Introduction

With the declining prevalence of Helicobacter pylori (Hp) infection, cases of Hp-naive gastric cancer, which were once considered rare, are now increasingly observed. Previous reports have indicated that Hp-naive gastric cancer tends to exhibit distinct morphological and histological features depending on its anatomical location within the stomach (1).

Aims & Methods

We analyzed the clinicopathological characteristics of Hp-naive gastric cancer cases diagnosed between April 2005 and March 2025. Hp negativity was defined as no history of eradication therapy, no endoscopic evidence of Hp-associated mucosal changes, negative results in at least two Hp diagnostic tests (including anti-Hp antibody, stool antigen, urea breath test, rapid urease test, histological examination, and bacterial culture), and no histological evidence of infection.
Adenocarcinomas of the cardia and esophagogastric junction (EGJ) corresponding to Siewert type 2 were included. Additionally, EGJ adenocarcinomas with ultra-short Barrett’s mucosa were included due to the difficulty of endoscopic differentiation, particularly in advanced stages. Cases of autoimmune gastritis and hereditary tumor syndromes were excluded.
For early gastric cancers, immunohistochemical staining was performed. Markers for gastric phenotype included MUC5AC (foveolar epithelium), MUC6 (fundic and pyloric glands), and pepsinogen I. Markers for intestinal phenotype included MUC2 (intestinal epithelium) and CD10 (brush border).

Results

A total of 130 cases were analyzed (mean age: 56.0 years; male:female = 88:42). Most cases could be classified into four major subtypes based on tumor location and histological phenotype. These included 30 cases of adenocarcinoma in the cardia, 40 cases of gastric-type adenocarcinoma in the fundic gland zone, 50 cases of signet-ring cell carcinoma in the transition zone between the fundic and pyloric glands, and 6 cases of differentiated mixed-type adenocarcinoma in the pyloric region.
There was a strong correlation between the endoscopic findings, histological types, and the glandular zones of origin. Among the gastric-type adenocarcinomas, 39 were early-stage and were mostly protruded lesions. Of the signet-ring cell carcinomas, 46 presented as flat, pale mucosal lesions. In the pyloric region, five of six mixed-type adenocarcinomas were small, depressed mucosal lesions. Each tumor type exhibited distinct endoscopic characteristics.
Among the 26 advanced cancers, 18 were located in the cardia. These represented the majority of advanced cases. This group included not only middle-aged stout men but also four elderly women with a mean age of 78.3 years, suggesting a possible association with acid reflux.

Conclusion

The endoscopic and histopathological characteristics of Hp-naive gastric tumors appear to be determined by the background mucosa and glandular zone. While most tumors were early-stage, cardia cancers had a notably higher frequency of advanced disease, indicating potentially greater biological aggressiveness.

References

(1) Yoshimura D, et al. Gastroenterology. 152, S260–61, 2017.

Introduction

The first-line treatment for gastric mucosa-associated lymphoid tissue (MALT) lymphoma is Helicobacter pylori (H. pylori) eradication when infection is present. In the absence of infection, treatment options include radiotherapy, chemotherapy, or surgery, depending on disease extent. ¹ However, the management of H. pylori-negative gastric MALT lymphoma remains controversial. Recently, endoscopic submucosal dissection (ESD) has been reported as a potential curative treatment, but data remain limited due to the rarity of such cases.

Aims & Methods

We report our experience with ESD in three consecutive cases of localized H. pylori-negative gastric MALT lymphoma identified among 29,331 esophagogastroduodenoscopies (EGDs) conducted at our large-scale health screening facility during the 2024 health check-up program. We aim to highlight the feasibility of ESD as a less invasive alternative to radiotherapy or chemotherapy and contribute to future treatment strategies.

Results

Three cases (0.01%, 3/29,331) of localized gastric MALT lymphoma were identified: a 71-year-old female, a 43-year-old female, and a 63-year-old male. Lesions were located in the upper body, middle body, and angular region, measuring 15 mm, 20 mm, and 7 mm, respectively. Larger lesions exhibited cobblestone-like mucosal patterns with depressed granular erythematous areas, while the smallest lesion appeared as a simple depressed lesion with discoloration. Biopsies confirmed CD20 and CD79a positivity, CD3 and CD10 negativity, and lymphoepithelial lesions on AE1/AE3 staining, leading to the diagnosis of gastric MALT lymphoma. Contrast-enhanced CT showed no lymph node involvement or distant lesions, classifying all cases as localized stage (Lugano classification). Absence of gastric mucosal atrophy, negative H. pylori IgG serology, negative urea breath test (UBT), and absence of H. pylori on Giemsa staining confirmed an H. pylori-negative status. All three cases underwent ESD, achieving complete en bloc resection with negative margins. No complications, such as delayed bleeding or perforation, were observed following ESD. Histopathological examination revealed clusters of B-cell lymphocytes confined to the mucosa and superficial submucosa. Follow-up EGD with biopsy showed no recurrence in any case.

Conclusion

We performed ESD for three cases of H. pylori-negative localized gastric MALT lymphoma, achieving complete resection with negative margins in all cases without any complications. Additionally, short-term outcomes were favorable. While observation, radiotherapy, and chemotherapy are available treatment options for H. pylori-negative localized gastric MALT lymphoma, cases of tumor progression and transformation into diffuse large B-cell lymphoma (DLBCL) after chemotherapy have been reported. ² Therefore, early resection may provide a safer approach. Our findings suggest that early resection may be a preferable approach for localized lesions. Further accumulation of cases and long-term follow-up are necessary to establish ESD as a viable treatment option.

References

1. Kwang R, Gwang K, Seong P, et al. Treatment Outcome for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma according to Helicobacter pylori Infection Status: A Single-Center Experience. Gut and Liver 2014; 8(4): 408-414.
2. Taiji A, Hideharu M, Tomoaki S, et al. Outcome of treatment and follow-up study for Helicobacter pylori-negative gastric mucosa associated lymphoid tissue (MALT) lymphoma. Jpn J Helicobacter Res 2011; 13: 21-27.

Introduction

Aims & Methods

Results

Conclusion

Introduction

Helicobacter pylori (HP) infection is the most significant environmental factor contributing to gastric carcinogenesis. However, the rising prevalence of antibiotic resistance in HP has become a global concern. Currently, there is limited research on the correlation between HP antibiotic resistance and early gastric cancer (EGC). This study aimed to detect HP resistance genes in EGC patients using qRT-PCR on paraffin-embedded ESD specimens and explore the association between HP resistance and EGC.

Aims & Methods

A total of 150 EGC patients who underwent endoscopic submucosal dissection (ESD) between January 1, 2023, and December 31, 2024, were enrolled. HP resistance genes were detected in post-ESD gastric mucosal paraffin sections. Resistance rates to various antibiotics were compared, and correlations between resistance and clinicopathological features were analyzed.

Results

Among the 150 EGC patients, 28 (18.67%) were HP-positive, with 18 (64.3%, 95% CI: 44.1%–81.4%) showing antibiotic resistance. Levofloxacin had the highest resistance rate (50.0%), followed by clarithromycin (38.9%), tetracycline (11.1%), and amoxicillin (5.6%). No resistance to furazolidone was observed. Multidrug resistance analysis revealed common combinations, including clarithromycin + quinolone (22.2%) and clarithromycin + quinolone + tetracycline (5.6%). No significant correlations were found between resistance and clinicopathological features such as tumor location, size, histologic type, differentiation, depth of invasion, or mucosal status (all *p* > 0.05).

Conclusion

HP antibiotic resistance is prevalent in EGC patients, with high resistance rates to levofloxacin and clarithromycin. However, no significant association was observed between HP resistance and clinicopathological characteristics of EGC. Further studies are needed to elucidate the role of resistant HP strains in gastric carcinogenesis.

References

[1]Yang L, Kartsonaki C, Yao P, de Martel C, Plummer M, Chapman D, Guo Y, Clark S, Walters RG, Chen Y, Pei P, Lv J, Yu C, Jeske R, Waterboer T, Clifford GM, Franceschi S, Peto R, Hill M, Li L, Millwood IY, Chen Z; China Kadoorie Biobank Collaborative Group. The relative and attributable risks of cardia and non-cardia gastric cancer associated with Helicobacter pylori infection in China: a case-cohort study. Lancet Public Health. 2021 Dec;6(12):e888-e896. doi: 10.1016/S2468-2667(21)00164-X.
[2]Lee YC, Chiang TH, Chou CK, Tu YK, Liao WC, Wu MS, Graham DY. Association Between Helicobacter pylori Eradication and Gastric Cancer Incidence: A Systematic Review and Meta-analysis. Gastroenterology. 2016 May;150(5):1113-1124.e5. doi: 10.1053/j.gastro.2016.01.028. Epub 2016 Feb 2.
[3]Dingsdag SA, Hunter N. Metronidazole: an update on metabolism, structure-cytotoxicity and resistance mechanisms. J Antimicrob Chemother. 2018 Feb 1;73(2):265-279. doi: 10.1093/jac/dkx351.
[4]Dingsdag SA, Hunter N. Metronidazole: an update on metabolism, structure-cytotoxicity and resistance mechanisms. J Antimicrob Chemother. 2018 Feb 1;73(2):265-279. doi: 10.1093/jac/dkx351.
[5]Lee SM, Kim N, Kwon YH, Nam RH, Kim JM, Park JY, Lee YS, Lee DH. rdxA, frxA, and efflux pump in metronidazole-resistant Helicobacter pylori: Their relation to clinical outcomes. J Gastroenterol Hepatol. 2018 Mar;33(3):681-688. doi: 10.1111/jgh.13906.

Introduction

The VAC-Stent is a fully covered stent encased in a polyurethane sponge cylinder, offering a promising approach for treating upper gastrointestinal (UGI) tract leaks and defects¹; however, available evidence remains limited and preliminary.

Aims & Methods

This prospective study enrolled all consecutive patients with UGI leaks treated with VACStent placement from May 2023 to September 2024 at San Raffaele Hospital, Milan, Italy. The primary outcome was clinical success (CS). Secondary outcomes included technical success (TS) and adverse events (AEs). CS was defined as defect healing confirmed by endoscopic and radiologic evaluation, while TS was defined as successful stent placement and removal.

Results

Fourteen patients [64.3% male, median age 65 years (IQR 59–75); 11 with anastomotic leaks after Ivor-Lewis esophagectomy and 3 with perforations after circumferential esophageal ESD] were enrolled. VACStent was the first-line treatment in 92.9% of cases, with a median leak size of 6 mm (IQR 5-11), and 28.6% of patients had previously undergone re-surgery. The median time from surgery/endoscopy to initial VACStent placement was 7 days (IQR 3-9). The median treatment duration was 9.5 days (IQR 7-14), with a median hospital stay of 29.5 days (IQR 21-63) and a median of 2 VACStents per patient (IQR 1-2).
CS rate was 69.2% (9/13 patients); among the 4 remaining cases, three required rescue surgery, and one patient died of sepsis. All patients treated for perforations following esophageal ESD achieved complete healing without developing strictures. TS was 96.7% (30/31); one case of technical failure occurred in a patient with an anastomotic leak who had previously received radiotherapy for mediastinal lymphoma. No VACStent-related AEs were observed (Table 1)

Table 1: VACStent outcomes

Conclusion

This prospective series suggests that the VACStent is an effective and safe treatment option for upper GI leaks, including perforations after esophageal ESD. Larger controlled studies are warranted to better define its role and optimize outcomes in this complex setting.

References

1. Dell'Anna G, Fanti L, Fanizza J, et al. VAC-Stent in the Treatment of Post-Esophagectomy Anastomotic Leaks: A New "Kid on the Block" Who Marries the Best of Old Techniques-A Review. J Clin Med. 2024;13(13):3805. Published 2024 Jun 28. doi:10.3390/jcm13133805

Introduction

Endoscopic diagnosis of gastric dysplasia (GD) and early gastric cancer (EGC) remains challenging. Raman spectral analysis is a biomolecular specific vibrational analytical technique which measures inelastic light scattering process within samples. This technique detects disease via biomolecular "fingerprinting", which may be applied to objectively diagnose gastric lesions.

Aims & Methods

We aim to develop a machine learning model based on Raman spectra to diagnose intestinal metaplasia (IM), GD and EGC with biomarker correlations. Raman spectra were prospectively collected prior to endoscopic resection and correlated with histopathology. GD and EGC were classified as high-risk (HR) lesions; while IM and gastritis as low-risk (LR). Two methods were employed to identify significant Raman wavenumber for group differentiation: Partial Least Squares-Discriminant Analysis with Variance Importance in Projection analysis, and a theory-based statistical approach. Next, these features were tested using XGBoost model for best accuracy. A similar approach was applied to differentiate IM versus LGD, and the model was tested with leave-one-out cross-validation (LOOCV) method for the Support Vector Machine (SVM).

Results

20 participants were recruited from April 2022 to July 2023. A total of 1961 Raman spectra were collected from 33 lesions for HR versus LR differentiation. The results are as shown in Table 1. The diagnostic accuracy and F1 score for PLS-DA VIP and theory-based ranking were similar at 75.5% and 0.8318, respectively. XGBoost testing revealed that the model attained peak performance with the top 400 wavenumbers from PLS-DA VIP sorting, and the top 200 wavenumbers from the theory-based ranking. An overlap of 192 wavenumbers emerged, and the model achieved a peak F1 Score of 0.84 and 76.9% accuracy. These 192 wavenumbers were then mapped to the Raman spectrum and can be correlated with 8 Raman peaks of biochemicals related to gastric cancer including lipids, proteins, phospholipids and leucine. For LGD versus IM, we utilized 487 Raman signals from 25 lesions. was an overlap of 100 wavenumbers with accuracy of 74.1%.
The diagnostic accuracy and F1 score for PLS-DA VIP and theory-based ranking were similar at 74.4% and 0.79 respectively. LOOCV with SVM testing revealed that the model attained peak performance with the top 200 wavenumbers from PLS-DA VIP sorting, and the top 100 wavenumbers from the theory-based ranking. An overlap of 100 wavenumbers emerged, and the model achieved a peak F1 Score of 0.80 and 74.7% accuracy.

Table 1 Current AI model (XGBoost for differentiaton high risk and low risk lesions; LOOC method with SVM performance: intestinal metaplasia ) performance with selected wavenumbers for differentiation between gastric lesions.

Conclusion

A Raman spectroscopy-based AI algorithm may be useful for real time diagnosis of GIM, GD and EGC.

Clinical Case Summary

An 81 year-old male, with no relevant medical history, presented to the emergency department with hematemesis, hemodynamic instability and hemoglobin of 4.5 g/dL. Upper gastrointestinal endoscopy (UGE) revealed 30 mm excavated gastric ulcer at the incisura angularis, with a visible vessel (Forrest IIa). Initial attempt using over-the-scope clip (OTSC) failed due to inability to pass the upper esophageal sphincter despite multiple expert attempts. Subsequent therapy with epinephrine and two through-the-scope (TTS) clips achieved initial hemostasis. However, patient experienced three rebleeding episodes in the following days, requiring repeated endoscopic interventions, including thermocoagulation with Bipolar Circum-Active Probe (BICAP). Biopsies of the ulcer margins were negative for dysplasia/malignancy.
During the third episode, combined therapy with epinephrine and 1% polidocanol (4 cc) was administered into the vessel. The following day, due to hematemesis, he repeated UGE that revealed extensive, friable, violet-colored ulceration of the gastric body and antrum, consistent with ischemic injury likely secondary to polidocanol injection. Patient was managed conservatively with proton pump inhibitors and antibiotics for one week.
After eight months of follow-up, he remains clinically stable, without episodes of rebleeding. A reassessment endoscopy showed only a scar retraction.
This case is presented based on the iconography of the adverse effect of polidocanol therapy (exuberant gastric ischemia), highlighting the risk of gastrointestinal necrosis. However, as this is a refractory ulcer with multiple episodes of rebleeding, polidocanol proved to be the most effective therapy. Literature describes similar risks with adrenaline and sclerosant agents. In this case, we suggest that direct arterial injury by the needle, followed by immediate luminal obliteration, led to ischemic damage.

References

Li WF, Gao RY, Xu JW, Yu XQ. Endoscopic treatment of bleeding gastric ulcer causing gastric wall necrosis: A case report. World J Gastrointest Surg 2024; 16(4): 1203-1207
Silva C, Monteiro C, Matos C, Martins A, Midões A. Extensive duodenal ischemia after endoscopic hemostatic therapy. Int J Case Rep Images 2022;13(2):202–204.
J. Molina-Infante, M. Fernandez-Bermejo, G. Vinagre-Rodríguez. Severe gastric ischemia after combined sclerotherapy for bleeding gastric ulcer. Endoscopy 2011; 43: E191.
G. Dorta, P. Michetti, P. Burckhardt, M. Gillet. Acute ischemia followed by hemorrhagic gastric necrosis after injection sclerotherapy for ulcer. Endoscopy 1996; 28.