Clinical Case Summary

Introduction: Multiple gastric cancers are more prevalent in early-stage cases than in advanced-stage cases.
Case: A 59-year-old male with gastric discomfort was diagnosed with gastric cancer through upper gastrointestinal endoscopy. Further evaluation at our institution identified two type 2 tumors in the middle and upper gastric body regions. A CT scan revealed no liver metastasis or ascites, but suggested possible direct liver invasion and peritoneal dissemination. The patient received preoperative chemotherapy with S-1 and CDDP, followed by total gastrectomy and D2 dissection, and recovered without complications.
Histopathological assessment uncovered two distinct advanced gastric carcinomas: the upper region lesion was characterized as pap, SS, INFb, ly0, V1a, HER2(+), and MSS; while the lower-middle region lesion was tub2 (>por2>muc), SE, INFb, ly0, V1a, HER2(-), and MSI-H. Lymph nodes in Nos. 6, 8a, and 11p were positive for HER2(-) and MSI-H. The patient underwent postoperative adjuvant chemotherapy with DOC and S-1. Following a delayed outpatient visit after the 10th course, rapid jaundice progression indicated a recurrence due to intrahepatic metastasis at the confluence of the right and left hepatic ducts.
After PTCD insertion and partial jaundice reduction, FOLFOX and nivolumab therapy were initiated. The tumor exhibited significant shrinkage, allowing for PTCD removal, and treatment is ongoing.
Conclusion: This report discusses a case of chemotherapy for recurrent HER2-positive and MSI-H multiple advanced gastric cancer, and includes a review of pertinent literature.

Clinical Case Summary

A 59-year-old male presented with upper abdominal discomfort. Endoscopic and radiologic evaluation revealed two Type 2 tumors in the upper and middle third of the stomach, with suspected hepatic invasion and peritoneal dissemination. The patient underwent neoadjuvant chemotherapy with S-1 and cisplatin, followed by total gastrectomy with D2 lymphadenectomy.
Histopathological Findings: Postoperative pathological analysis revealed two molecularly distinct synchronous gastric cancers. The upper tumor was a HER2-positive, microsatellite-stable (MSS), papillary adenocarcinoma (SS, INFb, ly0, V1a). The middle to lower tumor exhibited mixed histology (tub2 > por2 > muc) and was HER2-negative and microsatellite instability-high (MSI-High). Metastatic lymph nodes (N0.6, 8a, and 11p) were confirmed to be derived from the MSI-High tumor.
Treatment and Outcome: The patient received adjuvant chemotherapy with docetaxel and S-1, but therapy was interrupted due to intrahepatic recurrence. After PTCD, he was treated with FOLFOX plus nivolumab, which resulted in significant tumor shrinkage, but was complicated by immune-related interstitial pneumonitis. Subsequent treatment with RAM + PTX was also halted due to recurrence of pneumonitis. During a one-year treatment hiatus, remission was maintained. Upon detection of splenic metastasis, nivolumab was re-administered and led to a second radiological complete remission without further pneumonitis. The patient remains disease-free.
Conclusion: This case suggests that the recurrent gastric cancer was most likely the MSI-High tumor with lymph node metastases, as evidenced by a successful response to re-administration of nivolumab. It also highlights the potential risk of immune-related interstitial pneumonitis induced by the combination of FOLFOX and immune checkpoint inhibitors. This case underscores the importance of treatment strategies based on molecular profiling and the need for careful management of immune-related adverse events.

Clinical Case Summary

Case Presentation: We report a rare instance of complete remission in a 59-year-old male with advanced gastric cancer, presenting with gastric discomfort. Initial diagnosis revealed two Type 2 tumors in the middle and upper regions of the gastric body, indicating potential direct hepatic invasion and peritoneal dissemination. The patient was treated with preoperative chemotherapy consisting of S-1 and cisplatin, followed by total gastrectomy and D2 lymph node dissection.
Histopathological Findings: Examination identified two distinct gastric carcinomas. The upper tumor exhibited papillary features, SS, INFb, ly0, V1a, HER2-positive, and MSS. The lower-middle tumor was characterized by mixed tubular and poorly cohesive patterns (tub2 > por2 > muc), SE, similar growth pattern and vascular invasion, HER2-negative, and MSI-H. Lymph nodes in stations 6, 8a, and 11p were also HER2-negative and MSI-H positive.
Treatment and Outcome: Following total gastrectomy, the patient underwent 10 cycles of adjuvant chemotherapy with docetaxel and S-1, which was halted due to intrahepatic metastatic recurrence. The recurrence was managed initially with percutaneous transhepatic cholangiodrainage (PTCD) and subsequent FOLFOX combined with nivolumab therapy, leading to significant tumor shrinkage and removal of the PTCD. Despite achieving tumor resolution, the patient developed interstitial pneumonia as a treatment complication, necessitating discontinuation of therapy. However, the patient eventually achieved complete remission and is currently free of recurrence.
Conclusion: This case demonstrates the potential for complete remission in treatment-resistant gastric cancer through a combination of surgery, conventional chemotherapy, and immunotherapy. It highlights the importance of personalized treatment plans based on tumor characteristics such as HER2 status and MSI, contributing to the evolving landscape of gastric cancer management.

Introduction

Gastric cancer is a highly prevalent malignant tumor worldwide, and early diagnosis is crucial for improving survival rates. Claudin18.2 (CLDN18.2), a member of the tight junction protein family, is highly expressed in advanced gastric cancer and has emerged as a therapeutic target. However, its expression characteristics and diagnostic value in early gastric cancer remain unclear. This study aims to investigate the expression patterns of CLDN18.2 in early gastric cancer and evaluate its potential as a diagnostic biomarker.

Aims & Methods

The study enrolled 54 patients with early gastric cancer to analyze their clinicopathological characteristics (including age, gender, histological type, differentiation degree, etc.). Immunohistochemistry was employed to detect differential CLDN18.2 protein expression between the tumor group and control group (n=54). Statistical methods were applied to evaluate the correlation between CLDN18.2 expression and clinicopathological features.

Results

The early gastric cancer cohort was predominantly characterized by patients >60 years old (72.2%), male (64.8%), with adenocarcinoma (98.1%) and well-differentiated tumors (57.4%). CLDN18.2 expression analysis revealed significantly higher positivity in the tumor group compared to controls (38/54 vs. 9/54, P<0.001). A strong correlation was observed between CLDN18.2 expression and differentiation grade (100% positivity in poorly differentiated vs. 61.3% in well-differentiated tumors, P=0.046), while no significant associations were found with age, gender, or invasion depth (P>0.05).

Conclusion

CLDN18.2 demonstrates specific expression patterns in early gastric cancer, showing particularly strong association with poorly differentiated subtypes, suggesting its potential as an early diagnostic biomarker.

References

[1] Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin[J]. 2021;71(3):209-249. doi:10.3322/caac.21660
[2] Wagner AD, Syn NL, Moehler M, et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev[J]. 2017;8(8):CD004064.doi:10.1002/14651858.
[3] Jiao X, Wang Y, Wang F, Wang X. Recurrence pattern and its predictors for advanced gastric cancer after total gastrectomy. Medicine (Baltimore)[J]. 2020;99(51):e23795. doi:10.1097/MD.0000000000023795
[4] Xu B, Liu F, Liu Q, et al. Highly expressed Claudin18.2 as a potential therapeutic target in advanced gastric signet-ring cell carcinoma (SRCC). J Gastrointest Oncol[J]. 2020;11(6):1431-1439. doi:10.21037/jgo-20-344
[5] Rohde C, Yamaguchi R, Mukhina S, Sahin U, Itoh K, Türeci Ö. Comparison of Claudin 18.2 expression in primary tumors and lymph node metastases in Japanese patients with gastric adenocarcinoma. Jpn J Clin Oncol[J]. 2019;49(9):870-876. doi:10.1093/jjco/hyz068

Disclosure

All authors declare no potential conflicts of interest relevant to this study

Introduction

Background: Worldwide, gastric cancer (GC) is the fourth cause of death for neoplastic pathology and the fifth for incidence (1). To reduce GC mortality, a strategy is to timely diagnose preneoplastic lesions, especially in patients with significant risk factors. Since in 1^st degree relatives was found an up to 2.5 times increased risk for GC (2), recent guidelines suggest an esophagogastroduodenoscopy (EGDS) screening in patients who have a 1^st degree relative for GC (3). However, if the EGDS shows the absence of atrophy or intestinal metaplasia, no further EGDS is currently recommended. Otherwise, if precancerous conditions are diagnosed, European guidelines, MAPS II, suggest repeating EGDS shortening the interval (4).

Aims & Methods

The purpose of this cross-sectional study was to determine the endoscopic and histological findings and the prevalence of preneoplastic and neoplastic conditions in patients undergoing EGDS for 1^st degree relative for GC.
In this cross-sectional study, patients who underwent an EGDS with biopsies according to the updated Sydney system protocol, due to 1^st degree GC relative indication from January 2008 to September 2022, were included. The preneoplastic conditions were staged with OLGA and OLGIM systems. Exclusion criteria were patients with previous gastric surgery and patients with an incomplete biopsy sampling.

Results

Overall, 330 patients were considered [64% F; 56 (20-87) years]. Twenty patients were excluded from the study due to an incomplete biopsy sampling, thus 310 patients were finally included. The mere indication of 1^stdegree relative for GC was found in 55.7% of patients, whilst 18% also had anemia, 32% gastrointestinal symptoms, 11% performed EGDS for Hp eradication control, 1% for previous gastric dysplasia and 8% for other conditions. Histological examination identified 2 (0.6%) intestinal type gastric cancers and 2 (0.6%) low-grade dysplasia (none of these patients had previous dysplasia). Regarding precancerous conditions, 11 % were OLGA I-II, 0.3% OLGA III-IV whilst 10% were OLGIM I-II and 0.3% were OLGIM III-IV. Hp infection was found in 25.5% of patients. Furthermore, in 2.25% of cases, corpus-restricted atrophic gastritis was diagnosed.

Conclusion

Our study support the role of EGDS with biopsies in patients with 1^st degree relative for GC as 2 neoplastic lesions and 2 low-grade dysplasia were found in patients with low stages of OLGA/OLGIM, and 10% of patients would have required follow-up according to European guidelines.

References

1. Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 71(3), 209-249.
2. Yaghoobi, M., McNabb-Baltar, J., Bijarchi, R., & Hunt, R. H. (2017). What is the quantitative risk of gastric cancer in the first-degree relatives of patients? A meta-analysis. World journal of gastroenterology, 23(13), 2435.
3. Banks, M., Graham, D., Jansen, M., Gotoda, T., Coda, S., Di Pietro, M., ... & Dinis-Ribeiro, M. (2019). British Society of Gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma. Gut, 68(9), 1545-1575.
4. Pimentel-Nunes, P., Libânio, D., Marcos-Pinto, R., Areia, M., Leja, M., Esposito, G., ... & Dinis-Ribeiro, M. (2019). Management of epithelial precancerous conditions and lesions in the stomach (maps II): European Society of gastrointestinal endoscopy (ESGE), European Helicobacter and microbiota Study Group (EHMSG), European Society of pathology (ESP), and Sociedade Portuguesa de Endoscopia Digestiva (SPED) guideline update 2019. Endoscopy, 51(04), 365-388.

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.