Gastric Mucosa-associated Lymphoid Tissue Lymphoma Research Articles

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.

P327 Characteristics of esophago-gastro-duodenal Crohn’s disease in the biologic era: a nationwide study of the Young GETECCU Group

Abstract Background There is scarce information about Crohn’s disease (CD) affecting oesophagus, stomach and duodenum. The aim of the study was to describe phenotypic features, disease course and treatment response in these patients. Methods Patients with CD and upper involvement (oesophagus, stomach and/or duodenum) were included (upper CD=UCD). Extensive CD (ECD) was defined as concomitant distal involvement (jejunal, ileal and/or colonic). A multicentric, longitudinal and retrospective study was designed to evaluate disease characteristics at diagnosis and behaviour of UCD in patients >= 18 years between January 2000 and December 2019 with at least 1 year follow-up since diagnosis. All treatments for UCD diagnosis and reason to start them were recorded, as well as 14- and 52-week response. Incidence of malignancy was also evaluated. Descriptive statistics were applied for quantitative and qualitative variables. Exact Fisher test was used for comparison of proportions. Results 197 (0.9%) UCD among 21.670 patients with Crohn’s Disease (CD) from 28 Spanish centres were included with a median of 10.7 years follow-up (min 2.2– max 22.1). Nearly 55% were men: median age at CD diagnosis was 29 years whereas for UCD was 32 years, with a mean of 2 months between CD and UCD diagnosis (SD 0.4). Only 9 patients had isolated UCD, whereas the rest presented ECD. 97% were diagnosed by endoscopy, in 2/3 due to symptoms (epigastric pain and dyspepsia). Inflammatory phenotype was prevalent in UCD with aphthous ulcer as the main endoscopic lesion (42%). Isolated duodenal location was the most frequent, followed by the antrum. Systemic corticosteroids and thiopurines were the most used treatments after UCD diagnosis. Treatment response at 14- and 52-weeks is detailed in Figures 1 and 2. Treatment withdrawal due to UCD activity was seen in 2-11% of patients. Thiopurines was the most durable treatment (median 50 months, min 0–max 210) followed by infliximab and adalimumab. Ten patients presented phenotype change over time (90% from inflammatory to stricturing). 53% of patients underwent endoscopic control (44% due to symptoms). De novo metaplasia was detected in 3 patients, and low-grade visible dysplasia in one. Two patients developed neoplasia: 1 gastric MALT lymphoma and 1 oesophagus carcinoma 5.5 and 20 years after UCD diagnosis, respectively. Conclusion UCD in adult population is infrequent. Upper involvement does not have an impact on immunosuppressive treatment requirements, but extensive disease does, appreciating a similar response to treatments for proximal and distal disease, both in the short and medium term. Although rare, risk of malignancy in UCD exists.

Clinical Impact Assessment and Utilization Prospects of the t(11:18) Chromosomal Translocation in Gastric MALT Lymphoma in Koreans: A Single Center Retrospective Analysis

The gastric extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (gastric MALT lymphoma) are mostly related to Helicobacter pylori infections. However, chromosomal aberration involving translocation t(11;18) is also frequently reported in these patients. The study was a retrospective review and analysis of electronic medical records to assess the factors which affect complete remission (CR) in patients with gastric MALT lymphoma. Based on the medical records, subjects with gastric MALT lymphoma were enrolled consecutively from January 2004 to December 2021. Among the 77 subjects who were found with gastric MALT lymphoma in the database, 65 cases with complete records were analyzed. Of these, 66.2% (43/65) were H. pylori positive. Genetic analyses for t(11:18) were done on 41 subjects. The t(11:18) chromosomal translocation with MALT1:BIRC3 fusion was found in 31.7% (13/41) of the subjects. With H. pylori eradication therapy, 75% (21/28) of the subjects without t(11:18) achieved CR. However, only 23.1% (3/13) subjects with t(11:18) could achieve CR (p-value= 0.009). In the H. pylori-positive group, 85.7% (18/21) subjects without t(11:18) achieved CR with eradication therapy, but 71.4% (5/7) subjects with t(11:18) failed to achieve CR (p-value=0.004). In the H. pylori-negative group, 42.3% (3/7) of the subjects without t(11:18) achieved CR with eradication therapy. However, 83.3% (5/6) of H. pylori-negative subjects with t(11:18) failed to achieve CR with eradication therapy and needed additional radiotherapy (p-value=0.396). H. pylori negativity and the presence of t(11:18) were both risk factors for failure to achieve CR with H. pylori eradication therapy as the first line of treatment.

Uncovering the role of microRNA671-5p/CDCA7L/monoamine oxidase-A signaling in Helicobacter pylori mediated apoptosis in gastric epithelial cells.

Helicobacter pylori is a gram-negative microaerophilic bacterium and is associated with gastrointestinal diseases ranging from peptic ulcer and gastritis to gastric cancer and mucosa-associated lymphoid tissue lymphoma. In our laboratory, the transcriptomes and miRnomes of AGS cells infected with H. pylori have been profiled, and an miRNA-mRNA network has been constructed. MicroRNA 671-5p is upregulated during H. pylori infection of AGS cells or of mice. In this study, the role of miR-671-5p during infection has been investigated. It has been validated that miR-671-5p targets the transcriptional repressor CDCA7L, which is downregulated during infection (in vitro and in vivo) concomitant with miR-671-5p upregulation. Further, it has been established that the expression of monoamine oxidase A (MAO-A) is repressed by CDCA7L, and that MAO-A triggers the generation of reactive oxygen species (ROS). Consequently, miR-671-5p/CDCA7L signaling is linked to the generation of ROS during H. pylori infection. Finally, it has been demonstrated that ROS-mediated caspase 3 activation and apoptosis that occurs during H. pylori infection, is dependent on the miR-671-5p/CDCA7L/MAO-A axis. Based on the above reports, it is suggested that targeting miR-671-5p could offer a means of regulating the course and consequences of H. pylori infection.

Expression of Concern: Overexpression of miR-142-5p and miR-155 in Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma Resistant to Helicobacter pylori Eradication.

Expression of Concern: Overexpression of miR-142-5p and miR-155 in Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma Resistant to Helicobacter pylori Eradication.

Clinical relevance of molecular aspects in extranodal marginal zone lymphoma: a critical appraisal

Extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) is among the more common types of lymphoma accounting for up to 8% of newly diagnosed lymphoma cases. As opposed to other B-cell lymphomas, however, no predominant genetic hallmark has been defined in MALT lymphoma, but different localizations appear to be affected by different, sometimes distinct changes. Nonetheless, a high proportion of these genetic changes reported in MALT lymphomas dysregulate the pathways leading to NF-kB activation. t(11;18)(q21;q21)/BIRC3::MALT1 appears to be MALT lymphoma specific and is found in 24% of gastric and 40% of pulmonary MALT lymphomas. The translocation is associated with more disseminated disease in gastric MALT lymphoma and is found in a large percentage of patients whose lymphoma is unresponsive to antibiotic eradication of Helicobacter pylori. In addition to t(11;18)(q21;q21), nuclear expression of BCL10 or NF-kB appears to be highly associated with lymphoma cell survival independence of H. pylori-mediated stimulations. Antibiotic eradication, however, is the recommended therapy of choice irrespective of genetic findings, and molecular analysis is not required before initiation of therapy. The influence of genetic translocations including t(11;18)(q21;q21) on systemic therapies, however, is less clearly defined. While small series have shown no influence on the outcome for treatment with the anti-CD20 antibody rituximab (R) or treatment with cladribine (2-CdA), conflicting data have been reported for alkylating agents, especially chlorambucil and the combination of R + chlorambucil. None of other genetic changes seen in MALT lymphoma to date has discernible value in routine clinical applications, but recent data suggest that changes in TNFAIP3(A20), KMTD2 and CARD11 might be associated with response to Bruton kinase inhibitors.

Effects of 14-days bismuth- and tetracycline-containing quadruple therapy with concomitant regimen for the first line Helicobacterpylori eradication.

Helicobacter pylori (H. pylori) has infected about 50% of the world's population and it is the main cause for peptic ulcer, gastric adenocarcinoma and even a major cause for gastric MALT lymphoma. This study was performed in Mazandaran, Sari, situated in North of Iran. Three-hundred and twenty-eight adult patients with endoscopically approved gastric or duodenal ulcers or erosions and H. pylori infection were randomly divided into 2 groups to receive either 14 days PABT (Pantoprazole 40 mg, Amoxicillin 1 g, Bismuth 425 mg (all twice daily) and Tetracycline 500 mg four times a day) and PACM (Pantoprazole 40 mg, Amoxicillin 1g, Clarithromycin 500 mg, and Metronidazole 500 mg, all twice daily). To evaluate H. pylori eradication, fecal H. pylori antigen test was performed 8 weeks after treatment. The eradication rates were 94.51% in the PABT and 91.46% in PACM group based on the intention to treat analysis. Moreover, the eradication rates were 95.58% and 92.72% according to per-protocol analysis, respectively. Also, both groups had very low rates of severe side effects. Regarding the ideal eradication rates achieved by both treatment groups and the low rates of severe side effects, both treatment protocols can be prescribed for H. pylori eradication in North of Iran.

Clinical Practice Guidelines of Russian Gastroenterological Association, Scientific Society for the Clinical Study of Human Microbiome, Russian Society for the Prevention of Non-Communicable Diseases, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy for <i>H. pylori</i> Diagnostics and Treatment in Adults

Aim: bring to the attention of practitioners indications for anti-Helicobacter therapy, methods and procedure for diagnostics and eradication therapy of Н. pylori infection.Key points. Chronic gastritis caused by Н. pylori infection, including asymptomatic persons, may be considered as an indication for eradication therapy of Н. pylori as etiological therapy and opportunistic screening for gastric cancer prevention. Indications, for obligatory anti-Helicobacter therapy include peptic ulcer, gastric MALT lymphoma, early gastric cancer (EGC) with endoscopic resection. H. pylori primary diagnostics methods include 13C-urea breath test, H. pylori stool antigen lab test, rapid urease test and serological method. The serological method cannot be used after anti-Helicobacter therapy.In Russia H. pylori strains' resistance to clarithromycin does not exceed 15 % in most regional studies. The first line therapy for Н. pylori infection eradication is the standard triple therapy including a proton pump inhibitor (PPI), clarithromycin and amoxicillin, enhanced with bismuthate tripotassium dicitrate. A classic four-component therapy based on bismuthate tripotassium dicitrate or quadrotherapy without bismuth drug products which includes PPI, amoxicillin, clarithromycin and metronidazole, may be used as alternative to the first line eradication therapy. The standard triple therapy may be prescribed for 14 days only in those regions, where it has been proven to be effective. Quadrotherapy with bismuthate tripotassium dicitrate is also used as main second line therapy in case of standard triple therapy, bismuth enhanced standard triple therapy or combined therapy failure. Another second line therapy includes PPI, levofloxacin and amoxicillin, to which a bismuth-containing drug product may be added. The third line therapy is selected individually based on previously used treatment settings.Conclusion. In each case of H. pylori infection the decision for eradication therapy should be made, which is especially relevant as eradication of H. pylori has been recognized as an effective measure for the prevention of gastric cancer.

Diagnosis and Treatment for Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma

Mucosa-associated lymphoid tissue (MALT) lymphoma, which was first reported in 1984, shows an indolent clinical course. However, the detailed clinicopathological characteristics of gastric MALT lymphoma have not been fully elucidated. We performed a literature search concerning the clinical features and treatment for gastric MALT lymphoma using PubMED. MALT lymphomas develop in single or multiple extranodal organs, of which the stomach is one of the most frequent sites; gastric MALT lymphoma accounts for 7% to 9% of all B-cell lymphomas, and 40% to 50% of primary gastric lymphomas. The eradication of Helicobacter pylori (H. pylori) is the first-line treatment for patients with gastric MALT lymphoma, regardless of the clinical stage. Approximately 60-90% of cases with stage I/II1 disease only achieve a complete histological response via H. pylori eradication. In patients who do not respond to H. pylori eradication therapy, second-line treatments such as watch-and-wait, radiotherapy, chemotherapy, rituximab immunotherapy, and/or a combination of these are recommended. Thus, H. pylori plays a causative role in the pathogenesis of gastric MALT lymphoma, and H. pylori eradication leads to complete histological remission in the majority of cases.

Clarithromycin-, and metronidazole-resistant Helicobacter pylori isolated from raw and ready-to-eat meat in Mansoura, Egypt

Helicobacter pylori (H. pylori), classified as a class-I carcinogen, is one of the leading medical pathogens of global concern associated mainly with the development of gastric adenocarcinomas and gastric mucosa-associated lymphoid tissue lymphomas; nevertheless, its prevalence in food especially meat and meat products is not fully covered. Additionally, the resistance of H. pylori towards clarithromycin is increasing worldwide and consider the leading cause of H. pylori treatment failure. Thus, the present study was designed to determine the prevalence, molecular characterization, and antimicrobial resistance profiles of clarithromycin-, and metronidazole-resistant H. pylori isolated from raw and ready-to-eat meat samples retailed in Mansoura city, Egypt. Among the 250 samples tested, H. pylori were molecularly confirmed in 40.8 % (49/120) of raw meat products and in 29.2 % (38/130) of ready-to-eat meat products. Precisely, 53.3 % (32/60), 56.7 % (17/30), 40 % (8/20), 55 % (11/20), 60 % (12/20), 13.3 % (4/30), and 15 % (3/20) of raw ground beef, beef burger, beef burger sandwiches, beef shawarma sandwiches, beef kofta sandwiches, beef luncheon, and beef sausage sandwiches, respectively were positive for H. pylori. Of the 204 biochemically-identified H. pylori isolates, 53.9 % (110/204) were molecularly confirmed by PCR through the detection of glmM, cagA, or vacA genes, which were detected at an incidence of 95.5 % (105/110), 77.3 % (85/110), and 20.9 % (23/110) among the isolates, respectively. The antimicrobial sensitivity testing revealed that all of the 110 (100 %) molecularly-confirmed H. pylori isolates were multidrug-resistant (MDR; resistant to four or more antibiotics). Interestingly, 100 % and 61.8 % of H. pylori isolated from raw and ready-to-eat meat were resistant to metronidazole and clarithromycin, respectively which consider alarming results as metronidazole and clarithromycin are the mainstay antibiotics in the treatment of H. pylori infections. Additionally, 94.5 %, 94.5 %, 24.5 %, 23.6 %, and 13.6 % of isolates were resistant to vancomycin, sulphamethoxazole-trimethoprim, imipenem, levofloxacin, and nitrofurantoin, respectively. The widespread contamination of examined raw and ready-to-eat meat product samples with MDR H. pylori isolates could constitute a tremendous public health hazard. Further studies concerning the prevalence and possible methods of elimination of H. pylori in different food categories distributed in the various provinces in Egypt as well as in other countries is required for a better understanding the H. pylori as an emerging foodborne pathogen.

Mucosal Associated Lymphoid Tissue Lymphoma in Thailand, a Nationwide Multicenter Registry and Prognostic Index; Results from the Thai Lymphoma Study Group (TLSG) Registry

Introduction: Marginal zone lymphoma (MZL) is the second most common lymphoma subtype in Thailand. Extranodal MZL or mucosal associated lymphoid tissue (MALT) lymphoma is the highest prevalent entity. Although gastric MALT lymphoma is the most common organ of this entity but for Thai population, ocular adnexa MALT lymphoma is the most common primary organ of MALT lymphoma. Objective: This study aimed to describe epidemiology of MALT lymphoma in Thai population and develop prognostic model for MALT lymphoma. Patients and methods: Patients (pts) diagnosed with MALT lymphoma were enrolled to the TLSG registry. Demographic data, treatment modalities, survival data were gathered. Univariate and multivariate analyses were done by Cox regression. To test the prognostic indices, Kruskal-Wallis test was performed. Kaplan Meier curves were plotted and log rank test was used to test the difference between risk groups. STATA® version 17 was performed for statistical analyses. Results: From January 2007 to March 2022, the TLSG has prospectively enrolled 8,404 lymphoma patients to the registry from 15 nationwide medical institutes; of these 670 patients (7.97%) were histologically diagnosed with MZL. Among MZL, MALT lymphoma was the most common entity with 501 pts (77.8%) followed by nodal MZL (117; 17.5%), and splenic MZL (52; 7.7%). Of these MALT lymphoma population, 457 pts with completed follow-up data were eligible for long-term survivals analyses. The three most common primary organs were ocular adnexa (225; 49.2%), gastric (59; 12.9%), and sinonasal (57; 12.5%). Median age at diagnosis was 59 (range;20-95). 162 pts (35.4%) of these were 65 years or older. For gender, male was slightly predominant (56.9%). High ECOG performance status (3-4) in 15 (3.5%). Extensive extranodal organs (>2) in 78 (17%). Advanced stage (III-IV) in 162 (35.4%). High lactate dehydrogenase (LDH) in 112 (24.5%). Presence of B-symptoms in 103 (22.5%). Regarding treatment, chemotherapy (CMT) only was administered in 27.5%, CMT + rituximab (R) 13.4%, CMT + radiation (RT) 11.6%, R+CMT+RT 2.2%, R monotherapy 0.4%, antibiotic eradication 6.6%. Locoregional therapy with RT 24.2% and surgical removal alone in 3.6%. Univariate analysis was performed and found that ECOG>3, age>65, number of extranodal organs>2, B-symptom, stage III-IV, and LDH were potential factors to be used for multivariate analysis. For multivariate analysis, ECOG>3, age>65, and number of extranodal organs >2 were found to be statistically significant affected survivals. These prognostic factors were used and tested for overall and progression-free survivals (OS and PFS, respectively). Patients without any risk factor were classified to be low-risk pts and pts with any of these risk factors were categorized to be high-risk pts. Five-year PFS and OS were significantly better in low-risk pts; vs 83.3% vs 66.1% (p=0.028) and 97.8% vs 76.7% (p<0.001) respectively. (Figures 1A, B) Conclusion: MZL is the second most prevalent lymphoma subtype in Thailand and MALT lymphoma is the most common entity. The prognostic index for MALT lymphoma showed that patients without any risk factor (ECOG>3, age>65, and number of extranodal organs >2) had statistically significant better PFS and OS. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Risk of Diabetes Mellitus after Radiotherapy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

<h3>Purpose/Objective(s)</h3> The long-term effect of radiation on pancreas has been mostly studied for pediatric patients with the lack of individual radiation dosimetric data. The purpose of this study was to investigate the effect of radiotherapy (RT) on the risk of newly developed diabetes mellitus (DM) in patients with gastric mucosa-associated lymphoid tissue lymphoma (GML) using individual radiation dosimetric analysis. <h3>Materials/Methods</h3> We retrospectively reviewed 225 patients without history of DM who received curative aim treatment for stage IE GML between August 2007 and June 2020. Involved site RT to the whole stomach was delivered in 83 patients (36.9%). The pancreas was delineated in each patient's computerized tomography scan for dosimetric analysis. <h3>Results</h3> At a median follow-up time of 49.0 months (range, 3.0-155.3 months), the 3-year cumulative incidence of DM was 3.9% in all patients, and 7.9% and 1.6% in patients who received and did not receive RT, respectively (p=0.009). The mean pancreatic dose (D_mean) was independently associated with DM (p=0.027). As a result of recursive partitioning analysis, patients were classified into low (D_mean <21 Gy), intermediate (D_mean ≥21 Gy and BMI <27.0kg/m²), and high-risk groups (D_mean ≥21 Gy and BMI ≥27.0kg/m²) with 5-year DM incidence of 1.5%, 6.3%, and 54.3%, respectively (p<0.001). <h3>Conclusion</h3> Our results indicate that incidental irradiation to the pancreas can increase the risk of DM, which was dependent on pancreas D_mean. In addition, not only reducing pancreas D_mean but also controlling BMI may need to be combined to effectively prevent DM after RT.

Analysis of Helicobacter pylori in Saliva of Patients with Laryngopharyngeal Reflux and Non-Laryngopharyngeal Reflux

BACKGROUND : Helicobacter pylori is a gram-negative bacteria known as the causative agent of chronic gastritis, peptic ulcer, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Several studies have correlated H. pylori in the pathogenesis of upper airway diseases. H. pylori can be detected in saliva, oropharyngeal aphthae, nasal and sinus mucosa, secretions from the tympanic cavities, larynx, and pharyngeal lymphoid tissue. The diagnosis of LPR can be made simply by examining saliva.&#x0D; AIM : The aim of the study is to analyze the presence of H.pylori in the saliva of LPR and non LPR patients.&#x0D; METHODS : This study is an analytic observational study with a case control design. The research was conducted in the ENT-KL Department of Dr. M. Djamil Hospital, Padang, Indonesia. PCR examination was carried out at the Biomedical Laboratory of the Faculty of Medicine, Andalas University on saliva samples to detect the presence of H.Pylori. The study was conducted on 22 LPR patients and 22 control subjects.&#x0D; RESULT : LPR patients are more common in women than men, which were 12 women and 10 men. The average age of LPR patients is 43.7 years. The presence of H.pylori in LPR patients was 86.4%, while in the non-LPR group was 50%. After being tested using the Chi-square test, a significant difference was found between the presence of H. Pylori and the incidence of LPR (P = 0.010).&#x0D; CONCLUSION : There was an increase in the frequency of the presence of Helicobacter Pylori in patients with LPR compared to Non LPR patients after statistical analysis.&#x0D;

S3738 Agent Orange as a Possible Cause of Helicobacter pylori Negative Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

Introduction: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma was first described in 1983 as the most common extranodal site of non-Hodgkin lymphoma. Helicobacter pylori (H. pylori) infection is implicated in 90% of all gastric MALT lymphoma cases. Agent Orange (AO), with traces of oncogenic 2,3,7,8-tetrachlorodibenzo-p-dioxin, has also been classified as a causative agent in non-Hodgkin lymphoma, which includes gastric MALT lymphoma. Here we report a case of H. pylori negative gastric MALT lymphoma in a patient with history of significant AO exposure. Case Description/Methods: A 75-year-old Caucasian male veteran who served in the Vietnam War with significant AO exposure, as well as history of chronic gastroesophageal reflux disease, was referred for endoscopy to evaluate a reported history of un-staged Barrett’s esophagus 5-years prior but with two subsequent normal endoscopies at an outside facility. He noted symptoms of burning chest pain and dyspepsia following large meals, all of which were worsened with spicy foods and improved with omeprazole. Family history was negative for a history of gastric cancer, and he had a 25-pack year smoking history but quit 20 years prior to presentation.Initial esophagogastroduodenoscopy (EGD) revealed abnormal folds in the gastric fundus and erythema in the gastric antrum, but otherwise normal exam including normal duodenum and esophagus. Random gastric biopsies and biopsies of the abnormal folds were consistent with gastric MALT lymphoma, negative for H. pylori and t(11;18)(q21;q21). Repeat EGD 1 month later for further sampling demonstrated identical findings (Figure 1A). Stool testing for H. pylori antigen was also negative. The patient was referred to oncology and after staging imaging was found to have stage IE gastric MALT lymphoma. He was treated with involved site radiation therapy and EGD 3 months later showed both endoscopic and pathologic resolution (Figure 1B). Discussion: The 10% of cases of H. pylori negative gastric MALT lymphoma have an unclear etiology, although dysregulation of nuclear factor-kappa B (NF-κB) principally via translocations t(11;18)(q21;q21) is thought to be a potentially causative genetic alteration. In this patient, neither H. pylori nor the common t(11,18) genetic alteration were present. Given AO is implicated in non-Hodgkin lymphoma and the most common site of extranodal non-Hodgkin lymphoma is the gastric mucosa, AO exposure should be considered a risk factor for development of gastric MALT lymphoma.Figure 1.: (A) EGD demonstrating abnormal gastric mucosa with prominent gastric fundus folds seen on retroflexion during EGD prior to ISRT (radiation) therapy. (B) Post-radiation EGD demonstrating resolution of the abnormalities seen with the pre-treatment EGD including disappearance of the prominent gastric fundus folds.

S3745 An Uncommon Case of Helicobacter pylori-Negative Gastric MALT Lymphoma

Introduction: Gastric MALT (mucosa-associated lymphoid tissue) lymphoma is a type of non-Hodgkin's lymphoma with concomitant H. pylori infection. Approximately 5-10% of patients are not. Recent studies on H. pylori-negative gastric MALT lymphomas have suggested that H. pylori eradication therapy is effective in a proportion of patients with this disease and could even be considered a first-line treatment. Here, we present this uncommon and unique case. Case Description/Methods: A 58-year-old man, with PMH of prostate cancer and DVT not on anticoagulation, was initially admitted for seizures and altered mental status under the impression of bacterial meningitis. He had an upper GI bleed during the same hospitalization, and an inpatient upper endoscopy showed a Forrest 1a ulcer in the gastric fundus s/p clipping (Fig 1A). A repeat upper endoscopy three months later showed gastric erythema and a 6 mm non-bleeding healing gastric ulcer in the fundus (Fig 1B). The pathology report of antrum biopsy showed fundic and transitional zone gastric mucosa, mild chronic gastritis without intestinal metaplasia or dysplasia, and the presence of a few atypical lymphocytes. The body biopsy showed fundic/body type gastric mucosa, and findings were compatible with low-grade B-cell lymphoma, favoring extranodal marginal zone lymphoma of MALT lymphoma (Fig 1C). The patient was empirically treated for H. pylori with Bismuth-based quadruple therapy. The patient improved on follow-up with GI. Hematology-Oncology is currently planning for FISH for t(11;18) and/or MYD88 mutation status to assist in the differential, as the H. pylori strain was negative on biopsy. Discussion: Several theories describe pathways for lymphoid proliferation in H. pylori-negative patients, but the exact mechanism has yet to be determined. Currently, it is deemed multifactorial. There is a high incidence of translocation (11;18)(q21;q21) in H. pylori-negative MALT lymphomas is seen. Using radiation therapy for patients with early-stage (Lugano I/II) gastric MALT lymphomas that are negative for H. pylori infection is recommended, with clinical remission rates of up to 100%. Conversely, organ-preserving therapy has no added benefit and surgical treatment is rarely pursued. Therefore, it is recommended to eliminate the presence of H. pylori and evaluate for this translocation. Recent studies have suggested that H. pylori eradication therapy is effective in some proportion of these patients and could be considered a first-line treatment.Figure 1.: A) Upper endoscopy image of Forrest Class 1a ulcer s/p two clips. There is a spurting gastric ulcer with spurting hemorrhage. B) Upper endoscopy of gastric erythema and a 6 mm non-bleeding healing gastric ulcer in the fundus. C) Pathology: Low power view, H&E stain, of antrum biopsy showing fundic and transitional zone gastric mucosa, mild chronic gastritis without intestinal metaplasia or dysplasia, and the presence of a few atypical lymphocytes Immunohistochemistry studies showed atypical lymphocytes CD20+, CD79a+, PAX5+, CD5-, CD10-, BCL6-, BCL2+, CD43+, CyclinD1-, BCL6, and CD10, highlighting very small, scattered, disrupted germinal centers. CD3 and CD5 highlighted numerous admixed T-cells. Ki-67 was overall low (5-10%). Kappa(ish) and Lambda(ish) stains showed that the plasma cells were kappa-restricted, and had low mitotic activity, supporting the diagnosis of marginal zone lymphoma.

S1604 Prognostic Value of Systemic Inflammatory Markers in Gastric MALT Lymphoma

Introduction: Several studies have shown the role of inflammatory markers, especially the neutrophil-to-lymphocyte Ratio (NLR), as indicators of poor prognosis in various gastrointestinal malignancies. We aimed to examine the prognostic value of NLR, among other markers, and their relationship with the presence of baseline distant metastasis in patients with MALT Lymphoma. Methods: We retrospectively reviewed the charts of 139 patients with Gastric MALT Lymphoma treated at a tertiary care cancer center from 2012 to 2018. We examined the relationship between absolute eosinophilic count (AEC), absolute lymphocyte count (ALC), absolute monocytic count (AMC), absolute neutrophil count (ANC), monocyte to lymphocyte ratio (MLR), NLR, and platelet to lymphocyte ratio (PLR) with the presence distant metastases, and overall survival (OS). We used multivariable logistic regression analyses to test the association between the variables and the presence of baseline distant metastases. Results: The median age was 55 years, and males comprised 67.6% of the patients. The ROC value of 3.4 was determined as the cutoff value for NLR. High NLR (NLR > 3.4 µL) was significantly associated with the presence of distant metastasis at diagnosis (P-value, 0.02, Odds Ratio (OR): 2.4, CI: 1.14- 5.10). High ALC ( >1819) was also associated with the presence of baseline distant metastasis (P-value, 0.04, OR: 0.46, CI: 0.22- 0.98). Multivariable analysis showed that high NLR (P-value, 0.02, OR 2.4 95% CI 1.1-5.1) was an independent risk factor for distant metastasis at presentation (Figure). High ANC, NLR, and PLR, were associated with poor OS, (P-value, 0.027, 0.016, and 0.011 respectively). Conclusion: High systemic inflammatory markers are associated with poor prognosis (the presence of distant metastasis) and poor OS in patients with Gastric MALT Lymphoma. To our knowledge, this is the first study examining the association between these inflammatory markers and the presence of distant metastases in MALT Lymphoma. Whether these markers could predict the response to treatment is unknown (Table).Figure 1.: (Top)Kaplan Meier curve for overall survival of patients with ANC (Middle). Kaplan Meier curve for overall survival of patients with NLR (Bottom). Kaplan Meier curve for overall survival of patients with PLR Table 1. - The association between systemic inflammatory markers and overall survival Parameter Median OS P-value Hazard Ratio 95% Confidence Interval ANC >5100 6.4 months 0.027 1.5 1.04–2.1 ANC≤5100 10.9 months ALC >1819 7.6 months 0.19 0.80 0.55–1.1 ALC≤1819 6.7 months AMC > 603 6.3 months 0.66 1.1 0.76–1.6 AMC≤ 603 7.8 months NLR > 2.75 6.2 months 0.016 1.5 1.1–2.2 NLR ≤ 2.75 12.2 months MLR >0.32 6.3 months 0.36 1.2 0.83–1.7 MLR≤0.32 10.5 months PLR >0.16 6.2 months 0.011 1.6 1.1–2.3 PLR≤0.16 10.9 months

REVIEW ON STIMULATIONS OF THE SPREAD OF HELICOBACTER PYLORI INFECTION IN IRAQ

Helicobacter pylori (H. pylori) bacteria are microaerophilic Gram-negative bacteria that inhabit the human stomach and duodenum. If left untreated, it can lead to prolonged infection in human life. Numerous studies have shown that H. pylori infection can cause several important gastrointestinal diseases, ranging from chronic active gastritis without clinical symptoms to peptic ulcer, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Most modern publications are devoted to the pathogenic properties of microorganisms in the development of chronic gastritis, gastric ulcers, and gastric cancer, and methods for their eradication. Helicobacter pylori was the first officially recognized bacterial carcinogen and one of the most successful human pathogens, as more than half of the world's population is colonized by this Gram-negative bacterium. The disease course is the result of complex interactions between the host and bacteria. Host immunity gene polymorphisms and gastric acid secretion largely determine the ability of bacteria to colonize specific gastric niches. Bacterial virulence factors such as the cytotoxin-related gene pathogenicity island-encoded protein CagA and the vacuolar cytotoxin VacA support this colonization of the gastric mucosa and subsequently appear to regulate the host's immune system. This study focuses on the microbiological, clinical, and immunological aspects of H. pylori pathogenesis; it also reveals the prevalence of H. pylori in some Iraqi governorates

Risk of Diabetes Mellitus after Radiotherapy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma.

Simple SummaryIn patients with gastric mucosa-associated lymphoid tissue lymphoma (GML), irradiation of the pancreas is inevitable owing to its anatomical proximity to the stomach. This is the first study to demonstrate the association between RT exposure and the risk of development of diabetes mellitus (DM) in patients with GML by measuring individual-based dose parameters of the pancreas. The findings of this study demonstrate the association between incidental pancreatic irradiation and DM. Obesity and sex were key risk factors for DM. Considering the risk of DM, the pancreas should no longer be neglected during RT planning, particularly in male patients and patients with obesity.The long-term effect of radiation on the pancreas in pediatric patients has been studied without individual radiation dosimetric data. This study investigated the effect of radiotherapy on the risk of developing diabetes mellitus (DM) in patients with gastric mucosa-associated lymphoid tissue lymphoma (GML), using individual radiation dosimetric analysis. Retrospective analysis reviewed the data of 225 patients without a history of DM receiving curative treatment for stage IE GML. Involved-site radiotherapy was delivered to the whole stomach in 83 patients. The pancreas was delineated in each patient’s computed tomography scan for dosimetric analysis. At a median follow-up of 49.0 months, the 5-year cumulative incidence of DM was 4.5%, 9.6%, and 1.6% in all patients, patients who received radiotherapy, and patients who did not receive radiotherapy, respectively (p = 0.009). Mean pancreatic dose (Dmean; p = 0.009), sex (p = 0.043), and body mass index (BMI; p = 0.008) were independently associated with DM. Using recursive partitioning analysis, patients were classified into low, intermediate, and high-risk groups, with 5-year DM incidence rates of 0.0%, 3.1%, and 15.6%, respectively (p < 0.001). Incidental irradiation of the pancreas can increase the risk of DM, which may be stratified according to patient sex and BMI.

Endoscopic submucosal dissection for protruding Helicobacter pylori-negative mucosa-associated lymphoid tissue lymphoma of the stomach: a case report

Gastric mucosa-associated lymphoid tissue (MALT) lymphomas have various endoscopic appearances. We report a case of Helicobacter pylori-negative gastric MALT lymphoma with a protruding morphology similar to that of submucosal tumors. A 51-year-old man with a protruding tumor in the gastric cardia was referred to our hospital. Biopsy specimens showed no malignant epithelial tumors or lymphoid hyperplasia. Endoscopic submucosal dissection was performed and the patient was diagnosed with gastric MALT lymphoma. Lymphoma cells were present in the lamina propria mucosae and the submucosa under the non-atrophic fundic gland mucosa, with a feature of homogenous and monotonous growths, which was speculated to have resulted in a protruding morphology similar to that of submucosal tumors. Endoscopic submucosal dissection can be an alternative diagnostic option for gastric MALT lymphoma when the initial pathological diagnosis based on biopsy specimens is difficult.