Helicobacter pylori cagA status and gastric mucosa-associated lymphoid tissue lymphoma: a systematic review and meta-analysis

Background Recent studies have investigated the role of Helicobacter pylori infection in the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. It is estimated that approximately 0.1% of people infected with H. pylori develop gastric MALT lymphoma. However, the role of the CagA antigen, the highest causative agent of H. pylori, in increasing the risk of gastric MALT lymphoma remains unclear and controversial. A systematic review and meta-analysis were conducted to evaluate the effect of cagA status on the development of gastric MALT lymphoma. Methods All articles evaluating the status of the cagA gene in the development of gastric MALT lymphoma were collected using systematic searches in online databases, including PubMed, Scopus, Embase, and Google Scholar, regardless of publication date. The association between cagA and gastric MALT lymphoma was assessed using the odds ratio (OR) summary. In addition, a random-effects model was used in cases with significant heterogeneity. Results A total of 10 studies met our inclusion criteria, among which 1860 patients participated. No association between cagA status and the development of MALT lymphoma (extranodal marginal zone B-cell lymphoma) was found in this study (OR 1.30; 0.906–1.866 with 95% CIs; I2: 45.83; Q-value: 12.92). Surprisingly, a meaningful association was observed between cagA status and diffuse large B-cell lymphoma (OR 6.43; 2.45–16.84 with 95% CIs). We also observed an inverse association between vacA and gastric MALT lymphoma risk (OR 0.92; 0.57–1.50 with 95% CIs). Conclusions It seems that the infection with cagA-positive H. pylori strains does not have a meaningful effect on the gastric MALT lymphoma formation, while translocated CagA antigen into the B cells plays a crucial role in the development of diffuse large B-cell lymphoma.

Gastric MALT-Lymphoma: more than Helicobacter Pylori

In this case report, we describe two cases of gastric mucosa- associated lymphoid tissue (MALT) lymphoma. The first patient, who presented with complaints of indigestion, nausea and epigastralgy, had a solid ulcer on endoscopy. Biopsies showed, next to MALT, presence of Helicobacter Pylori. The second patient was admitted with hematemesis. The multiple ulcerations in his stomach were thought to be cocaine-induced. Only after multiple biopsies the diagnosis of MALT was made. No presence of Helicobacter Pylori could be detected. The first patient was successfully treated with Helicobacter Pylori eradication therapy. Localized radiotherapy resulted in complete remission in our second patient. Hence, in absence of Helicobacter Pylori, more aggressive treatment modalities are needed.

Long-Term Clinical Outcomes of Gastric MALT Lymphoma: A Nationwide Multicenter Study in Korea

BackgroundTreatment recommendations for gastric mucosa-associated lymphoid tissue (MALT) lymphoma are based on case series and expert opinions. Only a few previous studies have focused on the long-term outcomes of gastric MALT lymphoma, especially according to stage.MethodsPatients diagnosed with gastric MALT lymphoma from January 2000 to December 2018 at nine university hospitals in Korea were included. Clinical data of medical history, endoscopic features, histological diagnosis, results of Helicobacter pylori (H. pylori) testing, stage, treatment conditions, and outcomes were collected.ResultsA total of 1,163 patients was enrolled, and 97.6% (n=1,038) of patients were diagnosed as stage IE. 10-year overall survival (OS) for the entire population was 99.1% and was better for patients in stage IE compared with patients in stage III/IV (p=0.002). The 10-year OS for H. pylori-positive patients was better than that of H. pylori-negative patients (p=0.022). Multivariate analyses revealed initial stage III/IV as a prognostic factor associated with over-all survival.ConclusionThe majority of gastric MALT lymphoma patients are diagnosed at an early localized stage in Korea. The overall survival rate of gastric MALT lymphoma is excellent and is associated with the initial stage of the disease.

Helicobacter Pylori Caga Status and Gastric Mucosa-Associated Lymphoid Tissue Lymphoma: A Systematic Review and Meta-Analysis

Background Recent studies have investigated the role of Helicobacter pylori infection in the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. It is estimated that approximately 0.1% of people infected with H. pylori develop gastric MALT lymphoma. However, the role of the CagA antigen, the highest causative agent of H. pylori, in increasing the risk of gastric MALT lymphoma remains unclear and controversial. A systematic review and meta-analysis were conducted to evaluate the effect of cagA status on the development of gastric MALT lymphoma. Methods All articles evaluating the status of the cagA gene in the development of gastric MALT lymphoma were collected using systematic searches in online databases, including PubMed, Scopus, Embase, and Google Scholar, regardless of publication date. The association between cagA and gastric MALT lymphoma was assessed using the odds ratio (OR) summary. In addition, a random-effects model was used in cases with significant heterogeneity. Results A total of 10 studies met our inclusion criteria, among which 1,860 patients participated. No association between cagA status and the development of MALT lymphoma (extranodal marginal zone B-cell lymphoma) was found in this study (OR: 1.30; 0.906–1.866 with 95% CIs; I2: 45.83; Q-Value: 12.92). Surprisingly, a meaningful association was observed between cagA status and diffuse large B-cell lymphoma (OR: 6.43; 2.45–16.84 with 95% CIs). We also observed an inverse association between vacA and gastric MALT lymphoma risk (OR: 0.92; 0.57–1.50 with 95% CIs). Conclusions It seems that the infection with cagA-positive H. pylori strains does not have a meaningful effect on the gastric MALT lymphoma formation, while translocated CagA antigen into the B cells plays a crucial role in the development of diffuse large B-cell lymphoma.

CXCR4 PET/MRI for follow-up of gastric mucosa-associated lymphoid tissue lymphoma after first-line H. pylori eradication

Post-treatment evaluation of gastric mucosa-associated lymphoid tissue (MALT) lymphoma currently relies on esophagogastroduodenoscopy with histological assessment of biopsies. Overexpression of the G-protein-coupled C-X-C chemokine receptor type 4 (CXCR4) has been previously observed in MALT lymphoma. The aim of this prospective study was to evaluate PET with the novel CXCR4 tracer [68Ga]Pentixafor as a potential alternative to follow-up biopsies for assessment of residual disease (non-complete remission (CR)) after first-line H. pylori (HP) eradication. Forty-six post-HP eradication [68Ga]Pentixafor-PET/MRI examinations of 26 gastric MALT lymphoma patients, and 20 [68Ga]Pentixafor-PET/MRI examinations of 20 control group patients without lymphoma, were analyzed. In the MALT lymphoma group, time-matched gastric biopsies were used as reference standard, and showed CR in six cases. Pooled examination-based accuracy, sensitivity, specificity, and positive and negative predictive value of [68Ga]Pentixafor-PET for detection of residual gastric MALT lymphoma at follow-up, were 97.0%, 95.0%, 100.0%, 100.0%, and 92.9%, respectively. Maximum and mean PET standardized uptake values showed moderate correlation with immunohistochemistry-based CXCR4+ cell counts, with correlation coefficients of r=0.51 and r=0.52 (P=0.008 and P=0.006). In conclusion, CXCR4 imaging with [68Ga]Pentixafor-PET may represent a promising test for assessment of residual gastric MALT lymphomas after HP eradication.

Successful Endoscopic Resection of Primary Rectal Mucosa-Associated Lymphoid Tissue Lymphoma by Endoscopic Submucosal Dissection: A Case Report

Mucosa-associated lymphoid tissue (MALT) lymphoma arises in extra-nodal sites from the malignant transformation of B lymphocytes that are mainly triggered by infection or autoimmune process. MALT lymphoma is frequently detected in the gastrointestinal tract. As the causal relationship between Helicobacter pylori (H. pylori) infection and gastric MALT lymphoma, it was well-established that early-stage gastric MALT lymphoma could be cured by H. pylori eradication, and about 50–95% of cases achieved complete response with anti-H. pylori treatment. Compared to the stomach which is the most involved site due to the high prevalence of H. pylori infection, the colorectum is rarely affected. Primary rectal MALT lymphoma is a rare malignancy, and there are no specific therapeutic strategies so far. Here we report a case of rectal MALT lymphoma successfully resected by endoscopic submucosal dissection (ESD). ESD serves as a novel strategy to cure small localized rectal MALT lymphomas to avoid unnecessary surgery or chemo-radiotherapy.

The Helicobacter pylori CagY Protein Drives Gastric Th1 and Th17 Inflammation and B Cell Proliferation in Gastric MALT Lymphoma

Background: the neoplastic B cells of the Helicobacter pylori-related low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma proliferate in response to H. pylori, however, the nature of the H. pylori antigen responsible for proliferation is still unknown. The purpose of the study was to dissect whether CagY might be the H. pylori antigen able to drive B cell proliferation. Methods: the B cells and the clonal progeny of T cells from the gastric mucosa of five patients with MALT lymphoma were compared with those of T cell clones obtained from five H. pylori–infected patients with chronic gastritis. The T cell clones were assessed for their specificity to H. pylori CagY, cytokine profile and helper function for B cell proliferation. Results: 22 of 158 CD4+ (13.9%) gastric clones from MALT lymphoma and three of 179 CD4+ (1.7%) clones from chronic gastritis recognized CagY. CagY predominantly drives Interferon-gamma (IFN-γ) and Interleukin-17 (IL-17) secretion by gastric CD4+ T cells from H. pylori-infected patients with low-grade gastric MALT lymphoma. All MALT lymphoma-derived clones dose dependently increased their B cell help, whereas clones from chronic gastritis lost helper activity at T-to-B-cell ratios greater than 1. Conclusion: the results obtained indicate that CagY drives both B cell proliferation and T cell activation in gastric MALT lymphomas.