Review for 10.1186/s12876-025-03651-2 (2025)

Title: Short-term endoscopic alterations of early gastric cancer after successful eradication of
Helicobacter pylori
Version: 2 Date: 27 Nov 2024
Reviewer's report:
This is a prospective observational study evaluating the short-term effects of Helicobacter
pylori (H. pylori) eradication therapy on early gastric cancer (EGC). The authors propose that
eradication therapy clarifies the boundaries of cancerous lesions, making it an essential step
before EGC treatment. While the study is novel and original, there are several concerns that
need to be addressed.
Major Concerns:
1. Inflammation and Diagnostic Accuracy
The authors argue that inflammation caused by Helicobacter pylori (H. pylori) infection is one of
the factors leading to misdiagnosis and that eradication therapy contributes to accurate diagnosis
by alleviating inflammation. However, in routine clinical practice, alternative anti-inflammatory
methods, such as administration of proton pump inhibitors (PPIs) or potassium-competitive
acid blockers (PCABs), are also available. The authors should discuss the advantages and
disadvantages of these approaches compared to eradication therapy in the discussion section.
Additionally, there are potential drawbacks to performing eradication therapy prior to treatment.
These include possible adverse effects of the eradication drugs, cases of unsuccessful
eradication, diagnostic challenges arising from morphological changes after eradication, and
delays in the timing of treatment due to eradication procedures. These aspects should also be
addressed.
2. Eradication Confirmation
The manuscript states that eradication success was confirmed using a combination of the urea
breath test (UBT) or histological evaluation. While UBT and stool antigen tests are known
for their high accuracy, the use of histological evaluation as a primary method for confirming
eradication success is less common. Clarification is needed on what criteria were used to
define successful eradication and their diagnostic accuracy. Furthermore, did all 43 patients
achieve successful eradication with first-line therapy? What was the incidence of adverse effects
associated with the eradication therapy?
3. Evaluation of Demarcation Line (DL)
The methodology for evaluating the demarcation line is vague. It is unclear whether the
assessments were performed using white light imaging (WLI), non-magnified narrow-band
imaging (NBI), or magnified NBI. This should be explicitly stated. Additionally, previous
studies have employed techniques such as biopsies from tumor and non-tumor areas or pre-
marking the tumor boundary to evaluate the DL. Was there a specific reason for not incorporating
these methods into this prospective study? Figure 1 also shows markings placed significantly
outside the tumor region, raising concerns about the accuracy of DL evaluation. Further
clarification is needed.
4. Tumor Size Measurements
While the study reports a significant reduction in tumor diameter following eradication, it is
unclear whether tumor size was measured with calibrated forceps or similar tools to ensure
accuracy. If measurements were based solely on endoscopic imaging, a margin of error of 1–2
mm could be expected. This potential limitation should be addressed.
5. Morphological Changes by Histological Type
As mentioned in Reference 14, morphological changes after eradication are more likely to
occur in adenomas and well-differentiated adenocarcinomas but less so in moderately or poorly
differentiated adenocarcinomas. In the current study, morphological changes were observed in
only 3 of the 43 lesions. It would be helpful to provide a detailed breakdown of histological types
beyond the simplified categories of "differentiated" and "undifferentiated" listed in Table 1.
6. Discussion on Intervening Part (IP)
The discussion section mentions that eradication therapy improves the intervening part (IP)
of the non-tumor area, facilitating accurate diagnosis. However, this phenomenon is primarily
observed in cases where poorly differentiated carcinomas are present beneath the foveolar
epithelium. The cited references (4 and 16) specifically address undifferentiated carcinomas in
this context. Since only two cases of undifferentiated carcinomas are included in the present
study, this discussion does not seem fully aligned with the study's findings.
7. Confidence Level by Eradication Timing
The authors state that eradication therapy is effective even within one month, as there was no
significant difference in endoscopic confidence levels between the #1-month and >1-month
groups. To support this conclusion, the manuscript should confirm that baseline characteristics
(e.g., patient demographics, tumor location, histological type) were comparable between these
groups.
Minor Concerns:
1. Vienna Classification
Since the study included submucosal carcinomas, the Vienna Classification Category 5 should
also have been applied in addition to Category 4.
2. Study Cohort
The manuscript should specify how the 43 cases were selected from the total number of eligible
cases during the study period.
3. Histopathological Confidence Levels
It is unclear whether the "confidence level of histopathological classification" refers solely
to distinguishing between differentiated and undifferentiated types or includes more detailed
predictions.
4. Terminological Consistency
The manuscript inconsistently uses "xanthoma" and "xanthelasma" as well as "tumor" and
"tumour." These terms should be standardized throughout the text.