Reviewer's report
Title:Histological evaluation of duodenal biopsies from celiac patients: need for
different grading criteria during follow-up
Version:2Date:4 March 2015
Reviewer: Arzu Ensari
Reviewer's report:
I have read the above mentioned manuscript and would recommend major
revision on the below points:
1. This is a relatively well-written manuscript dealing with the mucosal pathology
in coeliac disease, particularly after GFD. There are few typographical errors
(see lines 190 “this” should be replaced by “these” and 209 “It” should be in
lowercase and 231 “whn” should be replaced by “when” …….) need to be
corrected. The wording used in methods is rather complex and needs to be
clarified with a simplified text.
2. Background: It is not clear what the authors mean by the sentence in lines
74-76, needs to be rephrased in correct English. I would disagree with the
authors regarding the aim of their study: Their aim is to highlight the histology of
treated coeliacs, to show that it may vary within a biopsy piece, hence the use of
the new method. There is no quantification of different histological findings. What
they do, by using MO system, is to examine the biopsy proprotionally rather than
as a whole and give a percentage for each degree of pathology classified
according to the MO system. So this cannot be called as a new classification
system nor can it be interpreted as a quantitative analysis.
3. Methods:
A. 552 biopsies from 69 patients (meaning what?)….2760 HPFs for 69 patients
(meaning what?)……What is the mean number of biopsiy pieces? Whatare min.
– max. numbers?….
B. x200 magnification should not be considered as “high power” but “medium
power”. The term “HPF” is commonly used for x400 magnification. It would not be
possible to determine the severity of mucosal pathology with the proposed
method on a true HPF (i.e. x400). Indeed, fig. 2 clearly illustrates that a maximum
of 6 villi can fit in the area of x200 magnification. Even this magnification wouldn’t
always allow the observer to determine on the presence of variation in villus
morphology. This is the main weakness of the methodology of the study.
C. Line 114 – ten HPFs per biopsy (per biopsy or biopsy piece?) The authors
need to clarify whether they have examined all biopsy pieces or only one biopsy
piece? If more than one-then one would expect to find variation between these
pieces in terms of the severity of mucosal pathology (personal observations as
well as others’….). A slightly dysoriented biopsy could also show some variation.
This point also weakens the methods used in the study.
D. It is very difficult to understand why the authors aimed to detect the mucosal
changes in coeliac disease after GFD since many internationally accepted
guidelines have long before stopped to recommend to take biopsies from
patients on a GFD (ESPGAN guidelines - JPGN 2012;54: 136–160). Patient
recovery is determined by clinical and serological recovery. Some do not
recommend biopsy even for the initial diagnosis. (see guidelines of NIH 2004….)
Therefore, the study is not designed to respond to a diagnostic problem or would
not help to monitor coeliac patients on a GFD as the authors have claimed.
Moreover, their method seems to be so tedious that even if it was needed as a
monitorization, surely their method wouldn’t be the method of choice.
4. Results: Line 149 – “histological findings” should be replaced by the term
“grade” or “severity”.
5. Discussion: EF method cannot and should not be regarded as a quantitative
analysis as the criteria applied are exactly similar to those of the MO system.
6. The conclusion that the authors have reached (i.e. the treated mucosa shows
variation in terms of severity in different biopsy pieces) is not at all surpising nor
novel as similar variation in severity is also a very common feature of the initial
biopsies taken for diagnosis. This has been defined as the patchiness of mucosal
lesions in coeliac disease. This is true not only for the site of involvement in the
small intestine but also in different biopsy pieces taken from the same patient
(Ravelli A et al,. Am J Gastroenterol 2005; 100: 177-185; Bonamico M et al. J
Paeditr Nutr 2004; 38: 204-207; Manuel PD et al. Gut 1979; 20: 211-215). The
authors, too, mention patchiness of histologic damage to the mucosa in CD (line
216). This is a widely accepted feature of CD and by itself it argues against the
design of the present study. Patchiness may give the wrong impression of partial
response to GFD as well as causing confusion in the grading of mucosal
pathology, particularly in Oberhuber’s Type 3 subtypes a, b, and c which
completely lack reproducibility, an important point which the authors also agree
upon (line 237).
Level of interest: An article of insufficient interest to warrant publication in a
scientific/medical journal
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
'I declare that I have no competing interests
Reviewer's report
Title:Histological evaluation of duodenal biopsies from celiac patients: need for
different grading criteria during follow-up
Version:2Date:4 March 2015
Reviewer: Arzu Ensari
Reviewer's report:
I have read the above mentioned manuscript and would recommend major
revision on the below points:
1. This is a relatively well-written manuscript dealing with the mucosal pathology
in coeliac disease, particularly after GFD. There are few typographical errors
(see lines 190 “this” should be replaced by “these” and 209 “It” should be in
lowercase and 231 “whn” should be replaced by “when” …….) need to be
corrected. The wording used in methods is rather complex and needs to be
clarified with a simplified text.
2. Background: It is not clear what the authors mean by the sentence in lines
74-76, needs to be rephrased in correct English. I would disagree with the
authors regarding the aim of their study: Their aim is to highlight the histology of
treated coeliacs, to show that it may vary within a biopsy piece, hence the use of
the new method. There is no quantification of different histological findings. What
they do, by using MO system, is to examine the biopsy proprotionally rather than
as a whole and give a percentage for each degree of pathology classified
according to the MO system. So this cannot be called as a new classification
system nor can it be interpreted as a quantitative analysis.
3. Methods:
A. 552 biopsies from 69 patients (meaning what?)….2760 HPFs for 69 patients
(meaning what?)……What is the mean number of biopsiy pieces? Whatare min.
– max. numbers?….
B. x200 magnification should not be considered as “high power” but “medium
power”. The term “HPF” is commonly used for x400 magnification. It would not be
possible to determine the severity of mucosal pathology with the proposed
method on a true HPF (i.e. x400). Indeed, fig. 2 clearly illustrates that a maximum
of 6 villi can fit in the area of x200 magnification. Even this magnification wouldn’t
always allow the observer to determine on the presence of variation in villus
morphology. This is the main weakness of the methodology of the study.
C. Line 114 – ten HPFs per biopsy (per biopsy or biopsy piece?) The authors
need to clarify whether they have examined all biopsy pieces or only one biopsy
piece? If more than one-then one would expect to find variation between these
pieces in terms of the severity of mucosal pathology (personal observations as
well as others’….). A slightly dysoriented biopsy could also show some variation.
This point also weakens the methods used in the study.
D. It is very difficult to understand why the authors aimed to detect the mucosal
changes in coeliac disease after GFD since many internationally accepted
guidelines have long before stopped to recommend to take biopsies from
patients on a GFD (ESPGAN guidelines - JPGN 2012;54: 136–160). Patient
recovery is determined by clinical and serological recovery. Some do not
recommend biopsy even for the initial diagnosis. (see guidelines of NIH 2004….)
Therefore, the study is not designed to respond to a diagnostic problem or would
not help to monitor coeliac patients on a GFD as the authors have claimed.
Moreover, their method seems to be so tedious that even if it was needed as a
monitorization, surely their method wouldn’t be the method of choice.
4. Results: Line 149 – “histological findings” should be replaced by the term
“grade” or “severity”.
5. Discussion: EF method cannot and should not be regarded as a quantitative
analysis as the criteria applied are exactly similar to those of the MO system.
6. The conclusion that the authors have reached (i.e. the treated mucosa shows
variation in terms of severity in different biopsy pieces) is not at all surpising nor
novel as similar variation in severity is also a very common feature of the initial
biopsies taken for diagnosis. This has been defined as the patchiness of mucosal
lesions in coeliac disease. This is true not only for the site of involvement in the
small intestine but also in different biopsy pieces taken from the same patient
(Ravelli A et al,. Am J Gastroenterol 2005; 100: 177-185; Bonamico M et al. J
Paeditr Nutr 2004; 38: 204-207; Manuel PD et al. Gut 1979; 20: 211-215). The
authors, too, mention patchiness of histologic damage to the mucosa in CD (line
216). This is a widely accepted feature of CD and by itself it argues against the
design of the present study. Patchiness may give the wrong impression of partial
response to GFD as well as causing confusion in the grading of mucosal
pathology, particularly in Oberhuber’s Type 3 subtypes a, b, and c which
completely lack reproducibility, an important point which the authors also agree
upon (line 237).
Level of interest: An article of insufficient interest to warrant publication in a
scientific/medical journal
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
'I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:Histological evaluation of duodenal biopsies from celiac patients: need for
different grading criteria during follow-up
Version:2Date:4 March 2015
Reviewer: Arzu Ensari
Reviewer's report:
I have read the above mentioned manuscript and would recommend major
revision on the below points:
1. This is a relatively well-written manuscript dealing with the mucosal pathology
in coeliac disease, particularly after GFD. There are few typographical errors
(see lines 190 “this” should be replaced by “these” and 209 “It” should be in
lowercase and 231 “whn” should be replaced by “when” …….) need to be
corrected. The wording used in methods is rather complex and needs to be
clarified with a simplified text.
2. Background: It is not clear what the authors mean by the sentence in lines
74-76, needs to be rephrased in correct English. I would disagree with the
authors regarding the aim of their study: Their aim is to highlight the histology of
treated coeliacs, to show that it may vary within a biopsy piece, hence the use of
the new method. There is no quantification of different histological findings. What
they do, by using MO system, is to examine the biopsy proprotionally rather than
as a whole and give a percentage for each degree of pathology classified
according to the MO system. So this cannot be called as a new classification
system nor can it be interpreted as a quantitative analysis.
3. Methods:
A. 552 biopsies from 69 patients (meaning what?)….2760 HPFs for 69 patients
(meaning what?)……What is the mean number of biopsiy pieces? Whatare min.
– max. numbers?….
B. x200 magnification should not be considered as “high power” but “medium
power”. The term “HPF” is commonly used for x400 magnification. It would not be
possible to determine the severity of mucosal pathology with the proposed
method on a true HPF (i.e. x400). Indeed, fig. 2 clearly illustrates that a maximum
of 6 villi can fit in the area of x200 magnification. Even this magnification wouldn’t
always allow the observer to determine on the presence of variation in villus
morphology. This is the main weakness of the methodology of the study.
C. Line 114 – ten HPFs per biopsy (per biopsy or biopsy piece?) The authors
need to clarify whether they have examined all biopsy pieces or only one biopsy
piece? If more than one-then one would expect to find variation between these
pieces in terms of the severity of mucosal pathology (personal observations as
well as others’….). A slightly dysoriented biopsy could also show some variation.
This point also weakens the methods used in the study.
D. It is very difficult to understand why the authors aimed to detect the mucosal
changes in coeliac disease after GFD since many internationally accepted
guidelines have long before stopped to recommend to take biopsies from
patients on a GFD (ESPGAN guidelines - JPGN 2012;54: 136–160). Patient
recovery is determined by clinical and serological recovery. Some do not
recommend biopsy even for the initial diagnosis. (see guidelines of NIH 2004….)
Therefore, the study is not designed to respond to a diagnostic problem or would
not help to monitor coeliac patients on a GFD as the authors have claimed.
Moreover, their method seems to be so tedious that even if it was needed as a
monitorization, surely their method wouldn’t be the method of choice.
4. Results: Line 149 – “histological findings” should be replaced by the term
“grade” or “severity”.
5. Discussion: EF method cannot and should not be regarded as a quantitative
analysis as the criteria applied are exactly similar to those of the MO system.
6. The conclusion that the authors have reached (i.e. the treated mucosa shows
variation in terms of severity in different biopsy pieces) is not at all surpising nor
novel as similar variation in severity is also a very common feature of the initial
biopsies taken for diagnosis. This has been defined as the patchiness of mucosal
lesions in coeliac disease. This is true not only for the site of involvement in the
small intestine but also in different biopsy pieces taken from the same patient
(Ravelli A et al,. Am J Gastroenterol 2005; 100: 177-185; Bonamico M et al. J
Paeditr Nutr 2004; 38: 204-207; Manuel PD et al. Gut 1979; 20: 211-215). The
authors, too, mention patchiness of histologic damage to the mucosa in CD (line
216). This is a widely accepted feature of CD and by itself it argues against the
design of the present study. Patchiness may give the wrong impression of partial
response to GFD as well as causing confusion in the grading of mucosal
pathology, particularly in Oberhuber’s Type 3 subtypes a, b, and c which
completely lack reproducibility, an important point which the authors also agree
upon (line 237).
Level of interest: An article of insufficient interest to warrant publication in a
scientific/medical journal
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
'I declare that I have no competing interests
assistant