Review for 10.1186/s12876-021-01819-0 (2021)

Title: Endoscopic resection combined with the Cryoballoon focal ablation system in the porcine
normal esophagus: A preclinical study
Version: 2 Date: 14 Feb 2021
Reviewer's report:
Comment to authors
This study aimed to clarify the feasibility and safety of procedures and pathological tissue
damage of endoscopic resection and cryoballoon focal ablation system combination therapy in
a porcine model. The contents of this manuscript were well described. However, there remains
some concerns following below comments.
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Major comments:
1. Page5 line 4
The authors are comparing (a) simultaneous procedure of EMR and CbFAS, (b) CbFAS for post-
EMR scar, and (c) ER for post-CbFAS scar. Please describe more detail about why did authors
choose these three procedures. In the light of real clinical practice, only CbFAS for post-EMR
scar is thought to be practical.
2. Page5 line 4
As the authors mentioned in the discussion part, there are already four hot ablation devices.
CbFAS should be compared with those devises.
3. Page 5 line 15
Please describe the size of EMR ulcers, EMR scars, and ablation size.
4. Page 5 line 15
Please describe the protocol of after EMR or CbFAS procedure. How long were the fasting
period? Further, did the authors prescribe the PPI or other mucosal protective agents for pigs?
5. Page 6 line 10
Please describe about the skill of those three endoscopists. Are those endoscopists only recruited
from experts? Or were beginners also included?
6. Page 9 line 2
The results written in the table 1 are very subjective and containing a high risk of self-serving
bias.
To evaluate the technical feasibility, objective evaluations like procedure time et al. are
necessary.
7. Page9 line 8
As the authors described in the discussion part, the sample size of this study is too small to
evaluate the safety of CbFAS.
8. Page 9 line 8
Please show the specific results of nutritional condition of weight loss between before and after
procedure. Did authors evaluate blood test or the weight of pigs?
9. Page 9 line 12, Page 10 line 13
The authors showed that the tissue damage of EMR+CbFAS spread all layers of the esophageal
wall several days after the procedure. That seems to be problematic from the viewpoint of the
safety. Fortunately, the perforation was not occurred, however, this may have the possibility of
just a coincidence due to the small sample size.
10. Page 12 line 4
The most important problem of esophageal carcinoma invaded into submucosal layer is the risk
of the lymph node metastasis. JCOG0508 trial showed the efficacy of Endoscopic resection
followed by chemoradiotherapy. CbFAS cannot treat the lymph node metastasis as well. It is
not adequate to expect the efficacy of CbFAS for the deep invasive lesion.
11. Page 12 line 4 and line 12
According to the Chinese trial in 2018 (ref 9), CbFAS were restricted to a length of #6cm and
a circumferential extent of <50%. It is also difficult to say about the efficacy of treating large
lesions from this study.
Minor comments:
12. Page 5 line 14
Why did authors choose cap-EMR instead of ESD?
13. Page 7 line 7
If the authors concerned about the difficulties of mucosal difficulties in EMR for CbFAS scar,
why did authors use only saline for injection into submucosa?
14. Page 9 line 8
According to the past study, about one fifth of the patients had a mild fever after CbFAS
treatment. Were there any minor troubles in this study?
15. Page 10 line 17
As the authors mentioned, CbFAS does not disrupt the extracellular matrix. However, there
are still some concerns of perforation. (There are some reports of perforation due to CbFAS
in the cardiovascular field.) The author should correct the sentence of “may not lead to##
complications” to “may reduce ##complications”
16. Table 1
The authors should describe the definition about the evaluation like “easy” and “moderate”.
17. Table 2
Please add the resected or ablation size of the lesions and body weights of pigs in table 2.