Gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML) is usually a low-grade B-cell neoplasia strongly associated with Helicobacter pylori (H. pylori)-induced chronic gastritis. Clinical practice guidelines currently recommend H. pylori eradication as the preferred initial treatment for early-stage GML. To determine the practical effect of bacterial eradication as the sole initial therapy for early-stage GML, an updated analysis and review of available evidence is imperative.

To perform a meta-analysis to assess the rate of complete remission (CR) of H. pylori-positive early-stage GML following bacterial eradication.

We performed independent, computer-assisted literature searches using the PubMed/MEDLINE, Embase, and Cochrane Central databases through September 2022. Prospective and retrospective observational studies evaluating the CR of early-stage GML following bacterial eradication in H. pylori-positive patients. The risk of bias was assessed using Joanna Briggs Institute (JBI) Critical Appraisal Tools. The pooled estimate of the complete histopathological remission rate and respective confidence intervals (95%CI) were calculated following the random-effects model. Heterogeneity and inconsistency were assessed using Cochran's Q test and I2 statistic, and heterogeneity was defined as P < 0.01 and I² > 50%, respectively. Subgroup and meta-regression analyses were conducted to explore potential sources of heterogeneity.

The titles and abstracts of 1576 studies were screened; 96 articles were retrieved and selected for full-text reading. Finally, 61 studies were included in the proportional meta-analysis (P-MA). Forty-six were prospective and fifteen were retrospective uncontrolled, single-arm, observational studies. The overall risk of bias was low to moderate in all but a single report, with an average critical appraisal score across all studies of 79.02%. A total of 2936 H. pylori-positive early-stage GML patients, in whom H. pylori was successfully eradicated, were included in the analysis. The pooled CR of H. pylori-positive early-stage GML after bacterial eradication was 75.18% (95%CI: 70.45%-79.91%). P-MA indicated the substantial heterogeneity in CR reported across studies (I 2 = 92%; P < 0.01). Meta-regression analysis identified statistically significant effect modifiers, including the proportion of patients with t(11;18)(q21;q21)-positive GML and the risk of bias in each study.

Comprehensive synthesis of available evidence suggests that H. pylori eradication is effective as the sole initial therapy for early-stage GML. Although the substantial heterogeneity observed across studies limits the interpretation of the pooled overall CR, the present study is a relevant to informing clinical practice.

Endoscopic diagnosis of stomach mucosa-associated lymphoid tissue (MALT) lymphoma is often difficult because few specific findings are indicated. Even when MALT lymphoma is suspected by endoscopy, it is still difficult to make a definitive diagnosis by biopsy because lymphoma cells sometimes distribute unevenly. We previously reported that a tree-like appearance (TLA) is a characteristic finding of MALT lymphoma by narrow-band imaging (NBI) magnifying endoscopy and it is valuable in the selection of an optimal biopsy site in MALT lymphoma. Here, we study the frequency of TLA and evaluate the relationship between the response to eradication therapy and TLA in MALT lymphoma.

We retrospectively examined the clinical background, endoscopic findings, response to eradication therapy, and Helicobacter pylori infection status of 16 patients diagnosed with MALT lymphoma who were referred to our hospital from April 2007 to August 2012. The regimen for eradicationtherapy consisted of rabeprazole, with amoxicillin and clarithromycin, all given for 7 days.

TLA was found in 75% (12/16) and H. pylori infection in 75% (12/16) of patients diagnosed with MALT lymphoma by NBI magnifying endoscopy. In all complete regression (CR) patients after eradication treatment, the TLA finding had disappeared (100%); however, in the non-CR patients, TLA remained the same as before the eradication therapy (P=0.002).

These results suggest that NBI magnifying endoscopy may be useful not only in the diagnosis but also in the evaluation of the response to eradication therapy of MALT lymphoma of the stomach.

This study was conducted to evaluate the long-term outcomes in patients with stage IE and IIE mucosa-associated lymphoid tissue (MALT) lymphomas treated with involved field radiotherapy (RT).

Between 1989 and 2004, 192 patients with stage I and II MALT lymphomas were treated. The report focuses on 167 patients who received RT. The median age of patients was 58 years with a female predominance (2:1). Presenting sites were as follows: orbital adnexa in 71 patients, salivary glands in 28 patients, stomach in 25 patients, thyroid in 21 patients, and other sites in 22 patients. The median dose to nonorbital sites was 30 grays (Gy) (range, 17.5-35 Gy) and was 25 Gy for the orbit (range, 25-35 Gy). The median follow-up was 7.4 years (range, 0.67-16.20 years).

Complete response and complete response, unconfirmed (CR/CRu) was noted in 166 (99%) patients. The 10-year recurrence-free rate (RFR) was 76%, the disease-free survival (DFS) rate was 68%, the overall survival (OS) rate was 87%, and the cause-specific survival rate was 98%. According to presenting site, the 10-year RFR was 95% for thyroid, 92% for stomach, 68% for salivary glands, and 67% for orbit. Patients with thyroid and gastric MALTs had better outcome compared with patients with MALTs diagnosed at other sites (P=.004). Among those patients who achieved CR, 19% developed disease recurrence (n=31), chiefly in distant sites or untreated contralateral-paired organs. At the time of disease recurrence, 7 patients (23%) had transformed to diffuse large B-cell lymphoma, 2 of whom died of lymphoma. The 5-year OS rate after treatment failure was 83%.

Patients with localized MALT lymphomas are reported to have excellent clinical outcome after moderate-dose RT, and some are likely cured. In the current study, thyroid and gastric MALTs were found to have significantly less risk of distant recurrence. Despite disease recurrence, the overall survival remains excellent in these patients.

Different remission rates of gastric low-grade, B-cell, mucosa-associated lymphoid tissue (MALT) lymphoma have been reported after Helicobacter pylori eradication. We assessed the long-term remission and relapse rates of early stage MALT lymphoma in patients treated only by H pylori eradication and identified factors that might predict outcome.

This systematic review analyzed data from 32 studies, including 1408 patients.

The MALT lymphoma remission rate was 77.5% (95% confidence interval, 75.3-79.7), and was significantly higher in patients with stage I than stage II(1) lymphoma (78.4% vs 55.6%; P = .0003) and in Asian than in Western groups (84.1% vs 73.8%; P = .0001). Neoplasia confined to the submucosa regressed more frequently than that with deeper invasion (82.2% vs 54.5%; P = .0001); patients with lymphoma localized to the distal stomach experienced regression more frequently than those with lymphoma of the proximal stomach (91.8% vs 75.7%; P = .0037). The remission rate was higher among patients without the API2-MALT1 translocation than in those with this translocation (78% vs 22.2%; P = .0001). In an analysis of data from 994 patients, 7.2% experienced lymphoma relapse during 3253 patient-years of follow-up evaluation, with a yearly recurrence rate of 2.2%. Infection and lymphoma were cured by additional eradication therapy in all patients with H pylori recurrence (16.7%). Five (0.05%) of the patients initially cured of lymphoma developed high-grade lymphoma within 6 to 25 months of therapy.

H pylori eradication is effective in treating approximately 75% of patients with early stage gastric lymphoma. Long-term follow-up evaluation of these patients is needed to detect early lymphoma relapse or progression.

Helicobacter pylori eradication is recognized as the initial therapy for gastric low-grade, B-cell, mucosa-associated lymphoid tissue (MALT) lymphoma. This study assesses (i) the H. pylori eradication rates for various first- and second-line and rescue therapies and (ii) the associated reinfection rates in patients.

Pooled data analysis of systematic review of the literature was performed in this study.

Data from 34 studies with 1,271 treated patients were used. After first-line therapy, the infection was cured in 91% (95% confidence interval (CI)=89.4-92.5) of cases, the eradication rate being higher after dual therapy compared with the 7- or 14-day triple therapies (P=0.0525). After second-line therapy, the eradication rate was 80.8% (95% CI=82.7-95.1), being higher after triple rather than quadruple therapy. Further therapies (from three to five attempts) cured the infection in 75% of patients. H. pylori infection was ultimately cured in 1,250 patients, resulting in eradication rates of 98.3% (95% CI=97.6-99) and 99.8% (95% CI=99.6-100) at intention-to-treat and per-protocol analysis levels, respectively. Bacterial reinfection occurred in 18 (2.7%; 95% CI=1.4-3.9) of 676 patients who were followed-up (0.7% yearly). Overall, gastric lymphoma remission was achieved in 973 (77.8%) of 1,250 patients successfully cured of H. pylori infection.

This was the first comprehensive ( approximately 1,300 patients) analysis of the therapeutic management of H. pylori in gastric lymphoma patients. Data suggest that this infection is easily managed in these patients, being cured in nearly all cases.

Data on management and long-term follow-up of Helicobacter pylori-associated MALT-lymphoma in clinical practice are scanty. We evaluate the long-term efficacy of H. pylori eradication on low-grade MALT-lymphoma, and the efficacy of further therapies in refractory patients.

This study enrolled patients with stages I-II(1) MALT-lymphoma and H. pylori infection. H. pylori eradication was attempted in all patients. Patients with lymphoma persistence or progression following H. pylori treatments received further lymphoma treatments. Both 5-year and disease-free survivals were calculated.

Sixty patients (stage I/II(1): 50/10) were followed up for a median time of 65 months (range 7-156). H. pylori infection was successfully eradicated in 53 (88.3%) patients following three consecutive therapeutic attempts, and lymphoma regressed in 42 (79.2%) of these patients. Sixteen patients received anti-neoplastic treatments due to either lymphoma persistence or progression, and lymphoma was cured in 14 (87.5%) cases. At follow-up, lymphoma relapsed in 13/42 (30.9%) patients within a median time of 19 months (range 3-41), and all but 1 patient were cured with further therapies. Overall, lymphoma regression was achieved in 56 patients (93.3%). The 5-year and disease-free survivals were 94.7% and 74.6%, respectively.

In clinical practice, a conservative approach with antibiotic eradication seems to be appropriate management for early-stage MALT-lymphoma, with oncologic therapy being reserved for those patients who fail to respond to H. pylori therapy.

The utility of magnifying endoscopy for diagnosis of epithelial tumors has been reported, but there are few reports for nonepithelial tumors.

To determine the characteristics of magnified images of gastric extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) before and after treatment.

This was a retrospective study.

Endoscopy Unit, Hokkaido University Hospital.

Eleven patients diagnosed with MALT lymphoma were enrolled.

The microstructural pattern, collecting venules, and abnormal vessels in gastric MALT lymphoma were assessed before treatment and at 4 to 7 months after treatment by using magnifying endoscopy. MAIN OUTCOME MEASUREMENT AND RESULTS: The characteristics of magnified endoscopic images before treatment were the disappearance of gastric pits and the appearance of abnormal vessels. Ten cases of Helicobacter pylori-infected MALT lymphoma were treated by H. pylori eradication, and 1 H. pylori-negative case was treated by radiation therapy after eradication therapy. Ten patients achieved complete disease remission. After the treatment, recovery of gastric pits and subepithelial capillary network, and the disappearance of abnormal vessels were revealed by magnifying endoscopy.

This was a small pilot study.

Magnified findings of gastric MALT lymphoma before and after therapy seem to correlate with complete response and no response.

Primary gastrointestinal lymphoma represents the most common location of extranodal lymphoma. With the bulk of disease manifesting within the gastrointestinal tract and contiguous lymph nodes, many of the lymphomas occurring in the peripheral lymph nodes can also present with primary gastrointestinal tract involvement. Molecular biology has recently enabled significant progress in the diagnosis and management of primary gastrointestinal lymphoma. Herein, we will discuss the major lymphomas affecting the bowel and highlight their key morphological, immunophenotypical and molecular diagnostic attributes. Similarly, in keeping with recent therapeutic advances, we will briefly discuss some important treatment considerations. Thus, this review is intended to offer clinicians and pathologists an overview of primary gastrointestinal lymphomas.

Mucosa-associated lymphoid tissue (MALT) lymphoma probably constitutes the best in vivo model showing how complex interplay between B lymphocytes and the surrounding microenvironment may lead to a neoplastic disorder. After the seminal discovery of the pathogenic association between Helicobacter pylori and gastric MALT lymphomas, evidence suggests the possible involvement of other infectious agents in the development of MALT lymphomas arising at different body sites. Although several other bacteria (Borrelia burgdorferi, Campylobacter jejuni, and Chlamydia psittaci) and viruses (Hepatitis C virus) seem to play a role in lymphomas presenting at different locations, a possible common pathogenic mechanism is emerging. Several lines of evidence suggest that different infectious agents might provide a chronic antigenic stimulation that elicits host immune responses able to promote clonal B-cell expansion. This model is also substantiated by the increasing number of patients with MALT lymphomas who exhibit objective clinical responses after antimicrobial therapy. A multidisciplinary approach is critical to better understand the complex etiopathogenesis of MALT lymphomas with the final goal to dissect the clinicopathologic heterogeneity of these disorders and design more tailored preventive and therapeutic approaches.

Primary gastrointestinal lymphomas are best exemplified by mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach and enteropathy-type T-cell lymphoma (ETL). Both lymphomas were initially recognized on morphological grounds and their identification as distinct clinicopathological entities has subsequently been vindicated following integrated immunophenotypic, molecular, and cellular biological investigations. Delineation of the phenotypic, molecular, and biological properties of these lymphomas at various clinicopathological stages of their development has also provided critical information for the clinical management of patients with these diseases. Here, the histopathology and recent advances in phenotypic and molecular characterization of gastric MALT lymphoma and ETL and their applications in diagnosis and clinical management are reviewed.

Endoscopic ultrasonography (EUS) is a useful tool for the evaluation of gastric wall infiltration including gastric lymphoma. The aims of this study were to characterize gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphoma according to EUS findings and to evaluate the role of a miniature ultrasound probe in the long-term follow up.

From January 1994 to March 2002, 20 patients were proven to have gastric low-grade MALT lymphoma. Endoscopic ultrasonography was performed with a conventional echoprobe and/or a miniature ultrasound probe for initial staging and a miniature ultrasound probe was performed during follow up. All patients positive for Helicobacter pylori received a 2-week course of omeprazole, amoxicillin and clarithromycin.

Helicobacter pylori infection was found in 17 (85%) patients. In all patients, H. pylori was eradicated after treatment. Initial EUS showed significantly greater wall thickness (6.1 +/- 3.0 mm) in MALT lymphoma patients when compared with control (2.8 +/- 0.3 mm). The infiltrative patterns included wall thickening (3.5-14.1 mm) in 18 patients: stage E-I1 in 16 (mucosa and/or submucosa), stage E-I2 in one and stage E-II in one. Complete regression of MALT lymphoma following treatment for H. pylori was noted in 14 patients, with a mean duration of 11.3 +/- 9.1 months. Follow-up miniature ultrasound probe sonography showed comparative reduction in wall thickness (P < 0.05).

Endoscopic ultrasonography plays a valuable role in the initial staging and long-term follow up of gastric low-grade MALT lymphoma. The application of a miniature ultrasound probe enables adequate evaluation in the majority of these patients, with additional benefits.

The development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is dependent on Helicobacter pylori infection. Bacterial colonisation of the gastric mucosa triggers lymphoid infiltration and the formation of acquired MALT. The bacterial infection induces and sustains an actively proliferating B-cell population through direct (autoantigen) and indirect (intratumoral T cells specific for H. pylori) immunological stimulation. Moreover, the bacterial infection provokes a neutrophilic response, which causes the release of oxygen free radicals. These reactive species may promote the acquisition of genetic abnormalities and malignant transformation of reactive B cells. A transformed clone carrying the translocation t(1;18)(q21;q21) forms a MALT lymphoma, the growth of which is independent of H. pylori and will not respond to bacterial eradication. Malignant clones without t(11;18)(q21;q21), but with other genetic abnormalities, such as trisomy 3 or microsatellite instability, depend critically on immune stimulation mediated by H. pylori for their clonal expansion. In the early stages, the tumour can be successfully treated by eradication of the bacterium, whereas at later stages the tumour may escape its growth dependency through acquisition of additional genetic abnormalities such as t(1;14)(p22;q32) and t(1;2)(p22,p12) involving the BCL-10 gene. Finally, further genetic abnormalities, such as inactivation of the tumour suppressor genes, p53 and p16, can lead to high-grade transformation. Detection of these abnormalities may help with the clinical management of patients with gastric MALT lymphoma.

Current standard treatment regimens for Helicobacter pylori infection provide eradication rates 80 to 90%. These rates have been achieved with a variety of 1-week triple therapies using two antibiotics and an acid suppressant. Antibiotic resistance, which may develop during failed treatment, is becoming increasingly common and has led to studies of new regimens for primary therapy, and new strategies for salvage of failed therapy. Other regimens have been designed and tested with the aim of decreasing the cost of initial therapy or to improve compliance, but abbreviated regimens have high incidence of failure and may add to the problem of resistance. Increasing attention has been paid to the need for, and timing of, the determination of antibiotic resistance of H. pylori isolates either at the time of initial diagnosis or after treatment failure. New, simpler, and noninvasive methods are offered for follow-up to determine if eradication has been successful. Treatment regimens should be chosen based on local drug susceptibility patterns and the availability of approved therapeutic agents in each country. Established indications for testing for H. pylori and administering therapy include active or inactive peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, as well as hyperplastic polyps, hyperplastic gastropathy, postendoscopic resection for gastric malignancy, and acute H. pylori gastritis. It is now largely accepted that noninvestigated dyspepsia is an indication for testing for and treating H. pylori, but that dyspeptic symptoms shown not to be associated with ulcer (nonulcer dyspepsia) do not now provide an indication for testing. Controversial or unresolved indications for testing and treating include planned use of chronic antisecretory therapy, planned use of nonsteroidal anti-inflammatory drugs, and use as a general approach to the prevention of gastric cancer.

For almost 10 years, we have been familiar with the concept of mucosa-associated lymphoid tissue (MALT)-type lymphoma of the stomach caused by chronic Helicobacter pylori infection. Many epidemiologic, biologic, and molecular genetic studies have implicated H. pylori for its role in lymphoma genesis. Since the first reports on complete remission of gastric MALT lymphomas after cure of bacterial infection, many clinical studies have investigated the effect of eradicating H. pylori on the course of MALT lymphoma, and indeed were able to confirm remission of the lymphoma. To date, more than 650 patients worldwide have been treated for gastric MALT lymphoma with antibiotics, and we have gained many new insights concerning the biologic behavior of this disease, especially from the deepened knowledge of cytogenetics. Furthermore, factors relevant for the prediction of treatment outcome have been identified, which has helped to stratify patients into risk groups.

A number of scientific breakthroughs since H pylori first became recognized as a human pathogen have increased our understanding of the pathogenesis of gastroduodenal disease. In particular, advances in molecular bacteriology and the complete sequencing of the H pylori genome in 1999, and soon thereafter the human genome, provide tools allowing better delineation of the pathogenesis of disease. These molecular tools for both bacteria and host should now be applied to multicenter pediatric studies that evaluate disease outcome. More recent developments indicate that a better understanding of the microbial-host interaction is critical to furthering knowledge with respect to H pylori-induced diseases. Studies are needed to evaluate either DNA-based or more traditional protein-based vaccines, to evaluate more specific antimicrobials that confer minimal resistance, and to evaluate probiotics for the management of H pylori infection. Multicenter multinational studies of H pylori infection in the pediatric population, which include specific, randomized controlled eradication trials, are essential to extend current knowledge and develop better predictors of disease outcome.

Mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct disease with specific clinical and pathologic features that may affect diverse organs. We analyzed our recent experience with Stage I/II MALT lymphoma presenting in the stomach and other organs to assess the outcome following involved field radiation therapy (RT).

Seventy patients with Stage IE (62) and IIE (8) disease were treated between 1989 and 1998. Patients with transformed MALT were excluded. The median age was 62 years (range, 24--83 years), M:F ratio 1:2.2. Presenting sites included stomach, 15; orbital adnexa, 19; salivary glands, 15; thyroid, 8; lung, 5; upper airways, 3 (nasopharynx, 2; larynx, 1); urinary bladder, 3; breast, 1; and rectum, 1. Staging included site-specific imaging, CT abdomen in 66 patients (94%) and bone marrow biopsy in 54 (77%). Sixty-two patients received radiation therapy: 52 received RT alone, 7 received chemotherapy and RT, and 3 received antibiotics followed by RT. Median RT dose was 30 Gy (range, 17.5--35 Gy). Most frequently used RT prescriptions were 25 Gy (26 patients-18 orbit, 6 stomach, and 2 salivary glands), 30 Gy (23 patients), and 35 Gy (8 patients). Five patients had complete surgical excision of lymphoma and no other treatment (stomach 1, salivary 2, lung 2), whereas 2 patients with gastric lymphoma received antibiotics only. One patient refused treatment and was excluded from the analysis of treatment outcome, leaving 69 patients with a median follow-up of 4.2 years (range, 0.3-11.4 years).

A complete response was achieved in 66/69 patients, and 3 patients had partial response (2 lung, 1 orbit). The 5-year disease-free survival (DFS) was 76%, and the overall survival was 96%. No relapses were observed in patients with stomach and thyroid lymphoma. The 5-year DFS for these patients was 93%, in contrast to 69% for patients presenting in other sites (p = 0.006). Among the 5 patients treated with surgery only, 2 relapsed locally (lung, and minor salivary gland). Among 62 patients who received RT, 8 relapsed (2 salivary, 3 orbit, 1 nasopharynx, 1 larynx, 1 breast). Three patients relapsed in the nonirradiated contralateral paired organ, 4 in distant sites, and 1 in both local and distant sites. The overall local control rate with radiation was 97% (60/62 patients).

Localized MALT lymphomas have excellent prognosis following moderate-dose RT. Gastric and thyroid MALT lymphomas have better early outcome, as compared to the other sites where distant failure is more common. Relapses were observed in nonirradiated paired organs or distant sites. Further follow-up is required to assess the impact of failure on survival.