Title: Diagnostic challenges of inflammatory submucosal tumor-like lesions: a multicenter
propensity score- matching analysis
Version: 0 Date: 18 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the study evaluates EUS and WLE in-depth, other advanced imaging modalities or
diagnostic tools (such as endomicroscopy or contrast-enhanced ultrasound) are not mentioned.
It would be beneficial to explore whether these newer techniques could improve the diagnostic
accuracy for differentiating I-SMTLs from other submucosal tumors.
-The criteria used to define chronic inflammatory responses are clearly laid out, but it would be
useful to discuss the limitations or variability in interpreting these features. Given that chronic
inflammation can have a broad spectrum of histopathological presentations, how reproducible
is this classification across pathologists?
-The reliance on a single pathologist (Y.Y. Chen) for the histopathological review could
introduce some degree of observer bias, even though the pathologist is experienced. A multi-
pathologist review or interobserver reliability analysis could strengthen the findings.
-The exclusion of cases with inconclusive pathological results could potentially lead to a
selection bias. It would be helpful to discuss how many patients had inconclusive diagnoses and
whether those patients could have provided valuable insights into the diagnostic challenges of
I-SMTLs.
-The study was conducted in five Chinese hospitals, and while the multicenter approach adds
external validity, there could be differences in the demographic and clinical characteristics
of patients in other regions. For example, ethnic and dietary differences may influence the
prevalence of certain conditions.
-Further validation in diverse international populations would strengthen the generalizability of
the results.
-The manuscript does not clarify whether any follow-up data on the clinical outcomes of patients
with I-SMTLs were gathered. Follow-up information would be valuable to assess the long-term
behavior of I-SMTLs and whether any of them evolve into malignant tumors or require further
interventions.
-The sample size for each group (I-SMTLs vs. non-I-SMTLs) should be presented more clearly,
along with a justification for the chosen sample size to ensure statistical power. It would be
helpful to see a more detailed analysis of power calculations to confirm that the study is
sufficiently powered to detect differences.
-The discussion provides an in-depth statistical analysis of the correlation between echogenicity
and echo heterogeneity with histopathological features. While this adds precision to the findings,
it might overwhelm some readers, particularly those less familiar with advanced statistical
techniques. It could be more effective to balance the technical details with more clinically
oriented language to ensure broader accessibility to clinicians.
-While the study mentions that EUS is more effective than WLE in distinguishing I-SMTLs,
it does not explore the potential role of other diagnostic tools (such as endomicroscopy or
contrast-enhanced ultrasound) in more depth. Given that these technologies have gained traction
in diagnosing gastrointestinal lesions, their omission feels like a missed opportunity to expand
on the comparative utility of diagnostic techniques.
-Including a brief mention of these newer techniques could offer a more comprehensive view
of the diagnostic landscape and show whether I-SMTLs can be accurately identified using other
modalities.
-The study mentions a high misdiagnosis rate, but the discussion could delve deeper into
the clinical impact of these errors. For instance, what are the consequences of misdiagnosing
I-SMTLs as malignant lesions? Does this lead to unnecessary surgeries, increased patient
anxiety, or delayed treatment for actual malignant tumors? A more thorough exploration of
the downstream effects of misdiagnosis could underscore the importance of refining diagnostic
methods.
-While the discussion briefly mentions follow-up as the preferred management strategy for small
I-SMTLs, it could benefit from more detailed recommendations on how to handle these lesions
over time. For instance, what factors should guide the decision to switch from follow-up to
resection? Is there a threshold size or certain risk factors that should prompt more aggressive
management?
-The conclusion calls for further research to develop optimal treatment strategies, but the
discussion could be more specific about what areas of research are most critical. For example,
would larger, multicenter prospective studies or long-term follow-up of patients with I-SMTLs
be most valuable? Additionally, how could new biomarkers or advanced imaging techniques
contribute to improving diagnostic accuracy?
Title: Diagnostic challenges of inflammatory submucosal tumor-like lesions: a multicenter
propensity score- matching analysis
Version: 0 Date: 18 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the study evaluates EUS and WLE in-depth, other advanced imaging modalities or
diagnostic tools (such as endomicroscopy or contrast-enhanced ultrasound) are not mentioned.
It would be beneficial to explore whether these newer techniques could improve the diagnostic
accuracy for differentiating I-SMTLs from other submucosal tumors.
-The criteria used to define chronic inflammatory responses are clearly laid out, but it would be
useful to discuss the limitations or variability in interpreting these features. Given that chronic
inflammation can have a broad spectrum of histopathological presentations, how reproducible
is this classification across pathologists?
-The reliance on a single pathologist (Y.Y. Chen) for the histopathological review could
introduce some degree of observer bias, even though the pathologist is experienced. A multi-
pathologist review or interobserver reliability analysis could strengthen the findings.
-The exclusion of cases with inconclusive pathological results could potentially lead to a
selection bias. It would be helpful to discuss how many patients had inconclusive diagnoses and
whether those patients could have provided valuable insights into the diagnostic challenges of
I-SMTLs.
-The study was conducted in five Chinese hospitals, and while the multicenter approach adds
external validity, there could be differences in the demographic and clinical characteristics
of patients in other regions. For example, ethnic and dietary differences may influence the
prevalence of certain conditions.
-Further validation in diverse international populations would strengthen the generalizability of
the results.
-The manuscript does not clarify whether any follow-up data on the clinical outcomes of patients
with I-SMTLs were gathered. Follow-up information would be valuable to assess the long-term
behavior of I-SMTLs and whether any of them evolve into malignant tumors or require further
interventions.
-The sample size for each group (I-SMTLs vs. non-I-SMTLs) should be presented more clearly,
along with a justification for the chosen sample size to ensure statistical power. It would be
helpful to see a more detailed analysis of power calculations to confirm that the study is
sufficiently powered to detect differences.
-The discussion provides an in-depth statistical analysis of the correlation between echogenicity
and echo heterogeneity with histopathological features. While this adds precision to the findings,
it might overwhelm some readers, particularly those less familiar with advanced statistical
techniques. It could be more effective to balance the technical details with more clinically
oriented language to ensure broader accessibility to clinicians.
-While the study mentions that EUS is more effective than WLE in distinguishing I-SMTLs,
it does not explore the potential role of other diagnostic tools (such as endomicroscopy or
contrast-enhanced ultrasound) in more depth. Given that these technologies have gained traction
in diagnosing gastrointestinal lesions, their omission feels like a missed opportunity to expand
on the comparative utility of diagnostic techniques.
-Including a brief mention of these newer techniques could offer a more comprehensive view
of the diagnostic landscape and show whether I-SMTLs can be accurately identified using other
modalities.
-The study mentions a high misdiagnosis rate, but the discussion could delve deeper into
the clinical impact of these errors. For instance, what are the consequences of misdiagnosing
I-SMTLs as malignant lesions? Does this lead to unnecessary surgeries, increased patient
anxiety, or delayed treatment for actual malignant tumors? A more thorough exploration of
the downstream effects of misdiagnosis could underscore the importance of refining diagnostic
methods.
-While the discussion briefly mentions follow-up as the preferred management strategy for small
I-SMTLs, it could benefit from more detailed recommendations on how to handle these lesions
over time. For instance, what factors should guide the decision to switch from follow-up to
resection? Is there a threshold size or certain risk factors that should prompt more aggressive
management?
-The conclusion calls for further research to develop optimal treatment strategies, but the
discussion could be more specific about what areas of research are most critical. For example,
would larger, multicenter prospective studies or long-term follow-up of patients with I-SMTLs
be most valuable? Additionally, how could new biomarkers or advanced imaging techniques
contribute to improving diagnostic accuracy?
Please review this paper.
user
Title: Diagnostic challenges of inflammatory submucosal tumor-like lesions: a multicenter
propensity score- matching analysis
Version: 0 Date: 18 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the study evaluates EUS and WLE in-depth, other advanced imaging modalities or
diagnostic tools (such as endomicroscopy or contrast-enhanced ultrasound) are not mentioned.
It would be beneficial to explore whether these newer techniques could improve the diagnostic
accuracy for differentiating I-SMTLs from other submucosal tumors.
-The criteria used to define chronic inflammatory responses are clearly laid out, but it would be
useful to discuss the limitations or variability in interpreting these features. Given that chronic
inflammation can have a broad spectrum of histopathological presentations, how reproducible
is this classification across pathologists?
-The reliance on a single pathologist (Y.Y. Chen) for the histopathological review could
introduce some degree of observer bias, even though the pathologist is experienced. A multi-
pathologist review or interobserver reliability analysis could strengthen the findings.
-The exclusion of cases with inconclusive pathological results could potentially lead to a
selection bias. It would be helpful to discuss how many patients had inconclusive diagnoses and
whether those patients could have provided valuable insights into the diagnostic challenges of
I-SMTLs.
-The study was conducted in five Chinese hospitals, and while the multicenter approach adds
external validity, there could be differences in the demographic and clinical characteristics
of patients in other regions. For example, ethnic and dietary differences may influence the
prevalence of certain conditions.
-Further validation in diverse international populations would strengthen the generalizability of
the results.
-The manuscript does not clarify whether any follow-up data on the clinical outcomes of patients
with I-SMTLs were gathered. Follow-up information would be valuable to assess the long-term
behavior of I-SMTLs and whether any of them evolve into malignant tumors or require further
interventions.
-The sample size for each group (I-SMTLs vs. non-I-SMTLs) should be presented more clearly,
along with a justification for the chosen sample size to ensure statistical power. It would be
helpful to see a more detailed analysis of power calculations to confirm that the study is
sufficiently powered to detect differences.
-The discussion provides an in-depth statistical analysis of the correlation between echogenicity
and echo heterogeneity with histopathological features. While this adds precision to the findings,
it might overwhelm some readers, particularly those less familiar with advanced statistical
techniques. It could be more effective to balance the technical details with more clinically
oriented language to ensure broader accessibility to clinicians.
-While the study mentions that EUS is more effective than WLE in distinguishing I-SMTLs,
it does not explore the potential role of other diagnostic tools (such as endomicroscopy or
contrast-enhanced ultrasound) in more depth. Given that these technologies have gained traction
in diagnosing gastrointestinal lesions, their omission feels like a missed opportunity to expand
on the comparative utility of diagnostic techniques.
-Including a brief mention of these newer techniques could offer a more comprehensive view
of the diagnostic landscape and show whether I-SMTLs can be accurately identified using other
modalities.
-The study mentions a high misdiagnosis rate, but the discussion could delve deeper into
the clinical impact of these errors. For instance, what are the consequences of misdiagnosing
I-SMTLs as malignant lesions? Does this lead to unnecessary surgeries, increased patient
anxiety, or delayed treatment for actual malignant tumors? A more thorough exploration of
the downstream effects of misdiagnosis could underscore the importance of refining diagnostic
methods.
-While the discussion briefly mentions follow-up as the preferred management strategy for small
I-SMTLs, it could benefit from more detailed recommendations on how to handle these lesions
over time. For instance, what factors should guide the decision to switch from follow-up to
resection? Is there a threshold size or certain risk factors that should prompt more aggressive
management?
-The conclusion calls for further research to develop optimal treatment strategies, but the
discussion could be more specific about what areas of research are most critical. For example,
would larger, multicenter prospective studies or long-term follow-up of patients with I-SMTLs
be most valuable? Additionally, how could new biomarkers or advanced imaging techniques
contribute to improving diagnostic accuracy?
assistant