Title: Endoscopic mucosal resection: still a reliable therapeutic option for gastrointestinal
neuroendocrine tumors
Version: 4 Date: 29 Apr 2021
Reviewer:  Davide Ravizza
Reviewer's report:
The aim of the study is not stated in an easily understandable way.
“… This study was designed to address the debate on the long-term follow-up of EMR for
localized NETs in the rectum and upper gastrointestinal (GI) tract. …”
The T stage of the treated NETs is reported in confusing way.
In PATIENTS AND METHOD it is still reported that T2 NETs were excluded although NETs
with a size > mm 10, which should be classified as T2, are included in the study.
“… Patients with advanced tumors unfit for endoscopic removal (larger than 2 cm in size,
higher than T1 stage on endoscopic ultrasound [EUS], and/or poorly differentiated lesions) were
excluded …”
A few lines below it is reported that T2 lesions were included.
“… In other words, we included T1, T2 lesions with N0 M0 and excluded lesions with N1 and
above and M1 and T3 lesions …”
In DISCUSSION it is reported that EMR was used for NETs below T1
“… In this study, we performed EMR as the only available technique for resection of GI NETs
smaller than 2 cm in diameter and below T1 on EUS. In fact, we did not excluded cases with
size up to 2 cm if there was no lymph node metastasis or invasion to muscularis propria (MP)
based on pre resection endosonography findings. In other words, we included T1, T2 lesions
with N0 M0 and excluded lesions with N1 and above and M1 and T3 lesions. …”
DISCUSSION
I do not understand very well the following sentences. What is the evidence to support them?
“… Our proposal is that with current definition of T2 and stage II in gastric and duodenal NET
there would be a heterogeneous group of cases with NETs. …”
“… It may be more appropriate to use the framework used for T staging in rectum for upper
gastrointestinal tract as well, at least in patients with G1 grade. …”
How does the experience of the Authors can expand the use of EMR for NETs up to mm 20
in size?
“… We believe our finding could expand the indications of the EMR in NET up to 2 cm if there
is no node or invasion to MP. …”
I do not understand very well the following sentence.
“… In our study, only 4 patients were treated with modified EMR and all of them had no
resection margin involvement.  We implemented the simple EMR technique with a submucosal
saline injection for the rest of individuals, which is why we could only achieve a 40% complete
resection rate. …”
The Author stated that “… conventional EMR could not be considered as a curable and
decisive procedure for gastrointestinal NETs smaller than 20 mm and limited to the mucosa
or sub mucosa due to its low chance of R0 (complete resection) achievement. …”. But, if “…
incomplete resection of the lesion is not relevant for the prognosis of these patients and tumor
recurrence, …“ why EMR should not be considered curative also in the case of R1 resection?
Title: Endoscopic mucosal resection: still a reliable therapeutic option for gastrointestinal
neuroendocrine tumors
Version: 4 Date: 29 Apr 2021
Reviewer:  Davide Ravizza
Reviewer's report:
The aim of the study is not stated in an easily understandable way.
“… This study was designed to address the debate on the long-term follow-up of EMR for
localized NETs in the rectum and upper gastrointestinal (GI) tract. …”
The T stage of the treated NETs is reported in confusing way.
In PATIENTS AND METHOD it is still reported that T2 NETs were excluded although NETs
with a size > mm 10, which should be classified as T2, are included in the study.
“… Patients with advanced tumors unfit for endoscopic removal (larger than 2 cm in size,
higher than T1 stage on endoscopic ultrasound [EUS], and/or poorly differentiated lesions) were
excluded …”
A few lines below it is reported that T2 lesions were included.
“… In other words, we included T1, T2 lesions with N0 M0 and excluded lesions with N1 and
above and M1 and T3 lesions …”
In DISCUSSION it is reported that EMR was used for NETs below T1
“… In this study, we performed EMR as the only available technique for resection of GI NETs
smaller than 2 cm in diameter and below T1 on EUS. In fact, we did not excluded cases with
size up to 2 cm if there was no lymph node metastasis or invasion to muscularis propria (MP)
based on pre resection endosonography findings. In other words, we included T1, T2 lesions
with N0 M0 and excluded lesions with N1 and above and M1 and T3 lesions. …”
DISCUSSION
I do not understand very well the following sentences. What is the evidence to support them?
“… Our proposal is that with current definition of T2 and stage II in gastric and duodenal NET
there would be a heterogeneous group of cases with NETs. …”
“… It may be more appropriate to use the framework used for T staging in rectum for upper
gastrointestinal tract as well, at least in patients with G1 grade. …”
How does the experience of the Authors can expand the use of EMR for NETs up to mm 20
in size?
“… We believe our finding could expand the indications of the EMR in NET up to 2 cm if there
is no node or invasion to MP. …”
I do not understand very well the following sentence.
“… In our study, only 4 patients were treated with modified EMR and all of them had no
resection margin involvement.  We implemented the simple EMR technique with a submucosal
saline injection for the rest of individuals, which is why we could only achieve a 40% complete
resection rate. …”
The Author stated that “… conventional EMR could not be considered as a curable and
decisive procedure for gastrointestinal NETs smaller than 20 mm and limited to the mucosa
or sub mucosa due to its low chance of R0 (complete resection) achievement. …”. But, if “…
incomplete resection of the lesion is not relevant for the prognosis of these patients and tumor
recurrence, …“ why EMR should not be considered curative also in the case of R1 resection?
Please review this paper.
user
Title: Endoscopic mucosal resection: still a reliable therapeutic option for gastrointestinal
neuroendocrine tumors
Version: 4 Date: 29 Apr 2021
Reviewer:  Davide Ravizza
Reviewer's report:
The aim of the study is not stated in an easily understandable way.
“… This study was designed to address the debate on the long-term follow-up of EMR for
localized NETs in the rectum and upper gastrointestinal (GI) tract. …”
The T stage of the treated NETs is reported in confusing way.
In PATIENTS AND METHOD it is still reported that T2 NETs were excluded although NETs
with a size > mm 10, which should be classified as T2, are included in the study.
“… Patients with advanced tumors unfit for endoscopic removal (larger than 2 cm in size,
higher than T1 stage on endoscopic ultrasound [EUS], and/or poorly differentiated lesions) were
excluded …”
A few lines below it is reported that T2 lesions were included.
“… In other words, we included T1, T2 lesions with N0 M0 and excluded lesions with N1 and
above and M1 and T3 lesions …”
In DISCUSSION it is reported that EMR was used for NETs below T1
“… In this study, we performed EMR as the only available technique for resection of GI NETs
smaller than 2 cm in diameter and below T1 on EUS. In fact, we did not excluded cases with
size up to 2 cm if there was no lymph node metastasis or invasion to muscularis propria (MP)
based on pre resection endosonography findings. In other words, we included T1, T2 lesions
with N0 M0 and excluded lesions with N1 and above and M1 and T3 lesions. …”
DISCUSSION
I do not understand very well the following sentences. What is the evidence to support them?
“… Our proposal is that with current definition of T2 and stage II in gastric and duodenal NET
there would be a heterogeneous group of cases with NETs. …”
“… It may be more appropriate to use the framework used for T staging in rectum for upper
gastrointestinal tract as well, at least in patients with G1 grade. …”
How does the experience of the Authors can expand the use of EMR for NETs up to mm 20
in size?
“… We believe our finding could expand the indications of the EMR in NET up to 2 cm if there
is no node or invasion to MP. …”
I do not understand very well the following sentence.
“… In our study, only 4 patients were treated with modified EMR and all of them had no
resection margin involvement.  We implemented the simple EMR technique with a submucosal
saline injection for the rest of individuals, which is why we could only achieve a 40% complete
resection rate. …”
The Author stated that “… conventional EMR could not be considered as a curable and
decisive procedure for gastrointestinal NETs smaller than 20 mm and limited to the mucosa
or sub mucosa due to its low chance of R0 (complete resection) achievement. …”. But, if “…
incomplete resection of the lesion is not relevant for the prognosis of these patients and tumor
recurrence, …“ why EMR should not be considered curative also in the case of R1 resection?
assistant