Review for 10.1186/s12876-020-01358-0 (2020)

Reviewer ’s report  
 
Title: Increased Incidence of Metachronous Gastric Neoplasm After Endoscopic Resection in  
Patients With Synchronous Gastric Neoplasm  
 
Version: 1 Date: 10 Apr 2020  
 
Reviewer's report:  
 
Comments to the Author:  
 
1. Abstract, Page 2  
Please re -write abstract according to the Journal's format.  
 
2. Methods, Page 4  
"This study was retrospectively performed in patients who underwent ER between January 1999 
and December 2015 at Seoul S t. Mary's Hospital in Seoul, Korea."  
Please revise this sentence so that the inclusion criteria can be clearly stated. Was endoscopic 
resection (ER) for gastric neoplasm?  
 
3. Methods, Page 4  
"We excluded patients with history of gastric cancer surgery, ad ditional treatment after non -
curative ER, and incomplete resection."  
Results, Page 6  
"Of these patients, 228 patients were excluded because of additional treatment due to non -
curative ER (n=40), no diagnosis of adenoma or EGC (n=188) and follow -up of less than 1 year 
(n=283)."  
The exclusion criteria in the Methods and in the Results do not match each other. Please revise 
them.  
 
4. Methods, Page 4  
"We excluded patients with history of gastric cancer surgery, additional treatment after non -
curative ER, and incomplete resection."  
Please clearly state whether the authors included the patients who underwent non -curative 
resection but did not undergo add itional surgical resection. If did, please provide justification in 
the Methods and add limitations in the Discussion.  
 
5. Methods, Page 4  
"We defined neoplasms as synchronous when the time interval between the appearance of the 
main and the other neoplasm s did not exceed 12 months"  
"Metachronous recurrence was defined as a new neoplasm that developed more than one year 
after ER."  
Please revise the definitions of synchronous and metachronous recurrences. Which one is right? 
Was the time interval from the 'd iagnosis' (appearance) of the main lesion or from the 'treatment' 
(endoscopic resection)?  
  
6. Methods, Page 4  
"A snare was used during EMR, while a Hook knife (Olympus Medical Systems Co. Ltd., 
Tokyo, Japan) was used during ESD."  
Did the authors used the Hook knife only for ESD? Wasn't IT knife used?  
 
7. Results, Page 6  
"The median follow -up period was 30 months (range, 1 -161 months)."  
The authors excluded the patients who followed less than 1 year. But, why the low range of 
follow -up duration is 1 month? Please revise this.  
 
8. Results, Page 6  
"In single group, the pathology of cancer consisted the differentiated cancer (n=576, 42%) and 
the undifferentiated cancer (n=22, 1.59%). In multiple group, the pathology of cancer consisted 
differentiated cancer was  (n=80, 44%) and the undifferentiated cancer (n=0, 0%)"  
In the Table 1, there were 605 cancers in the single group and 73 cancers in the multiple group. 
However, in these sentences, there were 598 (=576+22) cancers in the single group and 80 
(=80+0) cancer s in the multiple group. Am I misunderstanding? Please explain this.  
 
9. Results, Page 6  
"Kaplan -Meier analysis of the cumulative incidence of metachronous neoplasm and cancers after 
ER showed significant difference between 2 groups (P < 0.01, log -rank test)."  
The authors used two decimal points for the P -value in this sentence and in the Fig 2. But, they 
used four decimal points in the Table 1 and 2 and three decimal points in the Table 3. Please use 
single number of decimal points throughout the manusc ript. 
 
10. Results, Page 7  
"The incidence of metachronous gastric neoplasm and cancer was 9.7% (n=152) and 4.3% 
(n=68) respectively."  
It is necessary to remove this sentence or at least move to the subsection "Incidence of 
metachronous neoplasm after ER" i n the Results.  
 
11. Results, Page 7  
"We divided the patients of the multiple group into three subgroups: multiple cancers, multiple 
adenomas, and a combination of adenoma and cancer. Among the three subgroups, multiple 
adenomas were most commonly found (n=84, 46.1%), followed by a combinatio n of adenoma 
and cancer (n=68, 37.3%), and multiple cancers (n=30, 16.4%). To compare the incidence of 
metachronous neoplasm depending on pathology, the multiple group was further divided into 
two: patients with and without cancer in multiple lesions."  
I understand what the authors tried to show, but this is too complicated to understand. I 
recommend to remove the first two sentences.  
 
12. Results, Page 7  
"However, the proportion of recurred pathology was significantly different between the cancer -
included  and adenoma -only subgroups in the multiple group (P =0.001, Fisher's exact test). 
Among the metachronous neoplasms (n=18) of the cancer -included subgroup, six adenomas 
(33%, five low grade and one high grade) and 12 differentiated cancers (67%) were found  during 
the follow -up period. Among the metachronous neoplasms (n=15) of the adenoma -only 
subgroup, 13 adenomas (87%, ten low grade and three high grade) and two differentiated cancers 
(13%) were found."  
Although it is not statistically correct, I agree th at it is unavoidable to present proportions for 
time-to-event data to help readers understand the overall picture of data. For example, "During 
the follow -up period, metachronous recurrence was found in 152 patients (9.7%)." However, it is 
inappropriate to  present the results of statistical analysis using Fisher's exact test for time -to-
event data. I think it should be used only as supplementary. Please present whether there were 
statistically significant difference in the development of metachronous cancer  between the 
cancer -included and adenoma -only groups.  
 
13. Discussion, Page 9  
"If synchronous neoplasms were detected, more precious follow up would be needed than in case 
of a single neoplasm."  
What do you mean by "precious follow -up"? 
 
14. Discussion, P age 9  
"Furthermore, the intensity of surveillance may be tailored according to pathologic features of 
synchronous neoplasms."  
Please discuss more specifically how the intensity of surveillance can be tailored.  
 
15. Discussion, Page 10  
"In our study, the ca ncer-included group in patients with multiple gastric neoplasms had higher 
metachronous gastric cancer recurrence rate. This finding cannot be fully explained now. A 
previous genetic study suggested clues on the chronological sequence of somatic mutations and 
their clonal architectures in early gastric carcinogenesis with exome -wide multi -region 
mutational profiling of gastric adenomas [28]. In adenoma tissues, there was a lack of somatic 
mutations previously reported as frequent mutations in gastric adenoc arcinomas such as TP53 
and ARID1A, suggesting that gastric adenoma may represent a disease category distinguished 
from gastric adenocarcinomas. Further investigation is needed to find out whether gastric 
adenoma acquires additional, essential cancer driver s." 
Please remove or rephrase this paragraph. I think the contents of this paragraph is not relevant to 
the findings of the current study at all.  
 
16. Table 1  
Please check the percentages for "Cancer". 678 (43.2%), 605(43.2%), 73 (43.2%).  
Please use one de cimal points for the percentages. For example, "Open type" 895 (57.04%), 
"Mucosa" 1522 (97%).  
 
17. Table 2  
Age -> Age, years  
Single vs. Multiple groups -> Is this Multiple vs. Single groups?  
Please use type 2 only for H. pylori and remove "type 2" ex pression.  
Add 'ECG, early gastric cancer' in the Abbreviations  
 
18. Table 3  
Remove "(n=152)" from the title of the table.  
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your c omments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in yo ur comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in y our comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publi cation of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you curr ently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any  other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
No COI  
 
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