Low-grade Gastric Mucosa-associated Lymphoid Tissue Lymphoma Research Articles

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.

Helicobacter pylori Eradication and Gastric Cancer Prevention

Since Warren and Marshall demonstrated Helicobacter pylori (H. pylori) as a cause of gastritis in the early 1980s, H. pylori has been associated with various gastric diseases, including gastric ulcer, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, gastric adenoma, gastric adenocarcinoma, and hyperplastic gastric polyps. H. pylori eradication therapy can treat some associated diseases, including low-grade gastric MALT lymphoma, and significantly reduce the risk of peptic ulcer recurrence or progression of atrophic gastritis and intestinal metaplasia. In East Asia, where H. pylori and gastric cancer are prevalent, several studies have been conducted to prove whether the risk of gastric cancer development is reduced through H. pylori eradication therapy. Early studies failed to show the benefits of H. pylori eradication therapy in gastric cancer prevention. However, recent studies with extended follow-up periods have reported reduced risks of gastric cancer after treatment of H. pylori infection. H. pylori eradication therapy effectively prevents gastric cancer even in patients who were treated for early gastric cancer, and can be used in treating hyperplastic gastric polyps. Herein, we reviewed current evidence supporting the benefits of H. pylori eradication therapy to help clinicians understand its impact on gastric cancer prevention and hyperplastic polyp treatment.

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

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

Nuclear expression of BCL10 or nuclear factor kappa B helps predict Helicobacter pylori–independent status of low-grade gastric mucosa–associated lymphoid tissue lymphomas with or without t(11;18)(q21;q21)

AbstractThe t(11;11212121212127)(q21;q21) translocation is a specific marker for Helicobacter pylori–independent status of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, there are no reliable markers to predict tumor response to H pylori eradication in patients without t(11;18)(q21;q21). Nuclear expression of BCL10 and nuclear factor kappa B (NF-κB) was recently found to be closely associated with H pylori–independent status of the high-grade counterpart of gastric MALT lymphoma, which usually lacks t(11;18)(q21;q21). This study examined whether these 2 markers can also predict H pylori–independent status of low-grade gastric MALT lymphomas without t(11; 18)(q21;q21). Sixty patients who underwent successful H pylori eradication for low-grade gastric MALT lymphomas were included. Forty-seven (78.3%) patients were negative for t(11;18)(q21;q21); among them, 36 (76.6%) were H pylori dependent and 11 (23.4%) were H pylori independent. Nuclear expression of BCL10 was significantly higher in H pylori–independent than in H pylori–dependent tumors (8 of 11 [72.7%] vs 3 of 36 [8.3%]; P < .001). Nuclear expression of NF-κB was also significantly higher in H pylori–independent than in H pylori–dependent tumors (7 of 11 [63.6%] vs 3 of 36 [8.3%]; P < .001). Further, nuclear translocation of BCL10 and NF-κB was observed in 12 of the 13 patients with t(11;18)(q21;q21), and all these 12 patients were H pylori independent. In summary, nuclear expression of BCL10 or NF-κB is predictive of H pylori–independent status of low-grade gastric MALT lymphoma with or without t(11;18)(q21; q21).

PRIMARY SJOGREN SYNDROME CAUSING PULMONARY EXTRANODAL MARGINAL CELL LYMPHOMA

SESSION TITLE: Medical Student/Resident Lung Pathology SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Extranodal marginal zone lymphoma (MZL) of the lung is a rare pulmonary lymphoid malignancy and World Health Organization (WHO) classifies Mucosa associated lymphoid tissue (MALT) lymphoma as a subtype of B-cell MZL. CASE PRESENTATION: 80 year old Caucasian male with past medical history of obstructive sleep apnea, chronic kidney disease stage III, type II diabetes mellitus, hypertension and tobacco abuse, was first seen in pulmonary clinic for asymptomatic innumerate bilateral pulmonary nodules noted on Computed Tomography (CT) scan of the chest. He complained of occasional chronic dry mouth on further questioning. Antibody testing was positive for Antinuclear antibodies (245 AU/ml) and SS Ro antibody (188 AU/ml). His dry mouth and lower lobe predominant cystic and nodular changes were concerning for lymphoid interstitial pneumonia associated with Sjogren's syndrome. He was referred to rheumatology then subsequently lost to follow up. He presented two years later with increased shortness of breath and progressive weight loss. Pulmonary function tests (PFTs) showed an isolated low diffusing capacity for carbon monoxide at 33% predicted (down from 75% prior). CT scan revealed progression of his bilateral lung nodules and cystic changes in the lower lungs bilaterally. He then underwent bronchoscopy and surgical lung biopsy. This showed a low-grade B- cell lymphoma with plasmacytic differentiation, most consistent with MALT stage 1E Extranodal marginal zone lymphoma. Patient was started on rituximab weekly for 4 weeks and reported some improvement in his sicca symptoms. DISCUSSION: Roughly 10 to 20 percent of SS patients have clinically significant lung disease defined by symptoms most commonly cough and dyspnea. Abnormal imaging and PFTs are common. Thin-walled lung cysts are detected with CT imaging in 12 to 46 percent of SS patients. Interstitial lung disease can occur in SS in several forms (1). In a series of thirteen patients with pulmonary MALT lymphoma performed by Yachoui et. al, 54% were positive for primary sjogren syndrome (PSS) (2). No difference in outcomes was noted on two large retrospectives studies involving different treatment modalities including surgery, chemotherapy or combined therapy. Asymptomatic patients should be observed with no treatment indicated initially. It is indicated for patients with a high burden of lymphadenopathy with splenomegaly, organ dysfunction, bone marrow suppression, and/or rapid disease progression (3). Series performed by Yachoui et. al demonstrated a favorable prognosis in all cases of pulmonary MALT lymphoma with all treatment modalities resulting in complete and sustained response (2). CONCLUSIONS: SS can have wide ranging organ involvement. Prompt referral to rheumatology and active monitoring is paramount. Further investigation is warranted to better understand pulmonary MALT pathogenesis, treatment, and outcomes in PSS. Reference #1: Stojan, G., et al. (2013). “Pulmonary manifestations of Sjögren's syndrome.” Current allergy and asthma reports 13(4): 354-360. Reference #2: Yachoui R, Leon C, Sitwala K, Kreidy M. Pulmonary MALT lymphoma in patients with Sjögren's syndrome. Clinical medicine & research. 2017;15(1-2):6-12. Reference #3: Pinotti G, Zucca E, Roggero E, Pascarella A, Bertoni F, Savio A, et al. Clinical features, treatment and outcome in a series of 93 patients with low-grade gastric MALT lymphoma. Leukemia & lymphoma. 1997;26(5-6):527-37

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.

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.

Heterogeneity of clinical management of low-grade gastric lymphoma of mucosa-associated lymphoid tissue. An audit of 198 patients in Spain

IntroductionCure of Helicobacter pylori infection in patients with gastric lymphoma of mucosa-associated lymphoid tissue (MALT) leads to long-term clinical remission in the initial stages. As it is a rare disease, its management in clinical practice remains largely unknown and heterogeneity of care remains a concern.The aim was to audit the management and evolution of a large series of low-grade gastric MALT lymphomas from thirteen Spanish hospitals. Materials and methodsMulticentre retrospective study including data on the diagnosis and follow-up of patients with gastric low-grade MALT lymphoma from January 1998 to December 2013. Clinical, biological and pathological data were analyzed and survival curves were drawn. ResultsOne-hundred and ninety-eight patients were included. Helicobacter pylori was present in 132 (69%) patients and 103 (82%) in tumors confined to the stomach (stage EI) and was eradicated in 92% of patients. Chemotherapy was given in 90 (45%) patients and 43 (33%) with stage EI. Marked heterogeneity in the use of diagnostic methods and chemotherapy was observed. Five-year overall survival was 86% (89% in EI). Survival was similar in EI patients receiving aggressive treatment and in those receiving only antibiotics (p=0.577). DiscussionGastric MALT lymphoma has an excellent prognosis. We observed, however, a marked heterogeneity in the use of diagnostic methods or chemotherapy in early-stage patients.

2707 Gastric Mucosa-Associated Lymphoid Tissue Lymophoma Treated by Endoscopic Mucosal Resection

INTRODUCTION: Primary low-grade gastric Mucosa-associated lymphoid tissue (MALT) lymphoma is a distinctive type of B-cell lymphoma. Endoscopic appearances of low-grade gastric MALT lymphoma are quite varied and polypoid or subepithelial type (exophytic) is rare. Here, we reported the case of H. pylori negative gastric MALToma presenting as an exophytic subepithelial tumor, diagnosing and treating by endoscopic mucosal resection (EMR). CASE DESCRIPTION/METHODS: A 53-year-old man was referred to our hospital because of a large subepithelial tumor of the stomach, which was incidentally found on an endoscopy for a routine checkup in outside hospital. Initial outside endoscopic biopsy was a simple chronic gastritis. Physical examination and laboratory results were unremarkable. On endoscopic examination, a 2.0 cm sized round and hard exophytic subepithelial tumor was seen on the great curvature side of high body of the stomach. The tumor showed a well-demarcated smooth border without any erosion and ulceration. An abdominal pelvic CT demonstrated an enhancing subepithelial tumor without regional lymphadenopathy, such as gastrointestinal stromal tumor. EUS showed a hypoechoic and heterogeneous mass in the 2nd and 3rd layer with ill-defined internal margin. EMR was done for both the definite diagnosis and the treatment without complications because the tumor had a semipedunculated morphology. Results of a histopathologic examination of the resected tumor showed diffuse lymphocytic proliferation in the submucosa mimicking a subepithelial tumor with lymphoepithelial lesions. Dense lymphocytic infiltration composed of mainly B cells forming vague follicular colonization. Immunohistochemical stain of cytokeratin also showed presence of lymphoepithelial lesions. The Ki-67 was positive in 7%. Histologically, no H. pylori was observed in the luminal side. Finally, the patient was diagnosed as a H. pylori–negative extranodal marginal zone B-cell lymphoma (MALToma) (stage EI1). No additional treatment such as chemotherapy or radiation was performed. The follow-up endoscopic examination showed no recurrence until 2 years after EMR. DISCUSSION: We suggest that EMR may be an alternative treatment modality in the diagnosis and the treatment of gastric MALT lymphoma in cases of submucosal or polypoid morphology type, especially when H. pylori is negative. Further study in terms of feasibility, efficacy, and long-term safety of EMR as a curative treatment would be warranted.

The B-cell-activating factor signalling pathway is associated with Helicobacter pylori independence in gastric mucosa-associated lymphoid tissue lymphoma without t(11;18)(q21;q21).

We previously reported that activation of the B-cell-activating factor (BAFF) pathway upregulates nuclear factor-κB (NF-κB) and induces BCL3 and BCL10 nuclear translocation in Helicobacter pylori (HP)-independent gastric diffuse large B-cell lymphoma (DLBCL) tumours with evidence of mucosa-associated lymphoid tissue (MALT). However, the significance of BAFF expression in HP independence of gastric low-grade MALT lymphomas without t(11;18)(q21;q21) remains unexplored. Sixty-four patients who underwent successful HP eradication for localized HP-positive gastric MALT lymphomas without t(11;18)(q21;q21) were studied. BAFF expression was significantly higher in the HP-independent group than in the HP-dependent group [22/26 (84.6%) versus 8/38 (21.1%); p < 0.001]. Similarly, BAFF receptor (BAFF-R) expression (p = 0.004) and nuclear BCL3 (p = 0.004), BCL10 (p < 0.001), NF-κB (p65) (p = 0.001) and NF-κB (p52) (p = 0.005) expression were closely correlated with the HP independence of these tumours. Moreover, BAFF overexpression was significantly associated with BAFF-R expression and nuclear BCL3, BCL10, NF-κB (p65) and NF-κB (p52) expression. These findings were further validated in an independent cohort, including 40 HP-dependent cases and 18 HP-independent cases of gastric MALT lymphoma without t(11;18)(q21;q21). The biological significance of BAFF signalling in t(11;18)(q21;q21)-negative lymphoma cells was further studied in two types of lymphoma B cell: OCI-Ly3 [non-germinal centre B-cell origin DLBCL without t(11;18)(q21;q21) cell line] and MA-1 [t(14;18)(q32;q21)/IGH-MALT1-positive DLBCL cell line]. In both cell lines, we found that BAFF activated the canonical NF-κB and AKT pathways, and induced the formation of BCL10-BCL3 complexes, which translocated to the nucleus. BCL10 and BCL3 nuclear translocation and NF-κB (p65) transactivation were inhibited by either LY294002 or by silencing BCL3 or BCL10 with small interfering RNA. BAFF also activated non-canonical NF-κB pathways (p52) through tumour necrosis factor receptor-associated factor 3 degradation, NF-κB-inducing kinase accumulation, inhibitor of κB kinase (IKK) α/β phosphorylation and NF-κB p100 processing in both cell lines. Our data indicate that the autocrine BAFF signal transduction pathway contributes to HP independence in gastric MALT lymphomas without the t(11;18)(q21;q21) translocation. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Gastric Mucosa-associated Lymphoid Tissue Lymphoma Based on Outcome of Domestic Treatment

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is associated with Helicobacter pylori infection. H. pylori eradication can be performed as a primary therapy regardless of H. pylori status. In Korea, six articles were published about low-grade gastric MALT lymphoma with H. pylori. Complete regression rate after H. pylori eradication is reported at 74.5% to 94.4%. Radiotherapy results in favorable clinical long-term outcomes in patients with early-stage gastric MALT lymphoma who fail H. pylori eradication therapy and those who are H. pylori negative. Chemotherapy could be reserved for patients with metastatic or high-grade lymphoma. In gastric MALT lymphoma, patients with polypoid type on initial endoscopy had a higher likelihood of recurrence than those with diffuse infiltration or ulceration types. The depth of invasion, location of lesions, and chromosomal abnormality with t(11;18) together are predictive factors for failure to remission by H. pylori eradication.

Helicobacter heilmannii sensu lato‐induced MALT Lymphoma Formation in Lacrimal Gland as well as Fundic Gland in C57BL/6 mouse: Effect of Aprepitant

As to the pathogenesis of the Sjogren syndrome, Helicobacter pylori has been suggested to have some relation mostly from the epidemiological studies, while few experimental studies have clarified this point.We have established a gastric low‐grade MALT lymphoma model in C57BL/6 mouse by the infection of Helicobacter heilmannii sensu lato obtained from cynomolgus monkey. After the long term infection, we have detected the accumulation of lymphocytes in the lacrimal glands similar to the gastric MALT lymphoma. The characteristics of this lesion were investigated as well as the effect of aprepitant, an NK‐1R antagonist on this lesion.Materials and MethodsThe characteristics of the lymphocyte accumulation were investigated by the histochemical analysis using lymphocyte marker, CD4, B220, CD10, epithelial cell marker cytokeratin, mucus marker MUC7 and aquaporin‐4 and 5. The localization of the autonomic nerves was also clarified by the choline acetyltransferase, substance P and calcitonin gene‐related peptide.ResultsBy the histochemical analysis, the lymphoepithelial lesion was detected in the lymphocyte aggregation and the germinal center was formed in the center of the lesion, showing its characteristics as a mucosa‐associated lymphoid tissue (MALT) lymphoma. The lesion was also richly innervated by the autonomic nerves. Intraperitoneal administration of aprepitant induced the significant reduction in the lesion size.ConclusionHelicobacter heilmannii sensu lato infection to the C57BL/6 mouse induced the formation of the MALT lymphoma in the mouse lacrimal gland. This model could be one of the animal models of the Sjogren syndrome.

Helicobacter pylori and t(11;18)(q21;q21) translocation in gastric malt lymphoma.

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is clearly associated with Helicobacter pylori gastritis and can be cured with anti- H pylori therapy alone. The presence of t(11;18)(q21;q21) translocation is thought to predict a lower response rate to anti- H pylori treatment. To study the presence of t(11;18)(q21;q21) genetic translocation and its clinical impact in low-grade gastric MALT lymphoma Brazilian patients. A consecutive series of eight patients with gastric MALT lymphoma were submitted to gastroscopy, endoscopic ultrasound, histopathological examination, H pylori search and RT-PCR-based methodology. All patients received anti-H pylori treatment. Eradicated patients were followed-up every 3-6 months for 2 years. Eight patients were studied. All patients had tumor involvement restricted to the mucosa or submucosa and seven patients had low-grade gastric MALT lymphoma. All infected patients achieved H pylori eradication. Histological tumor regression was observed in 5/7 (71%) of the low-grade gastric MALT lymphoma patients. The presence of t(11;18)(q21;q21) translocation was found in 4 (57%) of these patients; among them only two had histological tumor regression following H pylori eradication. RT-PCR is a feasible and efficient method to detect t(11;18)(q21;q21) translocation, being carried out in routine molecular biology laboratories. The early detection of such translocation can be very helpful for better targeting the therapy to be applied to gastric MALT lymphoma patients.

Tu1085 Mantle Cell Lymphoma With Gastrointestinal Involvement: Characteristics and Clinical Outcome

Objective: Helicobacter pylori eradication has widely accepted as a primary treatment for gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). We evaluated long-term clinical outcome of low-grade gastric MALT lymphoma in a single center. Methods: From 1996 to 2010, a total of 205 H. pylori-infected patients with lowgrade gastric MALT lymphoma were prospectively enrolled in Seoul National University Hospital. Twelve patients were excluded due to presence of extra-gastric MALT lymphoma or other malignancy at initial diagnosis. Complete remission (CR) was defined as no endoscopic findings of lymphoma, and histopathology of complete histological response (ChR) or probable minimal residual disease (pMRD). Tumor response to H. pylori eradication therapy was evaluated by endoscopy and histopathology every 2-3 months till CR and every 6-12 months after achieving CR. Results: Median follow-up period was 5.4 years (range, 1.0-14.4 years). H. pylori was successfully eradicated in 187 (96.9%) of 193 eligible patients. CR was obtained in 170 (88.1%) patients and the median time to achieve CR was 3 months (range, 1-20 months) after H. pylori eradication therapy. Tumor recurrence was found in 7 (4.1%) patients and the median tumor recurrence time was 13 months (range, 3-61 months) after achieving CR. Cumulative recurrence rate was 1.9, 4.2 and 7.8% at 1, 3 and 5 years, respectively. Disease-free survival was 97.0, 96.1 and 94.8% at 3, 5 and 7 years, respectively. Other malignancies were found in 8 (4.1%) of 193 patients, none of whom had metachronous gastric cancer. Five-year and 10-year overall survival rate was 99.4 and 97.4%, respectively. Tumors of the proximal stomach (mid-body to fundus) (odds ratio [OR] 4.39, 95% confidence interval [CI] 1.34-14.43; p=0.015) and low serum total cholesterol level (,170 mg/dL) (OR 4.17, 95% CI 1.27-13.71; p=0.019) increased the risk of non-CR after H. pylori eradication therapy. Conclusions: Most patients with low-grade gastric MALT lymphoma treated by H. pylori eradication therapy showed excellent long-term outcomes. Serum total cholesterol might be a novel predictive marker for tumor response to H. pylori eradication therapy.

Tu1086 Management Strategy for Small Duodenal Carcinoid Tumors: Does Conservative Management With Close Follow-up Represent an Alternative to Endoscopic Treatment?

Objective: Helicobacter pylori eradication has widely accepted as a primary treatment for gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). We evaluated long-term clinical outcome of low-grade gastric MALT lymphoma in a single center. Methods: From 1996 to 2010, a total of 205 H. pylori-infected patients with lowgrade gastric MALT lymphoma were prospectively enrolled in Seoul National University Hospital. Twelve patients were excluded due to presence of extra-gastric MALT lymphoma or other malignancy at initial diagnosis. Complete remission (CR) was defined as no endoscopic findings of lymphoma, and histopathology of complete histological response (ChR) or probable minimal residual disease (pMRD). Tumor response to H. pylori eradication therapy was evaluated by endoscopy and histopathology every 2-3 months till CR and every 6-12 months after achieving CR. Results: Median follow-up period was 5.4 years (range, 1.0-14.4 years). H. pylori was successfully eradicated in 187 (96.9%) of 193 eligible patients. CR was obtained in 170 (88.1%) patients and the median time to achieve CR was 3 months (range, 1-20 months) after H. pylori eradication therapy. Tumor recurrence was found in 7 (4.1%) patients and the median tumor recurrence time was 13 months (range, 3-61 months) after achieving CR. Cumulative recurrence rate was 1.9, 4.2 and 7.8% at 1, 3 and 5 years, respectively. Disease-free survival was 97.0, 96.1 and 94.8% at 3, 5 and 7 years, respectively. Other malignancies were found in 8 (4.1%) of 193 patients, none of whom had metachronous gastric cancer. Five-year and 10-year overall survival rate was 99.4 and 97.4%, respectively. Tumors of the proximal stomach (mid-body to fundus) (odds ratio [OR] 4.39, 95% confidence interval [CI] 1.34-14.43; p=0.015) and low serum total cholesterol level (,170 mg/dL) (OR 4.17, 95% CI 1.27-13.71; p=0.019) increased the risk of non-CR after H. pylori eradication therapy. Conclusions: Most patients with low-grade gastric MALT lymphoma treated by H. pylori eradication therapy showed excellent long-term outcomes. Serum total cholesterol might be a novel predictive marker for tumor response to H. pylori eradication therapy.

Tu1084 Long-Term Outcome of Low-Grade Gastric Mucosa-Associated Lymphoid Tissue Lymphoma After Helicobacter pylori Eradication Therapy: A Prospective Single Center Study

Objective: Helicobacter pylori eradication has widely accepted as a primary treatment for gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). We evaluated long-term clinical outcome of low-grade gastric MALT lymphoma in a single center. Methods: From 1996 to 2010, a total of 205 H. pylori-infected patients with lowgrade gastric MALT lymphoma were prospectively enrolled in Seoul National University Hospital. Twelve patients were excluded due to presence of extra-gastric MALT lymphoma or other malignancy at initial diagnosis. Complete remission (CR) was defined as no endoscopic findings of lymphoma, and histopathology of complete histological response (ChR) or probable minimal residual disease (pMRD). Tumor response to H. pylori eradication therapy was evaluated by endoscopy and histopathology every 2-3 months till CR and every 6-12 months after achieving CR. Results: Median follow-up period was 5.4 years (range, 1.0-14.4 years). H. pylori was successfully eradicated in 187 (96.9%) of 193 eligible patients. CR was obtained in 170 (88.1%) patients and the median time to achieve CR was 3 months (range, 1-20 months) after H. pylori eradication therapy. Tumor recurrence was found in 7 (4.1%) patients and the median tumor recurrence time was 13 months (range, 3-61 months) after achieving CR. Cumulative recurrence rate was 1.9, 4.2 and 7.8% at 1, 3 and 5 years, respectively. Disease-free survival was 97.0, 96.1 and 94.8% at 3, 5 and 7 years, respectively. Other malignancies were found in 8 (4.1%) of 193 patients, none of whom had metachronous gastric cancer. Five-year and 10-year overall survival rate was 99.4 and 97.4%, respectively. Tumors of the proximal stomach (mid-body to fundus) (odds ratio [OR] 4.39, 95% confidence interval [CI] 1.34-14.43; p=0.015) and low serum total cholesterol level (,170 mg/dL) (OR 4.17, 95% CI 1.27-13.71; p=0.019) increased the risk of non-CR after H. pylori eradication therapy. Conclusions: Most patients with low-grade gastric MALT lymphoma treated by H. pylori eradication therapy showed excellent long-term outcomes. Serum total cholesterol might be a novel predictive marker for tumor response to H. pylori eradication therapy.

Two Cases of Diffuse Large B-Cell Lymphomas in the Cervical Lymph Nodes in Patients with Low-Grade Gastric Marginal Zone B-Cell Lymphoma (MALT Lymphoma)

It is well known that gastric mucosa-associated lymphoid tissue (MALT) lymphomas are associated with Helicobacter pylori infection and have a good prognosis. However, although rare, these low-grade lymphomas transform to the high-grade diffuse large B-cell lymphomas (DLBCLs) which are thought to be the important cause of death in patients with MALT lymphoma. We report two cases of DLBCLs in the cervical lymph nodes that occurred 10 years and 1.5 years after diagnosing low-grade gastric MALT lymphomas.

1075P - Detection of Caga Expression in Gastric Mucosa-Associated Lymphoid Tissue Lymphoma—Biologic Significance and Clinical Implication

ABSTRACT Background We recently reported that a direct contact of Helicobacter pylori (HP) with B cells resulted in CagA translocation into the cells (Cancer Res 2010;70:5740-8). The translocated CagA further activates extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK), and up-regulates the expressions of Bcl-2 and Bcl-xL. In this study, we sought to verify if CagA exists in the malignant B cells of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Methods Expression of CagA protein, phospho-SHP-2, phospho-ERK, phospho-p38MAPK, Bcl-2 and Bcl-xL in a series of 26 gastric MALT lymphoma was determined by immunohistochemistry. Western blot analysis was done to confirm immunohistochemical detection of CagA and biopsies from non-gastric MALT lymphoma served as negative controls. The association of CagA expression and the tumor response to HP-eradication (HPE) therapy was evaluated in 77 stage IE/IIE1 low-grade gastric MALT lymphoma patients. Results The expression of CagA was detected in 35 (45.5%) of 77 patients. CagA expression was closely associated with the expression phospho-SHP-2 (P = .016), phospho-ERK (P Conclusion CagA protein can be translocated into malignant B cells of MALT lymphoma. The expression of CagA in lymphoma cells appears to be biologically and clinically significant. Disclosure All authors have declared no conflicts of interest.

Long-term clinical outcome of gastric MALT lymphoma after eradication of Helicobacter pylori: a multicentre cohort follow-up study of 420 patients in Japan

ObjectiveA multicentre cohort follow-up study of a large number of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma was conducted to elucidate the long-term outcome of the disease after Helicobacter...

Role of 18F-FDG PET Scans in Patients with Helicobacter pylori-Infected Gastric Low-Grade MALT Lymphoma

Background/AimsEndoscopic ultrasound (EUS) plays a crucial role in the assessment and treatment of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma; however, interobserver variation, inadequate accuracy in judging the depth of tumor invasion, and histological heterogeneity of the tumor can limit its role. Thus, we have assessed the role of 18F-FDG PET scans in the management of Helicobacter pylori-infected gastric MALT lymphoma.MethodsEighteen patients with H. pylori-infected low-grade gastric MALT lymphoma underwent an 18F-FDG PET scan prior to receiving H. pylori eradication therapy. We analyzed these patients' clinicopathologic data and measured the baseline and change in the metabolic activity of the tumor using standardized uptake values (SUVs).ResultsTwo patients failed to achieve complete remission of the low-grade gastric MALT lymphoma after successful H. pylori eradication. The baseline SUVs were significantly higher in these patients compared to successfully treated patients, 13.35±0.07 vs 2.98±0.93, respectively (n=2 vs n=16, p<0.001). The reduction in the SUV was significantly greater in the complete remission patients compared to treatment failure patients (p=0.018).ConclusionsA high SUV at baseline 18F-FDG PET and a lower reduction in the SUV within 3 months after eradication therapy are associated with treatment failure in H. pylori-positive low-grade gastric MALT lymphoma patients undergoing eradication treatment.