Title: Long-standing Diabetes Mellitus Increases Concomitant Pancreatic Cancer Risk in
Patients with Intraductal Papillary Mucinous Neoplasms
Version: 3 Date: 10 Aug 2022
Reviewer's report:
General comment:  Authors revised according to comments and paper is improved; however,
see points below that should be addressed.
Specific comments:
1. Abstract: “Five intraductal papillary mucinous adenocarcinomas were encountered.”  There
appears to be only one IPMN with associated invasive carcinoma (not resected).  There are 5
high-grade IPMN, but these would not be adenocarcinoma.
2. Reliance on imaging alone to classify the pancreatic cysts should be considered a limitation
of the study since different cyst types may mimic each other on imaging.  If cyst type is
misclassified during surveillance (IPMN vs SCN vs other) or diagnosed incorrectly (low vs high
vs invasive), this may affect the study’s results/conclusions since only a small subset of patients
had surgery with definitive diagnosis.  As an example, in Supplementary Figure 1, two patients
were initially classified as “other” but were actually IPMN upon resection; similarly, a pre-
operative diagnosis of IPMN was actually SCN on final pathology.
3. Page 8, sentence: “If those 3 cysts were not IPMNs…” based on what criteria - imaging?  If
there were other IPMNs present, then you assumed that these 3 were in fact IPMNs?  Please
clarify.
4. Page 9: Criteria used for IPMN associated with invasive carcinoma vs concomitant PDAC
still not very detailed.  What exactly does “assessment of continuity” mean?  For example,
Ohtsuka et al (Pancreapedia, 2014) state that “PDAC concomitant with IPMN is usually defined
as occurring when the lesion is separated from the IPMN by an uninvolved segment of pancreatic
duct, and there is no transition area from adenoma to carcinoma in the distinct PDAC.”
5. Page 10 seems to have some missing words.
6. Page 11 seems to be duplication of prior text.
7. Page 16: “In 6 IPMN-derived carcinomas…” – high-grade IPMN are not considered
carcinoma (see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814593/).  There is only one
invasive IPMN.  The high-grade and invasive IPMNs can be grouped together as ‘high-risk”
versus “low-risk” IPMN (low-grade).
8. Figure 1 legend: Provide arrows for IPMN in A and C as well to clearly show difference
between concomitant vs IPMN-derived PDAC
Title: Long-standing Diabetes Mellitus Increases Concomitant Pancreatic Cancer Risk in
Patients with Intraductal Papillary Mucinous Neoplasms
Version: 3 Date: 10 Aug 2022
Reviewer's report:
General comment:  Authors revised according to comments and paper is improved; however,
see points below that should be addressed.
Specific comments:
1. Abstract: “Five intraductal papillary mucinous adenocarcinomas were encountered.”  There
appears to be only one IPMN with associated invasive carcinoma (not resected).  There are 5
high-grade IPMN, but these would not be adenocarcinoma.
2. Reliance on imaging alone to classify the pancreatic cysts should be considered a limitation
of the study since different cyst types may mimic each other on imaging.  If cyst type is
misclassified during surveillance (IPMN vs SCN vs other) or diagnosed incorrectly (low vs high
vs invasive), this may affect the study’s results/conclusions since only a small subset of patients
had surgery with definitive diagnosis.  As an example, in Supplementary Figure 1, two patients
were initially classified as “other” but were actually IPMN upon resection; similarly, a pre-
operative diagnosis of IPMN was actually SCN on final pathology.
3. Page 8, sentence: “If those 3 cysts were not IPMNs…” based on what criteria - imaging?  If
there were other IPMNs present, then you assumed that these 3 were in fact IPMNs?  Please
clarify.
4. Page 9: Criteria used for IPMN associated with invasive carcinoma vs concomitant PDAC
still not very detailed.  What exactly does “assessment of continuity” mean?  For example,
Ohtsuka et al (Pancreapedia, 2014) state that “PDAC concomitant with IPMN is usually defined
as occurring when the lesion is separated from the IPMN by an uninvolved segment of pancreatic
duct, and there is no transition area from adenoma to carcinoma in the distinct PDAC.”
5. Page 10 seems to have some missing words.
6. Page 11 seems to be duplication of prior text.
7. Page 16: “In 6 IPMN-derived carcinomas…” – high-grade IPMN are not considered
carcinoma (see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814593/).  There is only one
invasive IPMN.  The high-grade and invasive IPMNs can be grouped together as ‘high-risk”
versus “low-risk” IPMN (low-grade).
8. Figure 1 legend: Provide arrows for IPMN in A and C as well to clearly show difference
between concomitant vs IPMN-derived PDAC
Please review this paper.
user
Title: Long-standing Diabetes Mellitus Increases Concomitant Pancreatic Cancer Risk in
Patients with Intraductal Papillary Mucinous Neoplasms
Version: 3 Date: 10 Aug 2022
Reviewer's report:
General comment:  Authors revised according to comments and paper is improved; however,
see points below that should be addressed.
Specific comments:
1. Abstract: “Five intraductal papillary mucinous adenocarcinomas were encountered.”  There
appears to be only one IPMN with associated invasive carcinoma (not resected).  There are 5
high-grade IPMN, but these would not be adenocarcinoma.
2. Reliance on imaging alone to classify the pancreatic cysts should be considered a limitation
of the study since different cyst types may mimic each other on imaging.  If cyst type is
misclassified during surveillance (IPMN vs SCN vs other) or diagnosed incorrectly (low vs high
vs invasive), this may affect the study’s results/conclusions since only a small subset of patients
had surgery with definitive diagnosis.  As an example, in Supplementary Figure 1, two patients
were initially classified as “other” but were actually IPMN upon resection; similarly, a pre-
operative diagnosis of IPMN was actually SCN on final pathology.
3. Page 8, sentence: “If those 3 cysts were not IPMNs…” based on what criteria - imaging?  If
there were other IPMNs present, then you assumed that these 3 were in fact IPMNs?  Please
clarify.
4. Page 9: Criteria used for IPMN associated with invasive carcinoma vs concomitant PDAC
still not very detailed.  What exactly does “assessment of continuity” mean?  For example,
Ohtsuka et al (Pancreapedia, 2014) state that “PDAC concomitant with IPMN is usually defined
as occurring when the lesion is separated from the IPMN by an uninvolved segment of pancreatic
duct, and there is no transition area from adenoma to carcinoma in the distinct PDAC.”
5. Page 10 seems to have some missing words.
6. Page 11 seems to be duplication of prior text.
7. Page 16: “In 6 IPMN-derived carcinomas…” – high-grade IPMN are not considered
carcinoma (see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814593/).  There is only one
invasive IPMN.  The high-grade and invasive IPMNs can be grouped together as ‘high-risk”
versus “low-risk” IPMN (low-grade).
8. Figure 1 legend: Provide arrows for IPMN in A and C as well to clearly show difference
between concomitant vs IPMN-derived PDAC
assistant