Introduction

Gastric Cancer has been a heavy burden in far East Asian countries. Although there are national programs in South Korea and Japan, their evidence has been suggested as insufficient. We aimed to synthesize currently available comparative data on gastric cancer mortality in healthy, asymptomatic adults by explicitly classifying the screening effects through study designs and types of intervention effects.

Aims & Methods

We searched multiple databases through October 31, 2022, for this systematic review　and meta-analysis. Studies of any design that compared gastric cancer mortality among radiographic or endoscopic screening and no screening in a community-dwelling adult population was included. The method included a duplicate assessment of eligibility, double extraction of summary data, and validity assessment using the Risk Of Bias In Non-randomized Studies of Interventions tool. Bayesian three-level hierarchical random-effects meta-analysis synthesized data corrected for self-selection bias on the relative risk (RR) for per-protocol (PP) and intention-to-screening (ITS) effects. The study registration number at PROSPERO is CRD42021277126.

Results

We included seven studies in which a screening program was newly introduced (median attendance rate, 31%; at a moderate-to-critical risk of bias) and seven cohort and eight case-control studies with ongoing screening programs (median attendance rate, 21%; all at critical risk of bias); thus, data of 1,667,117 subjects were included. For the PP effect, the average risk reduction was significant for endoscopy (RR 0.58; 95% credible interval: 0.39–0.90) but non-significant for radiography (RR 0.80; 95%CI 0.60–1.06). The ITS effect was not significant for both radiography (0.98; 95%CI 0.86–1.21) and endoscopy (RR 0.94; 95%CI 0.74–1.44). The effects' magnitude depended on the self-selection bias correction assumptions. Restricting the scope of East Asian studies only did not change the results.

Conclusion

In limited-quality observational evidence from high-prevalence regions, screening reduced gastric cancer mortality; however, the effects diminished at a program level.

Disclosure

I have no conflict of interest.

Introduction

Discrepancies in gastric cancer (GC) mortality reduction are evident across global GC screening programs. Specifically, the reduction brought by endoscopic screening nearly doubled in Japan and Korea compared with China. Despite studies indicating that economic status, screening methods, and public health awareness may influence screening efficiency, there is no comprehensive study that has summarized and compared the outcomes of available screening programs and identified factors potentially influencing the cancer-preventive effects.

Aims & Methods

Here we present data, including response to invitation, uptake of endoscopy screening and cancer screening positivity, of global GC screening programs. By pooling three key indicators throughout screening process, including endoscopic compliance rate, GC detection rate and early diagnosis rate, we conducted a meta-analysis of global GC endoscopic screening programs, in order to compare the outcomes of available screening programs and identify possible influencing factors. PubMed, Embase, Web of Science, and Scopus were searched for relevant articles published until September 20, 2023. Original articles providing enough information to calculate the indicators in the general screening population were included. Pooled random effect estimates of the indicators were computed, and further subgroup analysis stratified according to study period, country or region, setting, screening interval, education level and socioeconomic status was conducted. This study was registered with PROSPERO (CRD42023464921).

Results

90 studies (59 reported endoscopic compliance rate, 68 reported GC detection rate and 33 reported GC early diagnosis rate) were included. Overall, the rates of endoscopic compliance, GC detection, and early-cancer diagnosis were 46.94% (95%CI 41.35-52.53%), 0.62% (95%CI 0.46-0.80%), and 61.41% (95%CI 51.42-71.40%), respectively. Subgroup analysis demonstrated a gradual increase in endoscopic compliance and a counterintuitive decline in GC detection rate over time. Stratified by countries, the three indicators in Japan (51.05% [37.06-65.05%] for endoscopic compliance rate, 0.89% [0.55-1.31%] for GC detection rate, and 78.98% [68.83-87.66%] for GC early diagnosis rate) and Korea (49.78% [38.77-60.80%] for endoscopic compliance rate, 1.07% [0.05-3.38%] for GC detection rate, and 69.84% [61.51-77.57%] for GC early diagnosis rate) were significantly higher in China (39.68% [31.84-47.52%] for endoscopic compliance rate, 0.51% [0.33-0.74%] for GC detection rate, and 51.35% [36.33-66.37%] for GC early diagnosis rate). The highest endoscopic compliance and GC detection rate was reported in hospital, while GC early diagnosis rate was higher in community and health checkup. Screening programs with 2-3 years intervals, public health campaigns, higher education levels, and socioeconomic status showed higher compliance. Screening programs based on new endoscopic techniques generally reported higher GC detection and early diagnosis rates.

Conclusion

Among high-incidence countries for GC, China lags behind Japan and Korea regarding endoscopic compliance rate, GC detection rate and early diagnosis rate. Screening settings, intervals, campaigns, education and socioeconomic stratum may affect endoscopic compliance, while GC detection and early diagnosis rates are mainly influenced by screening settings and endoscopic techniques. In the future, continuous monitoring of quality control indicators should be applied in GC screening programs and the screening strategy should be adjusted accordingly to improve screening effectiveness.

Introduction

The risk of gastric cancer is expected to decrease with reduced Helicobacter pylori (H. pylori) infection rate. Although periodic endoscopic screening for gastric cancer is widely performed in East Asia, the optimal screening strategy remains unclear. Cost-effectiveness analysis (CEA) is an effective method to objectively compare different screening methods. However, no studies have compared the cost-effectiveness of endoscopy-based screening strategies.

Aims & Methods

This study aimed to determine the most cost-effective endoscopic screening strategy for the detection and treatment of gastric cancer in a modern Japanese cohort. This study consisted of two phases: clinical data collection and analysis, followed by simulation model development. The following data was retrospectively extracted from participants who received screening endoscopy between April 2019 and March 2023: age, H. pylori infection status, presence of intestinal metaplasia, pathological diagnosis of gastric cancer, and the interval between the most recent endoscopies. A Markov state transition model was constructed based on the cohort data. In this model, the prevalence of H. pylori infection and intestinal metaplasia, the transition probabilities between each state, and the probabilities of incidence of gastric cancer and treatment were defined. In the base-case analysis, the cost-effectiveness of 15 strategies with different starting ages (40/50/60 years) and screening intervals (1/2/3/4/5 years) was compared. The net monetary benefit (NMB) and incremental cost-effectiveness ratio (ICER) of quality-adjusted life-years (QALY) gained by treatment were used as outcomes. The NMB is a measure of the difference between the cost required for a strategy and the cost threshold for the same effect; the larger the NMB of a strategy, the more cost-effective it is. In contrast, a lower ICER is considered more cost-effective.

Results

A simulation model was constructed based on the cohort data of 94,137 participants (mean age 54.5 years, males 57.9%; 74.4% H. pylori-naïve, 94.2% intestinal metaplasia-negative). The results of the base-case analysis showed that the screening strategy of 4-year intervals starting at the age of 40 years had the highest net monetary benefit (97,401,578 yen) (Table). Based on the Monte Carlo simulation, the cost-effectiveness acceptability curve demonstrated that the 4-year interval screening strategy starting at the age of 40 years was superior to the other strategies when the willingness-to-pay was set at 5,000,000 yen. In one-way sensitivity analysis with a varying probability of H. pylori infection status transition, the incremental cost-effectiveness ratio was superior in the screening strategy every 4 years, starting at age 40 years.

Conclusion

Gastric cancer screening strategies can be modified in terms of cost-effectiveness in a modern Japanese cohort. Our simulation showed that endoscopic screening at 4-year intervals starting at 40 years was the most cost-effective method.

Disclosure

The authors declare that there is no conflict of interest.

Introduction

The diagnosis of advanced gastric cancer (AGC) is occasionally challenging for endoscopists. In particular, scirrhous gastric cancer (SGC) is often missed by esophagogastroduodenoscopy (EGD) alone because it may not form obvious ulcers or tumors. Early detection of SGC is difficult, and the prognosis is often poor. Considering the rapid progression of SGC, an accurate endoscopic diagnosis of the disease is desirable. SGC is diagnosed using computed tomography, EGD, and EGD-biopsy. In AGC, except for SGC, a definitive diagnosis can be made in >90% of cases when EGD findings are combined with EGD-biopsy. However, SGC is often difficult to diagnose even with EGD-biopsy. One report has indicated that the false-negative proportion of EGD-biopsy in SGC is >50%, because compared to other AGCs, SGC presents a variety of endoscopic findings, as well as special growth forms and morphological features. Therefore, the usefulness of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) instead of EGD-biopsy in the diagnosis of SGC has recently been reported, and the positive diagnosis proportion is as high as 71.4%–82.6%. Against this background, we believe that EUS-FNA is an alternative for diagnosing EGD-biopsy-negative SGC. Therefore, we conducted a systematic review and meta-analysis to analyze the EUS-FNA diagnosis rate from previous reports in the diagnosis of SGC, verify the advantages and disadvantages of EUS-FNA, and evaluate the utility of EUS-FNA for the current SGC diagnostic landscape.

Aims & Methods

A systematic review was conducted using the PubMed (MEDLINE) and Ichushi-Web (NPO Japan Medical Abstracts Society) data and included all entries since their inception to October 10, 2022, in which SGC was evaluated using EUS-FNA. The following electronic search terms were used to retrieve the literature in PubMed: ("endosonography"[MeSH] OR "endosonography"[tiab] OR “EUS”[tiab] OR "biopsy, fine needle"[MeSH] OR “fine needle aspiration”[tiab] OR “fine needle biopsy”[tiab]) AND ("linitis plastica"[MeSH] OR “linitis plastica”[tiab] OR "stomach neoplasms"[MeSH] OR “gastric cancer”[tiab]). Additionally, Ichushi-Web created an electronic search strategy based on the above words. The primary outcome was the proportion of SGC diagnosed using EUS-FNA. In addition, we analyzed the proportion of adverse events associated with EUS-FNA. The study protocol was registered in the UMIN Clinical Trials Registry on October 10, 2022 (No: UMIN000049169).

Results

The electronic search identified 1890 studies; overall, 4 studies met the selection criteria and reported data on EUS-FNA performed on 114 patients with suspected SGC. In our systematic review, the overall diagnostic yield of EUS-FNA for SGC was 82.6% (95% confidence interval, 74.6–90.6%) and the statistical heterogeneity was 0% (I² = 0%), indicating a low heterogeneity. Furthermore, the EUS-FNA diagnostic proportion for SGC lymph node metastasis was 75–100%, indicating a high diagnostic performance. No apparent adverse events were observed in these 4 studies.

Conclusion

We believe that EUS-FNA is a useful examination because of its minimally invasive nature and high tissue diagnostic proportion. In particular, we consider it to be a useful alternative examination for patients with suspected SGC who cannot be definitively diagnosed by CT or EGD-biopsy.

Introduction

Gastric cancer (GC) incidence based on the endoscopic Kyoto classification of gastritis has not been systematically investigated using time-to-event analysis. Therefore, we examined GC incidence in an endoscopic surveillance cohort.

Aims & Methods

This study was retrospectively conducted at the Toyoshima Endoscopy Clinic. Patients who underwent two or more esophagogastroduodenoscopies (EGDs) were enrolled. GC incidence was based on Kyoto classification scores, such as atrophy, intestinal metaplasia (IM), enlarged folds (EF), nodularity, diffuse redness (DR), and total Kyoto scores. Atrophy was classified using the Kimura-Takemoto classification. Non-atrophy and Closed I, Closed II and III, and Open I to III were scored as atrophy scores of 0, 1, and 2, respectively. IM scores of 0, 1, and 2 were defined as the absence of IM, IM limited to the antrum, and IM extending into the corpus, respectively. The absence and presence of EF were scored as 0 and 1, respectively. The absence and presence of nodularity were scored 0 and 1, respectively. DR scores of 0, 1, and 2 were defined as the absence of DR, mild DR and/or DR with partial regular arrangement of collecting venules (RAC), and severe DR without RAC, respectively. The endoscopists diagnosed the Kyoto classification scores on-site during the index EGD. Hazard ratios [HRs] adjusted for age and sex were calculated using a Cox hazard model. This study was approved by the institutional review board of the Yoyogi Mental Clinic (approval no. RKK227).

Results

A total of 6718 patients were enrolled (mean age 55.0 years; men 44.2%). Of them, 3754, 2264, 700 patients were in H. pylori uninfected, eradicated, and currently infected status, respectively. Patients were followed up for up to 5.02 years. The mean Kyoto classification scores for atrophy, IM, EF, nodularity, DR, and total Kyoto were 0.585, 0.284, 0.039, 0.026, 0.312, and 1.247, respectively. During the follow-up period, 37 GCs occurred in 34 patients. All GCs were superficial and within the submucosal depth. Lauren’s intestinal type made up 89.1% of GCs. The annual incidence rates of GC were 0.04%, 0.17%, and 0.73% for atrophy scores of 0, 1, and 2; 0.07%, 0.25%, and 1.10% for IM scores of 0, 1, and 2; 0.17% and 0.92% for EF scores of 0 and 1; and 0.06%, 0.55%, and 0.74% for DR scores of 0, 1, and 2, respectively. The annual incidence rate of GC was 0.19%. The GC incidence rates were 0.05, 0.07, 0.47, and 1.27%/year for the total Kyoto scores of 0-1, 2-3, 4, and 5-8, respectively. Multivariate analysis showed that Kyoto atrophy scores 1 (HR with score 0 as reference: 3.66, 95% confidence interval [CI]: 1.06-12.61), 2 (11.60, 3.82-35.27), IM score 2 (9.92, 4.37-22.54), EF score 1 (4.03, 1.63-9.96), DR scores 1 (6.22, 2.65-14.56), and 2 (10.01, 3.73-26.86) were associated with GC incidence, whereas nodularity scores were not. The total Kyoto scores of 4 (HR with total Kyoto scores 0-1 as reference: 6.23, 95% CI: 1.93-20.13) and 5-8 (16.45, 6.29-43.03) were more likely to develop GC, whereas the total Kyoto scores 2-3 were not, as shown in table. The HR of the total Kyoto score for developing GC per 1 rank was 1.75 (95% CI: 1.46-2.09, P<0.001).

Conclusion

A high total Kyoto score (≥ 4) was associated with GC incidence. The endoscopy-based diagnosis of gastritis can stratify GC risk.

Disclosure

All authors disclosed no personal conflicts of interest.

Introduction

Gastric cancer screening is not formally recommended in Portugal, despite having an incidence rate of 26/100,000 inhabitants, which contrasts with recommendations from other countries with moderate incidence.

Aims & Methods

Aims: To assess the frequency of screening indications and correspondent diagnoses in patients referred for upper endoscopy from primary healthcare.
Methods: A multicenter cross-sectional study including patients who underwent upper endoscopy at 13 national endoscopy units from January to March 2024.

Results

6320 patients were included (57% male, mean age 58). Cancer screening was the indication for upper endoscopy in 1775 patients (28% of total; 52% male, mean age 60). Biopsies of the antrum and corpus were performed in 91% of those exams, and virtual chromoendoscopy was used in 19% of screening endoscopies (vs 34% for atrophic gastritis surveillance, p<0.05). Endoscopic staging for intestinal metaplasia was performed in 13%. By regions, screening indication was more common in Minho (35%) and less in the Lisbon region (15%, p<0.05 vs other regions). Only 21% of exams were considered normal, with the main findings being: erythematous gastritis (31%); atrophic gastritis (16%, 1% autoimmune gastritis), reflux esophagitis (15%), papular gastritis (10%), erosive gastritis (8%), gastric polyps (5%), erosive duodenitis (3%), peptic ulcers (3%), subepithelial lesions (1.5%) and Barrett's esophagus (0.5%). Histologically, 30% of patients had intestinal metaplasia, 5% in both the antrum and corpus. Fourteen neoplastic lesions (0.8%) were identified: 5 gastric neoplasms (0.3%), 4 superficial gastric lesions (0.2%), 2 esophagus/junction neoplasms (0.1%), 2 superficial junction lesions (0.2%), and 1 ampulloma (0.1%). Ten percent of patients would require future endoscopic surveillance.

Conclusion

A significant proportion of upper endoscopies in Portugal are already performed for cancer screening, which seems justifiable given the high proportion of clinically relevant alterations identified. The low proportion of exams with chromoendoscopy suggests that measures are needed to increase the use of this technique in clinical practice.

Introduction

Patient-derived organoids (PDOs) are a promising preclinical cancer model that has demonstrated an advantage in predicting drug susceptibility. Norcantharidin (NCTD) derived from traditional Chinese medicine has been used in the treatment of gastric cancer, but the sensitivity of different patients to NCTD has not been evaluated in human samples.

Aims & Methods

The purpose of this study was to use PDOs to predict the drug sensitivity of NCTD in gastric cancer, so as to guide clinical drug use. PDOs were established by surgical resection of gastric cancer patients. Hematoxylin-eosin staining and immunohistochemical staining were used to identify the pathological morphology and molecular characteristics of PDOs and original tumor tissues. Genome analysis of tumor tissue and PDOs was performed using whole exon sequencing. NCTD intervention PDOs were screened for sensitivity and area under the curve (AUC) and IC50 values were assessed.

Results

10 PDOs conforming to the standard of drug sensitivity test were successfully constructed. The organoids were spherical and hollow with upper skin sac structure. The pathological and genomic features of the corresponding tumor were preserved, and the expression of related molecular markers was consistent with that of the original tissue. All PDOs could be stably passed through, frozen and resuscitated. After adding different doses of NCTD, 10 organoids showed different drug sensitivities to NCTD, among which PDO4, PDO7 and PDO10 were most sensitive to NCTD.

Conclusion

NCTD has significant anti-gastric cancer effect, but there is obvious heterogeneity in drug response. PDOs can be used as a preclinical drug screening platform to guide the development of individualized cancer treatment, and bring new hope for the research of TCM treatment of gastric cancer.