Gastric Mucosa-associated Lymphoid Tissue Lymphoma Research Articles

An Overview of Selected Bacterial Infections in Cancer, Their Virulence Factors, and Some Aspects of Infection Management.

In cancer development and its clinical course, bacteria can be involved in etiology and secondary infection. Regarding etiology, various epidemiological studies have revealed that Helicobacter pylori can directly impact gastric carcinogenesis. The Helicobacter pylori-associated virulence factor cytotoxin-associated gene A perhaps plays an important role through different mechanisms such as aberrant DNA methylation, activation of nuclear factor kappa B, and modulation of the Wnt/β-catenin signaling pathway. Many other bacteria, including Salmonella and Pseudomonas, can also affect Wnt/β-catenin signaling. Although Helicobacter pylori is involved in both gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma, its role in the latter disease is more complicated. Among other bacterial species, Chlamydia is linked with a diverse range of diseases including cancers of different sites. The cellular organizations of Chlamydia are highly complex. Interestingly, Escherichia coli is believed to be associated with colon cancer development. Microorganisms such as Escherichia coli and Pseudomonas aeruginosa are frequently isolated from secondary infections in cancer patients. In these patients, the common sites of infection are the respiratory, gastrointestinal, and urinary tracts. There is an alarming rise in infections with multidrug-resistant bacteria and the scarcity of suitable antimicrobial agents adversely influences prognosis. Therefore, effective implementation of antimicrobial stewardship strategies is important in cancer patients.

RETRACTED ARTICLE: Clinical features of Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma: based on an injection nanocarbon tracer labeling method

RETRACTED ARTICLE: Clinical features of Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma: based on an injection nanocarbon tracer labeling method

Treatment of Helicobacter Pylori Infections Using Moxifloxacin-Triple Therapy Compared to Standard Triple and Quadruple Therapies

Helicobacter pylori (H. Pylori) is one of the most common infectious human pathogens. H. pylori could induce inflammation, that causes illnesses and disorders of upper gastrointestinal which including peptic ulcer diseases, dyspepsia, gastroesophageal reflux disease and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. It is important to use a better tolerated and greatly effective eradication regimen. In this study, 75 newly diagnosed adult patients with H. pylori infection were included and completed the study, they were allocated into three groups with three different treatment regimens for H. pylori eradications; Group A (25 patients) received oral standard clarithromycin-based triple therapy for 14 days. Group B (25 patients) received oral bismuth based-quadruple therapy for 10 days. Group C (25 patients) received oral moxifloxacin-based triple therapy for 14 days. The results reported in this study indicated a significant higher eradication rate of Group B and Group C (84% and 80%, respectively) of patients with H. pylori infections compared to that of Group A (52%). The incidence of adverse effects were appeared as 72%, 64% and 24% of patients in group A, B and C respectively. The use of moxifloxacin triple regimen for H. pylori eradication, present with eradication efficacy parallel to that of quadruple regimen which were significantly higher compared to that of clarithromycin triple regimen. Also moxifloxacin triple therapy is more tolerable and does not increase the incidence of overall adverse effects compared to other regimens used in this study.

Gastric Mucosa-associated Lymphoid Tissue Lymphoma Mimicking Signet Ring Cell Carcinoma

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is the most common type of extranodal non-Hodgkin lymphoma. Endoscopic findings are nonspecific and variable; therefore, differentiation of this malignancy from early gastric cancer is challenging during endoscopy. Although an endoscopic biopsy is the gold standard for diagnosis, a biopsy may not conclusively establish the diagnosis in all cases. Diagnostic confirmation requires interpretation of the biopsy specimen findings by an experienced histopathologist, and an additional immunoglobulin heavy chain (IgH) rearrangement test may aid with accurate diagnosis. We present a case of gastric MALT lymphoma that histopathologically mimicked signet ring cell carcinoma (SRCC) on evaluation of repeat endoscopic biopsies. Following endoscopic submucosal dissection (ESD), we confirmed the final diagnosis of gastric MALT lymphoma based on histopathological findings of prominent lymphoid infiltrates accompanied by lymphoepithelial lesions and results of the monoclonal IgH rearrangement test. Notably, a few carcinoma-like signet ring cells (SRCs) in the specimen were attributed to a reactive change. Clinicians should be mindful of possible SRCs in gastric MALT lymphoma specimens to avoid misdiagnosis of SRCC in patients with gastric MALT lymphoma. Confirmatory ESD may be useful for accurate diagnosis and appropriate management of such lesions.

Acute Thiamine Deficiency Detected by Video Head Impulse Test in a Patient with Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma

Thiamine deficiency may cause Wernicke encephalopathy (WE) characterized by ataxia, ophthalmoplegia, and confusion. Aside from the triad of cardinal symptoms, selective or predominant impairments of bilateral horizontal canals may be observed in WE. Here, we report a patient with gastric mucosa-associated lymphoid tissue (MALT)-lymphoma complicated by an early stage of WE due to thiamine deficiency manifesting bilateral vestibular dysfunctions. A 78-year-old man recently diagnosed gastric MALT-lymphoma presented with dizziness and disequilibrium for several weeks. He showed mild imbalance while tandem walking and abnormal catch-up saccades bilaterally during bedside head impulse test (HIT). Video HIT revealed decreased vestibulo-ocular reflex gains with catch-up saccades for the bilateral horizontal and several vertical canals. Diagnostic work-up demonstrated decreased serum thiamine and lesions in the mammillary body and periaqueductal gray matter on brain magnetic resonance images. Furthermore, with thiamine replacement, his clinical symptoms were markedly improved. Also, vestibular symptoms and signs may be an early manifestation of WE, and video HIT could be a useful diagnostic tool to aid early detections.

CLinicopathological characteristics of extranodal marginal zone B‐cell lymphoma of the intestine: a single center analysis

Extranodal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT-lymphoma) is mot commonly diagnosed in the stomach (30%–35%), but is exceedingly rare in the intestinal tract (2%). Consequently, data on this special subgroup are scarce. Out of 484 patients with MALt-lymphoma diagnosed and treated at our institution from 1999 to 2020, 42 (11%) had intestinal involvement (24 primary and 18 secondary) and were restrospectively analyzed. Out of 18 patients rated as secondary intestinal invlevement, 14 patients had gastric MALT-lymphoma as the primary origin. Median age at diagnosis was 67 years (interquartile range (IQR) 53–72) and the median follow-up time was 47 months (IQR 32–102). Patients presenting with lymphoma-associated symptoms were significantly more common in the group of primary versus secondary intestinal MALT lymphomas (52% vs. 20%, p = .047). Nine patients each, i.e. 9/18 secondary and 9/24 primary intestinal MALT lymphomas were found positive for Helicobacter pylori. Intestinal organs involved included the colon (n = 19), duodenum (n = 11), small intestine (n = 8) and rectum (n = 5). MALT-IPI could be calculated for 39 patients, with low MALT-IPI documented in 37/39 cases. Seven patients were found to be positive for translocation t(11;18)(q21;q21), 6 of whom had primary gastric MALT lymphoma, suggesting the presence of the translocation as highly suggestive for secondary involvement. Treatment data were available in 41 our of those 42 patients. Eleven patients (27%) received local therapy (ten surgery, and one radiotherapy, complete response rate 90%), 16 (38%) systemic therapy (overall response rate 87%) and 9 (22%) had only antibiotic therapy (complete response rate 38%). in 4/41 patients, only watchfuil waiting was applied. Eighteen patients progressed during follow-up; the median progression free survival following first line therapy was 50 mos (CI: 38.4–53.7 mos), with anumerical trend towards longer PFS in primary (134 mos) versus secondary MALT lmyphoma (35.5 mos). The estimated overall survival was 301 months, with 6 patients having died during follow up (two from lymphoma progression, the other 4 from unrelated conditions). A comparison in terms of PFS and Os with the cohort of 144 patients with gastric MALT-lmyphoma showed no significant difference in terms of outcome. Overall, patients with intestinal MALT-lymphoma appear to have a good prognosis irrespcetive of primary or secondary involvement, whichbappears to be comparable to our data obtined in gastric MALT-lymphoma. Keyword: Extranodal non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.

Spontaneous regression of secondary vitreoretinal lymphoma after diagnostic vitrectomy: case report

PurposeOur purpose is to report a patient with secondary intraocular mucosa-associated lymphoid tissue (MALT) who experienced spontaneous regression after diagnostic vitrectomy.MethodsWe retrospectively reviewed the clinical and imaging features of the case. Multimodal imaging, including fundus photograph, optical coherence tomography, fundus fluorescein angiography and ultrasound scan was presented.ResultsA 71-year-old female presented with a subretinal lesion temporal to macula and scattered multifocal creamy lesions deep to retina in her left eye. Optical coherence tomography of the left eye showed multifocal nodular hyper-reflective signals between the Bruch’s membrane and RPE. She had a history of gastric MALT lymphoma. Diagnostic vitrectomy was performed. IL-10 level of aqueous was 187.7pg/ml. Cytology, gene rearrangement and flow cytometry of the vitreous were inconclusive. Systemic evaluation was normal. Secondary vitreoretinal MALT lymphoma was considered. Interestingly, her subretinal lesions regressed gradually without any chemotherapy. And IL-10 level of aqueous declined to 64.3pg/ml.ConclusionsSecondary vitreoretinal MALT lymphoma is extremely rare. Spontaneous regression of intraocular lymphoma does occur.

The clinicopathological characteristics of gastric cancer and precancerous conditions in gastric DLBCL and MALT lymphoma patients: a multi-center retrospective study

Objective The objective of this study is to explore the clinicopathological characteristics of gastric cancer and precancerous conditions in patients with primary gastric lymphoma. Methods We analyzed 474 cases of primary gastric lymphoma, mainly DLBCL and MALT, from three clinical centres retrospectively, and compared the clinicopathological parameters of primary gastric lymphoma patients complicated with gastric cancer, precancerous conditions, or with no complications. Results A total of 5.1% of the patients with primary gastric lymphoma were diagnosed with gastric cancer, including metachronous gastric adenocarcinoma (3.2%) and synchronous gastric adenocarcinoma (1.9%). Of the patients with gastric lymphoma, 14.6% had precancerous conditions including atrophy (14.6%), intestinal metaplasia (8.9%), and low-grade intraepithelial neoplasia (1.9%). Primary gastric lymphoma patients with an ulcerative type (p = 0.009) and Lugano classification stage IIE + IV (p < 0.001) lymphoma had a higher risk of complicating with gastric cancers or precancerous conditions. The rate of infection of Helicobacter pylori (Hp) was 68.4% in patients with primary gastric lymphoma, which was higher in patients with MALT lymphoma (p < 0.001), Lugano classification stage I + II (p < 0.001), and patients complicated with precancerous conditions and gastric cancer (p < 0.001), especially gastric cancer of the intestinal type (p = 0.04). Gastric cancer (95.8%) and precancerous conditions (91.3%) occurred mostly in Hp-infected primary gastric lymphoma patients, with a minor subset of Hp-eradicated patients. Primary gastric lymphoma patients had a higher detection rate of early gastric cancer (25.0%) and a five-year survival rate (40.0%) than the general Chinese population. Conclusions Patients with primary gastric lymphoma have a high risk of developing gastric cancer and precancerous conditions, and this risk may be related to Helicobacter pylori infection. Follow-up of primary gastric lymphoma provides an opportunity for the detection of early gastric cancer. Key messages 5.1% of the patients with primary gastric lymphoma were diagnosed with gastric cancer. 14.6% of the patients with gastric lymphoma had premalignant lesions including atrophy (14.6%), intestinal metaplasia (8.9%), and low-grade intraepithelial neoplasia (1.9%). Primary gastric lymphoma patients complicating with gastric cancer had a higher infection rate of Helicobacter pylori (100.0%), a detection rate of early gastric cancer (25.0%) and a five-year survival rate (40.0%) than the general Chinese population.

Gastric MALT Lymphoma: a Rare Manifestation of a Common Disease

Gastric MALT Lymphoma: a Rare Manifestation of a Common Disease

Synchronous gastric MALT lymphoma and gastric adenocarcinoma of fundic gland type arising from a hamartomatous inverted polyp in a Helicobacter pylori naive patient.

We present a rare case that showed the coexistence of gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma in Helicobacter pylori-naive stomach. A 72-year-old man was followed up after surgery for epithelial carcinoma of the glottis at the Department of Otolaryngology. He underwent an upper gastrointestinal endoscopy for an abnormal PET-CT accumulation, which revealed gastric adenocarcinoma of fundic gland type in the gastric fundus and MALT lymphoma in the upper gastric body. Hence, we performed an endoscopic submucosal dissection for gastric cancer and diagnosed gastric adenocarcinoma of fundic gland type derived from a hamartomatous-inverted polyp. Subsequently, Gastric MALT lymphoma was treated with radiation therapy because the API2-MALT1 gene was positive and the Helicobacter pylori infection was negative. A complete response was observed. Even in Hp-naive stomachs, cases such as the present case are complicated by special types of gastric cancer and MALT lymphoma, and endoscopic examination should be performed with these diseases in mind.

Helicobacter pylori infection

Helicobacter pylori infection causes chronic gastritis, which can progress to severe gastroduodenal pathologies, including peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. H. pylori is usually transmitted in childhood and persists for life if untreated. The infection affects around half of the population in the world but prevalence varies according to location and sanitation standards. H. pylori has unique properties to colonize gastric epithelium in an acidic environment. The pathophysiology of H. pylori infection is dependent on complex bacterial virulence mechanisms and their interaction with the host immune system and environmental factors, resulting in distinct gastritis phenotypes that determine possible progression to different gastroduodenal pathologies. The causative role of H. pylori infection in gastric cancer development presents the opportunity for preventive screen-and-treat strategies. Invasive, endoscopy-based and non-invasive methods, including breath, stool and serological tests, are used in the diagnosis of H. pylori infection. Their use depends on the specific individual patient history and local availability. H. pylori treatment consists of a strong acid suppressant in various combinations with antibiotics and/or bismuth. The dramatic increase in resistance to key antibiotics used in H. pylori eradication demands antibiotic susceptibility testing, surveillance of resistance and antibiotic stewardship.

Effectiveness of Helicobacter pylori eradication in the treatment of early-stage gastric mucosa-associated lymphoid tissue lymphoma: An up-to-date meta-analysis.

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML) is usually a low-grade B-cell neoplasia strongly associated with Helicobacter pylori (H. pylori)-induced chronic gastritis. Clinical practice guidelines currently recommend H. pylori eradication as the preferred initial treatment for early-stage GML. To determine the practical effect of bacterial eradication as the sole initial therapy for early-stage GML, an updated analysis and review of available evidence is imperative. To perform a meta-analysis to assess the rate of complete remission (CR) of H. pylori-positive early-stage GML following bacterial eradication. We performed independent, computer-assisted literature searches using the PubMed/MEDLINE, Embase, and Cochrane Central databases through September 2022. Prospective and retrospective observational studies evaluating the CR of early-stage GML following bacterial eradication in H. pylori-positive patients. The risk of bias was assessed using Joanna Briggs Institute (JBI) Critical Appraisal Tools. The pooled estimate of the complete histopathological remission rate and respective confidence intervals (95%CI) were calculated following the random-effects model. Heterogeneity and inconsistency were assessed using Cochran's Q test and I2 statistic, and heterogeneity was defined as P < 0.01 and I² > 50%, respectively. Subgroup and meta-regression analyses were conducted to explore potential sources of heterogeneity. The titles and abstracts of 1576 studies were screened; 96 articles were retrieved and selected for full-text reading. Finally, 61 studies were included in the proportional meta-analysis (P-MA). Forty-six were prospective and fifteen were retrospective uncontrolled, single-arm, observational studies. The overall risk of bias was low to moderate in all but a single report, with an average critical appraisal score across all studies of 79.02%. A total of 2936 H. pylori-positive early-stage GML patients, in whom H. pylori was successfully eradicated, were included in the analysis. The pooled CR of H. pylori-positive early-stage GML after bacterial eradication was 75.18% (95%CI: 70.45%-79.91%). P-MA indicated the substantial heterogeneity in CR reported across studies (I 2 = 92%; P < 0.01). Meta-regression analysis identified statistically significant effect modifiers, including the proportion of patients with t(11;18)(q21;q21)-positive GML and the risk of bias in each study. Comprehensive synthesis of available evidence suggests that H. pylori eradication is effective as the sole initial therapy for early-stage GML. Although the substantial heterogeneity observed across studies limits the interpretation of the pooled overall CR, the present study is a relevant to informing clinical practice.

Abstract 5895: Analysis of microbiome in gastric MALT lymphoma

Abstract Gastric MALT (mucosa-associated lymphoid tissue) lymphoma is found at a rate of 50% or more among the types of MALT lymphoma. Majority of patients with gastric MALT lymphoma are infected with Helicobacter pylori and also have clinical improvement with eradication therapy. However, it is unclear how H. pylori cause gastric MALT lymphoma. To explore it, we prospectively collected 13 patients who are newly diagnosed with gastric MALT lymphoma with H. pylori. We gathered samples from normal regions and lesions during endoscopy for diagnosis. Samples of lesion were harvested again after eradication of H. pylori. we sequenced 10 of WES (whole exome sequencing) and 13 of WTS (whole transcriptome sequencing) with these samples. With sequencing data, we aligned the sequenced reads to human reference genome (hg19) using BWA and called the variants with Mutect2. We aligned the reads and calculated TPM (Transcripts Per Million) from WTS with STAR and RSEM. We performed DEG (Differentially Expressed Genes) and GSEA (Gene Set Enrichment Analysis) for three comparison groups which are divided into normal, lesion, and after eradication. Gene fusions were detected using STAR-Fusion and Arriba with WTS. To detect potential microbiome from the samples, we used Kraken2, a taxonomic classification tool. We found that MUC6 was mutated from all samples and some samples have mutated MUC3A, KMT2C, ZNF595, CDC27, etc., and two have BIRC3-MALT1 fusion. From DEG and GSEA analysis, G protein-coupled receptor activity was activated in the group of lesion samples and suppressed in normal samples and eradication samples. Lymphocyte activation and immune response were also activated in the cancerous lesion. Kraken2 classified the reads which were not aligned to the human reference genome as reads from microbiota including H. pylori. The reads of H. pylori were more abundant in the lesion group than the other groups. According to the result of differentially expressed species analysis between the groups of lesion and eradication, the following species were also more abundant in the lesion group; Veillonella dispar, Helicobacter hepaticus, Helicobacter winghamensis, etc. We analyzed genetic alterations and differentially expressed genes and also classified non-human reads as microbiome with sequencing data from gastric MALT lymphoma. Our results suggest how H.pylori infection is related to carcinogenesis of gastric MALT lymphoma. Citation Format: SeungJoo Yoo, Dong-Yeop Shin, Ja Min Byun, Junshik Hong, Hongseok Yun, Youngil Koh, Sung-Soo Yoon. Analysis of microbiome in gastric MALT lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5895.

Hematological manifestations of Helicobacter Pylori (literature review)

It is known that Helicobacter pylori to be a key factor in the etiology of various gastrointestinal diseases, ranging from chronic gastritis without clinical symptoms to peptic ulcer, autoimmune gastritis, adenocarcinoma and gastric MALT lymphoma. However, current research suggests that Helicobacter pylori may be associated with numerous extra-gastric diseases that lead to chronic local or systemic inflammation and the initiation of autoimmune reactions, including hematological ones. The article describes the role of Helicobacter pylori CagA in the pathogenesis of iron deficiency anemia, immune thrombocytopenic purpura and MALT lymphoma. Studies of the iron-deficiency anemia pathogenesis in infected H. pylori patients have shown a connection between the CagA oncoprotein and iron homeostasis. It was established that transferrin endocytosis is mediated and iron absorption increases. In the development of immune thrombocytopenic purpura, CagA leads to a systemic host immune response through mechanisms of molecular mimicry. In pathogenesis of MALT lymphoma, it is considered significant that after the transfer of CagA to B-cell lymphocytes, through the type 4 secretory system (T4SS), a phosphorylated CagA-SHP2 complex is formed by affecting endoplasmic reticulum kinases 1 and 2 (ERK1, ERK2), p38MAPK, BCL2 and NF -κB, as well as through inhibition of p53 accumulation or inhibition of the JAK-STAT signaling pathway, ultimately promoting lymphogenesis and immortalization of B-cell lymphocytes. So, it was established that the presence of CagA protein in the Helicobacter pylori strain is key to the development of inflammation and tumor transformation. The disclosure of these mechanisms is necessary for a more accurate understanding of some pathological processes caused by this bacterium, both in the stomach and outside it. This will help improve diagnosis, guide treatment and predict clinical prognosis. Keywords: hypomagnesaemia, blood pressure, diabetes mellitus.

Clinical significance and impact of gastric non-Helicobacter pylori Helicobacter species in gastric disease.

Gastric non-Helicobacter pylori Helicobacter (NHPH) species naturally associated with animals have been linked with gastric disease in human patients. The prevalence and clinical significance of zoonotic gastric NHPHs was determined in large and well-defined, H. pylori-negative, gastric patient populations. Patients were retrospectively (n=464) and prospectively (n=65) included for gastric biopsy collection: chronic gastritis (CG), peptic ulcer disease and gastric MALT lymphoma, without identified aetiology. PCR and sequencing was performed for the detection of gastric Helicobacter species. Retrospectively, asymptomatic gastric bypass patients (n=38) were included as controls. Prospectively, additional saliva samples and symptom and risk factor questionnaires were collected. In this group, patients with gastric NHPH infection were administered standard H. pylori eradication therapy and underwent follow-up gastroscopy post-therapy. In the retrospective samples, the prevalence of gastric NHPHs was 29.1%, while no gastric NHPHs were detected in control biopsies. In the prospective cohort, a similar proportion tested positive: 27.7% in gastric tissue and 20.6% in saliva. The sensitivity and accuracy for the detection of gastric NHPHs in saliva compared to gastric tissue was 27.8% and 69.8% respectively. Following eradication therapy, clinical remission was registered in 12 of 17 patients, histological remission in seven of nine and eradication in four of eight patients. These findings suggest a pathophysiological involvement of NHPHs in gastric disease. Patients presenting with gastric complaints may benefit from routine PCR testing for zoonotic gastric NHPHs.

Early gastric mucosa-associated lymphoid tissue lymphoma treated by endoscopic submucosal dissection.

A previously healthy 66-year-old woman was referred to our hospital for belching with a positive 13C-labeled urea breath test. A coarse nodular lesion was observed upon upper endoscopy ([Fig. 1 a]). She was treated with standard H. pylori quadruple therapy for 2 weeks.

Nomogram model predicting the overall survival for patients with primary gastric mucosa-associated lymphoid tissue lymphoma

Increasingly extranodal marginal B-cell lymphoma of mucosa-associated lymphoid tissue, known as mucosa-associated lymphoid tissue (MALT) lymphoma, is a type of non-Hodgkin's lymphoma. The prognosis of primary gastric MALT (GML) patients can be affected by many factors. Clinical risk factors, including age, type of therapy, sex, stage and family hematologic malignancy history, also have significant effects on the development of the disease. The available data are mainly focused on epidemiology; in contrast, few studies have investigated the prognostic variables for overall survival (OS) in patients with primary GML. Based on the realities above, we searched a large amount of data on patients diagnosed with primary GML in the Surveillance, Epidemiology and End Results (SEER) database. The aim was to develop and verify a survival nomogram model that can predict the overall survival prognosis of primary GML by combining prognostic and determinant variables. To create an effective survival nomogram for patients with primary gastric GML. All data of patients with primary GML from 2004 to 2015 were collected from the SEER database. The primary endpoint was OS. Based on the LASSO and COX regression, we created and further verified the accuracy and effectiveness of the survival nomogram model by the concordance index (C-index), calibration curve and time-dependent receiver operating characteristic (td-ROC) curves. A total of 2604 patients diagnosed with primary GML were selected for this study. A total of 1823 and 781 people were randomly distributed into the training and testing sets at a ratio of 7:3. The median follow-up of all patients was 71 mo, and the 3- and 5-year OS rates were 87.2% and 79.8%, respectively. Age, sex, race, Ann Arbor stage and radiation were independent risk factors for OS of primary GML (all P < 0.05). The C-index values of the nomogram were 0.751 (95%CI: 0.729-0.773) and 0.718 (95%CI: 0.680-0.757) in the training and testing cohorts, respectively, showing the good discrimination ability of the nomogram model. Td-ROC curves and calibration plots also indicated satisfactory predictive power and good agreement of the model. Overall, the nomogram shows favorable performance in discriminating and predicting the OS of patients with primary GML. A nomogram was developed and validated to have good survival predictive performance based on five clinical independent risk factors for OS for patients with primary GML. Nomograms are a low-cost and convenient clinical tool in assessing individualized prognosis and treatment for patients with primary GML.

Long-term clinical outcomes of gastric mucosa-associated lymphoid tissue lymphoma in real-world experience

This long-term, retrospective, single-center study evaluated real-world clinical outcomes of gastric mucosa-associated lymphoid tissue (MALT) lymphoma using different therapeutic modalities and analyzed factors affecting survival outcomes and long-term prognosis. We enrolled 203 patients with pathologically confirmed low-grade gastric MALT lymphoma and examined their treatment responses. Helicobacter pylori eradication was performed in all patients with H. pylori infection (HPI) and localized stage gastric MALT lymphoma. All patients underwent pre-treatment and physical evaluations, with complete blood count, biochemistry panel, and staging workup. Among 144 HPI-positive patients with stage I or II1–2 disease who underwent H. pylori eradication, 112 (77.8%) achieved complete remission (CR). All HPI-negative patients who received first-line radiotherapy achieved CR (100%), but only 22 of 27 first-line chemotherapy-treated patients achieved CR (81.5%). Lesions in the proximal upper-third or in multiple locations and an invasion depth to the submucosa or deeper were associated with poor response to eradication, and HPI negativity was significantly correlated with poor progression-free survival. HPI eradication treatment should be the first-line treatment for patients with localized stage HPI-positive gastric MALT lymphoma. The “watch-and-wait” strategy should be adopted for delayed responders. We suggest radiotherapy for patients with a localized HPI-negative status or when eradication has failed.

Anti-CD40L therapy prevents the formation of precursor lesions to gastric B-cell MALT lymphoma in a mouse model.

Mucosa-associated lymphoid tissue (MALT) lymphoma is a B-cell tumour that develops over many decades in the stomachs of individuals with chronic Helicobacter pylori infection. We developed a new mouse model of human gastric MALT lymphoma in which mice with a myeloid-specific deletion of the innate immune molecule, Nlrc5, develop precursor B-cell lesions to MALT lymphoma at only 3months post-Helicobacter infection versus 9-24 months in existing models. The gastric B-cell lesions in the Nlrc5 knockout mice had the histopathological features of the human disease, notably lymphoepithelial-like lesions, centrocyte-like cells, and were infiltrated by dendritic cells (DCs), macrophages, and T-cells (CD4+ , CD8+ andFoxp3+ ). Mouse and human gastric tissues contained immune cells expressing immune checkpoint receptor programmed death 1 (PD-1) and its ligand PD-L1, indicating an immunosuppressive tissue microenvironment. We next determined whether CD40L, overexpressed in a range of B-cell malignancies, may be a potential drug target for the treatment of gastric MALT lymphoma. Importantly, we showed that the administration of anti-CD40L antibody either coincident with or after establishment of Helicobacter infection prevented gastric B-cell lesions in mice, when compared with the control antibody treatment. Mice administered the CD40L antibody also had significantly reduced numbers of gastric DCs, CD8+ and Foxp3+ T-cells, as well as decreased gastric expression of B-cell lymphoma genes. These findings validate the potential of CD40L as a therapeutic target in the treatment of human gastric B-cell MALT lymphoma. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Comprehensive Analysis of Gene Expression Profiling to Explore Predictive Markers for Eradication Therapy Efficacy against Helicobacter pylori-Negative Gastric MALT Lymphoma.

Although radiotherapy is the standard treatment for Helicobacter pylori (Hp)-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma, eradication therapy using antibiotics and an acid secretion suppressor can sometimes induce complete remission. We explored predictive markers for the response to eradication therapy for gastric MALT lymphoma that were negative for both API2-MALT1 and Hp infection using comprehensive RNA sequence analysis. Among 164 gastric MALT lymphoma patients who underwent eradication therapy as primary treatment, 36 were negative for both the API2-MALT1 fusion gene and Hp infection. Based on eradication therapy efficacy, two groups were established: complete response (CR) and no change (NC). The Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that cancer-related genes and infection-related genes were highly expressed in the NC and CR groups, respectively. Based on this finding and transcription factor, gene ontology enrichment, and protein-protein interaction analyses, we selected 16 candidate genes for predicting eradication therapy efficacy. Real-time PCR validation in 36 Hp-negative patients showed significantly higher expression of olfactomedin-4 (OLFM4) and the Nanog homeobox (NANOG) in the CR and NC groups, respectively. OLFM4 and NANOG could be positive and negative predictive markers, respectively, for eradication therapy efficacy against gastric MALT lymphoma that is negative for both API2-MALT1 and Hp infection.