Title: Long-standing Diabetes Mellitus Increases Concomitant Pancreatic Cancer Risk in
Patients with Intraductal Papillary Mucinous Neoplasms
Version: 1 Date: 06 Jul 2022
Reviewer's report:
Yamaguchi et al retrospectively analyzed risk factors for concomitant PDAC in a cohort of
IPMN patients.  A total of 547 pancreatic cyst patients (initial visit 2005-2019) were selected and
underwent imaging (CT, MRCP, EUS) followed by surveillance.  Of these, 439 patients with
IPMN were identified of which 14 had distinct concomitant PDAC and 5 had high grade/invasive
IPMN.  Upon data analysis, longstanding diabetes mellitus was identified as a significant risk
factor for concomitant PDAC.
General Comment:  It is not clear how many patients underwent surgery with confirmed
pathological diagnosis for this study versus preoperative diagnosis only.  Final numbers of
patients with either high-grade/invasive IPMN or IPMN with concomitant PDAC were relatively
low.  To confirm and validate findings, larger patient numbers would be required.
Specific Comments:
1. Abstract wording:  In their concluding statement regarding the monitoring of IPMN, authors
write “…rather than…” but both concomitant PDAC and IPMN-derived carcinoma should be
considered.
2. Page 5: authors state that IPMN patients had “high” frequencies of concomitant PDAC.  What
is “high”?
3. Page 7-8: Patients were divided into IPMN, SCN and non-IPMN/SCN (P-cyst) groups for the
study based upon 2017 International Guidelines, but preoperative diagnosis by these criteria/
imaging may not be accurate.  Please clarify the two sentences describing IPMN/P-cysts as being
“nearly equal” to “suspected” or “presumed” IPMN, respectively.
4. Of the initial 547 patients, how many were resected?  Were the 14 concomitant PDAC and
5 high grade/invasive IPMN diagnosed on final pathology following surgery?  It appears only
a subset from Supplementary tables (12 of 14 and 3 of 5, respectively).  If not resected, how
are authors confident of diagnosis?
5. Page 9: Authors should provide more detail about how IPMN-derived carcinoma was
distinguished from concomitant PDAC by imaging and/or pathology.  For Figure 1, authors
should indicate regions of interest with arrows.
6. Why are the number of patients different between Tables 1 (initial) and 2 (follow-up)?
Authors should use current terminology for IPMN.  “IPMA” is no longer commonly used and
IPMC should refer to IPMN with associated invasive carcinoma.  Carcinoma in situ is high-grade
IPMN, not IPMC as written.  Patients with a final diagnosis and concomitant PDAC in Table
2 all underwent surgery (see question 4)?  “Final Diagnosis” implies pathological confirmation
following surgery.
7. Page 12: Authors state that “this difference was not statistically significant (P = 0.08), but
we presumed that IPMN diagnosed with 2017 international guidelines carried a higher risk of
concomitant PDAC than other cysts.”  If not significant, this statement cannot be made.
8. Paper, especially Discussion section, should be corrected for grammar.
Title: Long-standing Diabetes Mellitus Increases Concomitant Pancreatic Cancer Risk in
Patients with Intraductal Papillary Mucinous Neoplasms
Version: 1 Date: 06 Jul 2022
Reviewer's report:
Yamaguchi et al retrospectively analyzed risk factors for concomitant PDAC in a cohort of
IPMN patients.  A total of 547 pancreatic cyst patients (initial visit 2005-2019) were selected and
underwent imaging (CT, MRCP, EUS) followed by surveillance.  Of these, 439 patients with
IPMN were identified of which 14 had distinct concomitant PDAC and 5 had high grade/invasive
IPMN.  Upon data analysis, longstanding diabetes mellitus was identified as a significant risk
factor for concomitant PDAC.
General Comment:  It is not clear how many patients underwent surgery with confirmed
pathological diagnosis for this study versus preoperative diagnosis only.  Final numbers of
patients with either high-grade/invasive IPMN or IPMN with concomitant PDAC were relatively
low.  To confirm and validate findings, larger patient numbers would be required.
Specific Comments:
1. Abstract wording:  In their concluding statement regarding the monitoring of IPMN, authors
write “…rather than…” but both concomitant PDAC and IPMN-derived carcinoma should be
considered.
2. Page 5: authors state that IPMN patients had “high” frequencies of concomitant PDAC.  What
is “high”?
3. Page 7-8: Patients were divided into IPMN, SCN and non-IPMN/SCN (P-cyst) groups for the
study based upon 2017 International Guidelines, but preoperative diagnosis by these criteria/
imaging may not be accurate.  Please clarify the two sentences describing IPMN/P-cysts as being
“nearly equal” to “suspected” or “presumed” IPMN, respectively.
4. Of the initial 547 patients, how many were resected?  Were the 14 concomitant PDAC and
5 high grade/invasive IPMN diagnosed on final pathology following surgery?  It appears only
a subset from Supplementary tables (12 of 14 and 3 of 5, respectively).  If not resected, how
are authors confident of diagnosis?
5. Page 9: Authors should provide more detail about how IPMN-derived carcinoma was
distinguished from concomitant PDAC by imaging and/or pathology.  For Figure 1, authors
should indicate regions of interest with arrows.
6. Why are the number of patients different between Tables 1 (initial) and 2 (follow-up)?
Authors should use current terminology for IPMN.  “IPMA” is no longer commonly used and
IPMC should refer to IPMN with associated invasive carcinoma.  Carcinoma in situ is high-grade
IPMN, not IPMC as written.  Patients with a final diagnosis and concomitant PDAC in Table
2 all underwent surgery (see question 4)?  “Final Diagnosis” implies pathological confirmation
following surgery.
7. Page 12: Authors state that “this difference was not statistically significant (P = 0.08), but
we presumed that IPMN diagnosed with 2017 international guidelines carried a higher risk of
concomitant PDAC than other cysts.”  If not significant, this statement cannot be made.
8. Paper, especially Discussion section, should be corrected for grammar.
Please review this paper.
user
Title: Long-standing Diabetes Mellitus Increases Concomitant Pancreatic Cancer Risk in
Patients with Intraductal Papillary Mucinous Neoplasms
Version: 1 Date: 06 Jul 2022
Reviewer's report:
Yamaguchi et al retrospectively analyzed risk factors for concomitant PDAC in a cohort of
IPMN patients.  A total of 547 pancreatic cyst patients (initial visit 2005-2019) were selected and
underwent imaging (CT, MRCP, EUS) followed by surveillance.  Of these, 439 patients with
IPMN were identified of which 14 had distinct concomitant PDAC and 5 had high grade/invasive
IPMN.  Upon data analysis, longstanding diabetes mellitus was identified as a significant risk
factor for concomitant PDAC.
General Comment:  It is not clear how many patients underwent surgery with confirmed
pathological diagnosis for this study versus preoperative diagnosis only.  Final numbers of
patients with either high-grade/invasive IPMN or IPMN with concomitant PDAC were relatively
low.  To confirm and validate findings, larger patient numbers would be required.
Specific Comments:
1. Abstract wording:  In their concluding statement regarding the monitoring of IPMN, authors
write “…rather than…” but both concomitant PDAC and IPMN-derived carcinoma should be
considered.
2. Page 5: authors state that IPMN patients had “high” frequencies of concomitant PDAC.  What
is “high”?
3. Page 7-8: Patients were divided into IPMN, SCN and non-IPMN/SCN (P-cyst) groups for the
study based upon 2017 International Guidelines, but preoperative diagnosis by these criteria/
imaging may not be accurate.  Please clarify the two sentences describing IPMN/P-cysts as being
“nearly equal” to “suspected” or “presumed” IPMN, respectively.
4. Of the initial 547 patients, how many were resected?  Were the 14 concomitant PDAC and
5 high grade/invasive IPMN diagnosed on final pathology following surgery?  It appears only
a subset from Supplementary tables (12 of 14 and 3 of 5, respectively).  If not resected, how
are authors confident of diagnosis?
5. Page 9: Authors should provide more detail about how IPMN-derived carcinoma was
distinguished from concomitant PDAC by imaging and/or pathology.  For Figure 1, authors
should indicate regions of interest with arrows.
6. Why are the number of patients different between Tables 1 (initial) and 2 (follow-up)?
Authors should use current terminology for IPMN.  “IPMA” is no longer commonly used and
IPMC should refer to IPMN with associated invasive carcinoma.  Carcinoma in situ is high-grade
IPMN, not IPMC as written.  Patients with a final diagnosis and concomitant PDAC in Table
2 all underwent surgery (see question 4)?  “Final Diagnosis” implies pathological confirmation
following surgery.
7. Page 12: Authors state that “this difference was not statistically significant (P = 0.08), but
we presumed that IPMN diagnosed with 2017 international guidelines carried a higher risk of
concomitant PDAC than other cysts.”  If not significant, this statement cannot be made.
8. Paper, especially Discussion section, should be corrected for grammar.
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