Title: Risk Factors and Clinical Characteristics of Occult Pancreaticobiliary Reflux in Benign
Gallbladder Diseases
Version: 3 Date: 11 Mar 2025
Reviewer's report:
Summary
The authors conducted a retrospective analysis of 578 consecutive patients with NPBJ
who underwent surgery, highlighting the clinical features of OPBR in patients with benign
gallbladder diseases. However, the clinical significance of OPBR—particularly whether
it increases the risk of gallbladder cancer and/or cholangiocarcinoma—remains unclear.
Therefore, caution is needed when interpreting the authors’ claims, which are based on the
assumption that OPBR is a cancer risk factor.
Although the clinical impact of this study is limited as described above, the data hold
significance, and the manuscript is generally well-written. I recommend revising certain points
for publication, as outlined below.
I believe this manuscript would be suitable for publication once these concerns are appropriately
addressed.
Major comments
- Amylase Levels in Bile Samples: The manuscript does not provide specific amylase levels in
bile samples. Even among OPBR cases, the degree of amylase elevation likely varies depending
on factors such as PBJ dysfunction severity and pancreaticobiliary common channel length.
These variations could range from levels comparable to pancreaticobiliary maljunction to
those closer to the upper limit of normal. Additionally, no definitive, evidence-based cutoff
distinguishes normal from abnormal amylase levels in bile. Therefore, in addition to analyzing
OPBR as a binary variable, the authors should provide continuous variable data (e.g., mean
amylase levels across groups) and discuss their implications. This would add valuable insights
to the study.
- Exclusion of Cancer Cases: The rationale for excluding gallbladder cancer cases is unclear in
this study. If OPBR is being proposed as a cancer risk factor, including data from cancer cases
within the same surgical cohort as a positive control would strengthen the study. For instance,
assessing whether the prevalence of OPBR in each group is as high as that in gallbladder cancer
cases and whether amylase levels reach similar levels to those in gallbladder cancer cases could
provide valuable supporting evidence and strengthen the conclusions of this paper.
Minor comments
- The methods section lacks details on diagnostic criteria. Were GA and GP diagnosed
pathologically? How was gallbladder sludge identified (preoperative ultrasound, intraoperative
findings, etc.)?
- The conclusion should not include speculative suggestions, particularly since they are not
based on either the authors’ data or previous evidence, but rather on the assumption that OPBR
increases the cancer risk. Please remove the corresponding parts.
- To improve readability, define Group A, B, C, and D in the tables along with some
abbreviations.
- Table numbers appear inconsistent with those in the text. Please verify and revise them
accordingly.
Title: Risk Factors and Clinical Characteristics of Occult Pancreaticobiliary Reflux in Benign
Gallbladder Diseases
Version: 3 Date: 11 Mar 2025
Reviewer's report:
Summary
The authors conducted a retrospective analysis of 578 consecutive patients with NPBJ
who underwent surgery, highlighting the clinical features of OPBR in patients with benign
gallbladder diseases. However, the clinical significance of OPBR—particularly whether
it increases the risk of gallbladder cancer and/or cholangiocarcinoma—remains unclear.
Therefore, caution is needed when interpreting the authors’ claims, which are based on the
assumption that OPBR is a cancer risk factor.
Although the clinical impact of this study is limited as described above, the data hold
significance, and the manuscript is generally well-written. I recommend revising certain points
for publication, as outlined below.
I believe this manuscript would be suitable for publication once these concerns are appropriately
addressed.
Major comments
- Amylase Levels in Bile Samples: The manuscript does not provide specific amylase levels in
bile samples. Even among OPBR cases, the degree of amylase elevation likely varies depending
on factors such as PBJ dysfunction severity and pancreaticobiliary common channel length.
These variations could range from levels comparable to pancreaticobiliary maljunction to
those closer to the upper limit of normal. Additionally, no definitive, evidence-based cutoff
distinguishes normal from abnormal amylase levels in bile. Therefore, in addition to analyzing
OPBR as a binary variable, the authors should provide continuous variable data (e.g., mean
amylase levels across groups) and discuss their implications. This would add valuable insights
to the study.
- Exclusion of Cancer Cases: The rationale for excluding gallbladder cancer cases is unclear in
this study. If OPBR is being proposed as a cancer risk factor, including data from cancer cases
within the same surgical cohort as a positive control would strengthen the study. For instance,
assessing whether the prevalence of OPBR in each group is as high as that in gallbladder cancer
cases and whether amylase levels reach similar levels to those in gallbladder cancer cases could
provide valuable supporting evidence and strengthen the conclusions of this paper.
Minor comments
- The methods section lacks details on diagnostic criteria. Were GA and GP diagnosed
pathologically? How was gallbladder sludge identified (preoperative ultrasound, intraoperative
findings, etc.)?
- The conclusion should not include speculative suggestions, particularly since they are not
based on either the authors’ data or previous evidence, but rather on the assumption that OPBR
increases the cancer risk. Please remove the corresponding parts.
- To improve readability, define Group A, B, C, and D in the tables along with some
abbreviations.
- Table numbers appear inconsistent with those in the text. Please verify and revise them
accordingly.
Please review this paper.
user
Title: Risk Factors and Clinical Characteristics of Occult Pancreaticobiliary Reflux in Benign
Gallbladder Diseases
Version: 3 Date: 11 Mar 2025
Reviewer's report:
Summary
The authors conducted a retrospective analysis of 578 consecutive patients with NPBJ
who underwent surgery, highlighting the clinical features of OPBR in patients with benign
gallbladder diseases. However, the clinical significance of OPBR—particularly whether
it increases the risk of gallbladder cancer and/or cholangiocarcinoma—remains unclear.
Therefore, caution is needed when interpreting the authors’ claims, which are based on the
assumption that OPBR is a cancer risk factor.
Although the clinical impact of this study is limited as described above, the data hold
significance, and the manuscript is generally well-written. I recommend revising certain points
for publication, as outlined below.
I believe this manuscript would be suitable for publication once these concerns are appropriately
addressed.
Major comments
- Amylase Levels in Bile Samples: The manuscript does not provide specific amylase levels in
bile samples. Even among OPBR cases, the degree of amylase elevation likely varies depending
on factors such as PBJ dysfunction severity and pancreaticobiliary common channel length.
These variations could range from levels comparable to pancreaticobiliary maljunction to
those closer to the upper limit of normal. Additionally, no definitive, evidence-based cutoff
distinguishes normal from abnormal amylase levels in bile. Therefore, in addition to analyzing
OPBR as a binary variable, the authors should provide continuous variable data (e.g., mean
amylase levels across groups) and discuss their implications. This would add valuable insights
to the study.
- Exclusion of Cancer Cases: The rationale for excluding gallbladder cancer cases is unclear in
this study. If OPBR is being proposed as a cancer risk factor, including data from cancer cases
within the same surgical cohort as a positive control would strengthen the study. For instance,
assessing whether the prevalence of OPBR in each group is as high as that in gallbladder cancer
cases and whether amylase levels reach similar levels to those in gallbladder cancer cases could
provide valuable supporting evidence and strengthen the conclusions of this paper.
Minor comments
- The methods section lacks details on diagnostic criteria. Were GA and GP diagnosed
pathologically? How was gallbladder sludge identified (preoperative ultrasound, intraoperative
findings, etc.)?
- The conclusion should not include speculative suggestions, particularly since they are not
based on either the authors’ data or previous evidence, but rather on the assumption that OPBR
increases the cancer risk. Please remove the corresponding parts.
- To improve readability, define Group A, B, C, and D in the tables along with some
abbreviations.
- Table numbers appear inconsistent with those in the text. Please verify and revise them
accordingly.
assistant