Title: Endobiliary radiofrequency ablation in recurrence and unresectable perihilar
cholangiocarcinoma
Version: 0 Date: 22 Mar 2025
Reviewer's report:
Title: Endobiliary Radiofrequency Ablation in Recurrence and Unresectable Perihilar
Cholangiocarcinoma
This is a well-structured, prospective randomized controlled trial evaluating the safety and
efficacy of endobiliary radiofrequency ablation (EBRFA) combined with self-expandable
metallic stents (SEMS) versus SEMS alone in patients with unresectable perihilar
cholangiocarcinoma (pCCA). The authors demonstrate that EBRFA is a feasible and safe
procedure, although it did not show statistically significant improvement in stent patency or
overall survival compared to SEMS alone. The study adds value by addressing a critical gap in
palliative care for patients with unresectable pCCA.
However, several limitations should be addressed or more clearly discussed to strengthen the
manuscript.
1. A large proportion of patients (77%) had distant metastases at baseline, potentially
confounding survival outcomes. Subgroup analysis or exclusion criteria related to metastatic
status could be considered in future research.
2. One of the most critical limitations of this randomized controlled trial is that key prognostic
factors—such as tumor morphology (ID, PI, MF, combined), Bismuth classification, and the
presence of distant metastasis—were not fully considered during randomization. Although the
distribution of these variables between the SEMS and EBRFA groups was not statistically
different, the small sample size limits the power to detect imbalances, and the clinical
heterogeneity could have significantly influenced the outcomes. These factors are well known
to impact prognosis in pCCA and therefore should be discussed more thoroughly as potential
confounders in the Discussion section.
3. The authors conclude that EBRFA is a feasible and safe procedure. However, this conclusion
may be premature based on the current results. In the comparison between SEMS and EBRFA,
the rates of complications such as pancreatitis (11.8% vs. 22.7%) and mild cholangitis (29.4%
vs. 59.1%) were higher in the EBRFA group, although not statistically significant (p=0.376
and p=0.200, respectively). The stent patency time was also slightly shorter in the EBRFA
group (median 71 vs. 78 days). These trends raise concerns about the true safety profile of
EBRFA. Given the small sample size, it is possible that with a larger cohort, these differences
might become statistically significant, revealing higher morbidity with EBRFA. I recommend
the authors discuss this important limitation more clearly in the Discussion section.
Title: Endobiliary radiofrequency ablation in recurrence and unresectable perihilar
cholangiocarcinoma
Version: 0 Date: 22 Mar 2025
Reviewer's report:
Title: Endobiliary Radiofrequency Ablation in Recurrence and Unresectable Perihilar
Cholangiocarcinoma
This is a well-structured, prospective randomized controlled trial evaluating the safety and
efficacy of endobiliary radiofrequency ablation (EBRFA) combined with self-expandable
metallic stents (SEMS) versus SEMS alone in patients with unresectable perihilar
cholangiocarcinoma (pCCA). The authors demonstrate that EBRFA is a feasible and safe
procedure, although it did not show statistically significant improvement in stent patency or
overall survival compared to SEMS alone. The study adds value by addressing a critical gap in
palliative care for patients with unresectable pCCA.
However, several limitations should be addressed or more clearly discussed to strengthen the
manuscript.
1. A large proportion of patients (77%) had distant metastases at baseline, potentially
confounding survival outcomes. Subgroup analysis or exclusion criteria related to metastatic
status could be considered in future research.
2. One of the most critical limitations of this randomized controlled trial is that key prognostic
factors—such as tumor morphology (ID, PI, MF, combined), Bismuth classification, and the
presence of distant metastasis—were not fully considered during randomization. Although the
distribution of these variables between the SEMS and EBRFA groups was not statistically
different, the small sample size limits the power to detect imbalances, and the clinical
heterogeneity could have significantly influenced the outcomes. These factors are well known
to impact prognosis in pCCA and therefore should be discussed more thoroughly as potential
confounders in the Discussion section.
3. The authors conclude that EBRFA is a feasible and safe procedure. However, this conclusion
may be premature based on the current results. In the comparison between SEMS and EBRFA,
the rates of complications such as pancreatitis (11.8% vs. 22.7%) and mild cholangitis (29.4%
vs. 59.1%) were higher in the EBRFA group, although not statistically significant (p=0.376
and p=0.200, respectively). The stent patency time was also slightly shorter in the EBRFA
group (median 71 vs. 78 days). These trends raise concerns about the true safety profile of
EBRFA. Given the small sample size, it is possible that with a larger cohort, these differences
might become statistically significant, revealing higher morbidity with EBRFA. I recommend
the authors discuss this important limitation more clearly in the Discussion section.
Please review this paper.
user
Title: Endobiliary radiofrequency ablation in recurrence and unresectable perihilar
cholangiocarcinoma
Version: 0 Date: 22 Mar 2025
Reviewer's report:
Title: Endobiliary Radiofrequency Ablation in Recurrence and Unresectable Perihilar
Cholangiocarcinoma
This is a well-structured, prospective randomized controlled trial evaluating the safety and
efficacy of endobiliary radiofrequency ablation (EBRFA) combined with self-expandable
metallic stents (SEMS) versus SEMS alone in patients with unresectable perihilar
cholangiocarcinoma (pCCA). The authors demonstrate that EBRFA is a feasible and safe
procedure, although it did not show statistically significant improvement in stent patency or
overall survival compared to SEMS alone. The study adds value by addressing a critical gap in
palliative care for patients with unresectable pCCA.
However, several limitations should be addressed or more clearly discussed to strengthen the
manuscript.
1. A large proportion of patients (77%) had distant metastases at baseline, potentially
confounding survival outcomes. Subgroup analysis or exclusion criteria related to metastatic
status could be considered in future research.
2. One of the most critical limitations of this randomized controlled trial is that key prognostic
factors—such as tumor morphology (ID, PI, MF, combined), Bismuth classification, and the
presence of distant metastasis—were not fully considered during randomization. Although the
distribution of these variables between the SEMS and EBRFA groups was not statistically
different, the small sample size limits the power to detect imbalances, and the clinical
heterogeneity could have significantly influenced the outcomes. These factors are well known
to impact prognosis in pCCA and therefore should be discussed more thoroughly as potential
confounders in the Discussion section.
3. The authors conclude that EBRFA is a feasible and safe procedure. However, this conclusion
may be premature based on the current results. In the comparison between SEMS and EBRFA,
the rates of complications such as pancreatitis (11.8% vs. 22.7%) and mild cholangitis (29.4%
vs. 59.1%) were higher in the EBRFA group, although not statistically significant (p=0.376
and p=0.200, respectively). The stent patency time was also slightly shorter in the EBRFA
group (median 71 vs. 78 days). These trends raise concerns about the true safety profile of
EBRFA. Given the small sample size, it is possible that with a larger cohort, these differences
might become statistically significant, revealing higher morbidity with EBRFA. I recommend
the authors discuss this important limitation more clearly in the Discussion section.
assistant