Introduction

Gastric adenocarcinomas associated with Epstein-Barr virus (EBV) infection account for 5-10% of gastric cancers and is recognized as a distinct molecular subtype. Adenocarcinomas arising in the residual stomach after partial gastrectomy are named gastric remnant cancers (GRC) and usually develop decades after distal gastrectomy for benign disease. The relevance of GRC as a separate entity has been questioned since many tumour characteristics as well as prognosis of GRC does not seem to differ from other primary gastric cancers. However, it has been reported that a 5-fold higher proportion of GRC were EBV positive compared to other gastric adenocarcinomas in a meta-analysis of studies on Eastern patient cohorts. Symptoms and endoscopic findings at diagnosis may also differ between GRC and other gastric cancers. The aim of this study was to assess EBV infection as well as clinico-endoscopic characteristics in patients with GRC in a Western population-based patient cohort.

Aims & Methods

All incident gastric adenocarcinoma in Central Norway between 2001 and 2016 were identified by a combined search in the Norwegian Cancer Registry and Norwegian Patient Registry followed by manual assessment of all patient records. Patient and tumour characteristics were extracted. GRCs was defined as gastric adenocarcinomas in patients previously operated with a distal gastrectomy for either benign or malignant disease. Among 1217 patients with adenocarcinoma there were 78 with GRCs. All tumours were histologically classified according to Lauren and EBV-status was assessed by in situ hybridization (ISH) in GRC patients (n=78) and in proximal (localized in the gastric corpus) non-GRC (n=56) controls. Symptoms and findings at upper endoscopy at the time of diagnosis of GRC and proximal non-GRC patients were recorded.

Results

Seventy-eight patients had GRC, of whom 76 (97.4%) patients had benign disease as indication for primary distal gastrectomy. The median latency time from primary distal gastrectomy to GRC was 37.6 (range 15.7-68.0) years. Fourteen (18.7%) GRC and 6 (10.9%) proximal non-GRCs were EBV-ISH positive, but the proportions did not differ significantly (p=0.23). EBV-status was not associated with patient age, sex or Lauren histological type, neither for GRC-patients, nor for the study population overall.
The indication for upper endoscopy when the cancer was diagnosed was more frequently anaemia in GRC compared to proximal non-GRC patients (32.1% vs. 16.1%, p=0.036) and less frequently upper abdominal pain (12.8% vs. 35.7%, p=0.002). At the upper endoscopy, ulceration was a less frequent finding (17.9% vs. 57.1%, p<0.001) in GRC compared to proximal non-GRC patients. Median overall survival in EBV positive GRCs was 22.2 (0-64.9) months compared to proximal non-GRC 6.7 (4.0-9.5) months, p = 0.40, with 5-year survival of 28.6% and 22.6%, respectively.

Conclusion

A high proportion of GRC were EBV positive, but the proportion did not differ significantly from other proximal gastric cancers. At the time of diagnosis GRC patients did more often have anaemia, but less frequently upper abdominal pain or gastric ulceration.

Introduction

Gastric remnant cancers (GRC) are adenocarcinomas arising in the residual stomach after partial gastrectomy and has been considered a distinct clinical entity. GRC has been reported to account for 1-8% of all gastric adenocarcinomas. The advent of proton pump inhibitors and H. pylori eradication therapy have led to marked decline in distal gastrectomies for benign ulcer disease. However, there is a long latency period between surgery for benign disease and development of GRC. The clinical relevance of GRC as a separate entity has been questioned since the prognosis of GRC does not seem to differ from that of primary gastric cancers overall. In the current study we aimed to characterize patients with GRC and their prognosis in a large Western population-based cohort.

Aims & Methods

Patients with gastric adenocarcinoma in Central Norway between 2001 and 2016 (n=1217) were identified from combined searches in the Norwegian Cancer Registry (NCR) and Norwegian Patient Registry (NPR) with subsequent manual assessment of all patient records. GRCs were defined as gastric adenocarcinomas in patients previously operated with a distal gastrectomy for either benign or malignant disease (n=78). GRC patients were compared to non-GRC overall (n=1139) as well as to patients with proximal non-GRC (n=586). Patient, tumour and treatment characteristics, including indication for previous distal gastrectomy and reconstruction method, TNM stage, Lauren histological type and treatment were recorded. Minimum follow-up time was 6 years and 7 months. Survival was analysed by the Kaplan-Meier method. The Cox proportional hazard method was used in a multivariable analysis to identify factors independently associated with survival.

Results

The proportion of GRC was 6.4% for the entire cohort (78 of 1217 patients). The indication for primary distal gastrectomy was benign disease in 76 (97.4%) patients and median time to GRC was 37.6 (range 15.7-68.0) years. The annual number of GRC (p=0.002), number of non-GRC (p= 0.032) and GRC/non-GRC ratio (p=0.003) all declined during the study period. GRC patients were older at diagnosis (78.7 years) compared to non-GRC (74.9 years) and proximal non-GRC (72.7 years) patients. GRC patient were more frequently males (83.3%), compared to non-GRC (62.9%) and proximal non-GRC (71.6%) patients. A higher proportion of GRC (23.1%) were diagnosed in stages 0+I compared to non-GRC (12.8%) and proximal non-GRC (10.9%). Lauren histological classification did not differ significantly between groups. R0/R1 resection was performed in 41.6%, 41.7% and 39.7% of GRC, non-GRC and proximal non-GRC patients, respectively. The overall survival of GRC patients did not differ from non-GRC and proximal non-GRC, with median survival of 10.4 (9.3-11.5) months, 7.4 (5.1-9.9) months and 10.3 (8.6-12.1) months, and 5-year survival of 23.1%, 18.5% and 24.9%, respectively.In a multivariable Cox analysis, age (HR 1.01, 95%CI 1.00-1.02, p<0.001), Lauren diffuse histology (HR 1.25 95%CI 1.07-1.45, p=0.006), TNM stage (HR 1.45, 95%CI 1.40-1.50, p<0.001) and neoadjuvant chemotherapy (HR 0.68, 95%CI 0.54-0.85, p=0.002) were independently associated with mortality, whereas sex, proximal tumour location and GRC were not.

Conclusion

GRCs declined during the study period, but the latency between distal gastrectomy and GRC diagnosis was long. GRC patients were more often male and older than other gastric cancer patients, but GRC per se was not independently associated with survival after adjusting for TNM stage and tumour location.

Introduction

Early gastric cancers (EGC) are confined to the gastric mucosa and submucosa irrespective of lymph node metastases. The proportion of gastric cancers diagnosed at an early stage varies considerably between Western countries but is low compared to countries with a screening program for gastric cancer. The majority of EGC patients have been treated with surgical resection including standard lymphadenectomy in Western countries. In contrast, Asian countries have treated larger proportions of EGC with endoscopic submucosal dissection (ESD) followed by estimation of risk of lymph node metastases based on histopathological characteristics. The aim of the present study was to characterize EGCs in Central Norway before ESD was an available treatment option. Furthermore, we aimed to assess histopathological characteristics associated with lymph node metastases and long-term survival in our cohort of EGC patients.

Aims & Methods

The study was a retrospective population-based study using patients identified from the Norwegian Cancer Registry and Norwegian Patient Registry (NPR). The annual number of gastroscopies was retrieved from NPR. 1205 patients were diagnosed with gastric cancer from 2001 to 2016, a period when gastrectomy with a modified D2 resection was standard treatment. In accordance with Western diagnostic criteria, patients with carcinoma in situ were not included. Patients who received neoadjuvant chemotherapy and histologically ypT0 or ypT1 were excluded to study only chemo naïve (true) EGC. Histopathological specimens were re-examined and eCura score risk stratification was calculated. Finally, long-term survival and cause of death were assessed.

Results

Of the 1205 patients with gastric cancer 88 (7.3%) had EGC. The number of gastric cancers declined (p=0.010), but the relative proportion of EGC was unchanged during the study period despite a doubling of annual gastroscopies at a national level during the study period. Patients with EGC had median age 77 (43-91) years vs. 74 (21-99) years for non-EGC controls. EGCs were more often of the Lauren intestinal type (p<0.001) and were more often localized in the antrum or corpus. Eighty-three patients underwent surgical resection and eight (9.0%) of these had N+ disease. An eCura score could be calculated for 79 EGCs. A significant proportion (9.4%, n=5) of the patients with a low risk eCura had lymph node metastases, whereas further exclusion of tumours with histological ulceration or SM2 invasion in a post-hoc analysis identified a N0 cohort (n=36). Recurrence of cancer was diagnosed in seven (8.1%) patients after a median time of 29 (14-124) months from the EGC diagnosis. Fifty-five (62.5%) EGC patients died during follow-up, whereof 43 (78.2%) deaths were unrelated to EGC, seven (12.7%) died of cancer recurrence and five (9.1%) died from postoperative complications. Median survival for EGC patients was 117.1 months (95% CI 99.8-134.3) and 5-year overall survival 75%. Approximately half of deaths related to cancer recurrence (3 of 7) occurred more than five years after the EGC diagnosis.

Conclusion

EGCs constituted a minor but constant proportion of gastric cancers despite a considerable increase in gastroscopies. In this historic cohort with formal gastric resection for EGC, 9.0% had pN+ disease. Low risk eCura score alone was insufficient to predict pN0 disease whereas additional exclusion of patients with histological ulceration or SM2 infiltration identified a pN0 cohort. Long-term follow-up of more than five years is needed to assess EGC related mortality.

Introduction

Patients with gastric intestinal metaplasia (GIM) are at an increased risk of developing gastric cancer (GC). The histological Operative Link on Gastric Intestinal Metaplasia (OLGIM) classification aids in risk stratification. The recently developed endoscopic grading of GIM (EGGIM) may accurately predict the OLGIM stage. This study aimed to evaluate the diagnostic accuracy of EGGIM in assessing histological GIM using data from two large, prospective European consortia.

Aims & Methods

Interim data were derived from the Artificially Intelligent Diagnostic Assistant (AIDA) and Towards Gastric Cancer Screening Implementation in the European Union (TOGAS) consortia, both part of a European Horizon programme focused on gastric cancer prevention. Patients in AIDA underwent oesophagogastroduodenoscopy (OGD) for GIM surveillance or treatment of neoplastic lesions, while participants in TOGAS (aged 50–74) were offered an OGD during screening colonoscopy or polyp surveillance. Procedures were performed at eight academic centres by both expert and non-expert endoscopists, using high-resolution white-light endoscopy and virtual chromoendoscopy. The EGGIM score (range 0–10) was based on the extent of GIM (0: 0%, 1: ≤30%, 2: >30% of mucosa) across five anatomical sites: the lesser and greater curvatures of the antrum and corpus, and the incisura. Targeted biopsies were taken if GIM was suspected; otherwise, random biopsies were collected according to the Sydney system to determine the OLGIM stage. Healthy controls and GIM patients with an EGGIM score ≥1 but OLGIM stage 0 were also included. ROC curve and Spearman analyses assessed the diagnostic and ordinal correlation between EGGIM and OLGIM stages III–IV.

Results

A total of 252 patients were included (median age 60 years, IQR 9; 57.4% female): 91 from the TOGAS study (75 cancer screening, 16 polyp surveillance) and 161 from AIDA (117 GIM surveillance, 21 neoplasia treatment, 23 healthy controls). OLGIM staging identified 89 (35.3%) patients in stage 0, 74 (29.4%) in stage I, 49 (19.4%) in stage II, 35 (13.9%) in stage III, and 5 (2.0%) in stage IV. The area under the ROC curve for EGGIM in detecting OLGIM III/IV was 0.90 (95% CI 0.79–0.93, p < 0.001), with an optimal cut-off at EGGIM ≥5 (sensitivity 85%, specificity 89%).

Conclusion

Our findings prospectively validate the EGGIM score across two large European cohorts. This scoring system may serve as a practical tool to streamline gastric cancer surveillance by reducing the need for biopsies and enhancing endoscopic risk stratification.

References

Esposito G, Pimentel-Nunes P, Angeletti S, et al. Endoscopic grading of gastric intestinal metaplasia (EGGIM): a multicenter validation study. Endoscopy. 2019;51(6):515-521. doi:10.1055/a-0808-3186

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)

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

Early-onset gastric cancer (eoGC), defined as GC before 50, accounts for about 5% of GC and 3% are part of a hereditary syndrome. Its incidence is rising. eoGC was reported to present at an advanced stage at diagnosis, with a poor differentiation and a worse prognosis than in the elderly (late-onset GC, loGC), even though eoGC risk factors and characteristics remain unclear.

Aims & Methods

Therefore, we compared eoGCs with loGCs in terms of clinicopathological characteristics and risk factors. We conducted a retrospective case-case study of patients with eoGC and loGC diagnosed from 2015 to December 2022 at IRCCS San Raffaele Scientific Institute (Milan, Italy). We collected clinical data, tumor characteristics (including Helicobacter Pylori status, HP), family history of GC, smoking habit, alcohol intake, and BMI. We performed multi-gene panel testing on all eoGC.

Results

58 eoGC (51.7%M, 48.3%F; median age at diagnosis [IQR] 44.5y [39.00, 47.75]) and 290 loGCs (63.8%M, 36.2%F; median age at diagnosis [IQR] 70.33y [63.90, 75.00]) were enrolled. 19.2% eoGCs carried a germline pathogenic variant (4 CDH1; 2 TP53; 1 MMR; 1 ATM; 1 PTEN; 1 heterozygous MUTYH). Having a second-degree relative (SDR) with GC was significantly associated with eoGC (15.8% eoGCs vs. 4.6% loGCs, p = 0.015). eoGCs reported lower BMI (median 22 eoGC vs 24 loGC, p=0.016). We also found a statistically significant difference between groups in alcohol consumption (P = 0.042) and smoking status (P = 0.023). While eoGCs were mainly at the cardia (29.3% eoGCs vs. 1.7 % loGCs; p<0.001), loGCs were mostly at the antrum (19% eoGC vs. 36.9% oGCs; p=0.009). eoGCs reported more dysphagia (30.9% eoGCs, compared to 4.9% loGCs, p < 0.001), while most patients in the loGC cohort had anemia (25.3% loGCs vs 7.3% eoGCs, p = 0.002) and asthenia (9.1% loGCs vs 0% eoGCs, p = 0.012). 48.3% eoGCs were diffuse-type adenocarcinoma (p=0.014), while 51% loGCs were intestinal-type (p<0.001). No significant differences were observed in terms of T and N status, while more eoGC were M1 (26.3% eoGCs vs. 9.7% loGCs, p=0.001) and presented at stage III-IV (56.9% eoGCs vs. 41.7% loGCs, p=0.042) at diagnosis.

Conclusion

19.2% patients with eoGC carry a germline pathogenic variant, suggesting that patients with eoGC should be evaluated for germline testing at diagnosis. eoGC more often is localized at the cardia with dysphagia and presents as diffuse-type adenocarcinoma at an advanced stage (III-IV) ad diagnosis. However, 35.6% patients with eoGC presents with early gastric cancer T1 (vs 24.1% loGCs), possibly implying that younger age does not entail worse outcomes.