Title: Confocal endomicroscopy diagnostic criteria for early signet-ring cell carcinoma in
hereditary diffuse gastric cancer
Version: 1 Date: 31 Dec 2021
Reviewer:  Helga Bertani
Reviewer's report:
The primary aim of the study ‘Confocal endomicroscopy diagnostic criteria for early signet-ring
cell carcinoma in hereditary diffuse gastric cancer’  was to identify and validate pCLE diagnostic
criteria for early SRCC in HDGC syndrome and is clearly specified.
The paper is an original contribution about the use of confocal endomicroscopy in a selected
population at high risk of SRCC. Previous published paper about the use of high definition
endoscopy and/or pCLE in the stomach failed in the demonstration of a significant added value
of these techniques in the early detection, consequently an intensive random biopsies protocol
is recommended.
The paper is very well written and clear, and the study is well conducted with a strong
methodology.
The strength of the study is a serious and strict multi-stage process to identify and validate the
pCLE criteria. Moreover the investigators have and extensive expertise in the field of confocal
endomicroscopy and endoscopic detection of upper neoplastic disease.
Major comments:
1: pCLE criteria were not related to identification of “signet ring cell criteria” but to “indirect”
effect on nearby tissue modifications. This is indeed a weak spot of the study. The author
should evaluate if the same criteria are found in other conditions such as HP infection, intestinal
metaplasia, atrophic gastritis as none of this condition has been investigated in the study and are
commonly found. Is it possible to validate the established criteria in a dataset that includes HP
infection, intestinal metaplasia, atrophic gastritis?
2: Pale areas identified on WLI and NBI are used as a lighthouse to perform pCLE and in a
identification and in a “validation setting” this could be considered a bias.
3: SRCC usually develops under epithelial surface consequently pCLE weak spot is the depth
of penetration.
Title: Confocal endomicroscopy diagnostic criteria for early signet-ring cell carcinoma in
hereditary diffuse gastric cancer
Version: 1 Date: 31 Dec 2021
Reviewer:  Helga Bertani
Reviewer's report:
The primary aim of the study ‘Confocal endomicroscopy diagnostic criteria for early signet-ring
cell carcinoma in hereditary diffuse gastric cancer’  was to identify and validate pCLE diagnostic
criteria for early SRCC in HDGC syndrome and is clearly specified.
The paper is an original contribution about the use of confocal endomicroscopy in a selected
population at high risk of SRCC. Previous published paper about the use of high definition
endoscopy and/or pCLE in the stomach failed in the demonstration of a significant added value
of these techniques in the early detection, consequently an intensive random biopsies protocol
is recommended.
The paper is very well written and clear, and the study is well conducted with a strong
methodology.
The strength of the study is a serious and strict multi-stage process to identify and validate the
pCLE criteria. Moreover the investigators have and extensive expertise in the field of confocal
endomicroscopy and endoscopic detection of upper neoplastic disease.
Major comments:
1: pCLE criteria were not related to identification of “signet ring cell criteria” but to “indirect”
effect on nearby tissue modifications. This is indeed a weak spot of the study. The author
should evaluate if the same criteria are found in other conditions such as HP infection, intestinal
metaplasia, atrophic gastritis as none of this condition has been investigated in the study and are
commonly found. Is it possible to validate the established criteria in a dataset that includes HP
infection, intestinal metaplasia, atrophic gastritis?
2: Pale areas identified on WLI and NBI are used as a lighthouse to perform pCLE and in a
identification and in a “validation setting” this could be considered a bias.
3: SRCC usually develops under epithelial surface consequently pCLE weak spot is the depth
of penetration.
Please review this paper.
user
Title: Confocal endomicroscopy diagnostic criteria for early signet-ring cell carcinoma in
hereditary diffuse gastric cancer
Version: 1 Date: 31 Dec 2021
Reviewer:  Helga Bertani
Reviewer's report:
The primary aim of the study ‘Confocal endomicroscopy diagnostic criteria for early signet-ring
cell carcinoma in hereditary diffuse gastric cancer’  was to identify and validate pCLE diagnostic
criteria for early SRCC in HDGC syndrome and is clearly specified.
The paper is an original contribution about the use of confocal endomicroscopy in a selected
population at high risk of SRCC. Previous published paper about the use of high definition
endoscopy and/or pCLE in the stomach failed in the demonstration of a significant added value
of these techniques in the early detection, consequently an intensive random biopsies protocol
is recommended.
The paper is very well written and clear, and the study is well conducted with a strong
methodology.
The strength of the study is a serious and strict multi-stage process to identify and validate the
pCLE criteria. Moreover the investigators have and extensive expertise in the field of confocal
endomicroscopy and endoscopic detection of upper neoplastic disease.
Major comments:
1: pCLE criteria were not related to identification of “signet ring cell criteria” but to “indirect”
effect on nearby tissue modifications. This is indeed a weak spot of the study. The author
should evaluate if the same criteria are found in other conditions such as HP infection, intestinal
metaplasia, atrophic gastritis as none of this condition has been investigated in the study and are
commonly found. Is it possible to validate the established criteria in a dataset that includes HP
infection, intestinal metaplasia, atrophic gastritis?
2: Pale areas identified on WLI and NBI are used as a lighthouse to perform pCLE and in a
identification and in a “validation setting” this could be considered a bias.
3: SRCC usually develops under epithelial surface consequently pCLE weak spot is the depth
of penetration.
assistant