High frequency of CagA+ Helicobacter pylori infection in high-grade gastric MALT B-cell lymphomas

A high incidence of Helicobacter pylori infection has been found in patients with gastric MALT (mucosa-associated lymphoid tissue) B-cell lymphoma. Recent studies have indicated that the aggressive strains of the bacterium containing the CagA gene may have direct effects on tumourigenesis. To investigate the involvement of CagA+ strains in MALT lymphomagenesis, a sensitive polymerase chain reaction (PCR)-based detection assay for the gene was developed. DNA extracts from paraffin sections of 123 H. pylori-related gastric biopsies from Italy were analysed, including 56 cases of chronic gastritis, 37 low-grade, and 30 high-grade MALT lymphomas: 30·3 per cent (17/56) of the gastritis cases, 37·8 per cent (14/37) of the low-grade, and 76·7 per cent (23/30) of the high-grade MALT lymphomas were found to contain the CagA gene. The frequency of CagA+ strain infection was signfiicantly higher (P<0·05) in high-grade than in low-grade MALT lymphoma or gastritis. These results suggest that high-grade gastric MALT lymphoma transformation may be more likely to occur following infection by CagA+ strains of H. pylori. © 1998 John Wiley & Sons, Ltd.     

Helicobacter pylori antibodies and gastric cancer in Iceland - The decline in IgG antibody level is a risk factor

H. pylori infection is considered a causal agent of duodenal ulcer and a significant risk factor for gastric cancer. Retrospective cohort studies have demonstrated a significant association between presence of antibody to H. pylori and gastric cancer when using samples obtained years before the diagnosis but not at the time of diagnosis. The present study investigates, in a population-based cohort, whether a decline occurs in H. pylori antibody levels before the diagnosis of stomach cancer. Repeat samples (2 to 5) were available from 23 persons with gastric cancer taken up to 20 years before the diagnosis and 128 control subjects matched for gender, age, time and number of repeat samples. The odds ratio of developing stomach cancer was 1.16 (95% CI 1.05-1.28) for those showing decline in antibody levels of 1 relative antibody activity unit per year versus those with constant or rising levels. We conclude that this decline in antibody levels in cases, and not in controls, supports an active role of H. pylori in the pathogenesis of gastric cancer by causing atrophic gastritis, and provides a better risk assessment for gastric cancer compared to single measurements.     

Helicobacter pylori regulates TLR4 and TLR9 during gastric carcinogenesis

Objective: To investigated the influence of H. pylori on TLR4 and TLR9 in gastric mucosa during gastric carcinogenesis. Methods: Gastric biopsy specimens were taken from 148 patients and divided into five groups, including normal group (n = 10), chronic superficial gastritis group (n = 35), atrophy/intestinal metaplasia group (n = 35), dysplasia group (n = 34) and gastric carcinoma group (n = 34). Immunohistochemistry was used to detect the expression of TLR4 and TLR9. Geimsa staining and rapid urea test were used for determine H. pylori infection. Results: TLR4 was detected in gastric epithelium and monocytes/macrophages in superficial gastritis, atrophy/intestinal metaplasia, dysplasia or carcinoma. TLR9 was mainly accentuated in monocytes/macrophages. TLR4 positive cells in epithelium and in monocytes/macrophages with H. pylori infection were much more than those without H. pylori infection. Similar results were also found in TLR9. When gastric epithelium was accompanied with H. pylori infection, TLR4 was significant higher in superficial gastritis and atrophy/intestinal metaplasia groups compared with dysplasia and carcinoma groups. When gastric epithelium was infected by H. pylori, TLR9 was significant higher in carcinoma group compared with superficial gastritis, atrophy/intestinal metaplasia and dysplasia. TLR4 and TLR9 show significant correlation with the severity of inflammation. Conclusions: H. pylori infection was associated with increased expression of TLR4 and TLR9 in gastric mucosa. In superficial gastritis and atrophy/intestinal metaplasia the inflammation was predominately mediated by TLR4, while in gastric cancer the inflammation was mainly mediated by TLR9.     

Helicobacter pylori and gastric carcinoma

A retrospective study was performed on gastric carcinomas to establish the prevalence of Helicobacter pylori infection in gastric epithelium adjacent to the tumour. A total of 105 carcinomas were studied. The overall prevalence of Helicobacter pylori infection was 59%. The prevalence in different age cohorts from patients with gastric carcinoma was compared with that in patients suffering from non-ulcer dyspepsia and, based on serological testing, with that in healthy blood donors. The presence of Helicobacter pylori in cancer patients aged 41-50 and 51-60 was significantly higher than in blood donors. No difference was seen in comparison with non-ulcer dyspepsia patients. The presence of Helicobacter pylori showed an inverse correlation with the extent of intestinal metaplasia. The intestinal type of carcinoma was associated with a higher bacterial load than the diffuse type. These data suggest that the presence of Helicobacter pylori in gastric mucosa could play a role in the pathogenesis of gastric carcinoma, especially in the young age group.     

Epidemiology and role of Helicobacter pylori virulence factors in gastric cancer carcinogenesis

Infection with Helicobacter pylori is associated with the development of gastric cancer. Although the prevalence of gastric cancer has declined throughout years due to improvement in early screening strategy, mortality due to gastric cancer has not changed. Incidence and mortality due to gastric cancer are higher in developing countries as compared to developed countries. Diagnosis and prognosis of gastric cancer are still poor with patients usually diagnosed with cancer at an advanced stage. Eradication of H. pylori is pertinent for the prevention of gastric cancer. However, the rise in antimicrobial resistance among H. pylori isolates has complicated the prevention strategy. H. pylori express multiple virulence factors for survival in the hostile acid gastric environment. The expression of oncogenic protein cytotoxin-associated gene A (CagA), vacuolating cytotoxin A (VacA), and outer inflammatory protein is essential for H. pylori to exert pathogenesis towards the host. Interestingly, <3% of H. pylori-infected subjects develop gastric cancer, suggesting a unique way of interaction between the host's immune response and H. pylori virulence factors. This article is aimed to review the epidemiology and role of H. pylori in gastric carcinogenesis. A better understanding of the interaction between H. pylori virulence factors and host is required for better gastric cancer prevention.     

Helicobacter pylori stains and association between H. pylori and inflammation in gastric specimens

Gastric cancer has been strongly associated with presence of the bacterium Helicobacter pylori. To improve techniques in identifying H. pylori so that gastric cancer may be predicted early, this project was formulated to determine whether one particular stain is more effective in displaying H. pylori microscopically. In addition, this study attempted to determine whether the degree of inflammatory elements present in tissue could be used to predict the likelihood of H. pylori presence. Protocols for the staining techniques, Steiner and alcian yellow/toluidine blue (AY/TB), were employed on specimens to semi-quantitate H. pylori presence. Serial sections from the same specimens were stained with hematoxylin and eosin to determine the amount of inflammation. Spearman rho correlation was used to evaluate the association between amount of H. pylori and inflammation in each case. It was determined that AY/TB was more easily performed, more effective in demonstrating H. pylori, and more cost effective than the Steiner stain. Additionally, it was determined that a moderate positive association was indicated between high levels of inflammation and marked presence of H. pylori.     

A reassessment of primary thyroid lymphoma: high-grade MALT-type lymphoma as a distinct subtype of diffuse large B-cell lymphoma

AIMS: Primary lymphoma of the thyroid gland (PTL) is a relatively rare disease. During an 18-year period, 53 cases of primary non-Hodgkin's lymphoma involving this extranodal site were seen at our institutions. The aims of this study were to evaluate the spectrum of PTLs using current lymphoma classification concepts and immunocytochemical markers, determine whether features of MALT-type lymphoma were evident in PTL, and if there was any clinical significance of such a finding. METHODS AND RESULTS: The cases were retrospectively studied clinically, histologically and immunohistochemically. The tumours were classified according to the Revised European-American Lymphoma Classification of lymphoid malignancies (REAL classification). Thirty-eight patients were females, 15 were males and mean age at diagnosis was 66.3 years (range 38-90). Three cases were low-grade marginal zone lymphomas (low-grade MALT-type lymphomas). There were 45 diffuse large B-cell lymphomas (DLBCL) of which there were 27 DLBCL-NOS and 18 high-grade MALT-type lymphomas. Within the diffuse large B-cell lymphoma (DLBCL) category, cases were subdivided into those without (DLBCL-NOS) and those with features of 'high-grade' MALT-type lymphoma based on presence of a low-grade component or large cell lymphoepithelial lesions (HG MALT-type lymphoma). In addition there were three follicle centre lymphomas, one anaplastic large cell lymphoma and one peripheral T-cell lymphoma. Twenty cases were stage IE, 18 stage IIE, and four stage IV. All patients with low-grade MALT-type lymphoma are alive without disease. The 5-year survivals for DLBCL-NOS and HG MALT-type lymphoma were 75% and 25%, respectively. Univariate analysis (log rank) among the DLBCLs showed stage (P < 0.001) and subtype (P = 0.005) were associated with survival. Stage was associated with type of DLBCL, 65% of DLBCL-NOS being stage IE compared to 20% of HG MALT-type lymphomas. CONCLUSIONS: We conclude that primary thyroid lymphomas occur most commonly in elderly women and are frequently present in clinical stage IE and IIE. Low-grade MALT-type lymphomas are relatively uncommon but appear to have a favourable prognosis. DLBCL is the most common lymphoma and features of MALT can be seen in over one-third of cases. As a group, HG MALT-type lymphomas had a worse outcome than DLBCL-NOS, primarily due to higher clinical stage at diagnosis. These two subtypes of DLBCL appear to be distinct clinical and histological entities.     

Helicobacter pylori and gastric adenocarcinoma

Gastric cancer is the second most common cause of cancer death worldwide. A large body of evidence supports a causal role of Helicobacter pylori in the majority of gastric malignancies. Great strides have been made in understanding the pathogenesis of this relationship, but much remains to be learned. Moreover, because of the high prevalence of infection, the lack of definitive trials, and the challenges of H. pylori treatment, there remains no consensus on the role of routine screening and treatment of this infection to prevent cancer. This article reviews the current knowledge on H. pylori and gastric cancer and presents some of the clinical and public health challenges associated with this pathogen.     

Epithelial damage by Helicobacter pylori in gastric ulcers

On review of 136 consecutive biopsies of benign gastric ulcer, Helicobacter pylori was detected in 78 cases (57.3%). The gastric epithelium colonized by Helicobacter pylori showed a characteristic constellation of changes, including loss of apical mucous portion of individual cells, drop-out of epithelial cells, epithelial pits, erosions and cellular tufts, indicative of cellular injury and regeneration. Among the 58 Helicobacter-negative cases, similar changes were not observed in the ulcer edges, except for two cases which exhibited some cellular tufts. Thus, the topographic association of Helicobacter pylori with epithelial damage in the gastric ulcer edges in more than half of the cases suggests that this organism probably plays an aetiological role in ulcerogenesis, at least in these cases. Furthermore, the epithelial changes are so distinctive that they can serve as a helpful histological indicator for the presence of Helicobacter pylori in gastric biopsies.     

One patient with double lymphomas: simultaneous gastric MALT lymphoma and ileal diffuse large B-cell lymphoma

Multiple different lymphomas in a single person are very rare. The author herein reports the case of a 69- year-old Japanese woman with double gastrointestinal lymphoma. The patient presented with epigastralgia. Endoscopic examination revealed erosions and elevation of the gastric body and a large ulcerated tumor of the terminal ileum. Biopsies were obtained from these lesions. The gastric lesion was MALT lymphoma with monocytoid B-cell proliferation and lymphoepithelial lesions. Light chain restriction was present. Helicobacter pylori were present on Giemsa stain. The gastric lesions did not regress despite of therapy, which were confirmed by follow-up biopsy. The ileal lesion was obvious diffuse large B-cell lymphoma. The lesion regressed by chemotherapy. The patient is now alive 3 years after the first presentation.     

胃大部切除术后残胃幽门螺杆菌感染的临床研究

目的探讨胃大部切除术后残胃病变与幽门螺杆菌(Hp)感染的关系。方法采用快速尿素酶试验、组织切片W arth in-Starry银染及尿素呼气试验检测682例残胃病患者Hp感染情况,并进行流行病学分析。结果682例残胃病患者Hp感染检出率为27.42%,与年龄、性别以及术后时间无关;B illroth I式术后残胃Hp检出率(40.07%)明显高于B illroth II式术后残胃Hp检出率(17.37%),而伴有胆汁返流的残胃Hp感染阳性率(7.98%)明显低于不伴胆汁返流的残胃阳性率(33.53%)。同时,因溃疡、穿孔、出血行手术的残胃Hp检出率(47.88%)高于因胃癌手术的检出率(22.66%);不同病理学残胃中,残胃溃疡和残胃癌的Hp感染率明显高于慢性残胃炎及吻合口炎的Hp感染率。结论胃大部切除术后残胃病变与Hp感染密切相关,尤其是残胃癌,应及早进行Hp治疗,可减轻残胃病变,减少残胃癌的发生。     

The lymphoepithelial lesion of gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT): an ultrastructural study

Lymphoepithelial lesions are a characteristic feature of primary, gastric low-grade lymphomas of mucosa-associated lymphoid tissue (MALT). The lymphoepithelial lesions in 12 such lymphomas have been examined by electronmicroscopy and immunohistochemistry. The lymphocytes present in these lesions are neoplastic centrocyte-like (CCL) B-cells and are morphologically and immunophenotypically similar to those of the surrounding lymphoma. Once the CCL cells penetrate the gastric glands, there is marked structural distortion and disruption of the epithelial cells which leads to their ultimate death. The close association of the neoplastic CCL cells and epithelial cells suggests the presence of a factor, an antigen or other receptor, on the plasma membrane of the latter through which these effects are mediated.     

根除儿童口腔幽门螺杆菌预防胃内幽门螺杆菌感染的多中心研究

目的:探讨根除儿童口腔幽门螺杆菌（Hp）预防胃内Hp感染的可能性。方法:采用多中心前瞻随机研究,选取口腔Hp阳性但胃内Hp阴性的幼儿园儿童共计427例,随机分为使用“无幽梅”牙膏组与普通牙膏组,分别接受“无幽梅”牙膏和普通牙膏。疗程结束后,再次检测口腔Hp,将口腔Hp阳性及阴性患者各分为一组,1年后行C13呼气试验检查,分析两组患者胃内Hp感染情况。口腔Hp检测方法采用特异度及敏感度双高的套式PCR方法。结果:随访1年,口腔Hp阴性组胃内Hp感染率为0.51%,口腔Hp阳性组胃内Hp感染率为6.51%,两组统计差异具有显著性（P<0.01）。结论:儿童根除口腔Hp可以降低胃内Hp感染的发生。     

Primary low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma with polypoid appearance. Polypoid gastric MALT lymphoma: A clinicopathologic study of eight cases

In the current study, we report eight cases with primary low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma endoscopically characterized by polypoid lesions in order to highlight their clinicopathologic significance. Four patients were male, their ages ranging from 40 to 78 years old. The resected specimens revealed a histology of low-grade MALT lymphoma characterized by dense lymphocytic infiltration predominantly in the submucosa and a relatively monotonous proliferation of centrocyte-like cells with reactive follicles and infrequent lymphoepithelial lesions. The tumor cells were of CD5-, CD10-, CD20+, BCL2+ and cycline D1- phenotype, and showed a monoclonal rearrangement of immunoglobulin heavy chain genes in the five of six cases examined. Interestingly, Helicobacter pylori (H. pylori) was detected in three (37.5%) of the eight patients, which was significantly lower than previous reports. Two of the H. pylori-positive cases initially underwent H. pylori eradication, but showed no change in their lymphomas after the cure of H. pylori infection. The clinicopathologic findings of the present cases appeared to closely resemble those of colorectal MALT lymphoma with a polypoid appearance and few association of H. pylori infection in their pathogenesis. These gastric polypoid cases may merit separate consideration because of the therapeutic problems they pose.     

Role of abnormal microRNA expression in Helicobacter pylori associated gastric cancer

Epidemiological studies have shown that Helicobacter pylori (HP) infection is a risk factor for gastric cancer (GC). HP infection may induce the release of pro-inflammatory mediators, and abnormally increase the level of reactive oxygen species (ROS), nitric oxide (NO), and cytokines in mucosal epithelial cells of the stomach. However, the specific mechanism underlying the pathogenesis of HP-associated GC is still poorly understood. Recent studies have revealed that abnormal microRNA expression may affect the proliferation, differentiation, and apoptosis of mucosal epithelial cells of the stomach to further influence GC occurrence, development, and metastasis. Herein, we summarize the role of abnormal microRNAs in the regulation of HP-associated GC progression. Abnormal microRNA expression in HP-positive GC may be a biomarker for GC diagnosis, occurrence, and development as well as its targeted treatment and prognosis.     

Response of IgG1 and IgG2 subclasses to Helicobacter pylori in subjects with chronic inflammation of the gastric mucosa, atrophy and gastric cancer in a country with high Helicobacter pylori infection prevalence

Polarized immune response to Helicobacter pylori and induction of chronic inflammation may increase the risk of gastric atrophy and adenocarcinoma. We studied the association of the response of IgG1 and IgG2 antibodies to H. pylori with grade of gastric chronic inflammation and atrophy in a population with a high prevalence of H. pylori, and compared these data with the data obtained from the study of gastric cancer patients, as well as with the data for CagA positivity. Altogether, 114 persons from two adult population samples from Estonia and 45 consecutive gastric cancer patients were studied. All patients were positive for the H. pylori antibody determined by ELISA. Adenocarcinoma was classified histologically according to the Laurén's system. The response of the IgG subclasses to H. pylori (acid glycine-extracted whole cell proteins) was determined by ELISA and the results were compared with the ELISA results for the recombinant fragment of the CagA protein. Helicobacter pylori IgG level was lower in atrophic gastritis compared with nonatrophic gastritis (chronic inflammation) (p=0.001). In the group of cancer patients, the response of IgG and IgG1 was lower compared with both gastritis groups (p=0.01 and p=0.0002 for IgG, and p=0.001 and p=0.0005 for IgG1). IgG2 was lower for gastric cancer localized in the corpus (p=0.03). In conclusion, atrophic gastritis and gastric cancer were associated with a significant decline in IgG and IgG1 response to H. pylori compared with nonatrophic gastritis. Higher value of CagA antibodies was seen in gastric cancer and in gastric atrophy compared with nonatrophic gastritis; in gastric cancer patients, IgG1 response to H. pylori was correlated with CagA status.     

固有免疫分子DC-SIGN在幽门螺杆菌感染胃黏膜上皮细胞表达意义

探讨固有免疫分子DC-SIGN在幽门螺杆菌(H.pylori)感染的胃上皮细胞表达,及其与胃黏膜损伤的关系.选取经胃镜及组织病理检查确诊的72例慢性胃炎患儿胃黏膜活检标本,采用免疫组化检测胃黏膜上皮细胞DC-SIGN表达.体外建立幽门螺杆菌感染胃上皮细胞模型,采用流式细胞术检测幽门螺杆菌刺激的胃上皮细胞DC-SIGN以...     

Coexistence of primary pulmonary Hodgkin lymphoma and gastric MALT lymphoma associated with Epstein‐Barr virus infection: A case report

We describe a 66‐year‐old woman with Epstein‐Barr virus‐associated lymphoproliferative disorder with lung and gastric tumors. We identified two lung tumors measuring 13 and 20 mm in diameter that consisted of CD30‐, CD15‐, and CD20‐positive Hodgkin‐ and Reed‐Sternberg‐like cells and heterogeneous cellular infiltrates in a pronounced nodular pattern, with necrosis and vasculitis, diagnosed as nodular sclerosis classical Hodgkin lymphoma. A gastric tumor showed low‐grade extranodal marginal zone B‐cell lymphoma of the mucosa‐associated lymphoid tissue type. Neoplastic cells in all tumors expressed Epstein‐Barr virus‐encoded RNA based on in situ hybridization. The present case is a rare composite lymphoma arising from different extranodal organs, associated with EBV infection. Her medical history included gamma‐knife therapy for clinical diagnosis with a suspicion of cerebral lymphoma.