Low-grade Gastric Mucosa-associated Lymphoid Tissue Research Articles

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).

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.

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.

1081P - Efficacy of salvage therapy in the treatment of Helicobacter pylori-positive gastric low-grade mucosa-associated lymphoid tissue lymphoma

BackgroundHelicobacter pylori (H.pylori) infection has a critical role in the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and its eradication can lead to tumor regression. However, in patients who do not achieve a lymphoma regression or relapse following antibiotic therapy, outcome of the patients are scarce. We evaluated the long-term outcome of the patients who received salvage therapy with relapsed or refractory gastric MALT lymphoma. MethodsBetween June 2000 and June 2017, a total of 29H.pylori-positive gastric MALT lymphoma patients who received frontline H.pylori eradication were included in this study. H.pylori-positive status was defined by positive results for the biopsy urease test and histology. They had all been diagnosed by endoscopy and had a complete staging including CT-scan. Patients received standard triple therapy for eradication of H.pylori and after treatment were sequentially followed-up with endoscopies performed to evaluate the response. Tumors that had resolved to complete remission (CR) score of GELA histologic grading system were considered treatment-responsive. ResultsDuring the follow-up periods 16 patients were refractory, nine had probable minimal residual disease and four relapsed after the first-line antibiotics. Of these 29 patients, transformation into high-grade B-cell lymphoma did not occur. Among the non-responder and relapsed patients, three patients were subjected to a watch and wait, while 26 patients underwent second-line treatment including radiotherapy (n=20), chemotherapy (n=5), chemotherapy plus sequential radiotherapy (n=1). Of the 20 patients treated with radiotherapy, the median dose to stomach was 3060 cGy (range, 1620-5000 cGy). After radiotherapy a CR was achieved in 20 patients (100%). Among six patients who received chemotherapy, a CR was achieved in five patients and no change was in one. That patient was achieved CR after radiotherapy. Probabilities of freedom from treatment failure and overall survival after 10 years were 100% and 83%. ConclusionsOutcome of patients with first-line H.pylori eradication failure followed by delayed chemotherapy and/or radiotherapy on indication was excellent. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

First-line antibiotic therapy in Helicobacter pylori-negative low-grade gastric mucosa-associated lymphoid tissue lymphoma

First-line antibiotic treatment for eradicating Helicobacter pylori (HP) infection is effective in HP-positive low-grade gastric mucosa-associated lymphoid tissue lymphoma (MALToma), but its role in HP-negative cases is uncertain. In this exploratory retrospective study, we assessed the outcome and potential predictive biomarkers for 25 patients with HP-negative localized gastric MALToma who received first-line HP eradication (HPE) therapy. An HP-negative status was defined as negative results on histology, rapid urease test, 13C urea breath test, and serology. We observed an antibiotic response (complete remission [CR], number = 8; partial remission, number = 1) in 9 (36.0%) out of 25 patients. A t(11;18)(q21;q21) translocation was detected in 7 (43.8%) of 16 antibiotic-unresponsive cases, but in none of the 9 antibiotic-responsive cases (P = 0.027). Nuclear BCL10 expression was significantly higher in antibiotic-unresponsive tumors than in antibiotic-responsive tumors (14/16 [87.5%] vs. 1/9 [11.1%]; P = 0.001). Nuclear NF-κB expression was also significantly higher in antibiotic-unresponsive tumors than in antibiotic-responsive tumors (12/16 [75.0%] vs. 1/9 [11.1%]; P = 0.004). A substantial portion of patients with HP-negative gastric MALToma responded to first-line HPE. In addition to t(11;18)(q21;q21), BCL10 and NF-κB are useful immunohistochemical biomarkers to predict antibiotic-unresponsive status in this group of tumors.

Efficacy of frontline antibiotics therapy in the treatment of Helicobacter pylori-negative gastric low-grade mucosa-associated lymphoid tissue lymphoma.

e19024Background: Previous series reports revealed that certain proportions of Helicobacter pylori (HP)-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma may respond to antibiotics...

Helicobacter pylori CagA Translocation Is Closely Associated With the Expression of CagA-signaling Molecules in Low-grade Gastric Mucosa-associated Lymphoid Tissue Lymphoma

We previously reported that the direct contact of Helicobacter pylori (HP) and B cells results in CagA translocation into the latter and that the translocated CagA regulates intracellular signaling pathways. Similarly, we recently found that CagA does exist in the malignant B cells of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and that its presence is closely associated with HP dependence. In this study, we further evaluated whether CagA expression regulates signal transduction molecules in the tumor cells and further contributes to the lymphomagenesis of HP-dependent growth of gastric MALT lymphoma. Forty-seven patients with stage IE HP-positive gastric MALT lymphoma who received HP eradication as their frontline therapy were included. The expression of CagA and signaling pathway-related proteins, such as phospho-SHP-2 (p-SHP-2), p-ERK, p-p38 MAPK, Bcl-2, and Bcl-xL, in tumor cells was evaluated by immunohistochemistry. There were 25 HP-dependent and 22 HP-independent cases. We observed that the CagA expression rate was significantly higher in HP-dependent than in HP-independent tumors (72% [18/25] vs. 18.2% [4/22]; P<0.001). The expression of CagA was closely associated with p-SHP-2 (P=0.012), p-ERK (P=0.002), p-p38 MAPK (P=0.006), Bcl-2 (P=0.020), and Bcl-xL (P=0.006) expression. Spearman correlation coefficient analysis showed a strong correlation between CagA and signaling molecule expression. Combined CagA expression, p-SHP-2 expression, and p-ERK expression showed an increased positive predictive value (93.3% [14/15] vs. 81.8% [18/22]) and an increased specificity (95.5% [21/22] vs. 81.8% [18/22]) for HP dependence compared with CagA expression alone. Our results indicate that CagA protein expression is biologically relevant and is associated with the activation of its downstream signals in HP-dependent gastric MALT lymphoma.

New Guidelines forHelicobacter pyloriTreatment: Comparisons between Korea and Japan

Korea and Japan show the highest incidence of gastric cancer and Helicobacter pylori infection. New 2013 guidelines on H. pylori infection differ between the two countries with regard to the indications for H. pylori eradication, diagnostic methods, and treatment regimens. Indications for eradication in Korean guideline focus on specific diseases such as peptic ulcer disease, low-grade gastric mucosa-associated lymphoid tissue lymphoma, and after resection of early gastric cancer, while Japanese guideline includes all H. pylori-associated gastritis for the prevention of dissemination. With regard to the diagnosis, either noninvasive or invasive method (except for bacterial culture) is recommended in Korea, while two noninvasive tests including serum anti-H. pylori IgG antibody level are preferred in Japan. As for the treatment regimens, second-line treatment (quadruple bismuth-containing regimen) is recommended without first-line triple therapy in areas of high clarithromycin resistance in Korea. However, there is no bismuth-based second-line treatment in Japan, and the Japanese regimen consists of a lower dose of antibiotics for a shorter duration (7 days). Such discrepancies between the two countries are based not only on the differences in the literature search and interpretation, but also on the different approvals granted by the national health insurance system, manufacturing process of the antibiotics, and diagnostic techniques in each country. Collaborations are required to minimize the discrepancies between the two countries based on cost-effectiveness.

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.

Characteristics of Helicobacter pylori‐positive and Helicobacter pylori‐negative gastric mucosa‐associated lymphoid tissue lymphoma and their influence on clinical outcome

To compare clinicopathologic and molecular characteristics of low-grade gastric mucosa-associated lymphoid tissue lymphoma depending on Helicobacter pylori positivity and to find out a predictive factor for unresponsiveness to Helicobacter pylori eradication therapy in Korea. A total of 53 Helicobacter pylori-positive and 13 negative mucosa-associated lymphoid tissue lymphoma patients were enrolled, and tissues from 21 patients were investigated to examine the presence of t(11;18)(q21;q21) with fluorescence in situ hybridization. Clinicopathologic features such as the endoscopic appearance, dominant site of lesion, depth of invasion, clinical stage, and the existence of MALT1 gene rearrangement were compared between these two groups. Fifty-six patients who underwent H. pylori eradication therapy were divided into responder and nonresponder groups. The two groups were analyzed to calculate odds ratios for resistance to the eradication. Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma patients averaged a more advanced clinical stage than H. pylori-positive (p = .023) patients. The frequency of t(11;18)/API2-MALT1 did not differ between H. pylori-positive (45.5%) and H. pylori-negative cases (55.6%). Thirty-eight of 51 (74.5%) H. pylori-positive patients achieved complete regression after the eradication, while 2 of 5 (40%) H. pylori-negative patients obtained regression. Presence of lesions in both distal and proximal parts of stomach (p = .041) and bearing of t(11;18)(q21;q21) (p = .007) were predictors for nonresponsiveness for H. pylori eradication. Helicobacter pylori eradication could be performed as a primary therapy regardless of H. pylori status, and assessing t(11;18)/API2-MALT1 would be considered after failure to remission by H. pylori eradication.

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.

Low Grade Gastric Mucosa-associated Lymphoid Tissue Lymphoma: Clinicopathological Factors Associated withHelicobacter pyloriEradication and Tumor Regression

Background/AimsEradication of Helicobacter pylori is widely accepted as initial therapy for low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, approximately 20% of patients with this disease are not responsive to H. pylori eradication therapy. The aim of this study was to assess remission and relapse rates of low-grade gastric MALT lymphoma after H. pylori eradication and identify the clinical factors that affect remission.MethodsThirty-nine patients diagnosed with gastric MALT lymphoma (May 2003 to May 2010) were retrospectively analyzed.ResultsOf the 39 patients, 30 (77%) had a H. pylori infection. There were 35/39 (90%) patients with stage I. Among stage I, 25 patients with the infection underwent eradication therapy and 22/25 (88%) achieved remission. The total regression rate with eradication only in stage I was 24/28 (86%). The median time to remission was 98 days (range, 22 to 397 days). Age, tumor location, invasion depth, H. pylori burden, and severity of mononuclear leukocyte and neutrophil infiltration were not related to remission. However, patients with less neutrophil infiltration were more likely to achieve a successful first H. pylori eradication (p=0.049).ConclusionsThe results show that the rate of low-grade gastric MALT lymphoma regression (86%) with H. pylori eradication alone was higher than that in Western studies (77.8%) and that neutrophil infiltration was inversely related to success of the first H. pylori eradication procedure.

Treatment outcome of localizedHelicobacter pylori-negative low-grade gastric MALT lymphoma

To investigate treatment outcome of Helicobacter pylori (H. pylori)-negative low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. In this study, we retrospectively reviewed the clinical outcome and clinicopathologic factors of stage IE H. pylori-negative low-grade gastric MALT lymphoma cases from August 1998 to June 2009. A total of eleven patients with H. pylori-negative low-grade gastric MALT lymphoma were enrolled in the study and received anti-H. pylori eradication treatment and/or radiotherapy or excisional therapy. Complete remission (CR) of gastric MALT lymphoma was achieved in all patients. The time to CR was 1-66 mo (median, 1 mo). Eradication therapy may be offered as an initial treatment option even in cases of localized H. pylori-negative gastric MALT lymphoma.

Helicobacter pylori and Gastric Mucosa-associated Lymphoid Tissue (MALT) Lymphoma: Updated Review of Clinical Outcomes and the Molecular Pathogenesis

In most H. pylori-positive patients, gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphomas regress both endoscopically and histopathologically after H. pylori eradication, but no factors that can be predictive of the response to the eradication have been definitively identified, and there is little information on how to determine the optimal observation period before additional treatment can be started. Here, clinical studies dealing with the diagnosis and treatment of gastric MALT lymphomas and H. pylori published during the last 5 years were systematically reviewed, and studies identifying the molecular approaches involved in the pathogenesis were summarized. Most of the clinical studies indicate a favorable effect of H. pylori eradication on the clinical outcome of gastric MALT lymphomas. Some studies suggest the necessity of additional treatment in nonresponders to H. pylori eradication, while others suggest the adoption of a watch-and-wait strategy. The molecular characteristics of MALT lymphomas could play an important role in prognostic prediction and the selection of further therapeutic intervention after the eradication. This updated review of gastric MALT lymphomas illustrates the potential efficacy of H. pylori eradication in tumor remission, but further molecular characterization is necessary to establish the most suitable therapeutic strategy for patients who do not respond to eradication.

Clinical aspects of Helicobacter pylori infection

The Helicobacter pylori (Hp) infection is common. However, only 10-20% of infected individuals require antibacterial treatment. The main indications to such treatment are peptic ulcer disease, atrophic gastritis, dyspeptic symptoms, previous surgical procedure for gastric cancer, family history of gastric cancer and low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The treatment may also be undertaken at the patient's request. To detect the infection the urease test (when the patient has indications for gastroscopy), the urea breath test or serologic test are most commonly used. A standard treatment of Hp infection consists of a 7-day administration of one of the proton pump inhibitors and 2 out of 3 antibiotics such as amoxicillin, clarithromycin and metronidazole. After failure of the first-line treatment, the recommended second choice treatment is a quadruple treatment regimen consisting of bismuth salts, tetracycline, metronidazole and proton pump inhibitor. European guidelines (Maastricht III) allow the use of the quadruple treatment regimen already as the first choice treatment and therapy prolongation up to 14 days. Ineffectiveness of the second-line treatment is an indication for antimicrobial susceptibility testing. New antibiotics used for Hp eradication are levofloxacin and rifabutin. Eradication treatment should be obligatorily assessed with the use of the urease or breath test only in patients with peptic ulcer bleeding. The current guidelines do not envisage an active search for Hp infection in an asymptomatic population and treating people infected with this bacterium, for gastric cancer prevention.

Magnified endoscopic findings of gastric low-grade mucosa-associated lymphoid tissue lymphoma

We report magnified endoscopic findings of gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphoma before and after anti-tumor therapies. Magnifying chromoendoscopy with crystal violet was carried out in nine patients with low-grade MALT lymphoma of the gastric corpus with Helicobacter plyori infection. A Wotherspoon histologic score of 5 was used as the criterion to make the histopathologic diagnosis. On conventional endoscopy, each patient was classified as having a superficial spreading type of the lymphoma, varying from gastritis to adenocarcinoma-like appearance. Anti-H. pylori treatment was successful in all cases. Complete regression was observed in six of the nine patients with MALT lymphoma and no regression was seen in three during the median follow-up of 12 months. Magnified endoscopic findings consisted exclusively of irregular and destroyed gastric pits in the lymphoma lesions. Histopathologic examination of targeted biopsies obtained from the affected mucosa with the abnormal pit pattern revealed the characteristic features of lymphoepithelial lesions and centrocyte-like cell infiltration. In six patients who underwent repeat magnifying endoscopy at 6 months or more after anti-tumor therapies (five with complete regression following anti-H. pylori therapy and one who had been treated with radiation), the abnormal pits appeared to have returned to normal. Magnifying endoscopy can reliably identify irregular and destructive pit patterns in the lymphoma lesions, and aid the prediction ofhistopathlogic regression.

Helicobacter pylori eradication for low-grade gastric mucosa-associated lymphoid tissue lymphoma is more successful in inducing remission in distal compared to proximal disease

A series of studies has shown that Helicobacter pylori eradication induces remission in most patients with low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, there have been few reports about the effect of bacterial treatment on the gastric MALT lymphoma in Korea, a well-known H. pylori endemic area. A total of 111 H. pylori-infected patients were prospectively enrolled in Seoul National University Hospital and 99 among them were completely followed up according to our protocol. After H. pylori eradication, tumoural response was evaluated by endoscopy and histopathology every 2–3 months till complete remission (CR) and every 6 months after achieving CR. Median follow-up period was 41 months (range, 11–125 months). Helicobacter pylori was successfully eradicated in all 99 patients and CR was obtained in 84 (84.8%) of 99 patients. The median time to reach CR was 3 months and 94% of CR is in continuous complete remission. Five patients with CR relapsed after 10–22 months without the evidence of H. pylori reinfection. Cumulative recurrence rate was 2.3, 7.7 and 9.3% at 1, 2 and 3 years, respectively. Tumours were mainly located in distal stomach (67.7%) and tumours in distal stomach were associated with more favourable response than those in proximal stomach (P=0.001). Majority of patients with low-grade gastric MALT lymphoma treated by exclusive H. pylori eradication have a favourable long-term outcome, offering a real chance of cure. Tumour location could be a predictive factor for remission following H. pylori eradication.

Outcome of Radiotherapy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma Refractory to Helicobacter Pylori Eradication Therapy

Most low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphomas respond to eradication of H. pylori, however, some are refractory. The effectiveness of radiotherapy for MALT lymphoma refractory to H. pylori eradication has been demonstrated. However, the long-term outcome and associated late radiation morbidity of radiotherapy for gastric MALT lymphoma are unclear. We evaluated the efficacy of radiotherapy and the radiation-associated adverse effects for gastric MALT lymphoma refractory to H. pylori eradication therapy. Eighteen patients with H. pylori-positive gastric MALT lymphoma received H. pylori eradication therapy, of which three patients refractory to eradication of H. pylori were subsequently treated with irradiation (median 39 Gy, range 36-40 Gy). Efficacy of radiotherapy and associated radiation morbidity were evaluated. Adverse events were evaluated according to RTOG and NCI-CTC criteria. Radiation was well tolerated. All three patients treated with radiotherapy achieved complete remission, which was sustained for a median follow-up period of 42.0 months (range, 24-72 months). As acute radiation side effects, all patients experienced mild nausea (Grade 1 by RTOG and 1 point [1 category] in NCI-CTC). One patient had Grade 1 appetite loss. There were no severe late adverse events. One patient had left kidney atrophy of approximately 10%, but none had renal dysfunction. Radiotherapy for patients with gastric MALT lymphoma refractory to H pylori eradication was effective without any critical acute or late adverse events.

Long-term persistence of molecular disease after histological remission in low-grade gastric MALT lymphoma treated with H. pylori eradication. Lack of association with translocation t(11;18): a 10-year updated follow-up of a prospective study

Localized low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma can regress after Helicobacter pylori eradication, but IgV(H) gene monoclonality may persist. We studied the long-term histological and molecular follow-up of 24 patients and the possible association of t(11;18) with the persistent monoclonality. From January 1994, 24 untreated patients with stage I low-grade gastric MALT lymphoma associated with H. pylori were prospectively studied. They all received eradication treatment and were sequentially followed-up with endoscopies for histological and molecular studies. Rearrangement of the IgV(H) gene was studied by PCR analysis. MALT1 locus alterations were studied by FISH. Twenty-two of the 24 patients (91%) achieved disappearance of the lymphoma. Eighteen (82%) of the 22 histologically cured patients and 16 of the 19 (84%) with long follow-up had monoclonality. Three patterns of development of IgV(H) gene rearrangements were observed: four patients (21%) had polyclonal rearrangements; eight (58%) had maintained/intermittent monoclonality and four (21%) had occasional monoclonality, mostly after H. pylori reinfection. Only one patient (6%) with persistent monoclonality relapsed. The remaining 18 patients maintained the remission, despite the persistent monoclonality in 15, for a median of 66 months (range 20-113). t(11;18) was not found in any of the patients with persistent monoclonality. Time and the number of endoscopies performed were not related with the occurrence of monoclonality. In stage I low-grade gastric MALT lymphoma eradication of H. pylori achieves prolonged histological remission in 90% of patients, but molecular remission is not accomplished in most cases. Molecular disease persists for years, but is not associated with t(11;18).