Title: Development and validation of a prognostic nomogram for gallbladder cancer patients
after surgery
Version: 1 Date: 11 Feb 2022
Reviewer:  Zhisong Liu
Reviewer's report:
The manuscript " Development and validation of a prognostic nomogram for gallbladder cancer
patients after surgery" by Xu et al. aims to develop a nomogram based on TNM and clinical
information, which can better predict the overall survival of the patients. In short, it is an
interesting study. However, some issues need to be addressed, and the manuscript may need
further revision.
1. The manuscript uses the word “independent” a lot. Statistically, two events are independent
if the occurrence of one does not affect the probability of occurrence of the other. It is better to
use other words like “significant” unless you can prove two events are independent.
2. RESULTS (Page 1). “The model showed good discrimination, with a concordance index (C-
index) of 0.724 (95% CI, 0.708 - 0.740), and good calibration.”
If space permits, evidence of good calibration should also be provided.
3. RESULTS (Page 1). In addition, the C-index of the nomogram was higher than that of the
Nevin staging system and the eighth edition TNM staging system for predicting overall survival,
in both the primary cohort (C-index = 0.724 for Nomogram; C-index = 0.671 for Nevin system;
C-index = 0.682 for TNM system) and validation cohort (C-index = 0.715 for Nomogram; C-
index = 0.692 for Nevin system; C-index = 0.688 for TNM system).
It is desirable to test for significance of the differences. The evidence would be stronger
if statistical tests confirmed significant differences. “CsChange (Testing for Change in C-
Statistic)” is a helpful package.
4. References 1-4.
The more recent references may be more convincing.
5. Page 1. “It is believed that prognostic factors such as age, tumor size, histology and grade
might significantly contribute to the survival prediction.”
In my opinion, it is better not to go into detail without a detailed analysis. At least tumor grade
and tumor size were not included in your nomogram.
6. Page 3. “Definitions of different staging systems”.
What is the purpose of stating this paragraph? Is it necessary?
7. Page 4. “routine cut-off value”.
Mean? Median? Or Subjective understanding? For continuous variable Age, how did you select
70 as the cut off?
8. Results_ Patient characteristics (Page 4). “with a median survival of 24 months (95% CI, 22
to 27 months, Figure 1-2)”
Figure 2 doesn't capture the messages. Please check. In addition, CI appears here for the first
time and needs to be given in full.
9. Results_ Patient characteristics (Page 4). “with a median survival of 20 months (95%CI, 15-28
months, Figure 1-2).”
Figure 2 doesn't capture the messages. Please check. In addition, there should be a space between
95% and CI.
10. Page 5. “multivariarte analysis based on the cox regression”.
Please check the spelling.
11. Table 1 (Page 12).  (1) Seer dataset. Seer should be capitalized. (2) Percentage problem. In
group of TUMOR GRADE, 13+45+39+23=?
12. Table 2 (Page 14). (1) The format may need to be readjusted. At least, Adenocarcinoma
does not match to the corresponding message on one line. (2) The format of the table
should be uniform, with three decimal places reserved (sex 0.0828, resection type 0.0621). (3)
Adenocarcinoma or Adenocarcinoma and others? What you stated in table 1 is Adenocarcinoma
and others.
13. Figure 3. What’s PC, SC, and AC? In order to make it easier for other doctors and patients to
use this nomogram, it is best to use full spell in the picture to reduce the inconvenience caused
by abbreviations.
Title: Development and validation of a prognostic nomogram for gallbladder cancer patients
after surgery
Version: 1 Date: 11 Feb 2022
Reviewer:  Zhisong Liu
Reviewer's report:
The manuscript " Development and validation of a prognostic nomogram for gallbladder cancer
patients after surgery" by Xu et al. aims to develop a nomogram based on TNM and clinical
information, which can better predict the overall survival of the patients. In short, it is an
interesting study. However, some issues need to be addressed, and the manuscript may need
further revision.
1. The manuscript uses the word “independent” a lot. Statistically, two events are independent
if the occurrence of one does not affect the probability of occurrence of the other. It is better to
use other words like “significant” unless you can prove two events are independent.
2. RESULTS (Page 1). “The model showed good discrimination, with a concordance index (C-
index) of 0.724 (95% CI, 0.708 - 0.740), and good calibration.”
If space permits, evidence of good calibration should also be provided.
3. RESULTS (Page 1). In addition, the C-index of the nomogram was higher than that of the
Nevin staging system and the eighth edition TNM staging system for predicting overall survival,
in both the primary cohort (C-index = 0.724 for Nomogram; C-index = 0.671 for Nevin system;
C-index = 0.682 for TNM system) and validation cohort (C-index = 0.715 for Nomogram; C-
index = 0.692 for Nevin system; C-index = 0.688 for TNM system).
It is desirable to test for significance of the differences. The evidence would be stronger
if statistical tests confirmed significant differences. “CsChange (Testing for Change in C-
Statistic)” is a helpful package.
4. References 1-4.
The more recent references may be more convincing.
5. Page 1. “It is believed that prognostic factors such as age, tumor size, histology and grade
might significantly contribute to the survival prediction.”
In my opinion, it is better not to go into detail without a detailed analysis. At least tumor grade
and tumor size were not included in your nomogram.
6. Page 3. “Definitions of different staging systems”.
What is the purpose of stating this paragraph? Is it necessary?
7. Page 4. “routine cut-off value”.
Mean? Median? Or Subjective understanding? For continuous variable Age, how did you select
70 as the cut off?
8. Results_ Patient characteristics (Page 4). “with a median survival of 24 months (95% CI, 22
to 27 months, Figure 1-2)”
Figure 2 doesn't capture the messages. Please check. In addition, CI appears here for the first
time and needs to be given in full.
9. Results_ Patient characteristics (Page 4). “with a median survival of 20 months (95%CI, 15-28
months, Figure 1-2).”
Figure 2 doesn't capture the messages. Please check. In addition, there should be a space between
95% and CI.
10. Page 5. “multivariarte analysis based on the cox regression”.
Please check the spelling.
11. Table 1 (Page 12).  (1) Seer dataset. Seer should be capitalized. (2) Percentage problem. In
group of TUMOR GRADE, 13+45+39+23=?
12. Table 2 (Page 14). (1) The format may need to be readjusted. At least, Adenocarcinoma
does not match to the corresponding message on one line. (2) The format of the table
should be uniform, with three decimal places reserved (sex 0.0828, resection type 0.0621). (3)
Adenocarcinoma or Adenocarcinoma and others? What you stated in table 1 is Adenocarcinoma
and others.
13. Figure 3. What’s PC, SC, and AC? In order to make it easier for other doctors and patients to
use this nomogram, it is best to use full spell in the picture to reduce the inconvenience caused
by abbreviations.
Please review this paper.
user
Title: Development and validation of a prognostic nomogram for gallbladder cancer patients
after surgery
Version: 1 Date: 11 Feb 2022
Reviewer:  Zhisong Liu
Reviewer's report:
The manuscript " Development and validation of a prognostic nomogram for gallbladder cancer
patients after surgery" by Xu et al. aims to develop a nomogram based on TNM and clinical
information, which can better predict the overall survival of the patients. In short, it is an
interesting study. However, some issues need to be addressed, and the manuscript may need
further revision.
1. The manuscript uses the word “independent” a lot. Statistically, two events are independent
if the occurrence of one does not affect the probability of occurrence of the other. It is better to
use other words like “significant” unless you can prove two events are independent.
2. RESULTS (Page 1). “The model showed good discrimination, with a concordance index (C-
index) of 0.724 (95% CI, 0.708 - 0.740), and good calibration.”
If space permits, evidence of good calibration should also be provided.
3. RESULTS (Page 1). In addition, the C-index of the nomogram was higher than that of the
Nevin staging system and the eighth edition TNM staging system for predicting overall survival,
in both the primary cohort (C-index = 0.724 for Nomogram; C-index = 0.671 for Nevin system;
C-index = 0.682 for TNM system) and validation cohort (C-index = 0.715 for Nomogram; C-
index = 0.692 for Nevin system; C-index = 0.688 for TNM system).
It is desirable to test for significance of the differences. The evidence would be stronger
if statistical tests confirmed significant differences. “CsChange (Testing for Change in C-
Statistic)” is a helpful package.
4. References 1-4.
The more recent references may be more convincing.
5. Page 1. “It is believed that prognostic factors such as age, tumor size, histology and grade
might significantly contribute to the survival prediction.”
In my opinion, it is better not to go into detail without a detailed analysis. At least tumor grade
and tumor size were not included in your nomogram.
6. Page 3. “Definitions of different staging systems”.
What is the purpose of stating this paragraph? Is it necessary?
7. Page 4. “routine cut-off value”.
Mean? Median? Or Subjective understanding? For continuous variable Age, how did you select
70 as the cut off?
8. Results_ Patient characteristics (Page 4). “with a median survival of 24 months (95% CI, 22
to 27 months, Figure 1-2)”
Figure 2 doesn't capture the messages. Please check. In addition, CI appears here for the first
time and needs to be given in full.
9. Results_ Patient characteristics (Page 4). “with a median survival of 20 months (95%CI, 15-28
months, Figure 1-2).”
Figure 2 doesn't capture the messages. Please check. In addition, there should be a space between
95% and CI.
10. Page 5. “multivariarte analysis based on the cox regression”.
Please check the spelling.
11. Table 1 (Page 12).  (1) Seer dataset. Seer should be capitalized. (2) Percentage problem. In
group of TUMOR GRADE, 13+45+39+23=?
12. Table 2 (Page 14). (1) The format may need to be readjusted. At least, Adenocarcinoma
does not match to the corresponding message on one line. (2) The format of the table
should be uniform, with three decimal places reserved (sex 0.0828, resection type 0.0621). (3)
Adenocarcinoma or Adenocarcinoma and others? What you stated in table 1 is Adenocarcinoma
and others.
13. Figure 3. What’s PC, SC, and AC? In order to make it easier for other doctors and patients to
use this nomogram, it is best to use full spell in the picture to reduce the inconvenience caused
by abbreviations.
assistant