A Multicenter Retrospective and Prospective Real-World Observational Study of Helicobacter Pylori Infection Status and Pathological Features of Early Gastric Cancer for Predicting Biological Behavior and Prognosis Across Gastric Cancer Subtypes
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 1,500
- 试验地点
- 3
- 主要终点
- Concordance Rate Among Three H. pylori Testing Modalities in Post-Eradication Gastric Cancer
研究概览
简要总结
This multicenter retrospective and prospective real-world observational study will evaluate the relationship of Helicobacter pylori (H. pylori) infection status, intragastric distribution, and pathological features with gastric cancer biological behavior and long-term prognosis in patients with early gastric cancer or related gastric neoplastic lesions undergoing endoscopic submucosal dissection (ESD).
H. pylori infection is an important risk factor for gastric cancer. In clinical practice, H. pylori status can be assessed by several methods, including the 13C-urea breath test, serum H. pylori antibody testing, and pathological assessment of gastric tissue. These methods may not always provide the same result because they reflect different aspects of infection, including current active infection, previous exposure, prior eradication status, and local tissue-based detection.
The study will include approximately 1500 participants from participating medical centers. About 1000 participants will be retrospectively identified from existing clinical, endoscopic, pathological, H. pylori testing, and follow-up records, and about 500 additional participants will be prospectively enrolled.
The study will evaluate H. pylori infection status, prior eradication status, discordant testing patterns, tissue-based and intragastric H. pylori distribution, background mucosal changes, and pathological features of early gastric cancer or related gastric neoplastic lesions. These features will be analyzed in relation to different gastric cancer subtypes and biological behavior.
Follow-up information will be used to evaluate whether the integrated analysis of H. pylori infection status and pathological features can predict clinical outcomes at 1, 2, and 3 years after ESD and during long-term follow-up, including local recurrence, metachronous gastric cancer, synchronous or multifocal early gastric cancer detected within 1 year, additional surgical treatment, survival, and other clinically meaningful outcomes.
详细描述
Background and Rationale:
Helicobacter pylori (H. pylori) infection is a major risk factor for gastric cancer and is closely associated with chronic gastritis, mucosal atrophy, intestinal metaplasia, dysplasia, and gastric carcinogenesis. Although H. pylori eradication can reduce the risk of gastric cancer, some patients still develop gastric cancer after eradication therapy, and patients treated with endoscopic submucosal dissection (ESD) may remain at risk for local recurrence, metachronous gastric cancer, and other gastric neoplastic lesions during follow-up.
In clinical practice, H. pylori status can be evaluated by several methods, including the 13C-urea breath test, serum H. pylori antibody testing, and pathological assessment of gastric tissue. These methods reflect different biological and clinical information. The 13C-urea breath test mainly reflects current active infection, serum antibody testing may reflect previous or current exposure, and pathological assessment provides local tissue-based information from specific gastric sites.
However, these test results may be inconsistent. H. pylori colonization can be patchy and unevenly distributed within the stomach. In patients with early gastric cancer, local tumor-related changes, mucosal atrophy, intestinal metaplasia, spasmolytic polypeptide-expressing metaplasia, prior eradication therapy, and changes in the gastric mucosal microenvironment may influence bacterial density and detectability. Therefore, a negative pathological finding in the tumor area does not necessarily exclude previous H. pylori exposure or H. pylori-related background mucosal changes.
Current evidence suggests that H. pylori may be more frequently detected in non-tumor or peritumoral mucosa than in tumor tissue itself, and that H. pylori-related mucosal changes may be associated with specific pathological phenotypes of early gastric cancer. Nevertheless, the clinical meaning of discordant H. pylori test patterns and the relationship among H. pylori intragastric distribution, gastric pathological characteristics, post-eradication gastric cancer, and metachronous gastric cancer remain insufficiently understood.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults aged 18 to 80 years
- •Retrospectively identified or prospectively enrolled patients with early gastric cancer, high-grade intraepithelial neoplasia, or other gastric neoplastic lesions treated with or scheduled for endoscopic submucosal dissection according to standard clinical indications at participating medical centers
- •Availability or planned availability of sufficient Helicobacter pylori assessment data for study classification, including 13C-urea breath test, serum Helicobacter pylori IgG antibody testing, pathological assessment of gastric tissue, prior H. pylori infection history, prior eradication history, eradication confirmation, or follow-up H. pylori testing results when available
- •Availability or planned availability of gastric tissue pathological assessment from routine biopsy specimens and/or endoscopic submucosal dissection specimens for evaluation of tissue-based H. pylori detection, background mucosal changes, lesion pathological characteristics, and ESD-related pathological findings
- •Availability or planned availability of key clinical, endoscopic, and pathological information required to evaluate gastric cancer subtype, biological behavior, and curability after ESD, including lesion location, histological subtype, differentiation, depth of invasion, lymphovascular invasion, margin status, curative resection status, and additional treatment information when available
- •Availability of follow-up data for retrospectively included participants, or willingness and ability to participate in follow-up evaluations for prospectively enrolled participants, including endoscopic follow-up at approximately 1, 2, and 3 years after ESD and longer-term follow-up when available
- •Adequate cardiac, hepatic, renal, and pulmonary function to tolerate endoscopic treatment and routine follow-up for prospectively enrolled participants scheduled for ESD
- •Ability to provide written informed consent for prospectively enrolled participants, or availability of ethics-approved retrospective clinical data for retrospectively included participants
排除标准
- •Patients whose final diagnosis does not meet the study population definition, including those without early gastric cancer, high-grade intraepithelial neoplasia, or other eligible gastric neoplastic lesions
- •Insufficient clinical, H. pylori testing, endoscopic, pathological, or follow-up information to classify H. pylori infection or eradication status or to evaluate the main study outcomes
- •Lack of adequate pathological material or pathological information for assessment of gastric lesion characteristics, tissue-based H. pylori detection, or background mucosal changes
- •Previous gastrectomy or major gastric surgery that substantially alters gastric anatomy and prevents reliable assessment of lesion location, intragastric distribution, or background mucosal status
- •For prospectively enrolled participants scheduled for ESD, severe comorbid conditions, such as uncontrolled cardiovascular or cerebrovascular disease, severe coagulopathy, or very poor general condition, that make endoscopic submucosal dissection unsafe
- •For prospectively enrolled participants scheduled for ESD, anticoagulant or antiplatelet therapy that cannot be safely interrupted or managed during the perioperative period, or active bleeding tendency judged to significantly increase procedural risk
- •Pregnancy or breastfeeding for prospectively enrolled participants
- •Inability or unwillingness to comply with study procedures or follow-up requirements for prospectively enrolled participants
- •Any other condition judged by the investigators to make the participant unsuitable for the study
结局指标
主要结局
Concordance Rate Among Three H. pylori Testing Modalities in Post-Eradication Gastric Cancer
时间窗: From baseline H. pylori testing to pathological assessment within 2 weeks after endoscopic submucosal dissection
The concordance rate among three H. pylori testing modalities will be reported in participants with post-eradication gastric cancer. The three testing modalities include 13C-urea breath test, serum H. pylori antibody testing, and pathological assessment of gastric tissue. Each test result will be classified as positive or negative according to the corresponding clinical laboratory or pathology report. Concordance is defined as all three testing modalities yielding the same binary result, either all positive or all negative. The unit of measure is the percentage of participants with concordant results among participants with available results from all three testing modalities.
次要结局
- Positive Detection Rate of Serum H. pylori Antibody Testing in Post-Eradication Gastric Cancer(Baseline)
- Positive Detection Rate of Pathological H. pylori Assessment in Post-Eradication Gastric Cancer(Within 2 weeks after endoscopic submucosal dissection)
- Discordance Rate Among Three H. pylori Testing Modalities in Post-Eradication Gastric Cancer(From baseline H. pylori testing to pathological assessment within 2 weeks after endoscopic submucosal dissection)
- Kappa Coefficient for Agreement Among Three H. pylori Testing Modalities(From baseline H. pylori testing to pathological assessment within 2 weeks after endoscopic submucosal dissection)
- Percentage of Participants With Tissue-Based H. pylori Detection in Tumor Tissue(Within 2 weeks after endoscopic submucosal dissection)
- Percentage of Participants With Tissue-Based H. pylori Detection in Lesion-Adjacent Mucosa(Within 2 weeks after endoscopic submucosal dissection)
- Percentage of Participants With Tissue-Based H. pylori Detection in Non-Lesion Background Mucosa(Within 2 weeks after endoscopic submucosal dissection)
- Percentage of Participants With Background Gastric Mucosal Atrophy(Within 2 weeks after endoscopic submucosal dissection)
- Percentage of Participants With Background Intestinal Metaplasia(Within 2 weeks after endoscopic submucosal dissection)
- Percentage of Participants in Each H. pylori-Defined Gastric Cancer Subtype(Baseline to pathological assessment within 2 weeks after endoscopic submucosal dissection)
- Percentage of Participants With Synchronous or Multifocal Early Gastric Cancer Within 1 Year(The percentage of participants with synchronous or multifocal early gastric cancer or high-grade intraepithelial neoplasia detected at baseline or within 1 year after endoscopic submucosal dissection will be reported. Events will be identified by endosco)
- Cumulative Incidence of Metachronous Gastric Cancer After Endoscopic Submucosal Dissection(1 year, 2 years, 3 years, and through study completion, up to 8 years after endoscopic submucosal dissection)
- Percentage of Participants With Local Residual or Recurrent Gastric Neoplasia(1 year, 2 years, and 3 years after endoscopic submucosal dissection)
- Percentage of Participants Requiring Additional Surgical Treatment After Endoscopic Submucosal Dissection(1 year, 2 years, and 3 years after endoscopic submucosal dissection)
- Recurrence-Free Survival After Endoscopic Submucosal Dissection(From endoscopic submucosal dissection to 3 years after endoscopic submucosal dissection)
- Overall Survival After Endoscopic Submucosal Dissection(From endoscopic submucosal dissection to 3 years after endoscopic submucosal dissection)
- Distribution of SMIS-Cure Curability Grades After Endoscopic Submucosal Dissection(Within 2 weeks after endoscopic submucosal dissection)
- Distribution of eCure Classifications After Endoscopic Submucosal Dissection(Within 2 weeks after endoscopic submucosal dissection)
- Kappa Coefficient for Agreement Between SMIS-Cure and eCure Classifications(Within 2 weeks after endoscopic submucosal dissection)
研究者
He Zhou
Professor
Chinese PLA General Hospital