Title: Endobiliary radiofrequency ablation in recurrence and unresectable perihilar
cholangiocarcinoma
Version: 1 Date: 23 Apr 2025
Reviewer's report:
1. The manuscript provides a sample size calculation based on a log-rank test, aiming to
compare stent patency between the EBRFA and SEMS groups. However, there appears to
be a discrepancy in the expected event rates: the text states that the stent occlusion rate was
anticipated to be 50% in the experimental (EBRFA) group and 20% in the control (SEMS) group.
This seems counterintuitive, as the intervention is hypothesized to reduce stent occlusion. It is
likely that the group labels were reversed in the description. The authors are encouraged to clarify
this point to avoid confusion regarding the direction of expected effect. In addition, while the
sample size calculation was methodologically appropriate for a time-to-event outcome using a
log-rank test, the target enrollment (n=72) was not reached, with only 39 patients included in the
final analysis. This significant shortfall likely resulted in an underpowered comparison, which
may explain the non-significant differences observed between groups despite a numerically
longer survival in the EBRFA group.
2. The results section highlights a statistically significant difference in survival based on total
bilirubin levels (<15 vs #15 mg/dL), with a median survival of 201 vs 73 days (p = 0.004).
However, this important finding is not addressed or interpreted in the Discussion section. Given
its potential clinical relevance as a prognostic factor, I recommend that the authors provide a
dedicated discussion on the association between baseline bilirubin levels and patient survival,
including whether this factor could influence treatment response or patient selection in future
studies.
3. The Methods section contains overly detailed descriptions, particularly regarding the
procedural steps for EBRFA and PTBD. For example, the inclusion of information such as
patient positioning, dietary restrictions, or the timing of NSAID suppositories, while relevant
for a clinical protocol, may not be necessary in a research manuscript and could be summarized
more concisely. Additionally, the stent occlusion criteria and outcome definitions are repeated
in two different subsections, which may cause confusion. In contrast, other key methodological
aspects, such as the randomization procedure (e.g., block size, stratification, blinding) are not
sufficiently described. It is recommended that the authors streamline this section by: Merging
overlapping content (e.g., stent occlusion definition), Condensing procedural details, Expanding
on the trial design and randomization approach. These revisions would improve clarity and focus
the Methods section on information essential for reproducibility and interpretation.
4. The Abstract contains several grammatical errors and inconsistencies. For example, “Chi-
squad test” should be corrected to “Chi-square test.” Moreover, the expression “which is a lack
of knowledge and evident base data” is grammatically incorrect and unclear in meaning.
5. There is a discrepancy between the number of randomized patients (n=44) and the final
number analyzed (n=39). The reasons for exclusion of the 5 patients after randomization should
be clearly described, either in the text or in the figure legend.
6. Several abbreviations and terms are used inconsistently (e.g., EBRFA vs ERFA; SEMS vs
MS). For clarity, the authors should define all abbreviations upon first use and apply them
consistently throughout the manuscript.
Title: Endobiliary radiofrequency ablation in recurrence and unresectable perihilar
cholangiocarcinoma
Version: 1 Date: 23 Apr 2025
Reviewer's report:
1. The manuscript provides a sample size calculation based on a log-rank test, aiming to
compare stent patency between the EBRFA and SEMS groups. However, there appears to
be a discrepancy in the expected event rates: the text states that the stent occlusion rate was
anticipated to be 50% in the experimental (EBRFA) group and 20% in the control (SEMS) group.
This seems counterintuitive, as the intervention is hypothesized to reduce stent occlusion. It is
likely that the group labels were reversed in the description. The authors are encouraged to clarify
this point to avoid confusion regarding the direction of expected effect. In addition, while the
sample size calculation was methodologically appropriate for a time-to-event outcome using a
log-rank test, the target enrollment (n=72) was not reached, with only 39 patients included in the
final analysis. This significant shortfall likely resulted in an underpowered comparison, which
may explain the non-significant differences observed between groups despite a numerically
longer survival in the EBRFA group.
2. The results section highlights a statistically significant difference in survival based on total
bilirubin levels (<15 vs #15 mg/dL), with a median survival of 201 vs 73 days (p = 0.004).
However, this important finding is not addressed or interpreted in the Discussion section. Given
its potential clinical relevance as a prognostic factor, I recommend that the authors provide a
dedicated discussion on the association between baseline bilirubin levels and patient survival,
including whether this factor could influence treatment response or patient selection in future
studies.
3. The Methods section contains overly detailed descriptions, particularly regarding the
procedural steps for EBRFA and PTBD. For example, the inclusion of information such as
patient positioning, dietary restrictions, or the timing of NSAID suppositories, while relevant
for a clinical protocol, may not be necessary in a research manuscript and could be summarized
more concisely. Additionally, the stent occlusion criteria and outcome definitions are repeated
in two different subsections, which may cause confusion. In contrast, other key methodological
aspects, such as the randomization procedure (e.g., block size, stratification, blinding) are not
sufficiently described. It is recommended that the authors streamline this section by: Merging
overlapping content (e.g., stent occlusion definition), Condensing procedural details, Expanding
on the trial design and randomization approach. These revisions would improve clarity and focus
the Methods section on information essential for reproducibility and interpretation.
4. The Abstract contains several grammatical errors and inconsistencies. For example, “Chi-
squad test” should be corrected to “Chi-square test.” Moreover, the expression “which is a lack
of knowledge and evident base data” is grammatically incorrect and unclear in meaning.
5. There is a discrepancy between the number of randomized patients (n=44) and the final
number analyzed (n=39). The reasons for exclusion of the 5 patients after randomization should
be clearly described, either in the text or in the figure legend.
6. Several abbreviations and terms are used inconsistently (e.g., EBRFA vs ERFA; SEMS vs
MS). For clarity, the authors should define all abbreviations upon first use and apply them
consistently throughout the manuscript.
Please review this paper.
user
Title: Endobiliary radiofrequency ablation in recurrence and unresectable perihilar
cholangiocarcinoma
Version: 1 Date: 23 Apr 2025
Reviewer's report:
1. The manuscript provides a sample size calculation based on a log-rank test, aiming to
compare stent patency between the EBRFA and SEMS groups. However, there appears to
be a discrepancy in the expected event rates: the text states that the stent occlusion rate was
anticipated to be 50% in the experimental (EBRFA) group and 20% in the control (SEMS) group.
This seems counterintuitive, as the intervention is hypothesized to reduce stent occlusion. It is
likely that the group labels were reversed in the description. The authors are encouraged to clarify
this point to avoid confusion regarding the direction of expected effect. In addition, while the
sample size calculation was methodologically appropriate for a time-to-event outcome using a
log-rank test, the target enrollment (n=72) was not reached, with only 39 patients included in the
final analysis. This significant shortfall likely resulted in an underpowered comparison, which
may explain the non-significant differences observed between groups despite a numerically
longer survival in the EBRFA group.
2. The results section highlights a statistically significant difference in survival based on total
bilirubin levels (<15 vs #15 mg/dL), with a median survival of 201 vs 73 days (p = 0.004).
However, this important finding is not addressed or interpreted in the Discussion section. Given
its potential clinical relevance as a prognostic factor, I recommend that the authors provide a
dedicated discussion on the association between baseline bilirubin levels and patient survival,
including whether this factor could influence treatment response or patient selection in future
studies.
3. The Methods section contains overly detailed descriptions, particularly regarding the
procedural steps for EBRFA and PTBD. For example, the inclusion of information such as
patient positioning, dietary restrictions, or the timing of NSAID suppositories, while relevant
for a clinical protocol, may not be necessary in a research manuscript and could be summarized
more concisely. Additionally, the stent occlusion criteria and outcome definitions are repeated
in two different subsections, which may cause confusion. In contrast, other key methodological
aspects, such as the randomization procedure (e.g., block size, stratification, blinding) are not
sufficiently described. It is recommended that the authors streamline this section by: Merging
overlapping content (e.g., stent occlusion definition), Condensing procedural details, Expanding
on the trial design and randomization approach. These revisions would improve clarity and focus
the Methods section on information essential for reproducibility and interpretation.
4. The Abstract contains several grammatical errors and inconsistencies. For example, “Chi-
squad test” should be corrected to “Chi-square test.” Moreover, the expression “which is a lack
of knowledge and evident base data” is grammatically incorrect and unclear in meaning.
5. There is a discrepancy between the number of randomized patients (n=44) and the final
number analyzed (n=39). The reasons for exclusion of the 5 patients after randomization should
be clearly described, either in the text or in the figure legend.
6. Several abbreviations and terms are used inconsistently (e.g., EBRFA vs ERFA; SEMS vs
MS). For clarity, the authors should define all abbreviations upon first use and apply them
consistently throughout the manuscript.
assistant