Title: Cholelithiasis and Cholecystitis in Children and Adolescents: does this increasing
diagnosis require a common guideline for pediatricians and pediatric surgeons?
Version: 1 Date: 07 Feb 2021
Reviewer's report:
This manuscript evaluated the practise of cholecystectomy in children and young adults. This
is a relevant topic as the best management of cholelithiasis is not well established and can be
challenging. The authors should be complemented for exploring this subject, however, I have
some major comments on the methodology and presentation of this study.
Major:
In the retrospective analysis from the study centre, only cases of cholecystectomy are included.
As not all cases of cholelithiasis are managed by surgery, this part of care is not examined in this
study. Differences in frequency and selection of patients for surgery can also have an influence
of the findings in this study, this limitation should be discussed.
The authors approach cholecystolithiasis from the endpoint cholecystectomy. It merits
discussion to address the accidental finding of gall stones in children with symptoms that may or
may not be related. In these cases there is a high reported lack of resolve of symptoms in children.
The consideration the complications of cholecystectomy should also be taken into account. The
latter are not discussed in this manucript
In the survey many of the questions depicted in figure 1 are unclear as they are only described in
a condensed way. (e.g.Q12-15: what is exactly asked; concerning what time period?). I would
suggest to publish the questionnaire in full. More importantly I doubt whether the survey was
explicit enough for respondents to ascertain that all had a uniform concept of what was meant
by each question and by symptomatic cholelithiasis  and possibly also cholecystitis (acute vs
chronic?).
It is stated that ‘Our study reflected additionally the preference of an expectant management
in symptomatic and even acute and complicated cases. However in none of the questions in
figure 1 complicated cholelithiasis questions is described.It is hard to imagine doubt whether
physicians  would not perform a cholecystectomy in acute cholelithiasis not rapidly responding
to antibiotics
Major comment by section
Introduction:
Several statements are made without supporting literature: ‘increasing diagnosis’ –
‘management seems to be heterogeneous’
Method:
How were the cases of cholecystectomy identified. Please specify your search strategy.
Among the exclusion criteria: ‘all cholecystectomies based on non-inflammatory processes were
excluded’. For me this does imply that not all cholelithiasis cases were included as these are not
necessarily displaying inflammation.
Weight is only taken as measure of obesity should also be related to height in those <18 years
What statistical test was used to test for difference in variables with more than two outcomes
(e.g. secondary diagnosis in table 1) ?
Please specify when Chi-square and when Fishers’ exact test were used
Results
Retrospective study
Results are represented as both including complicated and uncomplicated cases (tabel2) and as
separately for the complicated cases (Table 3). Data in table 2 could be influenced by the slight
different case mix of complicated and uncomplicated cases. This merits discussion.
Among the outcomes complications before or after surgery are not reported. This merits
discussion.
Survey:
Many questions (Q5-Q14) are on detailed characteristics of cases seen in practices. These
reported data are at high risk of recollection bias. This should be discussed
In the results section of the manuscript some more results from the survey could be described
before discussing them in the discussion section, while some results can be described more in
detail ( e.g. how many times it was reported “there is no temporal limitation”)
Discussion
The first paragraph is rather elaborate and not directly related to study results.
Results from the retrospective study are discussed very limited.
Several studies are discussed with lack of detail on limitations of these studies: e.g. Curro is an
observational study n=30 that specifically refers to sickle cell disease not any other  comorbidity;
In the study of Serrami the way patients were searched and definition of symptomatic
cholelithiasis is not described.
Why is use of MRI considered ‘insecurity and variance in diagnostic measurements’? In
pediatrics use of MRI in case possible false neagtive US findings is generally accepted as the
preferred diagnostic tool.
The sample size of this study is small  especially for the complicated cases. Therefore the results
are prone to type 1 and 2 errors. This limitations should be stressed more explicitly in the
discussion.
Figure 3 should be presented in the results section and the methodology to come to this flowchart
should be described .
Tabels
Table 2 ‘duration of symptoms’ is unlikely to be normally distributed given the mean and range
reported. Report the median.
Minor:
Grammar and phrasing could be improved. Consider review by a native speaker: eg line 54
‘different guidelines are present in various’ and line 88 ‘This applied especially as well to’ These
are unclear phrases.
Please check this manuscript for typos: e.g. line 94 ‘exploited’ instead of ‘explored’
Line 106 ‘CRP’ should be written in full first.
Line 88 typo: ‘> 90. percentile, obesity > 97. Percentile’ should be ‘> 90th percentile, obesity
> 97th Percentile’.
Line 89 ‘This applied especially as well to three patients of the visceral surgery group, being <
18 years of age at time of surgery’ It is unclear what is meant here.
Line 104 ‘secondary diagnoses’ I would prefer to use the word ‘co-morbidity’ of ‘concomitant
disorder’.
Table 1 layout of table should be improved.
Figure 3 typo ‘MRT’.
Title: Cholelithiasis and Cholecystitis in Children and Adolescents: does this increasing
diagnosis require a common guideline for pediatricians and pediatric surgeons?
Version: 1 Date: 07 Feb 2021
Reviewer's report:
This manuscript evaluated the practise of cholecystectomy in children and young adults. This
is a relevant topic as the best management of cholelithiasis is not well established and can be
challenging. The authors should be complemented for exploring this subject, however, I have
some major comments on the methodology and presentation of this study.
Major:
In the retrospective analysis from the study centre, only cases of cholecystectomy are included.
As not all cases of cholelithiasis are managed by surgery, this part of care is not examined in this
study. Differences in frequency and selection of patients for surgery can also have an influence
of the findings in this study, this limitation should be discussed.
The authors approach cholecystolithiasis from the endpoint cholecystectomy. It merits
discussion to address the accidental finding of gall stones in children with symptoms that may or
may not be related. In these cases there is a high reported lack of resolve of symptoms in children.
The consideration the complications of cholecystectomy should also be taken into account. The
latter are not discussed in this manucript
In the survey many of the questions depicted in figure 1 are unclear as they are only described in
a condensed way. (e.g.Q12-15: what is exactly asked; concerning what time period?). I would
suggest to publish the questionnaire in full. More importantly I doubt whether the survey was
explicit enough for respondents to ascertain that all had a uniform concept of what was meant
by each question and by symptomatic cholelithiasis  and possibly also cholecystitis (acute vs
chronic?).
It is stated that ‘Our study reflected additionally the preference of an expectant management
in symptomatic and even acute and complicated cases. However in none of the questions in
figure 1 complicated cholelithiasis questions is described.It is hard to imagine doubt whether
physicians  would not perform a cholecystectomy in acute cholelithiasis not rapidly responding
to antibiotics
Major comment by section
Introduction:
Several statements are made without supporting literature: ‘increasing diagnosis’ –
‘management seems to be heterogeneous’
Method:
How were the cases of cholecystectomy identified. Please specify your search strategy.
Among the exclusion criteria: ‘all cholecystectomies based on non-inflammatory processes were
excluded’. For me this does imply that not all cholelithiasis cases were included as these are not
necessarily displaying inflammation.
Weight is only taken as measure of obesity should also be related to height in those <18 years
What statistical test was used to test for difference in variables with more than two outcomes
(e.g. secondary diagnosis in table 1) ?
Please specify when Chi-square and when Fishers’ exact test were used
Results
Retrospective study
Results are represented as both including complicated and uncomplicated cases (tabel2) and as
separately for the complicated cases (Table 3). Data in table 2 could be influenced by the slight
different case mix of complicated and uncomplicated cases. This merits discussion.
Among the outcomes complications before or after surgery are not reported. This merits
discussion.
Survey:
Many questions (Q5-Q14) are on detailed characteristics of cases seen in practices. These
reported data are at high risk of recollection bias. This should be discussed
In the results section of the manuscript some more results from the survey could be described
before discussing them in the discussion section, while some results can be described more in
detail ( e.g. how many times it was reported “there is no temporal limitation”)
Discussion
The first paragraph is rather elaborate and not directly related to study results.
Results from the retrospective study are discussed very limited.
Several studies are discussed with lack of detail on limitations of these studies: e.g. Curro is an
observational study n=30 that specifically refers to sickle cell disease not any other  comorbidity;
In the study of Serrami the way patients were searched and definition of symptomatic
cholelithiasis is not described.
Why is use of MRI considered ‘insecurity and variance in diagnostic measurements’? In
pediatrics use of MRI in case possible false neagtive US findings is generally accepted as the
preferred diagnostic tool.
The sample size of this study is small  especially for the complicated cases. Therefore the results
are prone to type 1 and 2 errors. This limitations should be stressed more explicitly in the
discussion.
Figure 3 should be presented in the results section and the methodology to come to this flowchart
should be described .
Tabels
Table 2 ‘duration of symptoms’ is unlikely to be normally distributed given the mean and range
reported. Report the median.
Minor:
Grammar and phrasing could be improved. Consider review by a native speaker: eg line 54
‘different guidelines are present in various’ and line 88 ‘This applied especially as well to’ These
are unclear phrases.
Please check this manuscript for typos: e.g. line 94 ‘exploited’ instead of ‘explored’
Line 106 ‘CRP’ should be written in full first.
Line 88 typo: ‘> 90. percentile, obesity > 97. Percentile’ should be ‘> 90th percentile, obesity
> 97th Percentile’.
Line 89 ‘This applied especially as well to three patients of the visceral surgery group, being <
18 years of age at time of surgery’ It is unclear what is meant here.
Line 104 ‘secondary diagnoses’ I would prefer to use the word ‘co-morbidity’ of ‘concomitant
disorder’.
Table 1 layout of table should be improved.
Figure 3 typo ‘MRT’.
Please review this paper.
user
Title: Cholelithiasis and Cholecystitis in Children and Adolescents: does this increasing
diagnosis require a common guideline for pediatricians and pediatric surgeons?
Version: 1 Date: 07 Feb 2021
Reviewer's report:
This manuscript evaluated the practise of cholecystectomy in children and young adults. This
is a relevant topic as the best management of cholelithiasis is not well established and can be
challenging. The authors should be complemented for exploring this subject, however, I have
some major comments on the methodology and presentation of this study.
Major:
In the retrospective analysis from the study centre, only cases of cholecystectomy are included.
As not all cases of cholelithiasis are managed by surgery, this part of care is not examined in this
study. Differences in frequency and selection of patients for surgery can also have an influence
of the findings in this study, this limitation should be discussed.
The authors approach cholecystolithiasis from the endpoint cholecystectomy. It merits
discussion to address the accidental finding of gall stones in children with symptoms that may or
may not be related. In these cases there is a high reported lack of resolve of symptoms in children.
The consideration the complications of cholecystectomy should also be taken into account. The
latter are not discussed in this manucript
In the survey many of the questions depicted in figure 1 are unclear as they are only described in
a condensed way. (e.g.Q12-15: what is exactly asked; concerning what time period?). I would
suggest to publish the questionnaire in full. More importantly I doubt whether the survey was
explicit enough for respondents to ascertain that all had a uniform concept of what was meant
by each question and by symptomatic cholelithiasis  and possibly also cholecystitis (acute vs
chronic?).
It is stated that ‘Our study reflected additionally the preference of an expectant management
in symptomatic and even acute and complicated cases. However in none of the questions in
figure 1 complicated cholelithiasis questions is described.It is hard to imagine doubt whether
physicians  would not perform a cholecystectomy in acute cholelithiasis not rapidly responding
to antibiotics
Major comment by section
Introduction:
Several statements are made without supporting literature: ‘increasing diagnosis’ –
‘management seems to be heterogeneous’
Method:
How were the cases of cholecystectomy identified. Please specify your search strategy.
Among the exclusion criteria: ‘all cholecystectomies based on non-inflammatory processes were
excluded’. For me this does imply that not all cholelithiasis cases were included as these are not
necessarily displaying inflammation.
Weight is only taken as measure of obesity should also be related to height in those <18 years
What statistical test was used to test for difference in variables with more than two outcomes
(e.g. secondary diagnosis in table 1) ?
Please specify when Chi-square and when Fishers’ exact test were used
Results
Retrospective study
Results are represented as both including complicated and uncomplicated cases (tabel2) and as
separately for the complicated cases (Table 3). Data in table 2 could be influenced by the slight
different case mix of complicated and uncomplicated cases. This merits discussion.
Among the outcomes complications before or after surgery are not reported. This merits
discussion.
Survey:
Many questions (Q5-Q14) are on detailed characteristics of cases seen in practices. These
reported data are at high risk of recollection bias. This should be discussed
In the results section of the manuscript some more results from the survey could be described
before discussing them in the discussion section, while some results can be described more in
detail ( e.g. how many times it was reported “there is no temporal limitation”)
Discussion
The first paragraph is rather elaborate and not directly related to study results.
Results from the retrospective study are discussed very limited.
Several studies are discussed with lack of detail on limitations of these studies: e.g. Curro is an
observational study n=30 that specifically refers to sickle cell disease not any other  comorbidity;
In the study of Serrami the way patients were searched and definition of symptomatic
cholelithiasis is not described.
Why is use of MRI considered ‘insecurity and variance in diagnostic measurements’? In
pediatrics use of MRI in case possible false neagtive US findings is generally accepted as the
preferred diagnostic tool.
The sample size of this study is small  especially for the complicated cases. Therefore the results
are prone to type 1 and 2 errors. This limitations should be stressed more explicitly in the
discussion.
Figure 3 should be presented in the results section and the methodology to come to this flowchart
should be described .
Tabels
Table 2 ‘duration of symptoms’ is unlikely to be normally distributed given the mean and range
reported. Report the median.
Minor:
Grammar and phrasing could be improved. Consider review by a native speaker: eg line 54
‘different guidelines are present in various’ and line 88 ‘This applied especially as well to’ These
are unclear phrases.
Please check this manuscript for typos: e.g. line 94 ‘exploited’ instead of ‘explored’
Line 106 ‘CRP’ should be written in full first.
Line 88 typo: ‘> 90. percentile, obesity > 97. Percentile’ should be ‘> 90th percentile, obesity
> 97th Percentile’.
Line 89 ‘This applied especially as well to three patients of the visceral surgery group, being <
18 years of age at time of surgery’ It is unclear what is meant here.
Line 104 ‘secondary diagnoses’ I would prefer to use the word ‘co-morbidity’ of ‘concomitant
disorder’.
Table 1 layout of table should be improved.
Figure 3 typo ‘MRT’.
assistant