Introduction

Serum pepsinogens (PGs) are the biomarkers for atrophic gastritis and severe gastric inflammation.

Aims & Methods

The aim of this study was to validate the role of PGs in gastric cancer (GC) screening. 1,705 gastric neoplasms (1,287 GC and 418 gastric adenoma (GA)) and 21,425 controls (total 23,130) were enrolled. PGs and anti-Helicobacter pylori (HP) antibody were measured. Area under the curve and receiver operating characteristic curve were calculated to identify the optimal cutoff values for PGs. Multivariate logistic regression and risk stratification were conducted by combining each PG value and anti-HP antibody in GC subtypes.

Characteristics		Total (23,130) (%)	Control (21,425) (%)	Gastric Adenoma (418) (%)	GC (1,287) (%)	p	Intestinal -GC 762 (%)	Diffuse- GC (489) (%)	p
Sex	Female	8,897 (38.5)	8,358 (39.0)	134 (32.1)	405 (31.5)	<0.001	175 (23.0)	219 (44.8)	<0.001
	Male	14,233 (61.5)	13,067 (61.0)	284 (67.9)	882 (68.5)		587 (77.0)	270 (55.2)
Age (mean)		54	54	63	62	<0.001	64	55	<0.001
HP status	Negative	8,119 (35.1)	7,857 (36.7)	54 (12.9)	208 (16.2)	<0.001	137 (18.0)	61 (12.5)	0.008
	Positive	15,009 (64.9)	13,566 (63.3)	364 (87.1)	1,079 (83.8)		625 (82.0)	428 (87.5)
	Missing	2 (0.0)	2 (0.0)	0 (0.0)	0 (0.0)		0 (0.0)	0 (0.0)
PG series (ng/mL)	PGI	52.1 (28.8)	52.4 (27.9)	40.3 (38.85)	50.6 (50.2)	<0.001	44 (42.65)	60.2 (56.75)	<0.001
	PGII	11.2 (10.8)	11.0 (10.3)	12.9 (11.7)	17.5 (19.2)	<0.001	16 (16.63)	21.2 (21.0)	<0.001
	PGI/II ratio	4.6 (2.6)	4.8 (2.6)	3.0 (2.4)	2.9 (2.3)	<0.001	2.9 (2.4)	2.9 (2.1)	0.328

GC, gastric cancer; HP, Helicobacter pylori; PG, pepsinogen.

Results

PGII ≥21 ng/ml was associated with the risk of GA (odds ratio (OR) 1.38, p<0.001), GC (OR 2.77, p<0.001), diffuse-type GC (DGC) (OR 4.26, p<0.001), especially, early-stage DGC (OR 7.11, p<0.001). When GC risk was assessed by combining each PG value and HP antibody, OR showed significance between categories, and even stepwise increment from HP negative to positive and from each PG value negative to positive after adjustment with other confounding GC risk factors.

Conclusion

Each PG value combining HP test can be used as a screening test for high risk subjects with GC, and especially the combination of PGII≥21ng/ml and positive HP status in young female was related to high risk of early-stage DGC.

Introduction

Programmed cell death ligand-1 (PD-L1) is known to negatively regulate T-cell activation. Immune checkpoint inhibitors (ICIs) such as nivolumab and pembrolizumab have prolonged survival in gastric cancer (GC) as well as malignant melanoma and lung cancer.

Aims & Methods

The aim of this study was to investigate the affecting factors on the expression of PD-L1 in GC tissue in the Korean population in terms of clinicopathological variables.
Total 216 patients with GC who underwent PD-L1 immunohistochemistry (22C3) were prospectively enrolled at Seoul National University Bundang Hospital from March 2018 to February 2024. Positive PD-L1 expression was defined as a CPS score of 5 or higher. Univariate and multivariate analysis was performed.

Results

Table.Univariate and Multivariate analysis for affecting factors on PD-L1 expression

		Univariate analysis		Multivariate analysis
Variables		OR (95% CI)	p value	OR (95% CI)	p value
EBV infection	EBV negative	Ref.		Ref.
	EBV positive	8.54 (1.59-158.42)	0.043	14.01 (2.23-278.16)	0.019
Tumor location	Non-cardia	Ref.		Ref.
	Cardia	2.78 (1.18-7.35)	0.026​	4.97 (1.17-16.08)	0.005
TNM stage	Stage I	Ref.		Ref.
	Stage II,III, or IV	1.38 (1.00-1.92)	0.049	1.61 (1.09-2.42)	0.018

Multivariate regression (Table) showed some few significant associations between PD-L1 expression and specific factors. EBV infection shows a strong effect in both univariate (odd ratio [OR] 8.54, 95% confidence interval [CI] 1.59-158.42, p=0.043) and multivariate analysis(OR 14.01, CI 2.23-278.16, p=0.019). Cardia portion involvement shows a significant correlation in both univariate (OR 2.78, CI 1.18-7.35, p=0.026) and multivariate analysis(OR 4.97, CI 1.71-16.08, p=0.005). And higher TNM stage also remains significant in both univariate (OR 1.38, CI 1.00-1.92, p=0.049) and multivariate analysis (OR 1.61, CI 1.09-2.42, p=0.018).

Conclusion

EBV infection, cardia involvement, and higher TNM stage were independent factors influencing PD-L1 expression.

Introduction

The sex differences in the incidence of gastric cancer have been well known. However, uncertainty still exists in terms of prognosis of GC. For example, the US SEER data reports a significantly better prognosis in females than in males, but the prognosis is better in males than in females in Korean Central Cancer Registry data. Roles of molecular markers and gut microbiota as new prognostic factor are emerging recently, but few studies seem to try to reveal sex differences.

Aims & Methods

In this background, we aimed to analyze the differences in GC characteristics according to sex in Korean patients, mainly focused on survival. This was a single-center retrospective study. A total of fifteen thousand patients diagnosed with GC at the Seoul National University Bundang Hospital between 2003 and 2023 were included. Clinicopathological characteristics, histologic types, survival rates with age- and stage-stratification, and associated risk factors were analyzed. Information related to death was cross-verified using medical record review and data from the National Statistical Office.

Results

The ratio of males and females was about 2:1, and there was no differences in stage between sexes. Female patients were significantly younger than males, had more gastric body cancers and tumors with diffuse type or poorly differentiated histology. Females underwent less endoscopic treatment and more surgery, and tumors with microsatellite instability was more common in females, while mutation of p53 was less common. In histological types according to Lauren classification, diffuse type histology was more common in younger patients in both males and females. The proportion of intestinal type GC increased with age, but the proportion increased rapidly in males while increased gradually in females. In Cox multivariate regression analysis for GC-related death, older age, proximal tumor location, diffuse type histology and advanced tumor stage were risk factors. In terms of survival, overall and GC-specific survival did not show significant differences between sexes in the analysis of the total population. However, sex differences in survival reversed with age, that younger females under 50 showed survival disadvantages, but the survival became similar in 50s, and older females over 60 showed survival advantages in both overall and GC-specific survival. Furthermore, in the stratification analysis according to the stage, there were no significant differences in stages I to III. But, stage IV female patients showed significant survival disadvantages. In subgroup analysis of stage IV patients, the differences between males and females in median survival were two months, and female patients were significantly younger and had a higher proportion of diffuse type GC than male patients, which shows aggressive feature and is related to poorer survival.

		Total (N=1,924) (%)	Male (n=1,282) (%)	Female (n=642) (%)	p
Median survival (mo)		10	11	9	0.022
Age (mean±SD)		61.59±14.25	62.41±13.23	59.96±15.97	0.001
Age (in diffuse type patients, mean±SD)		54.55±14.71	56.43±14.29	52.26±14.91	0.001
Lauren classification	Intestinal	554 (48.0)	438 (56.7)	116 (30.4)	<0.001
	Diffuse	574 (49.7)	315 (40.7)	259 (68.0)
	Mixed / Indeterminate	26 (2.3)	20 (2.6)	6 (1.6)

Conclusion

Significant differences in survival between sexes were observed with stratification analysis, although sex itself was not an independent prognostic factor. These age-dependent changes are thought to suggest the effect of sex hormones. These differences should be considered in clinical practice and later research in terms of tailored medicine.

Introduction

Gastric cancer remains a major global cause of cancer mortality. Early detection and accurate risk stratification are crucial for improving prognosis. Noninvasive, affordable serum tests are essential for mass screening. We compared the updated ABC method (pepsinogen I/II and gastrin-17) and a novel gastric cancer scoring system (“new scoring system”) regarding their effectiveness in screening early gastric cancer and precancerous lesions, risk stratification, and missed diagnosis prevention.

Aims & Methods

From April to November 2024, 7,304 asymptomatic individuals from Yuhang District, Hangzhou, China, participated in community-based screening. Serum pepsinogen I (PGI), PGII, PGI/II ratio (PGR), gastrin-17 (G-17), and H. pylori antibody were tested. Participants were stratified into low-, medium-, or high-risk groups using the ABC method and the new scoring system. A total of 654 medium- and high-risk participants underwent endoscopy and histopathology. Detection rates of gastric cancer, intraepithelial neoplasia, and atrophic gastritis were compared. Missed diagnosis rates in low-risk groups were analyzed assuming no endoscopy.

Results

The ABC method classified 90.55% as low-risk, 7.69% medium-risk, and 1.75% high-risk. The new scoring system classified 59.42% as low-risk, 32.67% medium-risk, and 7.91% high-risk. Endoscopy detected 11 gastric cancers (1.68%, 10 early-stage), 21 intraepithelial neoplasias (3.21%), and 98 atrophic gastritis cases (14.98%).
Gastric cancer detection rates in medium/high-risk groups were similar: ABC 1.58% (3/190), new scoring 1.77% (10/565) (p=1.000). Atrophic gastritis rates were comparable (ABC 14.21%, new scoring 15.04%, p=0.872). In the high-risk subgroup, the new scoring system detected significantly more atrophic gastritis cases (29.87% vs ABC 16.33%).
In low-risk groups, the ABC method would miss 8 of 11 gastric cancers (72.73%) without endoscopy; the new scoring system would miss only 1 case (9.09%, p=0.009). ROC analysis showed higher AUC for the new scoring system (0.60 vs 0.51). Decision curve analysis indicated superior net clinical benefit for the new scoring system at threshold probabilities above 0.2. The new scoring system showed higher sensitivity for early-stage disease detection, whereas ABC had slightly higher specificity.

Conclusion

Both systems showed similar performance in detecting gastric cancer and precancerous lesions among medium- and high-risk populations. The new scoring system significantly reduced missed diagnoses in low-risk groups and improved identification of high-risk precancerous conditions. Incorporating ROC, DCA, and accuracy metrics, the new scoring system offers enhanced flexibility for risk stratification, making it potentially more effective for population-based gastric cancer screening, especially in resource-limited settings. Further validation in larger cohorts is warranted.

Disclosure

Nothing to disclose.

Introduction

Epstein-Barr virus (EBV) associated gastric cancer (GC) has been reported to be about 5-16% of all gastric cancers with good prognosis compared to EBV-negative GC. The aim of this study was to evaluate the clinicopathological characteristics of EBV-positive GC including survival analysis in the prospective observational cohort study in a tertiary hospital in South Korea.

Aims & Methods

Total 4,586 patients who underwent EBV in situ hybridization (EBV-ISH) testing among 14,613 patients diagnosed with GC were prospectively enrolled at Seoul National University Bundang Hospital from 2003 to 2023. Data including age, sex, smoking, cancer type and stage, tumor size and location, histologic type, molecular features (p53 expression and MSI), and survival information including causes of death were collected and analyzed.

Results

EBV-positive cancer group showed significant differences compared to EBV-negative cancer group. That is, they showed higher proportion of males (p<0.001), predominant presence in the proximal stomach (p<0.001), higher proportion of undifferentiated cancer (p<0.001), and lower cancer stage (p=0.004) (Table). In Cox multivariate analyses, age (HR 1.022, p<0.001), tumor size (HR 1.118, p<0.001) along with cancer stage (stage 2 HR 5.843, p<0.001; stage3 HR 15.570, p<0.001; stage4 HR 50.075, p<0.001, respectively) were significant risk factors for GC-specific mortality, while EBV positivity was inversely correlated (HR 0.537, p=0.023). In the survival analyses, EBV-positive cancer group showed statistically significant survival advantages over EBV-negative cancer group in both overall (p=0.016) and gastric cancer-specific survival (p=0.005)

Variables		Total patients (n=4,586) (%)	EBV positive (n=456) (%)	EBV negative (n=4,130) (%)	P value
Sex	Male	3028 (66)	404 (88.6)	2624 (63.5)	<0.001
	Female	1558 (34)	52 (11.4)	1503 (36.5)
Location (n=4,579)	Cardia, Body	2076 (45.3)	367 (80.5)	1709 (41.5)	<0.001
	Antrum	2503 (54.7)	89 (19.5)	2414 (58.5)
Histology type (n=3,799)	Differentiated	1891 (49.8)	123 (35.5)	1768 (51.2)	<0.001
	Undifferentiated	1908 (50.2)	223 (64.5)	1685 (48.8)
TNM staging	1	2818 (61.4)	316 (69.3)	2502 (60.6)	0.001
	2	683 (14.9)	52 (11.4)	631 (15.3)
	3 or above	1085 (23.7)	88 (19.3)	997 (24.1)

Overall survival
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GC-specific survival
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Conclusion

EBV-positive GC group was associated with male sex, proximal location, poorly differentiated histology and lower cancer stage, and showed significantly better prognosis than EBV-negative gastric cancer. EBV might play a role in the gastric carcinogenesis to make less metastasis resulting in better survival.

Introduction

Borrmann type 4 gastric cancer is defined as a diffuse gastric cancer that infiltrates the gastric wall, often without an overt mass or ulceration. Clinically, it is associated with a poor prognosis and lower curative resection rate, but is easily missed in routine upper endoscopic exams. This study aimed to develop an artificial intelligence (AI) system that can detect Borrmann type 4 gastric cancer lesions in upper endoscopic images.

Aims & Methods

Endoscopic images of patients diagnosed with Borrmann type 4 gastric cancer, along with normal controls were collected from Seoul National University Hospital. A total of 227 gastric cancer patients (1,973 images) and 227 normal controls (1,554 images) were assigned to the train dataset, while 50 gastric cancer patients (417 images) and 50 normal controls (344 images) were assigned to the test dataset. A deep residual learning network model, ResNet-152 was used for training.

Results

The sensitivity, specificity and accuracy for identification of Borrmann type 4 gastric cancer images were 87.29% (95% confidence interval [CI] 84.09-90.49%), 97.97% (95% CI 96.47-99.46%) and 92.12% (95% CI 90.20-94.03%), respectively. When the diagnosis was made in patients with more than 50% of the endoscopic images identified as Borrmann type 4 gastric cancer, the sensitivity, specificity and accuracy was improved to 94% (95% CI 87.42-100%), 100% (95% CI 100-100%) and 97% (95% CI 96.66-100%), respectively.

Conclusion

A novel AI-based model that can identify Borrmann type 4 gastric cancer from endoscopic images was developed. Although further internal and external validation is needed, it is expected to assist clinicians in the early diagnosis of Borrmann type 4 gastric cancer with high accuracy.

Introduction

Recent research from the Netherlands, the United States, and Korea suggests that individuals who receive a positive result on the fecal immunochemical test (FIT) may be at a higher risk of developing gastroesophageal cancer (GEC) within the following 36 months. However, the associations reported in these studies may be biased due to differences in age and sex between the FIT-positive and FIT-negative groups and other confounding factors.

Aims & Methods

We aimed to evaluate the association between FIT results and the risk of GEC in a matched cohort by age and sex. Additionally, we assessed the cost-effectiveness of a one-time Esophago-Gastro-Duodenoscopy (EGD) for individuals with positive FIT results.. We created a matched cohort of individuals aged 50 to 75 who underwent FIT testing at Clalit Health in Israel between June 2016 and June 2019. For each FIT-positive individual, we matched three FIT-negative individuals based on age, sex, and H. pylori status. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were utilized to evaluate the association between a positive FIT result and the risk of GEC within 36 months. We calculated the incremental cost-effectiveness ratio (ICER) for a one-time EGD at $400 in individuals who tested positive for FIT. Screening is considered cost-effective if the ICER is below $50,000.

Results

The primary cohort included 483,710 individuals, while the matched cohort comprised 151,500 individuals (47.6% female, median age 62.5 years). During the follow-up period, 202 cases of GEC occurred: 0.2% (64/38,575) among FIT-positive individuals and 0.1% (138/112,925) among FIT-negative individuals, adjusted HR 1.39 (95% CI 1.03-1.87). Age, male sex, H. pylori exposure, country of birth, proton-pump inhibitor usage, smoking status, and anemia were all significantly associated with an increased risk of gastric cancer. A one-time EGD has been determined to be a cost-effective option in a range of ages and rates of localized disease at the time of EGD.

Conclusion

This matched cohort study suggests that individuals with a positive FIT may have an increased risk of GEC, which occurs at an overall rate of 0.2% within 36 months. A one-time EGD priced at $400 can be cost-effective in many scenarios.

Disclosure

NONE