Review for 10.1186/s12876-021-02034-7 (2022)

Reviewer’s report
Title: 
Effect of Helicobacter pylori infection on malignancy of undifferentiated-
type gastric cancer
Version: 
1 
Date: 
19 Oct 2021
Reviewer's report:
1. Abstract, Page 2, lines 12 - 14 
"Furthermore, 75% of patients with a tumor detected ≥5 years after eradication
had undergone yearly endoscopy. Submucosal or deeper invasion was observed
in 50% of patients and vascular invasion in 75% of patients whose UD-GC was
detected ≥10 years after eradication."
Please remove these sentences from the Abstract. There were only four patients
who had a cancer detected ≥5 years after eradication. Presenting percentage only
without numbers may mislead the readers of the journal as if there were
statistically higher proportion of patients had submucosal invasion or vascular
invasion in patients with UD-GC detected ≥10 years after eradication compared
to in those with UD-GC detected <10 years. Please replace these sentences to
more relevant findings of this study with statistical significance. 
2. Abstract, Page 2, lines 14 - 16. 
"The proportion of patients with UD-GC and submucosal or deeper invasion was
zero in the group without HP infection, 14.3% in the group with eradicated HP,
and 10.5% in the HP-infected group." 
There was no statistically significant difference in the proportion of submucosal
invasion (14.3% vs. 10.5% vs. 0%). Please avoid presenting results as if they
have substantial difference when they actually can be observed by chance (i.e. P
> 0.05). Please remove these sentences from the Abstract and rewrite the results
part of the Abstract with more relevant findings of this study with statistical
significance. 
3. Abstract, Page 2, lines 18 - 19. 
"Patients with eradicated HP whose UD-GC developed long after eradication
had high rates of vascular and submucosal invasion."
Please remove this sentence from the Abstract. This conclusion may mislead the
readers as commented in the comment #1.
4. Introduction, Page 3, line 17.
"…and a non-infected (UD-U) group)…" -> 
"…and a non-infected (UD-U)
group…"
5. Patients and methods, Page 4, line 2
"The UG-E group was defined as follows" -> "HP eradication group was defined
as follows"
6. Patients and methods, Page 4, lines 12 - 13. 
"HP status was confirmed in 66 cases (71 lesions) in the UD-E group, 503 cases
(616 lesions) in the UD-I group, and 446 cases (622 lesions) in the UD-U
group."
-> "HP status was confirmed in 446 cases (622 lesions) in HP-eradicated, 503
cases (616 lesions) in HP-infected, and 66 cases (71 lesions) in HP-uninfected."
Please notify both group names and numbers were wrong in this sentence.
7. Patients and methods, Page 4, lines 19 - 20. 
"The Kimura-Takemoto classification (Kimura and Takemoto 1969) was used
…"
Please cite (Kimura and Takemoto 1969) as a reference.
8. Patients and methods, Page 4, lines 20 - 21.
"…to evaluate the degree of atrophy (Close(C)-0, none; C-1 and C-2, mild; C-3
to Open(O)-3), moderate-severe)."
-> ""…to evaluate the degree of atrophy (Close[C]-0, none; C-1 and C-2, mild;
C-3 to Open[O]-3, moderate-severe)."
9. Patients and methods, Page 4, line 22.
"differentiated-type gastric cancer (D-GC)" -> "D-GC"
10. Results, Page 5, lines 5 - 6. 
"The ratio of UD-GC to all tumors in each HP infection status group was
significantly higher in the
UD-U group (33.8%) than in the UD-E and UD-I groups (4.5% and 6.2%,
respectively)."
-> "The ratio of UD-GC to all tumors in each HP infection status group was
significantly higher in the
UD-U group (33.8%) than in the UD-E and UD-I groups (4.5% and 6.2%,
respectively) (Fig. 1)."
It seems better to understand here to add 'Fig. 1'.
11. Results, Page 5, lines 8 - 9. 
"The male-to-female ratio was 18:10 in the UD-E group, 14:8 in the UD-I group,
and 20:3 in the UD-U group."
Please change to male or female proportion. It was difficult to understand.
12. Results, Page 5, line 12.
"The mean age was 63.1 ± 14.3, …" -> "The mean age ± standard deviation was
63.1 ± 14.3, …"
13. Results, Page 5, line 23.
"whereas all cases in the UD-D group were" -> "whereas all cases in the UD-U
group were"
14. Results, Page 6, lines 9 - 10.
"Two of the 3 lesions with lymphovascular invasion had a tumor diameter of
≥30 mm (no
significant difference compared with the UD-I and UD-I groups)."
-> "Two of the 3 lesions with lymphovascular invasion had a tumor diameter of
≥30 mm. There was no significant difference compared either with the UD-I or
UD-I group."
15. Discussion, Page 7, lines 1 - 4. 
"However, all tumors in the UD-U group were intramucosal lesions and not
highly malignant. These cases had the following features: (1) young age, (2) no
atrophy in the background mucosa, (3) discolored tone, (4) relatively small
tumor size, (5) predominantly pure signet ring cell carcinoma, (6) intramucosal
lesions, and (7) no lymphovascular invasion."
Please remove number and parentheses.
16. Discussion, Page 7, lines 7 - 9. 
"The clinicopathological features of UD-E and UD-I are similar in table2 and
table3, including tumor size, microscopic type, color, depth, and the rate of
vascular invasion, and the statistical findings are similar compared with UD-U."
Please remove "in table2 and table3".
17. Discussion, Page 7, lines 17 - 18. 
"A notable finding in this study was that UD-GC detected long after eradication
was more malignant than UDGC detected sooner."
Please remove this sentence. The difference in the malignant potential was not
statistically significant. Please avoid presenting results as if they have substantial
difference when they actually can be observed by chance. 
18. Discussion, Page 7, lines 18 - 19. 
"Alarmingly, 75% of patients in whom UD-E was detected ≥5 years after
eradication had undergone yearly follow-up endoscopy."
Please change "75%" to "three of four".
19. Conclusion, Page 8, lines 3 - 4. 
"Patients with eradicated HP whose UD-GC developed long after eradication
had high rates of vascular and submucosal invasion."
Please remove this sentence. This conclusion may mislead the readers as
commented in the comment #1.
20. Table 1. 
The statistical analysis for Atrophy is not correct. It is not possible to conduct
chi-square test for these numbers because there are too many (three in my
analysis) cells with expected numbers smaller than five. The authors should
combine cells to solve this problem. Please revise this issue.
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Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes