Title: Endoscopic Iatrogenic Esophageal Perforation and Management: A Retrospective
Outcome Analysis in the Modern Era
Version: 3 Date: 23 Sep 2023
Reviewer:  Takeshi Okamoto
Reviewer's report:
Dr .Montminy et al describe a retrospective study on iatrogenic esophageal perforations. While
this study is potentially a valuable addition to the literature, there are some shortcomings that
limit its value. My concerns are as detailed below.
1. This is a retrospective study on human subjects who suffered severe adverse events, including
death. I do not believe it is appropriate to exempt this study from IRB approval. Please provide
more information on the background behind the exemption. Also, were patients permitted to opt
out of the study through the hospitals’ websites, etc.?
2. The procedures included are unclear. A breakdown of the procedures included under “EGDs”
should be provided, such as how many EMRs, ESDs, balloon dilations, etc. were included in
the 134,443 UEPs. Without this baseline information, the reader cannot tell which procedures
present the highest incidence of IEPs.
3. Along the same lines, “an overall IEP rate of 0.024% or one out of every 4,166 UEPs” is
misleading given the heterogeneity of the procedures performed. Please provide percentages for
each type of procedures and point out the procedures that have the largest risks.
4. It appears that “EUS” included EUS-FNA. Were EUS-guided interventions also included? A
breakdown and details of included procedures should be provided.
5. A definition of IEP should be provided. If diagnosed on CT, note if a defect was required or if
pneumomediastinum was considered sufficient. Note that pneumomediastinum can occur after
esophageal ESD even without perforation.
6. Were only intraprocedural perforations included, or were delayed perforations also included?
If both were included, include this information in a table. Perhaps conduct a statistical
comparison between intraprocedural and delayed perforations.
7. “The diagnosis of IEP was made at a median 2 hours (0.5 -168 min) after the injury by
endoscopy (N=14, 44%), CT scan (N=12, 38%), barium esophagram (N=5, 16%), or plain x-
ray (N=1, 3%)”. Were none of the IEPs diagnosable during the procedure? Please elaborate.
8. In the fatal 30-mm balloon dilation case, was 30-mm dilation really necessary? Usually 15
mm will suffice, and incremental dilation is desirable to reduce the risk of perforation.
9. All information in the raw data excel sheet should be included in the manuscript, probably
in the form of multiple tables.
10. Also, key baseline characteristics are missing such as age, sex, hospital, indication for
endoscopy. Other information stated under Methods such as trainee involvement should also
be included.
11. STATA was used, but no statistical analyses are provided. Despite the small sample size, I
believe some minimal statistical analyses can and should be performed using the above data.
12. Please use consistent terminology: “clip placement (CP)” and “clip closure (CC)” appear to
be used interchangeably.
13. I do not believe 13% mortality is “low”. These are iatrogenic mortalities which should be as
close to 0% as possible. Please rephrase and provide context for the figure, providing mortality
rates for similar events in the literature.
Title: Endoscopic Iatrogenic Esophageal Perforation and Management: A Retrospective
Outcome Analysis in the Modern Era
Version: 3 Date: 23 Sep 2023
Reviewer:  Takeshi Okamoto
Reviewer's report:
Dr .Montminy et al describe a retrospective study on iatrogenic esophageal perforations. While
this study is potentially a valuable addition to the literature, there are some shortcomings that
limit its value. My concerns are as detailed below.
1. This is a retrospective study on human subjects who suffered severe adverse events, including
death. I do not believe it is appropriate to exempt this study from IRB approval. Please provide
more information on the background behind the exemption. Also, were patients permitted to opt
out of the study through the hospitals’ websites, etc.?
2. The procedures included are unclear. A breakdown of the procedures included under “EGDs”
should be provided, such as how many EMRs, ESDs, balloon dilations, etc. were included in
the 134,443 UEPs. Without this baseline information, the reader cannot tell which procedures
present the highest incidence of IEPs.
3. Along the same lines, “an overall IEP rate of 0.024% or one out of every 4,166 UEPs” is
misleading given the heterogeneity of the procedures performed. Please provide percentages for
each type of procedures and point out the procedures that have the largest risks.
4. It appears that “EUS” included EUS-FNA. Were EUS-guided interventions also included? A
breakdown and details of included procedures should be provided.
5. A definition of IEP should be provided. If diagnosed on CT, note if a defect was required or if
pneumomediastinum was considered sufficient. Note that pneumomediastinum can occur after
esophageal ESD even without perforation.
6. Were only intraprocedural perforations included, or were delayed perforations also included?
If both were included, include this information in a table. Perhaps conduct a statistical
comparison between intraprocedural and delayed perforations.
7. “The diagnosis of IEP was made at a median 2 hours (0.5 -168 min) after the injury by
endoscopy (N=14, 44%), CT scan (N=12, 38%), barium esophagram (N=5, 16%), or plain x-
ray (N=1, 3%)”. Were none of the IEPs diagnosable during the procedure? Please elaborate.
8. In the fatal 30-mm balloon dilation case, was 30-mm dilation really necessary? Usually 15
mm will suffice, and incremental dilation is desirable to reduce the risk of perforation.
9. All information in the raw data excel sheet should be included in the manuscript, probably
in the form of multiple tables.
10. Also, key baseline characteristics are missing such as age, sex, hospital, indication for
endoscopy. Other information stated under Methods such as trainee involvement should also
be included.
11. STATA was used, but no statistical analyses are provided. Despite the small sample size, I
believe some minimal statistical analyses can and should be performed using the above data.
12. Please use consistent terminology: “clip placement (CP)” and “clip closure (CC)” appear to
be used interchangeably.
13. I do not believe 13% mortality is “low”. These are iatrogenic mortalities which should be as
close to 0% as possible. Please rephrase and provide context for the figure, providing mortality
rates for similar events in the literature.
Please review this paper.
user
Title: Endoscopic Iatrogenic Esophageal Perforation and Management: A Retrospective
Outcome Analysis in the Modern Era
Version: 3 Date: 23 Sep 2023
Reviewer:  Takeshi Okamoto
Reviewer's report:
Dr .Montminy et al describe a retrospective study on iatrogenic esophageal perforations. While
this study is potentially a valuable addition to the literature, there are some shortcomings that
limit its value. My concerns are as detailed below.
1. This is a retrospective study on human subjects who suffered severe adverse events, including
death. I do not believe it is appropriate to exempt this study from IRB approval. Please provide
more information on the background behind the exemption. Also, were patients permitted to opt
out of the study through the hospitals’ websites, etc.?
2. The procedures included are unclear. A breakdown of the procedures included under “EGDs”
should be provided, such as how many EMRs, ESDs, balloon dilations, etc. were included in
the 134,443 UEPs. Without this baseline information, the reader cannot tell which procedures
present the highest incidence of IEPs.
3. Along the same lines, “an overall IEP rate of 0.024% or one out of every 4,166 UEPs” is
misleading given the heterogeneity of the procedures performed. Please provide percentages for
each type of procedures and point out the procedures that have the largest risks.
4. It appears that “EUS” included EUS-FNA. Were EUS-guided interventions also included? A
breakdown and details of included procedures should be provided.
5. A definition of IEP should be provided. If diagnosed on CT, note if a defect was required or if
pneumomediastinum was considered sufficient. Note that pneumomediastinum can occur after
esophageal ESD even without perforation.
6. Were only intraprocedural perforations included, or were delayed perforations also included?
If both were included, include this information in a table. Perhaps conduct a statistical
comparison between intraprocedural and delayed perforations.
7. “The diagnosis of IEP was made at a median 2 hours (0.5 -168 min) after the injury by
endoscopy (N=14, 44%), CT scan (N=12, 38%), barium esophagram (N=5, 16%), or plain x-
ray (N=1, 3%)”. Were none of the IEPs diagnosable during the procedure? Please elaborate.
8. In the fatal 30-mm balloon dilation case, was 30-mm dilation really necessary? Usually 15
mm will suffice, and incremental dilation is desirable to reduce the risk of perforation.
9. All information in the raw data excel sheet should be included in the manuscript, probably
in the form of multiple tables.
10. Also, key baseline characteristics are missing such as age, sex, hospital, indication for
endoscopy. Other information stated under Methods such as trainee involvement should also
be included.
11. STATA was used, but no statistical analyses are provided. Despite the small sample size, I
believe some minimal statistical analyses can and should be performed using the above data.
12. Please use consistent terminology: “clip placement (CP)” and “clip closure (CC)” appear to
be used interchangeably.
13. I do not believe 13% mortality is “low”. These are iatrogenic mortalities which should be as
close to 0% as possible. Please rephrase and provide context for the figure, providing mortality
rates for similar events in the literature.
assistant