Title: Preoperative CA19-9 and GGT ratio as a prognostic indicator in ampullary carcinoma
Version: 4 Date: 29 Oct 2022
Reviewer's report:
The authors present a thought provoking manuscript on the utility of a new prognostic indicator
for ampullary adenocarcinoma by creating a ratio of  CA 19-9 and GTT to increase the specificity
of each. I congratulate them on their efforts on this endeavor. I have several questions I would
like addressed.
-In the introduction of the manuscript, the authors list a variety of conditions that increase the
GGT in patients.  Was this laboratory value adjusted in participants with comorbidities that
lower the specificity of GGT?
-The final paragraph of the introduction where the authors state their hypothesis also appears to
hold a conclusion statement for the study. May require rewording so it is stated as a question
they look to answer.
-It is unclear when the laboratory data calculating the CA 19-9/GTT ratio is being collected. The
results state after hospitalization but is that at diagnosis or post-operatively? And why was this
time point chosen as the best time to make the prognostic measurements?
-One of the exclusion criteria, states that participants that died of “other diseases” were excluded.
Was this within a certain time frame after surgery? How was it determined that their disease
could not be contributed to ampullary cancer? Often the sequalae of ampullary cancer treatment
lead to death which would still result in ampullary cancer being the ultimate cause of death.
-The methods lists a variety of “predictors factors that may affect survival”. Is there any data
you can site as to why you chose these factors opposed to others such as positive lymph node
ratio or resection margin status?
-The authors state in the methods that AJCC 8th edition was used for staging. The AJCC staging
updated from the 7th edition to the 8th edition during the study period. Was staging of earlier
participants updated by a pathologist or the authors?
-The results state “8 cases of urine yellow” as the presenting symptoms. I would ask for
clarification on this symptom as I am not familiar with it.
-The results state that “some” patients received adjuvant therapy. What percentage of patients
received therapy and was it accounted for in the multi-variate analysis of recurrence free survival
and overall survival?
-Limitations of the study need to be expanded to include the fact that they had limited number
of patients to investigate and as such did not have a validation cohort for their nomogram.
The retrospective nature of the study limits their ability to assess a variety of variables such as
ampullary cancer subtype and adjuvant therapy regimens.
-I do not believe the data supports the conclusion made by the authors. The study suggests that
CA 19-9/GTT may be a useful tool in prognosis of ampullary cancer but this data has not been
validated even within their own patient population much less externally.
-Recommend reading through the manuscript for grammatical errors.
Title: Preoperative CA19-9 and GGT ratio as a prognostic indicator in ampullary carcinoma
Version: 4 Date: 29 Oct 2022
Reviewer's report:
The authors present a thought provoking manuscript on the utility of a new prognostic indicator
for ampullary adenocarcinoma by creating a ratio of  CA 19-9 and GTT to increase the specificity
of each. I congratulate them on their efforts on this endeavor. I have several questions I would
like addressed.
-In the introduction of the manuscript, the authors list a variety of conditions that increase the
GGT in patients.  Was this laboratory value adjusted in participants with comorbidities that
lower the specificity of GGT?
-The final paragraph of the introduction where the authors state their hypothesis also appears to
hold a conclusion statement for the study. May require rewording so it is stated as a question
they look to answer.
-It is unclear when the laboratory data calculating the CA 19-9/GTT ratio is being collected. The
results state after hospitalization but is that at diagnosis or post-operatively? And why was this
time point chosen as the best time to make the prognostic measurements?
-One of the exclusion criteria, states that participants that died of “other diseases” were excluded.
Was this within a certain time frame after surgery? How was it determined that their disease
could not be contributed to ampullary cancer? Often the sequalae of ampullary cancer treatment
lead to death which would still result in ampullary cancer being the ultimate cause of death.
-The methods lists a variety of “predictors factors that may affect survival”. Is there any data
you can site as to why you chose these factors opposed to others such as positive lymph node
ratio or resection margin status?
-The authors state in the methods that AJCC 8th edition was used for staging. The AJCC staging
updated from the 7th edition to the 8th edition during the study period. Was staging of earlier
participants updated by a pathologist or the authors?
-The results state “8 cases of urine yellow” as the presenting symptoms. I would ask for
clarification on this symptom as I am not familiar with it.
-The results state that “some” patients received adjuvant therapy. What percentage of patients
received therapy and was it accounted for in the multi-variate analysis of recurrence free survival
and overall survival?
-Limitations of the study need to be expanded to include the fact that they had limited number
of patients to investigate and as such did not have a validation cohort for their nomogram.
The retrospective nature of the study limits their ability to assess a variety of variables such as
ampullary cancer subtype and adjuvant therapy regimens.
-I do not believe the data supports the conclusion made by the authors. The study suggests that
CA 19-9/GTT may be a useful tool in prognosis of ampullary cancer but this data has not been
validated even within their own patient population much less externally.
-Recommend reading through the manuscript for grammatical errors.
Please review this paper.
user
Title: Preoperative CA19-9 and GGT ratio as a prognostic indicator in ampullary carcinoma
Version: 4 Date: 29 Oct 2022
Reviewer's report:
The authors present a thought provoking manuscript on the utility of a new prognostic indicator
for ampullary adenocarcinoma by creating a ratio of  CA 19-9 and GTT to increase the specificity
of each. I congratulate them on their efforts on this endeavor. I have several questions I would
like addressed.
-In the introduction of the manuscript, the authors list a variety of conditions that increase the
GGT in patients.  Was this laboratory value adjusted in participants with comorbidities that
lower the specificity of GGT?
-The final paragraph of the introduction where the authors state their hypothesis also appears to
hold a conclusion statement for the study. May require rewording so it is stated as a question
they look to answer.
-It is unclear when the laboratory data calculating the CA 19-9/GTT ratio is being collected. The
results state after hospitalization but is that at diagnosis or post-operatively? And why was this
time point chosen as the best time to make the prognostic measurements?
-One of the exclusion criteria, states that participants that died of “other diseases” were excluded.
Was this within a certain time frame after surgery? How was it determined that their disease
could not be contributed to ampullary cancer? Often the sequalae of ampullary cancer treatment
lead to death which would still result in ampullary cancer being the ultimate cause of death.
-The methods lists a variety of “predictors factors that may affect survival”. Is there any data
you can site as to why you chose these factors opposed to others such as positive lymph node
ratio or resection margin status?
-The authors state in the methods that AJCC 8th edition was used for staging. The AJCC staging
updated from the 7th edition to the 8th edition during the study period. Was staging of earlier
participants updated by a pathologist or the authors?
-The results state “8 cases of urine yellow” as the presenting symptoms. I would ask for
clarification on this symptom as I am not familiar with it.
-The results state that “some” patients received adjuvant therapy. What percentage of patients
received therapy and was it accounted for in the multi-variate analysis of recurrence free survival
and overall survival?
-Limitations of the study need to be expanded to include the fact that they had limited number
of patients to investigate and as such did not have a validation cohort for their nomogram.
The retrospective nature of the study limits their ability to assess a variety of variables such as
ampullary cancer subtype and adjuvant therapy regimens.
-I do not believe the data supports the conclusion made by the authors. The study suggests that
CA 19-9/GTT may be a useful tool in prognosis of ampullary cancer but this data has not been
validated even within their own patient population much less externally.
-Recommend reading through the manuscript for grammatical errors.
assistant