Gastric Mucosa-associated Lymphoid Tissue Lymphoma Research Articles

Dlaczego nie należy przerywać terapii inhibitorami pompy protonowej i antybiotykami stosowanymi w eradykacji Helicobacter pylori w czasie pandemii COVID-19?

Helicobacter pylori infection is one of the most widespread infectious diseases in the world, but its prevalence varies depending on geographical region and economic and social condition. The percent of infected adult persons in Poland is 67, among younger population under 18 years being as high as about 32%. This infection in some number of the concerned persons can be associated with chronic gastritis, peptic gastric and duodenal ulcers, gastric mucosa-associated lymphoid tissue lymphoma (MALT) and gastric cancer. Extra-gastric manifestation of H. pylori infection are iron deficiency anemia, idiopathic thrombocytopenic purpura and significant B12 deficiency. According to the Maastricht V/Florence Consensus Report considering H. pylori infection a contagious disease that requires treatment in each case, indications for diagnostic evaluation to detect its presence are established, and then to its eradication. The treatment of H. pylori infection is complex and based on the combination of the following groups of medicines: proton pump inhibitors (PPI), antibiotics and anti-microbial nitroimidazoles and bismuth salts and probiotics. Currently, the main challenge in the field of H. pylori infection is antibiotic resistance, which influences the efficacy of eradication regiments. According to Maastricht V/Florence Consensus, in Poland where H. pylori resistance to clarithromycin is more than 15%, quadruple therapy with bismuth, PPI, tetracycline and metronidazole/tinidazole for 10–14 days should be used as first-line treatment. Triple therapy with fluoroquinolone is recommended as second-line treatment. After two unsuccessful attempts to eradicate, bacterial cultures should be should be performed to asses antibiotic sensitivity of the H. pylori strain. There are no reasons in front of pandaemia of COVID-19 to delay eradication of H. pylori infection, when the urgent indications: peptic ulcer complicated with haemorrhage, MALT lymphoma or early gastric cancer exists.

New Study: Helicobacter Species as a Potential Zoonotic Infectious Carcinogen : A Review

In 1983 two Australian doctors discovered a spiral bacterium in the human stomach which was called Campylobacter pylori (or pyloridis) to be re-named (Helicobacter pylori) in 1990. Carried by half the global population it was first believed exclusive to Human causing chronic gastritis, peptic and duodenal ulcer, gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. This discovery revolutionized peptic ulcer treatment with antibiotics instead of surgery. H.pylori is the only bacterial agent classified as Class 1 carcinogen. In 1997 genetic advances allowed genome sequencing and detailed research particularly on genomic pathogenesis. Genome printing methods revealed that H.pylori was transmitted from domesticated animals to pre-stone-age man probably of African ancestry. New non-pylori Helicobacter species were found in farm, small, wild, and non-human primate animals. Some cause chronic gastritis and vomiting, occasionally lymphocytic gastric tissue proliferation and cancer. Some animal and avian species are contagious to human, sometimes sharing genomic similarities with H.pylori. There are currently about 35 Helicobacter species. In pathogenic strains, certain genes function as virulence factors making proteins responsible for chronic inflammatory reactions and carcinogenesis in variable degrees. This is called (genomic polymorphism), it create diverse species and strains with variable degrees of pathogenicity. Genomic heterogeneity is the result of Helicobacter adaptation in various environmental, geographic, and host circumstances. Helicobacter strains with diverse virulence may exist in different ethnic and geographic groups. Both H.pylori in human and non-pylori species in animal may co-exist mixed in one host. Sheep is believed the reservoir for H.pylori and H.canis.

Association between Helicobacter suis infection and the pathogenesis of gastric mucosa-associated lymphoid tissue lymphoma

This research was partially supported by the PUH Research Grant Program (Advanced Research A).

Clinical efficacy of the modified Helicobacter pylori eradication therapy for Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma: a meta analysis.

BackgroundHelicobacter pylori (HP) has been considered to be one of the primary causes of gastric mucosa-associated lymphoid tissue (MALT) lymphoma since 1993. Low-grade gastric MALT lymphoma with HP is widely treated with HP eradication therapy, according to each specific clinical situation. However, several studies and guidelines indicate that the modified HP eradication therapy is also valid for HP-negative gastric MALT lymphoma. The aim of this study was to perform a meta-analysis of the clinical efficacy of the modified HP eradication therapy for gastric MALT lymphoma without HP.MethodsWe searched studies that reported the response rate of the modified HP eradication therapy regimen for gastric MALT lymphoma without HP by using PubMed, Medline, and Ebsco from January 1971 until February 2019. All statistical analyses were carried out using R 3.5.3 (Mathsoft Company, Cambridge, MA, USA). The pooled response rate was expressed as a decimal. The heterogeneity test was performed using the I-squared (I2) statistic.ResultsA total of 14 studies were selected with a total of 148 patients with HP-negative gastric MALT lymphoma. The overall pooled response rate was 0.38 (95% confidence interval [CI]: 0.29–0.47). The combined estimate is I2 = 57% (P < 0.01). The study subjects were categorized by factors (area of patients). The pooled response rate of the sub-groups (Korea, Japan, China, and Western countries) was 0.63 (95% CI: 0.50–0.76), 0.16 (95% CI: 0.05–0.30), 0.38 (95% CI: 0.20–0.55), and 0.57 (95% CI: 0.08–1.00). The response rate showed that the modified HP eradication therapy was effective for patients with HP-negative gastric MALT lymphoma, especially in Korea and Western countries.ConclusionTherefore, the modified HP eradication therapy can be considered an optional therapy for patients with low-grade HP-negative gastric MALT lymphoma. However, several limitations were revealed in the meta-analysis. Further systematic reviews and research are required.

Helicobacter suis Infection in Mouse Induced not Only Gastric, but Hepatic and Pulmonary MALT Lymphoma: Relation to Substance P.

The hepatic and pulmonary MALT lymphoma (mucosa-associated lymphoid tissue lymphoma) is clinically occasionally observed but its pathogenesis is unknown and thought to be important to establish the treatment strategy. The present study was designed to clarify the characteristics of these lymphomas and the effect of the Helicobacter eradication regimen and substance P antagonist. After the long term infection of Helicobacter suis to the C57BL/6 mice stomach, the whole organ was surveyed pathologically. Histochemical characteristics of the lesion and the localization of bacteria were observed. In addition, the effect of the administration of antibiotics and a proton pump inhibitor or the substance P antagonist was investigated. We have detected the hepatic and pulmonary MALT lymphoma after the long term infection. In situ hybridization study revealed the positive reaction of Helicobacter suis in the hepatic and pulmonary MALT lymphoma. After the administration of antibiotics and a proton pump inhibitor, the bacterial number has significantly decreased and the tumor size in the fundus, liver and lung markedly reduced. Substance P immunoreactivity was clearly shown in the lymphoma cells in the liver and lung, and the spantide II administration induced the marked decrease in the size of tumors. By our experiments using the long term infection of Helicobacter suis to the C57BL/6 mice, we have detected the liver and pulmonary MALT lymphoma. In situ hybridization study suggested the direct interaction of this bacterium to the etiology of these lesions. Substance P within the lymphoma cells was suggested to work on the maintenance of the extragastric MALT lymphoma.

フランスにおける胃MALTリンパ腫の住民ベース研究：臨床像，治療および生存率

フランスにおける胃MALTリンパ腫の住民ベース研究：臨床像，治療および生存率

Duodenal Mucosa-associated Lymphoid Tissue Lymphoma Treated with Chemotherapy

Mucosa-associated lymphoid tissue (MALT) lymphomas most commonly occur in the stomach and rarely in the duodenum. Gastric MALT lymphoma is usually associated with &lt;i&gt;Helicobacter pylori&lt;/i&gt; (&lt;i&gt;H. pylori&lt;/i&gt;) infection that may be cured by eradication. However, duodenal MALT lymphoma is not associated with &lt;i&gt;H. pylori&lt;/i&gt; infection. Moreover, the pathophysiology and treatment methods for duodenal MALT lymphoma have not yet been established because the disease is rare. Here, we report a case of duodenal MALT lymphoma. A 58-year-old man was treated for a refractory duodenal ulcer. Based on repeated biopsy, a diagnosis of MALT lymphoma was made. The patient achieved complete remission after chemotherapy and was followed up without recurrence for three years.

Helicobacter pylori and Hematologic Diseases

&lt;i&gt;Helicobacter pylori&lt;/i&gt; (&lt;i&gt;H. pylori&lt;/i&gt;) is a Gram-negative spiral bacterium, classified as a group 1 carcinogen by the World Health Organization. &lt;i&gt;H. pylori&lt;/i&gt; infection is a major cause of gastritis, gastric and duodenal ulcers, and gastric cancer. It is associated with the pathogenesis of several hematologic diseases. &lt;i&gt;H. pylori&lt;/i&gt; eradication has been proven effective in gastric mucosa-associated lymphoid tissue lymphoma and primary immune thrombocytopenia. As &lt;i&gt;H. pylori&lt;/i&gt; causes iron deficiency anemia via several mechanisms, some recent guidelines recommended its eradication from patients with iron deficiency anemia. There are discussions of other conditions that are not included in the international consensus and management guides on &lt;i&gt;H. pylori&lt;/i&gt;, including monoclonal gammopathy, myelodysplastic syndrome, childhood leukemia, coagulation disorder, megaloblastic anemia, pernicious anemia, plasma cell dyscrasia, and Henoch-Schönlein purpura. Further studies are required to establish new strategies to improve the management of patients with an infection combined with a hematologic disease of controversial or peculiar association.

Transcriptome hallmarks in Helicobacter pylori infection influence gastric cancer and MALT lymphoma.

Aim: Altered long noncoding RNA (lncRNA) and mRNA is vital in the progression from Helicobacter pylori (H. pylori, HP) infection to gastric cancer (GC) and mucosa-associated lymphoid tissue (MALT)lymphoma. Materials & methods: Five independent Gene Expression Omnibus datasets (GSE5081, GSE84433, GSE15459, GSE66229 and GSE25638) were included in our study. Results: Differentially expressed lncRNAs and mRNAs in both H. pylori-positive gastritis and GC tissues were identified. Using two GC cohorts, the H. pylori-related mRNA DYNC1I1 and MMP7 were independent predictors of overall survival. Moreover, the expressions of lncRNA GHRLOS and 44 mRNAs were significantly changed in gastric MALT lymphoma patients. Conclusion: The lncRNA/mRNA response to H. pylori infection in gastritis and GC influence the outcome of GC and progression of MALT lymphoma.

Depth of Remission Following First-Line Treatment Is an Independent Prognostic Marker for Progression-Free Survival in Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma.

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma responding to upfront treatment has an excellent outcome and no further therapy is recommended, even in the presence of residual disease. However, no data exist on the influence of initial depth of remission on progression-free survival (PFS). Methods: We investigated a correlation between PFS and depth of response, categorizing them as complete remission (CR), partial remission (PR) and stable disease (SD) in 137 consecutive patients at the Medical University Vienna. Results: All patients with Helicobacter pylori (H. pylori)-positive, localized disease received H. pylori eradication (70%, 96/137), while the remaining patients were treated with various modalities. The response rate was 67% for the entire collective and 58% for eradication only, with corresponding CR-rates of 48% and 38%. At a median follow-up of 56.2 months, the estimated PFS for the entire cohort was 34.2 months (95% Confidence Interval 16.0–52.4). Responding patients (=CR/PR) had a significantly longer PFS compared to SD (68.3 vs. 17.3 months, p < 0.001). This was also applicable to the eradication only cohort (49.0 vs. 17.3 months, p < 0.001) and remained significant after correction for MALT-IPI. Furthermore, CR significantly prolonged PFS over PR (p = 0.007 entire cohort, p = 0.020 eradication). Conclusions: Remission status correlated significantly with PFS, suggesting depth of remission as prognostic marker for long-term relapse-free survival.

Nhân một trường hợp bệnh Malt lymphoma dạ dày

CASE STUDY: GASTRIC MUCOSA-ASSOCIATED LYMPHOID TISSUE (MALT) LYMPHOMA Extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (EMZL-MALT) have been linked to chronic immune stimulation due toinfection or autoimmune stimuli.The causal association between Helicobacter pylori(HP) and gastric MALT lymphoma has been well demonstrated. HPeradication with antibiotics has emerged as the standard therapy for early stage HPpositive gastric MALT lymphoma.High response rates and long-term survival have been reported inpatients with localized gastric MALT lymphomatreated with low-doseradiationtherapy.Monoclonal antibody and chemotherapy are reserved forpatients failing or recurring after RT and those with advanced stage disease. Key words: mucosa-associated lymphoid tissue, gastric lymphoma

Mucosal dysbiosis in patients with gastrointestinal follicular lymphoma.

Because the pathogenesis of gastrointestinal follicular lymphoma (GI-FL) remains unclear, no standardized treatment strategy has been established. Of the gastrointestinal lymphomas, gastric mucosa-associated lymphoid tissue lymphomas are strongly associated with Helicobacter pylori; hence, the microbiota may be involved in GI-FL pathogenesis. However, the association between GI-FL and the microbiota remains uninvestigated. Therefore, we compared the mucosal microbiotas of GI-FL patients with those of controls to identify microbiota changes in GI-FL patients. Mucosal biopsy samples were obtained from the second portion of the duodenum from 20 GI-FL patients with duodenal lesions and 20 controls. Subsequent 16S rRNA gene sequencing was performed on these samples. QIIME pipeline and LEfSe software were used to analyze the microbiota. The GI-FL patients had significantly lower alpha diversity (P = .049) than did the controls, with significant differences in the microbial composition (P = .023) evaluated by the beta diversity metrics between the two groups. Comparing the taxonomic compositions indicated that the genera Sporomusa, Rothia, and Prevotella and the family Gemellaceae were significantly less abundant in the GI-FL patients than in the controls. GI-FL patients presented altered duodenal mucosal microbial compositions, suggesting that the microbiota might be involved in the GI-FL pathogenesis.

Low-grade gastric mucosa-associated lymphoid tissue lymphoma: Clinicopathological factors associated with Helicobacter pylori eradication and tumor regression.

353 Background: Eradication of Helicobacter pylori is widely accepted as the initial therapy for low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The aim of this study was to assess the remission and relapse rates of low-grade gastric MALT lymphoma after H. pylori eradication and to identify the clinical factors affecting remission. Methods: We retrospectively analyzed 151 patients diagnosed with gastric MALT lymphoma from May 2003 to December 2018. Results: Of the 151 patients, 112 (74.2%) had an H. pylori infection. Total regression rates with eradication was 90.2% (101/112) in H. pylori-positive patients and 55% (11/20) in H. pylori-negative patients. Age, sex, tumor location, endoscopic findings, and the severity of mononuclear lymphocytes were not related to achieving successful initial H. pylori eradication and remission. However, patients with a smaller H. pylori burden ( p=0.030) and less neutrophil infiltration ( p=0.003) were more likely to achieve a successful initial H. pylori eradication. H. pylori ( p&lt;0.001) and the burden ( p=0.020) were significantly related to remission of MALT lymphoma. Conclusions: The results show that H. pylori burden and neutrophil infiltration were inversely related to the success of the initial H. pylori eradication procedure and that the H. pylori burden was inversely related to the remission of MALT lymphoma.

Tratamiento inicial y del fracaso en la erradicación de la infección por Helicobacter pylori

Helicobacter pylori is, probably, the most common bacterial infection in the world with a worldwide prevalence rate of 40-50%. In most cases is asymptomatic, but in some cases is associated with peptic ulcer, gastric adenocarcinoma, gastric MALT lymphoma, or dyspepsia. Effective H. pylori eradication therapy allows the complete healing of peptic ulcer, and the elimination of a key cofactor in the appearance of gastric adenocarcinoma and lymphoma. The following protocol includes currently accepted diagnosis methodology, treatment indications and the appropriate therapeutic regimens for the eradication of bacteria as related as acknowledged in recent guidelines

Myeloid-Derived Suppressor Cells and γδT17 Cells Contribute to the Development of Gastric MALT Lymphoma in H. felis-Infected Mice.

Helicobacter-induced chronic inflammation and immune disorders are closely associated with the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Myeloid-derived suppressor cells (MDSCs) exhibit strong immunosuppressive properties and promote the growth of various solid tumors. However, the role of MDSCs in the development of MALT lymphoma has not been elucidated so far. We detected significant infiltration and enrichment of MDSCs in patients with MALT lymphoma, as well in Helicobacter felis-infected mouse model of gastric MALT lymphoma. In addition, the expression of arginase-1 and inducible nitric oxide synthase was significantly elevated both in gastric MALT lymphoma tissues and H. felis-infected stomach. Persistent H. felis infection closely reproduced the development of gastric MALT lymphoma and was accompanied by increased numbers of γδT17 cells. Accumulation of γδT17 cells was also validated in the human gastric MALT lymphoma tissues. Furthermore, the elevated cytokines interleukin-23 and interleukin-1β, as well as chemokines CCL20/CCR6, may be involved in the accumulation of γδT17 cells and the subsequent immunosuppression. These findings highlight the role of MDSCs and γδT17 cells in immune dysregulation during gastric MALT lymphoma development and their potential as therapeutic targets.

Influence of N-acylhomoserine lactonase silver nanoparticles on the quorum sensing system of Helicobacter pylori: A potential strategy to combat biofilm formation.

The treatment of Helicobacter pylori usually fails due to their ability to form biofilms and resistance to antibiotics. This might potentially lead to gastric carcinoma and mucosa-associated lymphoid tissue lymphoma. In the present study, we elucidate the potential role of N-acylhomoserine lactonase stabilized silver nanoparticles (AiiA-AgNPs) in treating biofilms produced by H. pylori. AiiA-AgNPs inhibited quorum sensing (QS) by degradation of QS molecules, thereby reducing biofilm formation, urease production, and altering cell surface hydrophobicity of H. pylori. AiiA-AgNPs showed no cytotoxic effects on RAW 264.7 macrophages at the effective concentration (1-5 µM) of antibiofilm activity. In addition, AiiA-AgNP in high concentration (80-100 µM) exhibited cytotoxicity against HCT-15 carcinoma cells, depicting its therapeutic role in treating cancer.

Clinicopathologic analysis of gastric mucosa-associated lymphoid tissue lymphoma with or without c-Met expression.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach is mainly associated with Helicobacter pylori infection, and H. pylori eradication therapy is often effective. However, 20-30% of the cases of MALT lymphoma are resistant to the eradication therapy, and translocation of the API2-MALT1 gene is often found in these cases. Most cases without translocation of API2-MALT1 are localized to the stomach, whereas some cases with this translocation are a more advanced stage of MALT lymphoma that spreads to other organs. The c-Met receptor is a prognostic factor involved in infiltration and metastasis in many malignant tumors, including gastric, pancreatic, lung, and kidney cancer. In the present study, the expression of c-Met in 43 cases of gastric MALT lymphomas was immunohistochemically examined and compared with clinicopathological factors. To elucidate the significance of c-Met in MALT lymphoma, the expression intensity of c-Met in 22 API2-MALT1 translocation-positive and 21 API2-MALT1 translocation-negative cases was scored, compared, and examined. The immunohistochemistry analysis revealed strong staining for c-Met in 21 API2-MALT1 translocation-positive cases and in 1 translocation-negative case (P = 0.00). This result indicates the relationship between strong expression of c-Met and the progression of MALT lymphoma with API2-MALT1 gene translocation.

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma: clinicopathological study and treatment outcome in 50 patients.

The stomach is the most frequent site of extranodal lymphoma. Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade, B-cell neoplasm strongly associated with Helicobacter pylori (HP) infection. The presenting complaints of gastric MALT lymphoma are usually nonspecific. HP eradication is regarded as the first-line therapy in early stage disease. Management of patients who failed to achieve remission following HP eradication include chemotherapy, radiotherapy and in selected cases, surgery. The aim of the present study was to examine the clinical characteristics and treatment outcome of patients with gastric MALT lymphoma.

Genomic Diversity, Virulence, and Antimicrobial Resistance of &lt;i&gt;Helicobacter suis&lt;/i&gt; Isolated from Human Stomachs

Background: Helicobacter suis, a bacterial species naturally hosted by pigs, can colonize the human stomach in the context of gastric diseases, such as gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Because H. suis has been successfully isolated from pigs, but not from humans, evidence linking human H. suis infection to gastric diseases has remained incomplete. The aim of this study is to elucidate the pathogenicity of H. suis by genetic characterization and through animals infected with H. suis isolated from human stomachs. Methods: H. suis from human gastric biopsies was isolated as previously described in pigs, with modifications. Mice were orally infected with H. suis for 4 months, and then pathogenesis was analyzed. Whole-genome analysis of H. suis isolates was performed by short-read and long-read sequencing, and their genomes were subjected to comparative analysis. Findings: H. suis was successfully isolated from three patients with gastric diseases, including gastric MALT lymphoma. Successful eradication of H. suis yielded significant improvements in endoscopic and histopathological findings in all patients. H. suis infection in mice using clinical isolates elicited gastric and systemic inflammatory responses, and H. suis could be isolated from the stomachs of infected mice. Therefore, according to Koch’s postulates, these findings demonstrate that H. suis is a human gastric pathogen. Genomic analysis revealed high similarity between isolates from humans and pigs, suggesting possible horizonal transmission of H. suis. Interpretation: This is the first study to directly demonstrate virulence-associated features of H. suis infection using isolates obtained from human stomachs. Since H. suis would have been missed by routine diagnostic tests for Helicobacter pylori, large-scale epidemiological research on H. suis is needed to identify causal relationships with gastric diseases and develop novel diagnostic methods. Funding: MEXT/JSPS KAKENHI Grant numbers JP19H03474 for (HM) and JP20K08365 for (KT), and AMED Grant Numbers JP20fk0108148 (ER) and JP20fk0108133 (MS). Conflict of Interest: ER has received research funding from GlaxoSmithKline, outside the submitted work. All other authors declare no competing interests. Ethical Approval: Ethical approvals were obtained from all participating hospitals and the National Institute of Infectious Diseases (NIID). Written informed consent was obtained from all participants.

Evaluation of the Genes Expression Related to the Immune System in Response to Helicobacter pylori Catalase Epitopes

Helicobacter pylori is the main cause of gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma (MALT) and gastric cancer. H. pylori Infects more than half of the world’s population. Antibiotic treatments are not ideal because of antibiotic side effects, re-infection and increased antibiotic resistance. Vaccination against H. pylori is considered as an alternative with the suitable cost for eradication therapy. Th1 immune response plays an important role in vaccine-induced protection against H. pylori infection. An effective vaccine should be able to change the immune balance in favor of the Th1 immune response. Epitope vaccines are believed to elicit more specific and safe immune responses than other vaccines against Helicobacter pylori infection. Catalase is one of the most important immunogenic antigens of H. pylori. We found that the seven epitopes of H. pylori catalase can produce a significant Th1responses by expressing IFN-γ. A decrease in regulation levels of IL-4 was observed after stimulation with catalase epitopes. These results confirm strong response of Th1 immune to H. pylori compared to Th2 immune responses. Understanding of cellular immunity against H. pylori infection guides us to design of H. pylori appropriate vaccines better.