Transformed gastric mucosa-associated lymphoid tissue lymphoma originating in the colon and developing metachronously after Helicobacter pylori eradication:A case report

BACKGROUND Helicobacter pylori(H.pylori)eradication treatment for primary gastric mucosaassociated lymphoid tissue(MALT)lymphoma has already been established.However,t(11;18)(q21;q21)/API2-MALT1 translocation-positive lesions are a type of primary gastric MALT lymphoma in which a response to eradication treatment is difficult to achieve.In addition,trisomy 18 may be associated with diffuse large B-cell lymphoma(DLBCL)transformation of gastric MALT lymphoma.CASE SUMMARY A 66-year-old man was diagnosed with MALT lymphoma in the ascending colon by colonoscopy and biopsy.Two years later,esophagogastroduodenoscopy revealed chronic atrophic gastritis that was positive for H.pylori,and eradication treatment was administered.Two years and nine months later(at the age of 70),a new ulcerative lesion suggestive of MALT lymphoma appeared in the gastric body,and six months later,a similar lesion was also found in the fundus.One year later(4 years and 3 months after H.pylori eradication),at the age of 72,the lesion in the gastric body had become deeper and had propagated.A biopsy revealed a pathological diagnosis of DLBCL.Both MALT lymphoma lesions in the ascending colon and DLBCL lesions in the stomach were positive for the t(11;18)(q21;q21)/API2-MALT1 translocation,and trisomy 18q21 was also detected.After 6 courses of R-CHOP(rituximab,cyclophosphamide,doxorubicin,vincristine and prednisone)chemotherapy,all of the above lesions disappeared[complete remission(CR)],and CR has been maintained for more than 3 years.In addition,both the colonic and gastric lesions were proven to have the same clonality.CONCLUSION Because the patient had a MALT1 translocation with trisomy 18q21,it was thought that this gastric MALT lymphoma developed independently of H.pylori infection and progressed.

Therapy of gastric mucosa associated lymphoid tissue lymphoma

Gastric mucosa associated lymphoid tissue （MALT） lymphoma has recently been incorporated into the World Health Organization （WHO） lymphoma classification, termed as extranodal marginal zone B-cell lymphoma of MALT-type. In about 90% of cases this lymphoma is associated with H pylori infection which has been dearly shown to play a causative role in lymphomagenesis. Although much knowledge has been gained in defining the clinical features, natural history, pathology, and molecular genetics of the disease in the last decade, the optimal treatment approach for gastric MALT lymphomas, especially locally advanced cases, is still evolving. In this review we focus on data for the therapeutic, stage dependent management of gastric MALT lymphoma. Hence, the role of eradication therapy, surgery, chemotherapy and radiotherapy is critically analyzed. Based on these data, we suggest a therapeutic algorithm that might help to better stratify patients for optimal treatment success.

Role of Helicobacter pylori in gastric mucosa-associated lymphoid tissue lymphomas

Mucosa-associated lymphoid tissue (MALT) lymphoma is an indolent extranodal marginal zone B-cell lymphoma, originating in acquired MALT that is induced in mucosal barriers as part of a normal adaptive immune response to a chronic immunoinflammatory stimulus, most notably chronic infection by Helicobacter pylori (H. pylori). This antigenic stimulation initially leads to lymphoid hyperplasia; the acquisition of additional genetic aberrations culminates in the activation of intracellular survival pathways, with disease progression due to proliferation and resistance to apoptosis, and the emergence of a malignant clone. There are descriptions of MALT lymphomas affecting practically every organ and system, with a marked geographic variability partially attributable to the epidemiology of the underlying risk factors; nevertheless, the digestive system (and predominantly the stomach) is the most frequently involved location, reflecting the gastrointestinal tract’s unique characteristics of contact with foreign antigens, high mucosal permeability, large extension and intrinsic lymphoid system. While early-stage gastric MALT lymphoma can frequently regress after the therapeutic reversal of the chronic immune stimulus through antibiotic eradication of H. pylori infection, the presence of immortalizing genetic abnormalities, of advanced disease or of eradication-refractoriness requires a more aggressive approach which is, presently, not consensual. The fact that MALT lymphomas are rare neoplasms, with a worldwide incidence of 1-1.5 cases per 105 population, per year, limits the ease of accrual of representative series of patients for robust clinical trials that could sustain informed evidence-based therapeutic decisions to optimize the quality of patient care.

Synchronous and metachronous occurrence of gastric adenocarcinoma and gastric lymphoma: A review of the literature

The occurrence of both primary gastric lymphoma and gastric adenocarcinoma in the same patient is a rare entity. The possible causative factors of synchronous or metachronous occurrence of both malignancies and varieties in the treatment modalities are reviewed according to published cases in English language medical literature.

Gastric low-grade mucosal-associated lymphoid tissue-lymphoma: Helicobacter pylori and beyond

The stomach is the most frequently involved site for extranodal lymphomas,accounting for nearly two-thirds of all gastrointestinal cases.It is widely accepted that gastric B-cell,low-grade mucosal-associated lymphoid tissue(MALT)-lymphoma is caused by Helicobacter pylori(H.pylori)infection.MALT-lymphomas may engender different clinical and endoscopic patterns.Often,diagnosis is confirmed in patients with only vague dyspeptic symptoms and without macroscopic lesions on gastric mucosa.H.pylori eradication leads to lymphoma remission in a large number of patients when treatment occurs at an early stage(Ⅰ-Ⅱ1).Neoplasia confined to the submucosa,localized in the antral region of the stomach,and without API2-MALT1 translocation,shows a high probability of remission following H.pylori eradication.When both bacterial infection and lymphoma recur,further eradication therapy is generally effective.Radiotherapy,chemotherapy and,in selected cases,surgery are the available therapeutic options with a high success rate for those patients who fail to achieve remission,while data on immunotherapy with monoclonal antibodies (rituximab)are still scarce.The 5-year survival rate is higher than 90%,but careful,long-term follow-up is required in these patients since lymphoma recurrence has been reported in some cases.

Helicobacter pylori and gastric mucosa-associated lymphoid tissue lymphoma:Recent progress in pathogenesis and management

Recent progress in the research regarding the molecular pathogenesis and management of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is reviewed. In approximately 90% of cases, Helicobacter pylori (H. pylori) infection plays the causative role in the pathogenesis, and H. pylori eradication is nowadays the first-line treatment for this disease, which leads to complete disease remission in 50%-90% of cases. In H. pylori-dependent cases, microbe-generated immune responses, including interaction between B and T cells involving CD40 and CD40L co-stimulatory molecules, are considered to induce the development of MALT lymphoma. In H. pylori-independent cases, activation of the nuclear factor-κB pathway by oncogenic products of specific chromosomal translocations such as t(11;18)/API2-MALT1, or inactivation of tumor necrosis factor alpha-induced protein 3 (A20) are considered to contribute to the lymphomagenesis. Recently, a large-scale Japanese multicenter study confirmed that the long-term clinical outcome of gastric MALT lymphoma after H. pylori eradication is excellent. Treatment modalities for patients not responding to H. pylori eradication include a “watch and wait” strategy, radiotherapy, chemotherapy, rituximab immunotherapy, and a combination of these. Because of the indolent behavior of MALT lymphoma, second-line treatment should be tailored in consideration of the clinical stage and extent of the disease in each patient.

Primary gastric non-Hodgkin lymphomas:Recent advances regarding disease pathogenesis and treatment

Primary gastric lymphomas(PGLs)are distinct lymphoproliferative neoplasms described as heterogeneous entities clinically and molecularly.Their main histological types are diffuse large B-cell lymphoma(DLBCL)or mucosaassociated lymphoma tissue.PGL has been one of the main fields of clinical research of our group in recent years.Although gastric DLBCLs are frequent,sufficient data to guide optimal care are scarce.Until today,a multidisciplinary approach has been applied,including chemotherapy,surgery,radiotherapy or a combination of these treatments.In this minireview article,we provide an overview of the clinical manifestations,diagnosis and staging of these diseases,along with their molecular pathogenesis and the most important related clinical published series.We then discuss the scientific gaps,perils and pitfalls that exist regarding the aforementioned studies,in parallel with the unmet need for future research and comment on the proper methodology for such retrospective studies.Aiming to fill this gap,we retrospectively evaluated the trends in clinical presentation,management and outcome among 165 patients with DLBCL PGL who were seen in our institutions in 1980-2014.The study cohort was divided into two subgroups,comparing the main 2 therapeutic options[cyclophosphamide doxorubicin vincristine prednisone(CHOP)vs rituximab-CHOP(R-CHOP)].A better outcome with immunochemotherapy(R-CHOP)was observed.In the next 2 mo,we will present the update of our study with the same basic conclusion.

Molecular markers(PECAM-1,ICAM-3,HLA-DR)determine prognosis in primary non-Hodgkin's gastric lymphoma patients

AIM： To investigate the prognostic significance of PECAM-1, ICAM-3 and HLA-DR antigens in patients with primary non-Hodgkin＇s gastric lymphoma. METHODS： We immunohistochemically studied PECAM-1, ICAM-3 and HLA-DR antigen expression in 36 B-cell MALT-type primary gastric lymphoma patients. Ten non-malignant and ten healthy gastric tissue specimens were used as controls. Clinicopathological and survival data were correlated with the staining results. RESULTS： HLA-DR antigen expression was detected in 33 gastric lymphoma patients （91.7%） and 6 nonmalignant patients （54.5%）. PECAM-1 stained tumor cells of 10 patients （27.8%）, endothelial cells of 9 patients （25%） and inflammatory infiltrate of 4 patients （40%） with benign gastric disease. ICAM-3 expression was observed on the tumor cells of 17 patients （47.2%）, while 5 non-malignant patients （50%） were stained positive as well. None of the healthy controls was stained for any of the genes studied. In the multivariate analysis, HLA-DR antigen and PECAM-1 were proved to be statistically significant independent prognostic factors associated with a favourable and an unfavourable prognosis respectively （P= 0.009 and P= 0.003）. In the univariate analysis, PECAM-1（＋）/ICAM-3（-） and HLA-DR（-）/ICAM-3（-） patients exhibited a significantly decreased overall survival compared to those with the exactly opposite gene expression patterns （P=0.0041 and P= 0.0091, respectively）. Those patients who were HLA-DR（＋ ）/ICAM-3（＋ ）/PECAM-I（-） （n = 8） had a significantly higher survival rate compared to the rest of the group （n = 24） （P= 0.0289）. CONCLUSION： PECAM-1, ICAM-3 and HLA-DR are representative markers of tumor expansion potential and host immune surveillance respectively. Their combined use may help us to identify high-risk patients who could benefit from more aggressive therapeutic protocols.

Trisomy 3 may predict a poor response of gastric MALT lymphoma to Helicobacter pylori eradication therapy

AIM: To investigate the relation of the response to Helicobacter pylori eradication therapy to the depth of tumor invasion and chromosome abnormalities in patients with mucosaassociated lymphoid tissue (MALT) lymphoma and to determine the clinical value of aneuploidy.METHODS: We studied 13 patients with localized gastric MALT lymphoma of stage E1. Before eradication therapy,the depth of tumor invasion was assessed by endoscopic ultrasonography in 8 patients and by endoscopic examination and gastrointestinal series in the remaining patients. To detect chromosomal abnormalities, paraffin-embedded tissue sections of diagnostic biopsy specimens underwent tissuefluorescence in situ hybridization (FISH), using chromosomespecific α-satellite DNA probes for chromosomes 3,7,12,and 18 and YAC clones for t(11;18)(q21;q21).RESULTS: Seven of the 13 patients had complete regression(CR) in response to H pylori eradication therapy. No patient with CR had submucosal tumor invasion. Trisomy 18 was seen in 1 patient with CR, and both trisomies 12 and 18 were present in another patient with CR. All patients with no response or progressive disease had deep submucosal tumor invasion and showed t(11;18)(q21;q21) or trisomy 3. Trisomy 7 was not detected in this series of patients.CONCLUSION: The depth of tumor invasion is an accurate predictor of the response of stage E1 MALT lymphoma to H pylori eradication therapy and is closely associated with the presence of chromosomal abnormalities. Trisomy 3 may predict the aggressive development of MALT lymphoma.

EXPRESSION OF PTEN AND CASPASE-3 AND THEIR CLINICOPATHOLOGICAL SIGNIFICANCE IN PRIMARY GASTRIC MALIGNANT LYMPHOMA

Objective To investigate the expression of PTEN and Caspase-3 in malignant lymphoma of the stomach and explore their role in progression of primary gastric malignant lymphoma. Methods Formalin-fixed paraffin embedded tissues from 56 cases of primary gastric malignant lymphoma and their adjacent non-tumor mucosa were evaluated for PTEN and Caspase-3 protein ex-pression by streptavidin-biotin-complex (SABC) immunohistochemistry. Their expression was compared with clinical tumor parameters with the relationship between PTEN and Caspase-3 expression concerned as well. Results The positive rate of PTEN expression in primary gastric lymphomas(50.0%, 28/56) was significantly lower than that in adjacent non-tumor gastric mucosa(96.4%, 27/28)(P < 0.05). Meanwhile,43 of 56(76.8%)gastric lymphomas indicated Caspase-3 expression, less than that in adjacent non-tumor mucosa (93.5%, 29/31) (P < 0.05). The expression of PTEN was negatively correlated with invasion and lymph node metastasis of gastric lymphoma(P < 0.05), while the Caspase-3 expression was negatively associated with the latter one(P < 0.05). Additionally, the PTEN expression was posi-tively correlated with Caspase-3 expression in the primary gastric malignant lymphoma(P < 0.05). Conclusions The down-regulated expression of PTEN and Caspase-3 played an important role in progression of primary malignant gastric lymphoma. PTEN, as a molecular marker of pathobiological behaviors of tumor, contributes to tumor progression by increasing cell mobility and angiogenesis, as well as decreasing cell adhesion and apoptosis.

Remission of primary low-grade gastric lymphomas of the mucosa-associated lymphoid tissue type in immunocompromised pediatric patients

We report the remission of primary gastric lymphoma of the mucosa-associated lymphoid tissue （MALT） type in two immunocompromised pediatric patients. Patient 1, a 14-year-old boy in an immunocompromised state of unknown cause, complained of repeated abdominal pain. Examinations revealed gastric MALT with local invasion and lymph node involvement. Serum anti-Helicobacter pylori （H pylon） antibody was positive. H pylori eradication was abandoned due to its adverse effects. The MALT lesion spontaneously regressed over the next 24 months without any treatment for lymphoma. Patient 2, a 6-year-old boy, underwent cord blood transplantation for the treatment of adrenoleukodystrophy. He was administered immunosuppressants for graft-versus-host disease after transplantation. Nausea and hematochezia appeared and further examinations revealed gastric MALT with H pylori gastritis. Treatment consisting of medication for the Hpylori infection alone eradicated the Hpylori and completely resolved the patient＇s MALT lesion, as well. Patients i and 2 were followed up over periods of 10 years and 3 years, respectively, without any signs of relapse. In conclusion, gastric lymphoma of the MALT type can be cured by conservative treatment even in immunocompromised pediatric patients.

^(18)F-Fluorodeoxyglucose positron emission tomography/computed tomography comparison of gastric lymphoma and gastric carcinoma

AIM To compare ^(18)F-fluorodeoxyglucose positron emission tomography/computed tomography(^(18)F-FDG PET/CT) features in gastric lymphoma and gastric carcinoma.METHODS Patients with newly diagnosed gastric lymphoma or gastric carcinoma who underwent ^(18)F-FDG PET/CT prior to treatment were included in this study. We reviewed and analyzed the PET/CT features of gastric wall lesions,including FDG avidity,pattern(focal/diffuse),and intensity [maximal standard uptake value:(SUVmax)]. The correlation of SUVmax with gastricclinicopathological variables was investigated by χ~2 test,and receiver-operating characteristic(ROC) curve analysis was performed to determine the differential diagnostic value of SUVmax-associated parameters in gastric lymphoma and gastric carcinoma. RESULTS Fifty-two patients with gastric lymphoma and 73 with gastric carcinoma were included in this study. Abnormal gastric FDG accumulation was found in 49 patients(94.23%) with gastric lymphoma and 65 patients(89.04%) with gastric carcinoma. Gastric lymphoma patients predominantly presented with type Ⅰ and type Ⅱ lesions,whereas gastric carcinoma patients mainly had type Ⅲ lesions. The SUVmax(13.39 ± 9.24 vs 8.35 ± 5.80,P < 0.001) and SUVmax/THKmax(maximal thickness)(7.96 ± 4.02 vs 4.88 ± 3.32,P < 0.001) were both higher in patients with gastric lymphoma compared with gastric carcinoma. ROC curve analysis suggested a better performance of SUVmax/THKmax in the evaluation of gastric lesions between gastric lymphoma and gastric carcinoma in comparison with that of SUVmax alone.CONCLUSION PET/CT features differ between gastric lymphoma and carcinoma,which can improve PET/CT evaluation of gastric wall lesions and help differentiate gastric lymphoma from gastric carcinoma.

Clonal immunoglobulin heavy chain and T-cell receptor γ gene rearrangements in primary gastric lymphoma

AIM:To study the diagnostic value of immunoglobulin heavy chain(IgH)and T-cell receptorγ (TCR-γ)gene monoclonal rearrangements in primary gastric lymphoma(PGL).METHODS:A total of 48 patients with suspected PGL at our hospital were prospectively enrolled in this study from January 2009 to December 2011.The patients were divided into three groups(a PGL group,a gastric linitis plastica group,and a benign gastric ulcer group)based on the pathological results(gastric mucosal specimens obtained by endoscopy or surgery)and follow-up.Endoscopic ultrasonography(EUS)and EUSguided biopsy were performed in all the patients.The tissue specimens were used for histopathological examination and for IgH and TCR-γ gene rearrangement polymerase chain reaction analyses.RESULTS:EUS and EUS-guided biopsy were successfully performed in all 48 patients.In the PGL group(n=21),monoclonal IgH gene rearrangements were detected in 14(66.7%)patients.A positive result for each set of primers was found in 12(57.1%),8(38.1%),and 4(19.0%)cases using FR1/JH,FR2/JH,and FR3/JH primers,respectively.Overall,12(75%)patients with mucosal-associated lymphoid tissue lymphoma(n=16)and 2(40%)patients with diffuse large B-cell lymphoma(n=5)were positive for monoclonal IgH gene rearrangements.No patients in the gastric linitis plastica group(n=17)and only one(10%)patient in the benign gastric ulcer group(n=10)were positive for a monoclonal IgH gene rearrangement.No TCRgene monoclonal rearrangements were detected.The sensitivity of monoclonal IgH gene rearrangements was 66.7%for a PGL diagnosis,and the specificity was96.4%.In the PGL group,8(100%)patients with stage IIE PGL(n=8)and 6(46.1%)patients with stage IE PGL(n=13)were positive for monoclonal IgH gene rearrangements.CONCLUSION:IgH gene rearrangements may be associated with PGL staging and may be useful for the diagnosis of PGL and for differentiating between PGL and gastric linitis plastica.

De-escalating therapy in gastric aggressive lymphoma

The treatment of primary gastric diffuse large B-cell lymphoma(DLBCL) has changed radically over the last 10–15 years, with the abandonment of routine gastrectomy in favor of more conservative therapies. Low-level evidence suggests that consolidation radiotherapy could be avoided in patients with limited-stage DLBCL of the stomach who achieve complete remission after rituximab-CHOP combination. Small, recent prospective trials suggest that selected patients with limited-stage Helicobacter pylori(H. pylori)-positive DLBCL of the stomach and favorable prognostic factors can be managed with antibiotics alone, with excellent disease control and cure rates, keeping chemo-radiotherapy for unresponsive patients. This recommendation should equally regard patients with mucosa-associated lymphoid tissue-related or de novo DLBCL. Future studies should be focused on the establishment of reliable variables able to distinguish the best candidates for exclusive treatment with H. pylori eradication from those who need for conventional chemo-immunotherapy.

Complete remission of gastric Burkitt's lymphoma after eradication of Helicobacter pylori

Burkitt＇s lymphoma is a highly aggressive non-Hodgkin lymphoma, often presenting in extra-nodal sites. It generally has a poor spontaneous outcome and needs aggressive treatment with systemic and intrathecal chemotherapy. Occurrence at the gastric site is rare. We report the case of a 39-year old woman who presented with a prominent ulcerated lesion of the antrum corresponding histologically to a Burkitt＇s lymphoma associated with He/icobacter py/ori （H pylori） infection. Interphase fluorescence in situ hybridization （FISH） demonstrated c-MYC gene rearrangement in tumour cells without BCL2 or BCL6 gene translocations. Ulcer healing and tumour regression with a complete histological response were obtained 8 wk after Hpylori eradication. In spite of this complete remission, taking into account the high risk of recurrence, the patient received systemic and intrathecal chemotherapy. Two years later, the patient remained in complete remission. This is the first report of a gastric Burkitt＇s lymphoma responding to Hpylori eradication. These findings raise the question of the potential role of H pylori in the pathogenesis of some gastric Burkitt＇s lymphomas, and show the importance of searching for and eradicating the bacteria in combination with conventional chemotherapy regimens.

Individualized Treatment and Palliative Care for A90-Year-Old Patient with Primary Gastric Diffuse Large-B Cell Lymphoma:4 Year Follow-up and Inspiration

A 90-year-old man was diagnosed with primary gastric diffuse large B-cell lymphoma(PGDLBL)by PET/CT examination,gastroscopy,biopsy and histopathological analysis at a regular physical check in April,2016.The patient received R-CO chemotherapy(rituximab,cyclophosphamide,and vincristine)and radiotherapy subsequently,with enteral nutritional treatment through 3-cavity nasogastric tube due to development of pyloric obstruction.To satisfy patient's strong desire of eating by himself,we performed surgery of exploratory laparotomy and Roux-en-Y gastric bypass(RGB)to relieve pylorus obstruction.Postoperatively,the patient resumed oral feeding,supplemented by nasogastric tube feeding at 1350-1550 Kcal daily.He is now 94 years old with fairly well nutrition and normal communication.The outcome of 4 year follow-up suggests that nutritional treatment and palliative medicine are important for improving prognosis and life-quality of very elderly patients with end-stage tumors apart from the effective chemotherapy,radiotherapy,and surgery.

Isolated gastric variceal bleeding caused by splenic lymphoma-associated splenic vein occlusion

Isolated gastric varices(IGV) can occur in patients with left-sided portal hypertension resulting from splenic vein occlusion caused by thrombosis or stenosis. In left-sided portal hypertension,blood flows retrogradely through the short and posterior gastric veins and the gastroepiploic veins,leading to the formation of an IGV. The most common causes of splenic vein occlusion are pancreatic diseases,such as pancreatic cancer,pancreatitis,or a pseudocyst. However,various other cancers,such as colon,gastric,or renal cancers,have also been known to cause splenic vein occlusion. Our patient presented with a rare case of IGV bleeding induced by splenic lymphoma-associated splenic vein occlusion. Splenectomy,splenic artery embolization,and stenting of the splenic vein are the current treatment choices. Chemotherapy,however,is an alternative effective treatment for splenic vein occlusion caused by chemotherapy-sensitive tumors. Our patient responded well to chemotherapy with a cyclophosphamide,hydroxydaunorubicin,oncovin,and prednisolone regimen,and the splenic vein occlusion resolved after the lymphoma regressed.

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

BACKGROUND 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.AIM To perform a meta-analysis to assess the rate of complete remission(CR)of H.pylori-positive early-stage GML following bacterial eradication.METHODS 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.RESULTS 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(I2=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.CONCLUSION 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.

Role of non-Helicobacter pylori gastric Helicobacters in helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma

Marginal zone lymphomas rank as the third most prevalent form of non-Hodgkin B-cell lymphoma,trailing behind diffuse large B-cell lymphoma and follicular lymphoma.Gastric mucosa-associated lymphoid tissue lymphoma(GML)is a low-grade B-cell neoplasia frequently correlated with Helicobacter pylori(H.pylori)-induced chronic gastritis.On the other hand,a specific subset of individuals diagnosed with GML does not exhibit H.pylori infection.In contrast to its H.pylori-positive counterpart,it was previously believed that H.pylori-negative GML was less likely to respond to antimicrobial therapy.Despite this,surprisingly,increasing evidence supports that a considerable proportion of patients with H.pylori-negative GML show complete histopathological remission after bacterial eradication therapy.Nonetheless,the precise mechanisms underlying this treatment responsiveness are not yet fully comprehended.In recent years,there has been growing interest in investigating the role of non-H.pylori gastric helicobacters(NHPHs)in the pathogenesis of H.pylori-negative GML.However,additional research is required to establish the causal relationship between NHPHs and GML.In this minireview,we examined the current understanding and proposed prospects on the involvement of NHPHs in H.pylori-negative GML,as well as their potential response to bacterial eradication therapy.

Role of Helicobacter pylori virulence factor cytotoxin-associated gene A in gastric mucosa-associated lymphoid tissue lymphoma

Helicobacter pylori(H.pylori)infection might initiate and contribute to the progression of lymphoma from gastric mucosa-associated lymphoid tissue(MALT).Increasing evidence shows that eradication of H.pylori with antibiotic therapy can lead to regression of gastric MALT lymphoma and can result in a 10-year sustained remission.The eradication of H.pylori is the standard care for patients with gastric MALT lymphoma.Cytotoxin-associated gene A(CagA)protein,one of the most extensively studied H.pylori virulence factors,is strongly associated with the gastric MALT lymphoma.CagA possesses polymorphisms according to its C-terminal structure and displays different functions among areas and races.After being translocated into B lymphocytes via typeⅣsecretion system,CagA deregulates intracellular signaling pathways in both tyrosine phosphorylation-dependent and-independent manners and/or some other pathways,and thereby promotes lymphomagenesis.A variety of proteins including p53and protein tyrosine phosphatases-2 are involved in the malignant transformation induced by CagA.Mucosal inflammation is the foundational mechanism underlying the occurrence and development of gastric MALT lymphoma.