Reviewer's report
Title:Early ultrasonographic detection and assessment of the severity of Crohn's
disease recurrence after curative ileal resection
Version: 1Date:10 March 2010
Reviewer: Odd Helge Gilja
Reviewer's report:
Here comes the details:
The introduction is OK and to the point and refers to previous relevant work, but
could be better if it incorporated some of the points that should be cut from the
start of the Discussion (See below).
Of the four study questions posed, question 1 is poorly formulated. What does
limited and minimal involvement really mean? Furthermore, if one wants to detect
the initial/early recurrence, the method described is not appropriate. The patients
are examined from 6 months up to 2 years after resection and the author has no
way of knowing if the changes seen are early or initial. One would expect that the
changes became more severe the further away from the operation date the
patients were examined. Actually this is also shown by data in this study as
Median time from surgery increases significantly with increasing Rutgeert score
(Table 2). The title indicates that this method is used for early detection of
recurrence of Crohns disease after ileal resection while the study is not designed
for this. It should be more in the line of "Detection of recurrence....and so forth."
The expression "transmural" is introduced in the first paragraph of the
introduction is used through the article as synonymous to wall thickening on
SICUS. This is not correct as thickening of the gastrointestinal may be detected
on ultrasound even though the pathological changes are not transmural. The
thickening can be solely caused by edema in the mucosa and submucosa
without involvement of the proper muscle and would then not be considered as
transmural. The term transmural should therefore not be used.
The patient population in the material and methods (M&M) section is poorly and
insufficiently described (Page 3, paragraph 6). There is no explanation as to how
and when the patients were recruited, if this was consecutive from a cohort or on
a case by case basis. According to M&M (page 4, paragraph 3) all the patients
were examined with SICUS and ileocolonoscopy 6 and 12 months after surgery
and at regular intervals 6-12 months after. According to Results, however, 19
patients were examined after 6 months, 16 after 12 months, 5 after 18 months
and 18 after 24 months (Page 6 paragraph 4). This adds up to 58 patients as
described, but only one examination per patient. Furthermore, 111 examinations
were included in the study (Page 6, paragraph 5). When were the extra
examinations performed, on which patients? How many patients went through 2
examinations? How many patients went through 3 examinations? And so on.
How many patients were excluded and for what reasons?
It is not clear in the M&M what is actually measured in the anastomosis (Page 4,
paragraph 5). The author claims to measure wall thickness, but in Figure 1A the
cursors actually traverse a fold in the intestine and measure from mucosa to
mucosa. In the Discussion (page 10, paragraph 4) the author states that the
combined wall thickness of the ileal and colonic limb in the anastomosis is
measured. What is actually measured? Between which echo layers are the
cursors set? Furthermore, the definition of a bowel stenosis (page 5, paragraph
1) does not make sense and must be rephrased.
The remaining description on how SICUS and ilecolonscopy was performed and
scored is clear, but I wonder why a higher frequency probe was not used? I
would argue that it is difficult to properly delineate the GI wall with a 5 Mhz probe
and even worse with a 3,5 MHz probe. Since the GI wall can be only 1 mm thick
in areas this introduces a selection bias.( Haber, HP, Stern, M. Intestinal
ultrasonography in children and young adults: bowel wall thickness is age
dependent. J Ultrasound Med. 2000 May;19(5):315-21.)
There is no indication as to why the author would choose to dichotomise the wall
thickness data with a cut off of 3,5mm with a reference to previous studies in the
text (page 5, paragraph 5). This is especially odd when the definition of
pathological wall thickening was set to 3 mm. Again it comes down to what you
measure in the anastomosis, but I suspect that this cut off was chosen after the
collection of the data. When hypothesis are developed post hoc, this should be
mentioned. If this cut off was chosen before the study was performed I would like
the author to explain why it was set to 3,5 mm.
It is not clear from the descriptive data when all the 111 different examinations
were performed or if some patients were examined more than twice. And I
wonder if Fischers exact test be performed on variables which contain a mix of
dependent an independent values? Regarding the results from the multiple
regression analysis I would leave it to a statistician to evaluate if the criteria for
using multiple regression and ordinal logistic regression have been met.
The discussion needs to be shortened. The first three paragraphs are mostly
repetition of the introduction and should be removed (Page 9, paragraph 2 and 3.
Page 10, paragraph 1 and 2) Content the author feels is essential for the article
in these three paragraphs that is currently not in the introduction can be
incorporated there.
Previous relevant work is acknowledged, but the author states that MRI does not
have resolution to show early recurrence while supporting the claim with a
reference on CT enterography. A relevant reference should be provided. (Page
10, paragraph 4) Furthermore, limitations are not discussed properly.
Inter-observer variation is mentioned briefly, but the author argues that this may
be amended by reducing intra-observer variability, which is not the case. I could
think of a number of weaknesses beside this. The patients are for instance
examined at different time instances. This means that the author can not be sure
if the findings on ultrasound and ileo-colonoscopy represent early or initial
findings. There are 58 patients and 111 examinations which mean that both
independent and dependent variables have been pooled. Maybe this can be
corrected for, but this must reviewed by a statistician. Finally, the author initially
operates with a cut off of 3mm of wall thickness between pathological and
healthy intestine in the material and methods. During the analysis of the data,
however, the wall thickness data are dichotomised using 3,5mm as cut off and
then the Fisher exact test is performed. This hypothesis was probably posed post
hoc.
Major compulsory revisions:
Specifically research question 1 should be dropped as the study is not designed
to answer this and only the first exam from the 58 patients should be used for
data analysis if there is no way of correcting for the pooling of independent and
dependent variables. Since these were consistent with the data presented (but
not shown) this should not be a problem. The recruitment of the patients must be
described better in the M&M section. The definition of what is measured in the
anastomosis is unclear and must be defined better. When the author speaks of
"transmural lesions" measured on SICUS this should be replaced with wall
thickening.
Minor essential revisions:
Figure 1 is of poor quality and offer very little information to the reader. It is
difficult to believe that it is possible to measure the intestinal wall thickness at all
from these images.
Figure 3: The cut off values that offer the best sensitivity and specificity should be
added to the ROC curves. There are some language issues that need to be
corrected as some sentences in the manuscript does not seem to make sense.
For specific manuscript editions, also look at the attachment.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
no competing interests with the author
Reviewer's report
Title:Early ultrasonographic detection and assessment of the severity of Crohn's
disease recurrence after curative ileal resection
Version: 1Date:10 March 2010
Reviewer: Odd Helge Gilja
Reviewer's report:
Here comes the details:
The introduction is OK and to the point and refers to previous relevant work, but
could be better if it incorporated some of the points that should be cut from the
start of the Discussion (See below).
Of the four study questions posed, question 1 is poorly formulated. What does
limited and minimal involvement really mean? Furthermore, if one wants to detect
the initial/early recurrence, the method described is not appropriate. The patients
are examined from 6 months up to 2 years after resection and the author has no
way of knowing if the changes seen are early or initial. One would expect that the
changes became more severe the further away from the operation date the
patients were examined. Actually this is also shown by data in this study as
Median time from surgery increases significantly with increasing Rutgeert score
(Table 2). The title indicates that this method is used for early detection of
recurrence of Crohns disease after ileal resection while the study is not designed
for this. It should be more in the line of "Detection of recurrence....and so forth."
The expression "transmural" is introduced in the first paragraph of the
introduction is used through the article as synonymous to wall thickening on
SICUS. This is not correct as thickening of the gastrointestinal may be detected
on ultrasound even though the pathological changes are not transmural. The
thickening can be solely caused by edema in the mucosa and submucosa
without involvement of the proper muscle and would then not be considered as
transmural. The term transmural should therefore not be used.
The patient population in the material and methods (M&M) section is poorly and
insufficiently described (Page 3, paragraph 6). There is no explanation as to how
and when the patients were recruited, if this was consecutive from a cohort or on
a case by case basis. According to M&M (page 4, paragraph 3) all the patients
were examined with SICUS and ileocolonoscopy 6 and 12 months after surgery
and at regular intervals 6-12 months after. According to Results, however, 19
patients were examined after 6 months, 16 after 12 months, 5 after 18 months
and 18 after 24 months (Page 6 paragraph 4). This adds up to 58 patients as
described, but only one examination per patient. Furthermore, 111 examinations
were included in the study (Page 6, paragraph 5). When were the extra
examinations performed, on which patients? How many patients went through 2
examinations? How many patients went through 3 examinations? And so on.
How many patients were excluded and for what reasons?
It is not clear in the M&M what is actually measured in the anastomosis (Page 4,
paragraph 5). The author claims to measure wall thickness, but in Figure 1A the
cursors actually traverse a fold in the intestine and measure from mucosa to
mucosa. In the Discussion (page 10, paragraph 4) the author states that the
combined wall thickness of the ileal and colonic limb in the anastomosis is
measured. What is actually measured? Between which echo layers are the
cursors set? Furthermore, the definition of a bowel stenosis (page 5, paragraph
1) does not make sense and must be rephrased.
The remaining description on how SICUS and ilecolonscopy was performed and
scored is clear, but I wonder why a higher frequency probe was not used? I
would argue that it is difficult to properly delineate the GI wall with a 5 Mhz probe
and even worse with a 3,5 MHz probe. Since the GI wall can be only 1 mm thick
in areas this introduces a selection bias.( Haber, HP, Stern, M. Intestinal
ultrasonography in children and young adults: bowel wall thickness is age
dependent. J Ultrasound Med. 2000 May;19(5):315-21.)
There is no indication as to why the author would choose to dichotomise the wall
thickness data with a cut off of 3,5mm with a reference to previous studies in the
text (page 5, paragraph 5). This is especially odd when the definition of
pathological wall thickening was set to 3 mm. Again it comes down to what you
measure in the anastomosis, but I suspect that this cut off was chosen after the
collection of the data. When hypothesis are developed post hoc, this should be
mentioned. If this cut off was chosen before the study was performed I would like
the author to explain why it was set to 3,5 mm.
It is not clear from the descriptive data when all the 111 different examinations
were performed or if some patients were examined more than twice. And I
wonder if Fischers exact test be performed on variables which contain a mix of
dependent an independent values? Regarding the results from the multiple
regression analysis I would leave it to a statistician to evaluate if the criteria for
using multiple regression and ordinal logistic regression have been met.
The discussion needs to be shortened. The first three paragraphs are mostly
repetition of the introduction and should be removed (Page 9, paragraph 2 and 3.
Page 10, paragraph 1 and 2) Content the author feels is essential for the article
in these three paragraphs that is currently not in the introduction can be
incorporated there.
Previous relevant work is acknowledged, but the author states that MRI does not
have resolution to show early recurrence while supporting the claim with a
reference on CT enterography. A relevant reference should be provided. (Page
10, paragraph 4) Furthermore, limitations are not discussed properly.
Inter-observer variation is mentioned briefly, but the author argues that this may
be amended by reducing intra-observer variability, which is not the case. I could
think of a number of weaknesses beside this. The patients are for instance
examined at different time instances. This means that the author can not be sure
if the findings on ultrasound and ileo-colonoscopy represent early or initial
findings. There are 58 patients and 111 examinations which mean that both
independent and dependent variables have been pooled. Maybe this can be
corrected for, but this must reviewed by a statistician. Finally, the author initially
operates with a cut off of 3mm of wall thickness between pathological and
healthy intestine in the material and methods. During the analysis of the data,
however, the wall thickness data are dichotomised using 3,5mm as cut off and
then the Fisher exact test is performed. This hypothesis was probably posed post
hoc.
Major compulsory revisions:
Specifically research question 1 should be dropped as the study is not designed
to answer this and only the first exam from the 58 patients should be used for
data analysis if there is no way of correcting for the pooling of independent and
dependent variables. Since these were consistent with the data presented (but
not shown) this should not be a problem. The recruitment of the patients must be
described better in the M&M section. The definition of what is measured in the
anastomosis is unclear and must be defined better. When the author speaks of
"transmural lesions" measured on SICUS this should be replaced with wall
thickening.
Minor essential revisions:
Figure 1 is of poor quality and offer very little information to the reader. It is
difficult to believe that it is possible to measure the intestinal wall thickness at all
from these images.
Figure 3: The cut off values that offer the best sensitivity and specificity should be
added to the ROC curves. There are some language issues that need to be
corrected as some sentences in the manuscript does not seem to make sense.
For specific manuscript editions, also look at the attachment.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
no competing interests with the author
Please review this paper.
user
Reviewer's report
Title:Early ultrasonographic detection and assessment of the severity of Crohn's
disease recurrence after curative ileal resection
Version: 1Date:10 March 2010
Reviewer: Odd Helge Gilja
Reviewer's report:
Here comes the details:
The introduction is OK and to the point and refers to previous relevant work, but
could be better if it incorporated some of the points that should be cut from the
start of the Discussion (See below).
Of the four study questions posed, question 1 is poorly formulated. What does
limited and minimal involvement really mean? Furthermore, if one wants to detect
the initial/early recurrence, the method described is not appropriate. The patients
are examined from 6 months up to 2 years after resection and the author has no
way of knowing if the changes seen are early or initial. One would expect that the
changes became more severe the further away from the operation date the
patients were examined. Actually this is also shown by data in this study as
Median time from surgery increases significantly with increasing Rutgeert score
(Table 2). The title indicates that this method is used for early detection of
recurrence of Crohns disease after ileal resection while the study is not designed
for this. It should be more in the line of "Detection of recurrence....and so forth."
The expression "transmural" is introduced in the first paragraph of the
introduction is used through the article as synonymous to wall thickening on
SICUS. This is not correct as thickening of the gastrointestinal may be detected
on ultrasound even though the pathological changes are not transmural. The
thickening can be solely caused by edema in the mucosa and submucosa
without involvement of the proper muscle and would then not be considered as
transmural. The term transmural should therefore not be used.
The patient population in the material and methods (M&M) section is poorly and
insufficiently described (Page 3, paragraph 6). There is no explanation as to how
and when the patients were recruited, if this was consecutive from a cohort or on
a case by case basis. According to M&M (page 4, paragraph 3) all the patients
were examined with SICUS and ileocolonoscopy 6 and 12 months after surgery
and at regular intervals 6-12 months after. According to Results, however, 19
patients were examined after 6 months, 16 after 12 months, 5 after 18 months
and 18 after 24 months (Page 6 paragraph 4). This adds up to 58 patients as
described, but only one examination per patient. Furthermore, 111 examinations
were included in the study (Page 6, paragraph 5). When were the extra
examinations performed, on which patients? How many patients went through 2
examinations? How many patients went through 3 examinations? And so on.
How many patients were excluded and for what reasons?
It is not clear in the M&M what is actually measured in the anastomosis (Page 4,
paragraph 5). The author claims to measure wall thickness, but in Figure 1A the
cursors actually traverse a fold in the intestine and measure from mucosa to
mucosa. In the Discussion (page 10, paragraph 4) the author states that the
combined wall thickness of the ileal and colonic limb in the anastomosis is
measured. What is actually measured? Between which echo layers are the
cursors set? Furthermore, the definition of a bowel stenosis (page 5, paragraph
1) does not make sense and must be rephrased.
The remaining description on how SICUS and ilecolonscopy was performed and
scored is clear, but I wonder why a higher frequency probe was not used? I
would argue that it is difficult to properly delineate the GI wall with a 5 Mhz probe
and even worse with a 3,5 MHz probe. Since the GI wall can be only 1 mm thick
in areas this introduces a selection bias.( Haber, HP, Stern, M. Intestinal
ultrasonography in children and young adults: bowel wall thickness is age
dependent. J Ultrasound Med. 2000 May;19(5):315-21.)
There is no indication as to why the author would choose to dichotomise the wall
thickness data with a cut off of 3,5mm with a reference to previous studies in the
text (page 5, paragraph 5). This is especially odd when the definition of
pathological wall thickening was set to 3 mm. Again it comes down to what you
measure in the anastomosis, but I suspect that this cut off was chosen after the
collection of the data. When hypothesis are developed post hoc, this should be
mentioned. If this cut off was chosen before the study was performed I would like
the author to explain why it was set to 3,5 mm.
It is not clear from the descriptive data when all the 111 different examinations
were performed or if some patients were examined more than twice. And I
wonder if Fischers exact test be performed on variables which contain a mix of
dependent an independent values? Regarding the results from the multiple
regression analysis I would leave it to a statistician to evaluate if the criteria for
using multiple regression and ordinal logistic regression have been met.
The discussion needs to be shortened. The first three paragraphs are mostly
repetition of the introduction and should be removed (Page 9, paragraph 2 and 3.
Page 10, paragraph 1 and 2) Content the author feels is essential for the article
in these three paragraphs that is currently not in the introduction can be
incorporated there.
Previous relevant work is acknowledged, but the author states that MRI does not
have resolution to show early recurrence while supporting the claim with a
reference on CT enterography. A relevant reference should be provided. (Page
10, paragraph 4) Furthermore, limitations are not discussed properly.
Inter-observer variation is mentioned briefly, but the author argues that this may
be amended by reducing intra-observer variability, which is not the case. I could
think of a number of weaknesses beside this. The patients are for instance
examined at different time instances. This means that the author can not be sure
if the findings on ultrasound and ileo-colonoscopy represent early or initial
findings. There are 58 patients and 111 examinations which mean that both
independent and dependent variables have been pooled. Maybe this can be
corrected for, but this must reviewed by a statistician. Finally, the author initially
operates with a cut off of 3mm of wall thickness between pathological and
healthy intestine in the material and methods. During the analysis of the data,
however, the wall thickness data are dichotomised using 3,5mm as cut off and
then the Fisher exact test is performed. This hypothesis was probably posed post
hoc.
Major compulsory revisions:
Specifically research question 1 should be dropped as the study is not designed
to answer this and only the first exam from the 58 patients should be used for
data analysis if there is no way of correcting for the pooling of independent and
dependent variables. Since these were consistent with the data presented (but
not shown) this should not be a problem. The recruitment of the patients must be
described better in the M&M section. The definition of what is measured in the
anastomosis is unclear and must be defined better. When the author speaks of
"transmural lesions" measured on SICUS this should be replaced with wall
thickening.
Minor essential revisions:
Figure 1 is of poor quality and offer very little information to the reader. It is
difficult to believe that it is possible to measure the intestinal wall thickness at all
from these images.
Figure 3: The cut off values that offer the best sensitivity and specificity should be
added to the ROC curves. There are some language issues that need to be
corrected as some sentences in the manuscript does not seem to make sense.
For specific manuscript editions, also look at the attachment.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
no competing interests with the author
assistant