Title: Optical biopsy for esophageal squamous cell neoplasia by using endocytoscopy
Version: 3 Date: 09 Mar 2022
Reviewer's report:
Comments to the Author
In this article, the authors reported a prospective study to assess the performance of
endocytoscopy for optical biopsy of esophageal squamous cancer. Among 197 high-risk
subjects, 90 patients were detected to have suspected esophageal lesions after WLI and NBI,
37 of them (41 lesions) were characterized as esophageal SCC by endocytoscopy. They found
endocytoscopy has a high diagnostic accuracy (98.9%) and there were no false positives in
cases of SCC. They concluded that optical biopsy by using ECS for esophageal lesions that are
suspected to be tumorous is sufficient in clinical practice. The topic is interesting, but I have
the following comments.
Major and specific comments:
1. The definition of SCC, and high-grade intraepithelial neoplasia (HGIN), low-grade IN,
should be clarified. Also, how to classify the HGIN based on the EC classification?  Could all
intraepithelial neoplasia (HGIN, LGIN) be followed up alone without resection?
2. According to the flow-chart of patients’ enrollment, 90 patients were detected to have
suspected tumor in esophagus by WLI and NBI. However, finally only 37 patients (41 lesions)
have confirmed SCC. The diagnostic accuracy of NBI seems to be very poor (<50%) and is not
consisted with previous reports. The author should clarify this point.
3. In method section, the author mentioned “ESD was later performed for lesions that were
diagnosed to be esophageal SCC by ECS”. However, in the result section, one patient was
diagnosed EC3 lesion (cancer) received biopsy not ESD. These data are not consistent.
4. Did the patients receive NBI with conventional magnification or ultra-high magnification
(endocytoscope) to observe the IPCL pattern and to predict the histology? If it is true, these
should be described.
5. Because all patients had received WLI, NBI and endocyto, the additional benefit of endocyto
on other modality should be analyzed. Currently, we have so many image-enhanced modalities
for diagnosis of ESCC, the author should emphasize the advantages of endocyto and convince
the readers about the benefit of a new modality. Especially, conventional magnifying endoscopy
is now a commonly used and easily operated tool for diagnosis of ESCC with a high accuracy
in daily practice. The procedure time may be longer, and the operation skills or interpretation
may be more complicated by endocytoscopy. These potential disadvantages of endocyto should
be discussed in the discussion section.
6. It’s difficult to differentiate the EC3 in figure 3 from the EC2 in figure 4. The cellular structures
under endocytoscopy seemed to be preserved in figure 3, and it may be classified as EC2. The
authors should demonstrate more clearly the features of EC classification.
Title: Optical biopsy for esophageal squamous cell neoplasia by using endocytoscopy
Version: 3 Date: 09 Mar 2022
Reviewer's report:
Comments to the Author
In this article, the authors reported a prospective study to assess the performance of
endocytoscopy for optical biopsy of esophageal squamous cancer. Among 197 high-risk
subjects, 90 patients were detected to have suspected esophageal lesions after WLI and NBI,
37 of them (41 lesions) were characterized as esophageal SCC by endocytoscopy. They found
endocytoscopy has a high diagnostic accuracy (98.9%) and there were no false positives in
cases of SCC. They concluded that optical biopsy by using ECS for esophageal lesions that are
suspected to be tumorous is sufficient in clinical practice. The topic is interesting, but I have
the following comments.
Major and specific comments:
1. The definition of SCC, and high-grade intraepithelial neoplasia (HGIN), low-grade IN,
should be clarified. Also, how to classify the HGIN based on the EC classification?  Could all
intraepithelial neoplasia (HGIN, LGIN) be followed up alone without resection?
2. According to the flow-chart of patients’ enrollment, 90 patients were detected to have
suspected tumor in esophagus by WLI and NBI. However, finally only 37 patients (41 lesions)
have confirmed SCC. The diagnostic accuracy of NBI seems to be very poor (<50%) and is not
consisted with previous reports. The author should clarify this point.
3. In method section, the author mentioned “ESD was later performed for lesions that were
diagnosed to be esophageal SCC by ECS”. However, in the result section, one patient was
diagnosed EC3 lesion (cancer) received biopsy not ESD. These data are not consistent.
4. Did the patients receive NBI with conventional magnification or ultra-high magnification
(endocytoscope) to observe the IPCL pattern and to predict the histology? If it is true, these
should be described.
5. Because all patients had received WLI, NBI and endocyto, the additional benefit of endocyto
on other modality should be analyzed. Currently, we have so many image-enhanced modalities
for diagnosis of ESCC, the author should emphasize the advantages of endocyto and convince
the readers about the benefit of a new modality. Especially, conventional magnifying endoscopy
is now a commonly used and easily operated tool for diagnosis of ESCC with a high accuracy
in daily practice. The procedure time may be longer, and the operation skills or interpretation
may be more complicated by endocytoscopy. These potential disadvantages of endocyto should
be discussed in the discussion section.
6. It’s difficult to differentiate the EC3 in figure 3 from the EC2 in figure 4. The cellular structures
under endocytoscopy seemed to be preserved in figure 3, and it may be classified as EC2. The
authors should demonstrate more clearly the features of EC classification.
Please review this paper.
user
Title: Optical biopsy for esophageal squamous cell neoplasia by using endocytoscopy
Version: 3 Date: 09 Mar 2022
Reviewer's report:
Comments to the Author
In this article, the authors reported a prospective study to assess the performance of
endocytoscopy for optical biopsy of esophageal squamous cancer. Among 197 high-risk
subjects, 90 patients were detected to have suspected esophageal lesions after WLI and NBI,
37 of them (41 lesions) were characterized as esophageal SCC by endocytoscopy. They found
endocytoscopy has a high diagnostic accuracy (98.9%) and there were no false positives in
cases of SCC. They concluded that optical biopsy by using ECS for esophageal lesions that are
suspected to be tumorous is sufficient in clinical practice. The topic is interesting, but I have
the following comments.
Major and specific comments:
1. The definition of SCC, and high-grade intraepithelial neoplasia (HGIN), low-grade IN,
should be clarified. Also, how to classify the HGIN based on the EC classification?  Could all
intraepithelial neoplasia (HGIN, LGIN) be followed up alone without resection?
2. According to the flow-chart of patients’ enrollment, 90 patients were detected to have
suspected tumor in esophagus by WLI and NBI. However, finally only 37 patients (41 lesions)
have confirmed SCC. The diagnostic accuracy of NBI seems to be very poor (<50%) and is not
consisted with previous reports. The author should clarify this point.
3. In method section, the author mentioned “ESD was later performed for lesions that were
diagnosed to be esophageal SCC by ECS”. However, in the result section, one patient was
diagnosed EC3 lesion (cancer) received biopsy not ESD. These data are not consistent.
4. Did the patients receive NBI with conventional magnification or ultra-high magnification
(endocytoscope) to observe the IPCL pattern and to predict the histology? If it is true, these
should be described.
5. Because all patients had received WLI, NBI and endocyto, the additional benefit of endocyto
on other modality should be analyzed. Currently, we have so many image-enhanced modalities
for diagnosis of ESCC, the author should emphasize the advantages of endocyto and convince
the readers about the benefit of a new modality. Especially, conventional magnifying endoscopy
is now a commonly used and easily operated tool for diagnosis of ESCC with a high accuracy
in daily practice. The procedure time may be longer, and the operation skills or interpretation
may be more complicated by endocytoscopy. These potential disadvantages of endocyto should
be discussed in the discussion section.
6. It’s difficult to differentiate the EC3 in figure 3 from the EC2 in figure 4. The cellular structures
under endocytoscopy seemed to be preserved in figure 3, and it may be classified as EC2. The
authors should demonstrate more clearly the features of EC classification.
assistant