Title: Health-related quality of life and anxiety levels among patients under surveillance for
intraductal papillary mucinous neoplasm
Version: 1 Date: 06 Nov 2022
Reviewer's report:
Nieminen and colleagues report the findings of their study on the quality of life and anxiety
in patients with intraductal papillary mucinous neoplasms under surveillance. As the authors
write, this topic is of interest because the benefit of surveillance must outweigh any potential
harms, and both the benefit and potential harms have not been definitely established for IPMN
surveillance. The study is presented clearly and well-written. Strengths of the manuscript are its
relatively large sample size, and the comparison to age- and sex-matched data from the general
population. There are however some major and minor issues that should be addressed.
Major
1. Novelty
As the authors write, several studies have previously established that the presence of an IPMN
did not impact quality of life, and that being under (short-term) surveillance did not meaningfully
impact their anxiety levels. Although the current study does present a much larger cohort than
what is available in literature, their findings do not give us new insights. The results would have
been more novel, had they compared their study outcomes over a longer time interval, as the
long-term effects of cyst surveillance have not been properly reported as of yet. Seeing as they
now selected a time interval of only 3 months, just before and after a single visit, this is almost
a cross-sectional measurement rather than a follow-up study.
2. Selection bias
There is a clear possibility of a selection bias, that has not been properly addressed in the
methods section and discussion. The authors report they 'randomly' selected 899 patients of the
IPMN surveillance program. There needs to be me a more detailed description how this was
performed. Were they consecutive patients in a certain time interval? Might these be patients
who adhere to their surveillance (because of anxiety?) where other patients have dropped out
along the way? Furthermore, the response rate has not been reported in percentages, but is very
low (232/899=26%). Why was there such a low response rate, and how did this effect the results?
The authors present some comparison of responders to non-responders, but only in terms of
sex and age. There are other factors of interest that need to be presented: type of cyst, size,
multifocality, presence of worrisome features or high-risk stigmata, duration of FU, other
factors possibly influencing their psychological state such as having a support system, any co-
morbidities, any earlier malignancy diagnoses, etc.). Table 1 is too brief and should be expanded
so that these factors can be interpreted, and then discussed in the discussion.
Minor
3. Introduction:
In line 66 it is suggested that the extrapancreatic malignancy risk is a reason to perform
surveillance. However, this risk is disputed and is not the reason IPMNs are under surveillance.
Please clarify this in the text.
4. Methods: throughout the manuscript 'gender' is used where the authors presumably intend to
use 'sex'. Gender is reserved for the gender identification of the individual, but here the analysis
seems based on biological sex.
5. Methods: the paragraph on the 15D (specifically the sentences referencing to the single index
score and dimension-level values) is difficult to read for non-experts. I would suggest shortening
the sentences and clarification of the terms.
6. Results: the authors describe their hypothesis that anxiety might normalize after a visit if the
findings remained unchanged as compared to previous imaging. However, the authors do not
present data if this was indeed the case. Out of 232 patients, a (potentially significant) proportion
of patients will have shown growth of the IPMN, or even the development of worrisome features.
These data should be presented and incorporated on how they have influenced the results. How
many patients for example needed additional follow-up visits? Did these patients display higher
anxiety levels?
7. Results: the 15D profile values are presented as means, but with such scales oftentimes the
data is not normally distributed. Can the authors confirm that it was indeed normally distributed,
or otherwise report the data as medians?
8. Results:  in the figures a distinction is made between P-values of 0.05, 0.01, and 0.001, but
this has not been described in the methods, where a P-value of 0.05 is considered statistically
significant. Did the authors perform a Bonferroni correction (not described) and if not, why
report different cut-offs?
9. Discussion: the discussion of the manuscript is on the short side. More text could be dedicated
to the discussion of the above-mentioned limitations and how they have potentially influenced
the results.
As said, the study is well-described and the authors are to be commended for their work. The
results can be of relevance to the field,  if the authors are able to address said issues.
Title: Health-related quality of life and anxiety levels among patients under surveillance for
intraductal papillary mucinous neoplasm
Version: 1 Date: 06 Nov 2022
Reviewer's report:
Nieminen and colleagues report the findings of their study on the quality of life and anxiety
in patients with intraductal papillary mucinous neoplasms under surveillance. As the authors
write, this topic is of interest because the benefit of surveillance must outweigh any potential
harms, and both the benefit and potential harms have not been definitely established for IPMN
surveillance. The study is presented clearly and well-written. Strengths of the manuscript are its
relatively large sample size, and the comparison to age- and sex-matched data from the general
population. There are however some major and minor issues that should be addressed.
Major
1. Novelty
As the authors write, several studies have previously established that the presence of an IPMN
did not impact quality of life, and that being under (short-term) surveillance did not meaningfully
impact their anxiety levels. Although the current study does present a much larger cohort than
what is available in literature, their findings do not give us new insights. The results would have
been more novel, had they compared their study outcomes over a longer time interval, as the
long-term effects of cyst surveillance have not been properly reported as of yet. Seeing as they
now selected a time interval of only 3 months, just before and after a single visit, this is almost
a cross-sectional measurement rather than a follow-up study.
2. Selection bias
There is a clear possibility of a selection bias, that has not been properly addressed in the
methods section and discussion. The authors report they 'randomly' selected 899 patients of the
IPMN surveillance program. There needs to be me a more detailed description how this was
performed. Were they consecutive patients in a certain time interval? Might these be patients
who adhere to their surveillance (because of anxiety?) where other patients have dropped out
along the way? Furthermore, the response rate has not been reported in percentages, but is very
low (232/899=26%). Why was there such a low response rate, and how did this effect the results?
The authors present some comparison of responders to non-responders, but only in terms of
sex and age. There are other factors of interest that need to be presented: type of cyst, size,
multifocality, presence of worrisome features or high-risk stigmata, duration of FU, other
factors possibly influencing their psychological state such as having a support system, any co-
morbidities, any earlier malignancy diagnoses, etc.). Table 1 is too brief and should be expanded
so that these factors can be interpreted, and then discussed in the discussion.
Minor
3. Introduction:
In line 66 it is suggested that the extrapancreatic malignancy risk is a reason to perform
surveillance. However, this risk is disputed and is not the reason IPMNs are under surveillance.
Please clarify this in the text.
4. Methods: throughout the manuscript 'gender' is used where the authors presumably intend to
use 'sex'. Gender is reserved for the gender identification of the individual, but here the analysis
seems based on biological sex.
5. Methods: the paragraph on the 15D (specifically the sentences referencing to the single index
score and dimension-level values) is difficult to read for non-experts. I would suggest shortening
the sentences and clarification of the terms.
6. Results: the authors describe their hypothesis that anxiety might normalize after a visit if the
findings remained unchanged as compared to previous imaging. However, the authors do not
present data if this was indeed the case. Out of 232 patients, a (potentially significant) proportion
of patients will have shown growth of the IPMN, or even the development of worrisome features.
These data should be presented and incorporated on how they have influenced the results. How
many patients for example needed additional follow-up visits? Did these patients display higher
anxiety levels?
7. Results: the 15D profile values are presented as means, but with such scales oftentimes the
data is not normally distributed. Can the authors confirm that it was indeed normally distributed,
or otherwise report the data as medians?
8. Results:  in the figures a distinction is made between P-values of 0.05, 0.01, and 0.001, but
this has not been described in the methods, where a P-value of 0.05 is considered statistically
significant. Did the authors perform a Bonferroni correction (not described) and if not, why
report different cut-offs?
9. Discussion: the discussion of the manuscript is on the short side. More text could be dedicated
to the discussion of the above-mentioned limitations and how they have potentially influenced
the results.
As said, the study is well-described and the authors are to be commended for their work. The
results can be of relevance to the field,  if the authors are able to address said issues.
Please review this paper.
user
Title: Health-related quality of life and anxiety levels among patients under surveillance for
intraductal papillary mucinous neoplasm
Version: 1 Date: 06 Nov 2022
Reviewer's report:
Nieminen and colleagues report the findings of their study on the quality of life and anxiety
in patients with intraductal papillary mucinous neoplasms under surveillance. As the authors
write, this topic is of interest because the benefit of surveillance must outweigh any potential
harms, and both the benefit and potential harms have not been definitely established for IPMN
surveillance. The study is presented clearly and well-written. Strengths of the manuscript are its
relatively large sample size, and the comparison to age- and sex-matched data from the general
population. There are however some major and minor issues that should be addressed.
Major
1. Novelty
As the authors write, several studies have previously established that the presence of an IPMN
did not impact quality of life, and that being under (short-term) surveillance did not meaningfully
impact their anxiety levels. Although the current study does present a much larger cohort than
what is available in literature, their findings do not give us new insights. The results would have
been more novel, had they compared their study outcomes over a longer time interval, as the
long-term effects of cyst surveillance have not been properly reported as of yet. Seeing as they
now selected a time interval of only 3 months, just before and after a single visit, this is almost
a cross-sectional measurement rather than a follow-up study.
2. Selection bias
There is a clear possibility of a selection bias, that has not been properly addressed in the
methods section and discussion. The authors report they 'randomly' selected 899 patients of the
IPMN surveillance program. There needs to be me a more detailed description how this was
performed. Were they consecutive patients in a certain time interval? Might these be patients
who adhere to their surveillance (because of anxiety?) where other patients have dropped out
along the way? Furthermore, the response rate has not been reported in percentages, but is very
low (232/899=26%). Why was there such a low response rate, and how did this effect the results?
The authors present some comparison of responders to non-responders, but only in terms of
sex and age. There are other factors of interest that need to be presented: type of cyst, size,
multifocality, presence of worrisome features or high-risk stigmata, duration of FU, other
factors possibly influencing their psychological state such as having a support system, any co-
morbidities, any earlier malignancy diagnoses, etc.). Table 1 is too brief and should be expanded
so that these factors can be interpreted, and then discussed in the discussion.
Minor
3. Introduction:
In line 66 it is suggested that the extrapancreatic malignancy risk is a reason to perform
surveillance. However, this risk is disputed and is not the reason IPMNs are under surveillance.
Please clarify this in the text.
4. Methods: throughout the manuscript 'gender' is used where the authors presumably intend to
use 'sex'. Gender is reserved for the gender identification of the individual, but here the analysis
seems based on biological sex.
5. Methods: the paragraph on the 15D (specifically the sentences referencing to the single index
score and dimension-level values) is difficult to read for non-experts. I would suggest shortening
the sentences and clarification of the terms.
6. Results: the authors describe their hypothesis that anxiety might normalize after a visit if the
findings remained unchanged as compared to previous imaging. However, the authors do not
present data if this was indeed the case. Out of 232 patients, a (potentially significant) proportion
of patients will have shown growth of the IPMN, or even the development of worrisome features.
These data should be presented and incorporated on how they have influenced the results. How
many patients for example needed additional follow-up visits? Did these patients display higher
anxiety levels?
7. Results: the 15D profile values are presented as means, but with such scales oftentimes the
data is not normally distributed. Can the authors confirm that it was indeed normally distributed,
or otherwise report the data as medians?
8. Results:  in the figures a distinction is made between P-values of 0.05, 0.01, and 0.001, but
this has not been described in the methods, where a P-value of 0.05 is considered statistically
significant. Did the authors perform a Bonferroni correction (not described) and if not, why
report different cut-offs?
9. Discussion: the discussion of the manuscript is on the short side. More text could be dedicated
to the discussion of the above-mentioned limitations and how they have potentially influenced
the results.
As said, the study is well-described and the authors are to be commended for their work. The
results can be of relevance to the field,  if the authors are able to address said issues.
assistant