Title: CD63-positive extracellular vesicles are potential diagnostic biomarkers of pancreatic
ductal adenocarcinoma
Version: 2 Date: 24 Nov 2021
Reviewer:  Mohamed M. Zaid
Reviewer's report:
This manuscript investigates the utility of EVs in the early detection of pancreatic ductal
adenocarcinoma. The authors tested their hypothesis on three retrospective cohorts, and the
results supported the utilization of EVs in combination with CA-19 for the early detection
purposes.
I have few minor comments and questions for the authors:
-The nomenclature is not consistent, sometimes you refer to the healthy controls as healthy
donors, and my understanding is that they are the same thing.
-The used cohorts are really small in number, did you do power calculation to determine if the
numbers sufficient for this power and alpha?
-In the method section you referred to the healthy donors as patients, which is not true. Right?
-What is the chemo/radiotherapy statuses for these patients? Did they receive neoadjuvant or
adjuvant therapy? How does that impact the quantification of the EVs?
-It would be interesting to show if the  EVs can also detect the recurrence
-Do you think imaging can play a complementary role to the EVs and CA-19?
Title: CD63-positive extracellular vesicles are potential diagnostic biomarkers of pancreatic
ductal adenocarcinoma
Version: 2 Date: 24 Nov 2021
Reviewer:  Mohamed M. Zaid
Reviewer's report:
This manuscript investigates the utility of EVs in the early detection of pancreatic ductal
adenocarcinoma. The authors tested their hypothesis on three retrospective cohorts, and the
results supported the utilization of EVs in combination with CA-19 for the early detection
purposes.
I have few minor comments and questions for the authors:
-The nomenclature is not consistent, sometimes you refer to the healthy controls as healthy
donors, and my understanding is that they are the same thing.
-The used cohorts are really small in number, did you do power calculation to determine if the
numbers sufficient for this power and alpha?
-In the method section you referred to the healthy donors as patients, which is not true. Right?
-What is the chemo/radiotherapy statuses for these patients? Did they receive neoadjuvant or
adjuvant therapy? How does that impact the quantification of the EVs?
-It would be interesting to show if the  EVs can also detect the recurrence
-Do you think imaging can play a complementary role to the EVs and CA-19?
Please review this paper.
user
Title: CD63-positive extracellular vesicles are potential diagnostic biomarkers of pancreatic
ductal adenocarcinoma
Version: 2 Date: 24 Nov 2021
Reviewer:  Mohamed M. Zaid
Reviewer's report:
This manuscript investigates the utility of EVs in the early detection of pancreatic ductal
adenocarcinoma. The authors tested their hypothesis on three retrospective cohorts, and the
results supported the utilization of EVs in combination with CA-19 for the early detection
purposes.
I have few minor comments and questions for the authors:
-The nomenclature is not consistent, sometimes you refer to the healthy controls as healthy
donors, and my understanding is that they are the same thing.
-The used cohorts are really small in number, did you do power calculation to determine if the
numbers sufficient for this power and alpha?
-In the method section you referred to the healthy donors as patients, which is not true. Right?
-What is the chemo/radiotherapy statuses for these patients? Did they receive neoadjuvant or
adjuvant therapy? How does that impact the quantification of the EVs?
-It would be interesting to show if the  EVs can also detect the recurrence
-Do you think imaging can play a complementary role to the EVs and CA-19?
assistant