Reviewer's report
Title:Relation of cholesterol metabolism to pediatric gallstone disease. A
retrospective controlled study
Version:1Date:27 April 2015
Reviewer: Frank Lammert
Reviewer's report:
In the current study Koivusalo et al aim to investigate the cholesterol
homeostasis in pediatric patients with gallstones. To this end they retrospectively
analysed a cohort of cholecystectomised children. The gallstone composition as
well as serum markers of cholesterol synthesis and transport were investigated.
These were compared with matched children without gallstones (n = 82) and
gallstone-free adults (n=187). Having analysed gallstone composition and serum
sterol levels the authors conclude that pediatric patients with gallstones have
increased cholesterol synthesis and that cholesterol stones are associated wit
low cholesterol absorption whilst the cholesterol metabolism is not affected.
Patients with black pigment stones are in turn characterised by an increased
accumulation of cholestanol, campesterol and sitosterol in serum and in stones.
The study is interesting, however I have several comments to the authors:
1. The study cohort is small – serum markers of cholesterol metabolism were
analysed in 28 children and gallstone composition in 46 children. Then the cohort
was analysed separately for black pigment stones (n = 26) and cholesterol
stones (n = 20). Hence, to validate the results in this small cohort, the authors
should replicate them in the aditionl cohort of pediatric gallstones.
2. In line with the above comment, is it possible that lack of differences in
cholesterol metabolism in children with cholesterol stones is simply related to a
low power of the study? Please provide power calculation and discuss.
3. Please define who were the ‘adult controls’. At first sight it may seem that
these are adults without gallstones, however this assumption seems to be
incorrect. Please also provide more details about this cohort. Did they have any
concomitant liver diseases? HCV or HBV? Liver cirrhosis? NASH? Please
specify. Overall, I am not very comfortable with using adults as controls for this
study. The authors should stick to children and not mix them in adults since most
likely different triggers of stones are to be expected in both groups. Once again –
who were ‘adult controls’, did they have gallstones?
4. The study lacks information about gallstone composition in the cohort of 28
children by whom sterol serum levels were analyzed. This lowers the value of the
study.
5. Indeed, as correctly stated by the authors, phytosterols are not synthesized in
the human body and their serum levels provide direct insights into the transport
function of hepatic and intestinal cholesterol transporter. Measurements of
cholesterol precursors in serum allow indirect estimation of de novo cholesterol
synthesis. However the authors of the study could extend their analyses by
calculating ratios of phytosterols to cholesterol precursors, which will provide
direct info about source of cholesterol in a given individual.
6. Which test was used to detect the P value in the Table 3? Was it ANOVA?
Please provide exact p-values in this table instead of signs (i.e. *).
7. What was the ethnicity of included patients? Were they all Caucasians?
8. P. 4, Methods: ‘Preoperative bile duct stones were detected in five patients, for
of whom had removal of stones by endoscopic sphinterectomy and in one the
bile stone passed spontaneously into the duodenum‘. In which cohort are these
patients included? In the one with serum measurements of in the cohort of
patients with measured gallstone composition? Please specify, and analyse
sterol levels separately in these patients.
9. Please provide an additional table presenting basic laboratory tests that as
listed on p. 4 were measured in all patients.
10. Since sonography was performed, did any children have - a known risk factor
for gallstones?
Reviewer's report
Title:Relation of cholesterol metabolism to pediatric gallstone disease. A
retrospective controlled study
Version:1Date:27 April 2015
Reviewer: Frank Lammert
Reviewer's report:
In the current study Koivusalo et al aim to investigate the cholesterol
homeostasis in pediatric patients with gallstones. To this end they retrospectively
analysed a cohort of cholecystectomised children. The gallstone composition as
well as serum markers of cholesterol synthesis and transport were investigated.
These were compared with matched children without gallstones (n = 82) and
gallstone-free adults (n=187). Having analysed gallstone composition and serum
sterol levels the authors conclude that pediatric patients with gallstones have
increased cholesterol synthesis and that cholesterol stones are associated wit
low cholesterol absorption whilst the cholesterol metabolism is not affected.
Patients with black pigment stones are in turn characterised by an increased
accumulation of cholestanol, campesterol and sitosterol in serum and in stones.
The study is interesting, however I have several comments to the authors:
1. The study cohort is small – serum markers of cholesterol metabolism were
analysed in 28 children and gallstone composition in 46 children. Then the cohort
was analysed separately for black pigment stones (n = 26) and cholesterol
stones (n = 20). Hence, to validate the results in this small cohort, the authors
should replicate them in the aditionl cohort of pediatric gallstones.
2. In line with the above comment, is it possible that lack of differences in
cholesterol metabolism in children with cholesterol stones is simply related to a
low power of the study? Please provide power calculation and discuss.
3. Please define who were the ‘adult controls’. At first sight it may seem that
these are adults without gallstones, however this assumption seems to be
incorrect. Please also provide more details about this cohort. Did they have any
concomitant liver diseases? HCV or HBV? Liver cirrhosis? NASH? Please
specify. Overall, I am not very comfortable with using adults as controls for this
study. The authors should stick to children and not mix them in adults since most
likely different triggers of stones are to be expected in both groups. Once again –
who were ‘adult controls’, did they have gallstones?
4. The study lacks information about gallstone composition in the cohort of 28
children by whom sterol serum levels were analyzed. This lowers the value of the
study.
5. Indeed, as correctly stated by the authors, phytosterols are not synthesized in
the human body and their serum levels provide direct insights into the transport
function of hepatic and intestinal cholesterol transporter. Measurements of
cholesterol precursors in serum allow indirect estimation of de novo cholesterol
synthesis. However the authors of the study could extend their analyses by
calculating ratios of phytosterols to cholesterol precursors, which will provide
direct info about source of cholesterol in a given individual.
6. Which test was used to detect the P value in the Table 3? Was it ANOVA?
Please provide exact p-values in this table instead of signs (i.e. *).
7. What was the ethnicity of included patients? Were they all Caucasians?
8. P. 4, Methods: ‘Preoperative bile duct stones were detected in five patients, for
of whom had removal of stones by endoscopic sphinterectomy and in one the
bile stone passed spontaneously into the duodenum‘. In which cohort are these
patients included? In the one with serum measurements of in the cohort of
patients with measured gallstone composition? Please specify, and analyse
sterol levels separately in these patients.
9. Please provide an additional table presenting basic laboratory tests that as
listed on p. 4 were measured in all patients.
10. Since sonography was performed, did any children have - a known risk factor
for gallstones?
Please review this paper.
user
Reviewer's report
Title:Relation of cholesterol metabolism to pediatric gallstone disease. A
retrospective controlled study
Version:1Date:27 April 2015
Reviewer: Frank Lammert
Reviewer's report:
In the current study Koivusalo et al aim to investigate the cholesterol
homeostasis in pediatric patients with gallstones. To this end they retrospectively
analysed a cohort of cholecystectomised children. The gallstone composition as
well as serum markers of cholesterol synthesis and transport were investigated.
These were compared with matched children without gallstones (n = 82) and
gallstone-free adults (n=187). Having analysed gallstone composition and serum
sterol levels the authors conclude that pediatric patients with gallstones have
increased cholesterol synthesis and that cholesterol stones are associated wit
low cholesterol absorption whilst the cholesterol metabolism is not affected.
Patients with black pigment stones are in turn characterised by an increased
accumulation of cholestanol, campesterol and sitosterol in serum and in stones.
The study is interesting, however I have several comments to the authors:
1. The study cohort is small – serum markers of cholesterol metabolism were
analysed in 28 children and gallstone composition in 46 children. Then the cohort
was analysed separately for black pigment stones (n = 26) and cholesterol
stones (n = 20). Hence, to validate the results in this small cohort, the authors
should replicate them in the aditionl cohort of pediatric gallstones.
2. In line with the above comment, is it possible that lack of differences in
cholesterol metabolism in children with cholesterol stones is simply related to a
low power of the study? Please provide power calculation and discuss.
3. Please define who were the ‘adult controls’. At first sight it may seem that
these are adults without gallstones, however this assumption seems to be
incorrect. Please also provide more details about this cohort. Did they have any
concomitant liver diseases? HCV or HBV? Liver cirrhosis? NASH? Please
specify. Overall, I am not very comfortable with using adults as controls for this
study. The authors should stick to children and not mix them in adults since most
likely different triggers of stones are to be expected in both groups. Once again –
who were ‘adult controls’, did they have gallstones?
4. The study lacks information about gallstone composition in the cohort of 28
children by whom sterol serum levels were analyzed. This lowers the value of the
study.
5. Indeed, as correctly stated by the authors, phytosterols are not synthesized in
the human body and their serum levels provide direct insights into the transport
function of hepatic and intestinal cholesterol transporter. Measurements of
cholesterol precursors in serum allow indirect estimation of de novo cholesterol
synthesis. However the authors of the study could extend their analyses by
calculating ratios of phytosterols to cholesterol precursors, which will provide
direct info about source of cholesterol in a given individual.
6. Which test was used to detect the P value in the Table 3? Was it ANOVA?
Please provide exact p-values in this table instead of signs (i.e. *).
7. What was the ethnicity of included patients? Were they all Caucasians?
8. P. 4, Methods: ‘Preoperative bile duct stones were detected in five patients, for
of whom had removal of stones by endoscopic sphinterectomy and in one the
bile stone passed spontaneously into the duodenum‘. In which cohort are these
patients included? In the one with serum measurements of in the cohort of
patients with measured gallstone composition? Please specify, and analyse
sterol levels separately in these patients.
9. Please provide an additional table presenting basic laboratory tests that as
listed on p. 4 were measured in all patients.
10. Since sonography was performed, did any children have - a known risk factor
for gallstones?
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