Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective
cohort study
Version: 1 Date: 16 Dec 2024
Reviewer's report:
This study investigates the association between choledocholithiasis (common bile duct stones)
and cholangiocarcinoma (CCA) using a nationwide cohort from South Korea. Over a 10-
year follow-up of 20,808 patients, the authors observed significantly elevated standardized
incidence ratios (SIRs) for both intrahepatic and extrahepatic CCA among patients with
choledocholithiasis compared to the general population. The results emphasize the increased
risk in specific age groups, notably in individuals aged 60–79.
This is an interesting and potentially impactful study, as it explores the long-debated link
between choledocholithiasis and cholangiocarcinoma. However, as a retrospective cohort study,
its design cannot infer causation, which is crucial to acknowledge in both the abstract and
discussion. The descriptive findings are compelling, but the authors should ensure they do not
overstate the implications of the results without further experimental or mechanistic evidence.
Tumor-Induced Cholestasis:  It is unclear how the authors accounted for the possibility that
some cases of choledocholithiasis might have been secondary to tumor-induced cholestasis. Was
imaging reviewed systematically to exclude underlying malignancy at the time of diagnosis?
Addressing this limitation in the discussion would strengthen the study's credibility.
Choledochal Cysts: The analysis does not appear to include an assessment of choledochal cysts,
which are a known risk factor for CCA. Were such cases excluded or accounted for? If not, their
potential contribution to the observed association should be discussed.
Clarity in Methods:  While the study design is robust, more detail on the methodology is
necessary. For instance, the rationale for excluding cases diagnosed within two years of
choledocholithiasis is sound but needs additional justification and elaboration in the methods
section.
Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective
cohort study
Version: 1 Date: 16 Dec 2024
Reviewer's report:
This study investigates the association between choledocholithiasis (common bile duct stones)
and cholangiocarcinoma (CCA) using a nationwide cohort from South Korea. Over a 10-
year follow-up of 20,808 patients, the authors observed significantly elevated standardized
incidence ratios (SIRs) for both intrahepatic and extrahepatic CCA among patients with
choledocholithiasis compared to the general population. The results emphasize the increased
risk in specific age groups, notably in individuals aged 60–79.
This is an interesting and potentially impactful study, as it explores the long-debated link
between choledocholithiasis and cholangiocarcinoma. However, as a retrospective cohort study,
its design cannot infer causation, which is crucial to acknowledge in both the abstract and
discussion. The descriptive findings are compelling, but the authors should ensure they do not
overstate the implications of the results without further experimental or mechanistic evidence.
Tumor-Induced Cholestasis:  It is unclear how the authors accounted for the possibility that
some cases of choledocholithiasis might have been secondary to tumor-induced cholestasis. Was
imaging reviewed systematically to exclude underlying malignancy at the time of diagnosis?
Addressing this limitation in the discussion would strengthen the study's credibility.
Choledochal Cysts: The analysis does not appear to include an assessment of choledochal cysts,
which are a known risk factor for CCA. Were such cases excluded or accounted for? If not, their
potential contribution to the observed association should be discussed.
Clarity in Methods:  While the study design is robust, more detail on the methodology is
necessary. For instance, the rationale for excluding cases diagnosed within two years of
choledocholithiasis is sound but needs additional justification and elaboration in the methods
section.
Please review this paper.
user
Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective
cohort study
Version: 1 Date: 16 Dec 2024
Reviewer's report:
This study investigates the association between choledocholithiasis (common bile duct stones)
and cholangiocarcinoma (CCA) using a nationwide cohort from South Korea. Over a 10-
year follow-up of 20,808 patients, the authors observed significantly elevated standardized
incidence ratios (SIRs) for both intrahepatic and extrahepatic CCA among patients with
choledocholithiasis compared to the general population. The results emphasize the increased
risk in specific age groups, notably in individuals aged 60–79.
This is an interesting and potentially impactful study, as it explores the long-debated link
between choledocholithiasis and cholangiocarcinoma. However, as a retrospective cohort study,
its design cannot infer causation, which is crucial to acknowledge in both the abstract and
discussion. The descriptive findings are compelling, but the authors should ensure they do not
overstate the implications of the results without further experimental or mechanistic evidence.
Tumor-Induced Cholestasis:  It is unclear how the authors accounted for the possibility that
some cases of choledocholithiasis might have been secondary to tumor-induced cholestasis. Was
imaging reviewed systematically to exclude underlying malignancy at the time of diagnosis?
Addressing this limitation in the discussion would strengthen the study's credibility.
Choledochal Cysts: The analysis does not appear to include an assessment of choledochal cysts,
which are a known risk factor for CCA. Were such cases excluded or accounted for? If not, their
potential contribution to the observed association should be discussed.
Clarity in Methods:  While the study design is robust, more detail on the methodology is
necessary. For instance, the rationale for excluding cases diagnosed within two years of
choledocholithiasis is sound but needs additional justification and elaboration in the methods
section.
assistant