Review for 10.1186/s12876-025-03925-9 (2025)

Title: CA19-9/DBil: A Promising Indicator to Distinguish Between CA19-9-Elevated
Pancreatic Head-Type Autoimmune Pancreatitis and Pancreatic Head Cancer
Version: 1 Date: 22 Jan 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the introduction is generally well-structured, some sentences could benefit from further
clarity. For instance, the phrase "Benign cholestasis, such as cholelithiasis, compression of the
bile ducts by an enlarged pancreatic head, and cholangitis, can likewise cause elevated CA19-9"
could be reworded to avoid ambiguity and improve readability. A clearer explanation of how
cholestasis and its associated factors specifically complicate the use of CA19-9 would make this
section even more accessible to readers who may not be familiar with these concepts.
-The rationale behind using the CA19-9/DBil ratio is introduced well, but a bit more detail
about why DBil specifically was chosen as a corrective factor (as opposed to other potential
biomarkers) could strengthen this argument. Additionally, clarifying how DBil is impacted by
cholestasis and why this adjustment improves diagnostic accuracy would enhance the reader’s
understanding of the novel aspect of the study.
-Although the introduction mentions the limitations of CA19-9 and IgG4, a more explicit review
of current diagnostic methods or a comparison with previous studies would further highlight the
study's novelty. For example, some reference to the state-of-the-art imaging or biopsy techniques
for diagnosing PH-AIP and PHC would provide a more comprehensive background.
-While the inclusion and exclusion criteria are clearly outlined, more information on how the
study cohort was selected from the single center could be valuable. For example, were the
PH-AIP and PHC cases matched for age, gender, or other factors? Did the study consider any
potential biases in patient selection (e.g., referral bias)? Providing additional details would help
readers assess the generalizability of the study’s findings.
-While the study controls for gender, age, and CEA, there may be other confounders not
accounted for, such as comorbidities or pre-existing conditions that could influence CA19-9
levels or the diagnosis of PH-AIP and PHC. A brief mention of potential unmeasured
confounders or biases would add depth to the interpretation of the study's findings.
-While the statistical results are generally well-documented, the phrase "did not reach statistical
significance" appears multiple times (e.g., in the comparison of AUCs between Model 1 and
the adjusted models). It would be beneficial to specify the exact p-values to clarify the non-
significance more precisely. Providing these values in the text, or referring the reader to the
table, would help avoid any ambiguity.
-While the study's findings are presented, there could be more discussion around the clinical
impact of the CA19-9/DBil ratio in everyday practice. How might clinicians incorporate this
ratio into their decision-making process, especially in a clinical setting where imaging and
biopsy results might still be inconclusive? More emphasis on the real-world utility of Model 1
would help ground the results in clinical practice.
-The discussion could benefit from a brief mention of alternative diagnostic methods or
biomarkers being used to distinguish PH-AIP from PHC, especially given that CA19-9 and IgG4
alone are insufficient in some cases. This would help readers understand why the CA19-9/DBil
ratio is a useful addition to existing diagnostic methods.
-The authors mention that the limited sample size prevented adjustment for more covariates
in the logistic regression models, but it would be helpful to provide examples of what these
unadjusted covariates might be. A more detailed discussion on potential confounders (e.g., liver
function tests, imaging findings, or other biomarkers) could strengthen the argument for why
these factors weren't included and how they might affect the results if included in a larger sample.