserves clarification or omission. 
The section on imaging modalities should be re-written given extensive
grammatical issues. Additionally, hypotonic duodenography is a fairly dated
diagnostic tool and not frequently used within the United States. Not sure if this
should be included in discussion. "Diagnostic rate" is frequently mentioned as
"low" throughout this paragraph but not substantiated with any data for
ultrasound, CT, or MRI. This should be supported with objective data or omitted.
Clarification regarding what is meant by "high-degree malignant cancer" is
needed. Additionally, supporting evidence should be used to substantiate the
claim that SRCC does not respond to chemotherapy or radiation. Could consider
further expanding on the role of chemotherapy in this type of malignancy. 
In the discussion section on surgical procedures, it should be noted that
pancreaticoduodenectomy has been considered the preferred surgical option for
primary duodenal malignancy. See: 
Khanal S, Joshi U, Bhattarai A, et al. "Primary Duodenal Adenocarcinoma:
Uncommon Tumor, Uncommon Presentation. A Case Report and Review of the
Literature". Int Medical Case Reports Journal. 2020;13:165-9.
Kawahira H, Miura F, Saigo K, et al. "Survival predictors of patients with
primary duodenal adenocarcinoma." Int Surg. 2011;96(2):111-6. 
Dabaja BS, Suki D, Pro B, et al. "Adenocarcinoma of the small bowel:
presentation, prognostic factors, and outcome of 217 patients." Cancer.
2004;101(3):518-26.
In line 97, "better long-term efficacy" should be substantiated with evidence.
Additionally, #3 Distal gastrectomy was highlighted as a potential surgical
treatment, however, this would not accomplish resection given the duodenum
would remain. The authors should clarify how this is pertinent to discussion of
primary duodenal cancer and likely omit. 
According to Line 107, malignancy was not considered pre-operation. The case
narrative does not reflect this as tumor markers are discussed prior to
gastrectomy. Case presentation should be amended to better reflect flow of
information as it resulted within the case and how this impacted the medical
decisions that were made. 
Line 109: authors should elaborate on what is meant by "the prognosis was
poor". Is this because SRCC was identified?
Line 109-110: this claim is not fully supported by evidence presented earlier in
which the patient developed post-operative abdominal infection and intestinal
obstruction that could be a direct post-operative complication irreflective of
baseline health status. Post-operative complications could be further discussed
given the multitude of complications experienced by the patient. 
Line 113: therapy utilized should have been elaborated on in the case
presentation. "Anti-ulcer therapy" is not a sufficient description nor accepted
medical jargon. 
Line 117-119 
sentence needs evidence to support this claim. 
Line 123-126 needs supporting evidence, consider citing recommendations from
large Gastroenterology organization like ACG or AGA.
Line 132: again there is reference to subtotal gastrectomy, however, this would
not accomplish resection of a duodenal malignancy. 
Grammar/writing suggestions:
Line 71-72: omit this sentence, does not belong in discussion section and does
not add to discussion
Line 72-72: omit the sentence "After the…" as this does not add to the
discussion
Line 79-80: "which can be the main diagnostic method at present" should be
changed to a stronger statement such as "Endoscopy is the diagnostic modality
of choice for evaluation of primary duodenal malignancy."
Line 82: "abdominal flatulence" should be changed to "abdominal gaseous
distension" or "bowel gas patterns". 
Line 82-85 is a run-on sentence and should be edited. 
Line 88 belongs in the case report section. 
Line 89: misspelling of cancer
Line 91: citations belong at end of sentence
Line 93-94: change sentence to "Duodenal bulb SRCC prognosis is largely
impacted by tumor infiltration and lymph node metastasis [4,11]".
Line 94-95: could change to "Surgical resection is accomplished via four main
procedures."
Line 103-105: run-on sentence needs rewriting
Line 116: omit "with SRCs could be seen"
Line 127: sentence is confusing and needs re-writing
Line 127-129 repeats previously stated information and should be omitted
Line 129-130 sentence is confusing and not substantiated with evidence. 
Line 132-133: consider changing to "Prognosis is potentially improved through
early diagnosis and radical surgical resection" - though this statement should be
supported with objective evidence. 
References:
Thorough review of the literature. Additional sources for consideration provided
above. 
Figures:
Recommend obtaining higher quality images as they appeared grainy and
distorted in the PDF. 
Figure Legend:
Fig 1 and Fig 2 after "endoscopy" add the word image
Unclear what is meant by a "delle with active bleeding" in Fig 2 description.
Fig 3 should expand on SRC components in greater description
Manuscript Overall Scientific Quality: 
Rare case that is worthy of publication. Several areas of improvement regarding
the flow and details of case presentation are necessary to improve. Additionally,
there were several scientific phrases/words that were used and are inconsistent
with current English medical literature/jargon. Lastly, I recommend further
discussion on the histopathological findings that define SRCC and how this case
exemplifies these findings. 
See the following citation for additional information regarding SRCC of different
organs:
Chu PG and Weiss LM. "Immunohistochemical Characterizations of Signet-
Ring Cell Carciomas of the Stomach, Breast, and Colon". Am J Clin Pathol.
2004;121:884-92.
Manuscript Overall Language Quality: 
Needs significant improvement as indicated and outlined in detail above. Poor
language quality distracts from this unique case and, from the standpoint of this
reviewer, is not considered publishable in present form. 
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report.
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
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