Gastric MALT lymphoma and Helicobacter pylori.

Primary gastric low-grade B-cell lymphomas are neoplastic mimics of mucosa associated lymphoid tissue (MALT) as exemplified by Peyer''s patches in the terminal ileum. Architectural and immunophenotypic properties of the neoplastic cells suggest that they originate from MALT-derived marginal zone B-cells. Paradoxically, the normal human stomach is devoid of organized MALT within which a lymphoma can develop. Lymphoid tissue is acquired in the stomach in response to antigenic stimulation, predominantly associated with Helicobacter pylori infection. Studies of patients with low-grade MALT lymphoma have confirmed a high incidence of H. pylori infection and suggest that the infection predates neoplastic transformation. Certain morphological features of MALT lymphomas suggest that the tumor cells remain responsive to antigen drive. Given the close association between gastric MALT lymphoma and H. pylori, it is possible that this organism provides such a drive. In vitro studies have shown that the tumor cells proliferate in a T-cell-dependent way to the presence of H. pylori. Several studies have now demonstrated that eradication of the organism in patients with low-grade gastric MALT lymphoma can result in regression of the tumor. In cases with a high-grade component, the associated low-grade part may regress, but most high-grade gastric MALT lymphomas are unresponsive to this conservative therapy.     

A prospective analysis of low-grade gastric malt lymphoma after Helicobacter pylori eradication

BACKGROUND: Primary gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is known to be successfully treated with anti-Helicobacter pylori (H. pylori) therapy alone. However, there are few reports on long-term results after eradication therapy. The aims of this study were to analyze the rate and the interval to reach complete remission (CR), and to assess the rate and the factors affecting recurrence of MALT lymphoma. MATERIALS AND METHODS: Between 1996 and 2003, a total of 90 H. pylori-infected patients with low-grade MALT lymphoma were included in this study. For initial staging, endoscopic ultrasonography, chest-abdomen-pelvis CT scans, and bone marrow examination were taken. All patients were made to take anti-H. pylori therapy for 14 days. Tumoral response was assessed by endoscopy every 3 months till CR and every 6 months after achieving CR. RESULTS: Among 90 treated patients, 85 (94.4%) reached CR. The median interval to CR was 3 months (range, 1-24). Seventy-nine (92.9%) patients were in CR at 12 months. Median follow-up period after CR was 45 months (range 15-109). Among 77 patients who were followed-up after CR, 8 (10.4%) patients were proved with recurrence of MALT lymphoma. Cumulative recurrence rate was 2.7, 11.5, and 12.2% at 1, 2, and 3 years. The presence of H. pylori was only a significant risk factor affecting recurrence. CONCLUSIONS: The status of H. pylori is the most important risk factor affecting recurrence. Therefore, adequate eradication regimen and accurate regular evaluation for H. pylori status are needed during follow up of primary gastric low-grade B-cell MALT lymphoma.     

Comparison of localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma with and without Helicobacter pylori infection

BACKGROUND: The clinical features and clinical course of Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma are unclear and a treatment strategy has not yet been established. AIM: To clarify the clinical differences between H. pylori-positive and H. pylori-negative gastric MALT lymphoma, we compared these two types of gastric MALT lymphoma. MATERIALS AND METHODS: Fifty-seven patients with localized gastric MALT lymphoma were studied. H. pylori infection was present in 41 and absent in 16. Treatment consisted of antibiotic therapy and/or 30 Gy radiation therapy. Response assessment was performed every 3-6 months by esophagogastroduodenoscopy including gathering biopsy samples, endoscopic ultrasonography, clinical examination, and various imaging procedures. The median follow-up period was 37 months. RESULTS: There were no significant differences between H. pylori-positive and H. pylori-negative gastric MALT lymphoma patients in terms of sex, age, stage, gross phenotype, affected area of the stomach, or the presence of monoclonality. Complete regression was achieved with antibiotic therapy against H. pylori-negative gastric MALT lymphoma in one of nine patients (11.1%), compared to 28 of 38 patients (73.7%) with H. pylori-positive gastric MALT lymphoma (p < .001). Radiation therapy showed high effectiveness for the local control of H. pylori-negative or antibiotic-resistant gastric MALT lymphoma (92.9%), although distant recurrence was recognized in three of 14 patients (21.4%). Two of 16 patients (12.5%) with H. pylori-negative gastric MALT lymphoma died because of the transformation of the disease into diffuse large B-cell lymphoma. There was a significant difference in both the overall and cause-specific survival rate between the two groups (p = .038). CONCLUSION: Radiation therapy is the effective treatment for H. pylori-negative or antibiotic-resistant localized gastric MALT lymphoma. However, careful systemic follow-up for distant involvement should be required. Transformation into diffuse large B-cell lymphoma is thought to be the important cause of death in patients with gastric MALT lymphoma.     

Modulation of lymphocyte proliferation induced by gastric MALT lymphoma-associated Helicobacter pylori strains

Background: Helicobacter pylori infection leads to different chronic diseases, suggesting that this bacterium can evade the host immune defense system. The ability to control lymphocyte proliferation may be a mechanism leading to the development of gastric pathologies. Our aim was to characterize the effects of mucosa‐associated lymphoid tissue (MALT) associated H. pylori strains on lymphocyte proliferation. Materials and methods: We measured the in vitro proliferation of human lymphocytes originally from blood or tonsil samples in the presence or absence of viable bacteria or lysates. Results: We showed that MALT lymphoma‐associated strains are not likely to be directly responsible for anarchical B‐cell proliferation in vitro. On the other hand, proliferation of prestimulated T lymphocytes was abolished in vitro by the presence of all H. pylori strains, whether associated with MALT lymphoma or not. Conclusion: Inhibition of T‐cell proliferation may be of major importance in the gastric colonization and in the persistence of the infection. Furthermore, this inhibition may favor anarchical B‐cell proliferation in vivo and predispose the host to gastric MALT lymphoma, whereas MALT‐associated H. pylori strains do not appear to possess a specific capability to directly stimulate B‐lymphocyte proliferation.     

Helicobacter pylori, T cells and cytokines: the "dangerous liaisons"

Helicobacter pylori infection is the major cause of gastroduodenal pathologies, but only a minority of infected patients develop chronic and life threatening diseases, as peptic ulcer, gastric cancer, B-cell lymphoma, or autoimmune gastritis. The type of host immune response against H. pylori is crucial for the outcome of the infection. A predominant H. pylori-specific Th1 response, characterized by high IFN-gamma, TNF-alpha, and IL-12 production associates with peptic ulcer, whereas combined secretion of both Th1 and Th2 cytokines are present in uncomplicated gastritis. Gastric T cells from MALT lymphoma exhibit abnormal help for autologous B-cell proliferation and reduced perforin- and Fas-Fas ligand-mediated killing of B cells. In H. pylori-infected patients with autoimmune gastritis cytolytic T cells infiltrating the gastric mucosa cross-recognize different epitopes of H. pylori proteins and H+K+ ATPase autoantigen. These data suggest that peptic ulcer can be regarded as a Th1-driven immunopathological response to some H. pylori antigens, whereas deregulated and exhaustive H. pylori-induced T cell-dependent B-cell activation can support the onset of low-grade B-cell lymphoma. Alternatively, H. pylori infection may lead in some individuals to gastric autoimmunity via molecular mimicry.     

Helicobacter pylori activates NF-kappaB via the alternative pathway in B lymphocytes

Helicobacter pylori causes various gastroduodenal diseases including gastric MALT lymphoma, but the mechanism underlying H. pylori-induced carcinogenesis is not known. The alternative pathway for NF-kappaB activation, which involves the processing of NF-kappaB2/p100 to p52, has been implicated in lymphocyte survival, attenuated apoptosis, and secondary lymphoid tissue development. In this study, we investigated H. pylori-induced activation of NF-kappaB through the alternative pathway in B lymphocytes. In immunoblot and EMSA, H. pylori induced NF-kappaB2/p100 processing to p52 and subsequent nuclear accumulation in IM-9 (human B cell line) cells and human peripheral blood B cells, but not in AGS (human gastric cancer cell line) cells. The activation of the alternative pathway was LPS-dependent but not cag pathogenicity island-dependent. Alternative pathway activation by H. pylori was associated with attenuated apoptosis. The expression levels of B lymphocyte chemoattractant, EBI-1 ligand chemokine, and stromal cell-derived factor-1alpha mRNAs were up-regulated in cocultured human B cells and in infected human gastric mucosa. In the infected mucosa, NF-kappaB2/p100 and p52 were detected immunohistochemically in the cytoplasm and nuclear compartments of lymphocytes, but not in epithelial cells. In summary, H. pylori activates the alternative NF-kappaB pathway in B lymphocytes. The effects on chemokine production and antiapoptosis mediated by H. pylori-induced processing of NF-kappaB2/p100 to p52 may drive lymphocytes to acquire malignant potential.     

Influence of polymorphisms in the NOD1/CARD4 and NOD2/CARD15 genes on the clinical outcome of Helicobacter pylori infection

Host immune response influences the clinical outcome of Helicobacter pylori infection leading to ulcer disease, gastric carcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. A genetic risk profile for gastric cancer has been identified, but genetic susceptibility to develop MALT lymphoma is still unclear. We investigated the role of NOD1 and NOD2 as intracellular recognition molecules for pathogen-associated molecules in H. pylori infection in vitro and analysed the influence of single nucleotide polymorphisms on susceptibility to ulcer disease and MALT lymphoma. Expression of NOD1 and NOD2 significantly sensitized HEK293 cells to H. pylori-induced NF-kappaB activation in a cag pathogenicity island (cagPAI)-dependent manner. In cells carrying the Crohn-associated NOD2 variant R702W the NF-kappaB response was significantly diminished. NOD1/NOD2 expression levels were induced in the gastric epithelium in H. pylori-positive patients. No mutations were found to be associated with gastritis or gastric ulcer development. However, the R702W mutation in the NOD2/CARD15 gene was significantly associated with gastric lymphoma. Carrier of the rare allele T had a more than doubled risk to develop lymphoma than controls [odds ratio (OR): 2.4, 95% confidence interval (CI): 1.2-4.6; P < 0.044]. H. pylori-induced upregulation of NOD1 and NOD2 in vivo may play a critical role in the recognition of this common pathogen. A missense mutation in the leucine-rich region of CARD15 is associated with gastric lymphoma.     

Expression cloning of cholesterol alpha-glucosyltransferase, a unique enzyme that can be inhibited by natural antibiotic gastric mucin O-glycans, from Helicobacter pylori

Helicobacter pylori infects over half the world's population, but only 3% of those infected develop peptic ulcer, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. In H. pylori, alpha-glucosyl cholesterol constitutes more than 25% of cell wall lipids, and it has been suggested that alpha-glucosyl cholesterol is essential for H. pylori viability. Here, we identified cholesterol alpha-glucosyltransferase (CHLalphaGcT) using an expression cloning strategy and showed that this enzyme is distinctively inhibited by mucin-type O-glycans similar to those present in deeper portions of the gastric mucosa. Moreover, inactivation of CHLalphaGcT by homologous recombination led to H. pylori lethality. These results indicate that H. pylori CHLalphaGcT is a unique enzyme targeted by a natural antibiotic mucin and constitutes an excellent therapeutic target to prevent H. pylori-induced peptic ulcer, gastric carcinoma, and MALT lymphoma.     

The Helicobacter pylori virulence factor CagA promotes Erk1/2-mediated Bad phosphorylation in lymphocytes: a mechanism of CagA-inhibited lymphocyte apoptosis

The Helicobacter pylori virulence factor, CagA, is causally linked to lymphoma of gastric mucosa-associated lymphoid tissue (MALT). However, it is unclear how CagA promotes the development of gastric MALT lymphoma. We investigated whether CagA modulates the activation of Erk1/2 and their downstream apoptosis regulators in B lymphocytes. Transfection of B1 lymphocytes with cagA transiently increased Erk1/2 phosphorylation, which was negatively regulated by MKP-1 and MKP-6. Activation of Erk1/2 led to phosphorylation of Bad at Ser-112, as confirmed with a chemical Erk1/2 inhibitor. However, CagA-induced Erk1/2 activation did not alter expression of either Bcl-2 or Bax. Importantly, cagA-transfected B1 cells were significantly protected against apoptosis induced by hydroxyurea. Our results reveal that CagA, to some extent like IL-3, can enhance lymphocytes' ability to evade apoptosis through phosphorylation of Bad. This may account, at least in part, for the ability of CagA to promote lymphomagenesis.     

Helicobacter pylori antigen-specific T-cell responses at gastric level in chronic gastritis,peptic ulcer,gastric cancer and low-grade mucosa-associated lymphoid tissue (MALT) lymphoma

Host T-cell response to Helicobacter pylori is important for the clinical outcome of the infection. A Th1-polarized response, preferentially against CagA, is associated with peptic ulcer, whereas mixed Th1 and Th0 responses are present in non-ulcer gastritis. A deregulated H. pylori-driven Th0 cell-dependent B-cell activation is found in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue.     

Serological responses of FldA and small-molecular-weight proteins of Helicobacter pylori: correlation with the presence of the gastric MALT tissue

PURPOSE: We tested whether the serological response to Flavodoxin-A (FldA) protein and anti-Helicobacter pylori immunoblots correlated to the degree of mucosaassociated lymphoid tissue (MALT) in the stomach. METHODS: Eighty H. pyloni-infected patients with different degrees of MALT in the stomach were investigated with serum sampling and endoscopy on enrolment, the 2nd and the 12th months after anti-H. pylori therapy. All sera were tested for the anti-FldA protein and anti-H. pylon immunoblots, including 19.5, 26.5, 30, 35, 89, and 116 KDa (CagA). Regression of follicular gastritis was assessed by histology. RESULTS: Patients with dense lymphoid follicles had higher prevalence rates of anti-FldA protein, 19.5, 26.5, and 30 KDa antibodies of H. pylori (p < .05). Histologic downgrade of MALT was observed in 25% (10/40) of patients in the 2nd month and in 60% (23/38) in the 12th month after H. pylori therapy. After H. pylori eradication, the patients with MALT and dense lymphoid follicles had significantly negative seroconversions of 19.5, 26.5, 30, and 35 KDa antibodies (p < .05), but not of CagA and FldA. CONCLUSION: Patients with gastric MALT and dense lymphoid follicles had different anti-H. pylori serological responses to those with scanty or an absence of lymphoid follicles. The negative seroconversion of the smaller-molecular-weight proteins, but not CagA and FldA, may correlate with the regression of MALT by H. pylori eradication.     

Increased apoptosis and angiogenesis in gastric low-grade mucosa-associated lymphoid tissue-type lymphoma by Helicobacter heilmannii infection in C57/BL6 mice

Helicobacter heilmannii has been reported to cause gastric low-grade mucosa-associated lymphoid tissue-type (MALT) lymphoma, but its precise pathophysiological mechanism remains to be clarified. We recently established a model of gastric B-cell MALT lymphoma in C57BL/6 mice by means of peroral infection of H. heilmannii primarily obtained from cynomolgus monkeys. Using this model, macroscopic, immunohistochemical, and electron microscopic observations of MALT lymphomas were carried out in order to examine the development of apoptosis and angiogenesis. Enhancement of the microvascular network and an increase in vascular endothelial growth factor-A were detected in the central region of the MALT lymphoma tissue in the infected mouse stomach, while vascular endothelial growth factor-C was detected at the margins of the MALT lymphomas. In addition, many H. heilmannii-invaded parietal cells showed caspase-3 immunoreactivity in the fundic mucosal tissue surrounding the MALT lymphoma. In conclusion, in H. heilmannii-induced MALT lymphoma, enhanced immunoreactivity of vascular endothelial growth factor-A and factor-C was observed in areas encircled by increased parietal cell apoptosis, which indicates the pathophysiological relevance of both angiogenesis and apoptosis in MALT lymphoma formation.     

Overexpression of miR-142-5p and miR-155 in Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma Resistant to Helicobacter pylori Eradication

microRNAs (miRNAs) are small non-coding RNAs that can function as endogenous silencers of target genes and play critical roles in human malignancies. To investigate the molecular pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma, the miRNA expression profile was analyzed. miRNA microarray analysis with tissue specimens from gastric MALT lymphomas and surrounding non-tumor mucosae revealed that a hematopoietic-specific miRNA miR-142 and an oncogenic miRNA miR-155 were overexpressed in MALT lymphoma lesions. The expression levels of miR-142-5p and miR-155 were significantly increased in MALT lymphomas which do not respond to Helicobacter pylori (H. pylori) eradication. The expression levels of miR-142-5p and miR-155 were associated with the clinical courses of gastric MALT lymphoma cases. Overexpression of miR-142-5p and miR-155 was also observed in Helicobacter heilmannii-infected C57BL/6 mice, an animal model of gastric MALT lymphoma. In addition, miR-142-5p and miR-155 suppress the proapoptotic gene TP53INP1 as their target. The results of this study indicate that overexpression of miR-142-5p and miR-155 plays a critical role in the pathogenesis of gastric MALT lymphoma. These miRNAs might have potential application as therapeutic targets and novel biomarkers for gastric MALT lymphoma.     

Inflammation, Immunity, and Vaccines for Helicobacter pylori

Helicobacter pylori infects almost half of the population worldwide and represents the major cause of gastroduodenal diseases, such as duodenal and gastric ulcer, gastric adenocarcinoma, autoimmune gastritis, and B-cell lymphoma of mucosa-associated lymphoid tissue. Helicobacter pylori induces the activation of a complex and fascinating cytokine and chemokine network in the gastric mucosa. Different bacterial and environmental factors, other concomitant infections, and host genetics may influence the balance between mucosal tolerance and inflammation in the course of H. pylori infection. An inverse association between H. pylori prevalence and the frequencies of asthma and allergies was demonstrated, and the neutrophil activating protein of H. pylori was shown to inhibit the allergic inflammation of bronchial asthma. During the last year, significant progress was made on the road to the first efficient vaccine for H. pylori that will represent a novel and very important bullet against both infection and gastric cancer.     

幽门螺杆菌与胃黏膜相关淋巴瘤相关性研究

目的研究幽门螺杆菌(H.pylori)与胃黏膜相关淋巴瘤相关性。方法通过胃镜和相关辅助检查,对24例胃黏膜相关淋巴瘤病人胃内幽门螺杆菌进行动态观察。结果24例胃黏膜相关淋巴瘤病人中,18例出现H.pylori感染(75%);治疗后H.pylori感染例数减少(6/24,25%);1年后H.pylori病人感染又增加(11/24,46%)。结论抗H.pylori及胃黏膜相关淋巴瘤常规治疗方法有效,但易反复,可考虑辅以微生态调节剂治疗。     

Interaction of Helicobacter pylori with professional phagocytes: role of the cag pathogenicity island and translocation, phosphorylation and processing of CagA

Chronic infection of the human gastric mucosa with Helicobacter pylori is a major cause of gastroduodenal pathologies, including peptic ulcerations, mucosa-associated lymphoid tissue (MALT) lymphoma and adenocarcinoma. Helicobacter pylori strains carrying the cag pathogenicity island, which encodes an active type IV protein secretion system ( cag ⁺ or type I strains), are preferentially associated with strong gastric inflammation and severe disease. We show here that cag ⁺ H. pylori strains use the type IV secretion system to inject the bacterial protein CagA into various types of professional phagocytes, including human polymorphonuclear leucocytes (PMNs) and the human and murine macrophage cell lines THP-1 and J774A.1 CagA is rapidly tyrosine phosphorylated and proteolytically processed to generate a stable 35–45 kDa C-terminally tyrosine-phosphorylated protein fragment. H. pylori was efficiently ingested by the different types of phagocytic cells. A chromosomal deletion of the complete pathogenicity island had no significant effect on the rate of ingestion. Furthermore, the survival rate of H. pylori in the phagosome was unchanged between the wild type and a deletion mutant lacking the type IV secretion system. Thus, the type IV secretion system seems to be involved neither in active phagocytosis resistance nor in prolonged survival of the bacteria in phagocytic cells.     

Serum antibodies to Helicobacter pylori and its heat-shock protein 60 correlate with the response of gastric mucosa-associated lymphoid tissue lymphoma to eradication of H. pylori

Background and aims. Eradication of Helicobacter pylori leads to regression of mucosa‐associated lymphoid tissue (MALT) lymphomas. In this study, we measured serum antibodies to H. pylori and H. pylori‐recombinant heat‐shock protein 60 (rHSP60) in patients with gastric MALT lymphoma to determine whether humoral immune responses to the bacterial antigens correlate with the efficacy of eradication therapy. Methods. Serum samples were obtained from 33 patients with H. pylori‐positive gastric MALT lymphoma before undergoing therapy to eradicate the bacteria. Anti‐H. pylori antibodies were measured in a commercial assay and in immunoassays to lysates and rHSP60 which were prepared from ATCC 43504 strain. Results. Helicobacter pylori were eradicated in all 33 patients, and the lymphoma completely regressed histologically in 26 patients (79%). Pre‐treatment titers of serum antibody to H. pylori and to rHSP60 in the patients whose tumor regressed were significantly higher than titers in patients whose tumors did not regress (p = .0011 and .035, respectively). By logistic regression analysis, age (odds ratio = 0.88, 95% confidence interval = 0.80–0.99), endoscopic appearance (0.053, 0.004–0.65), titers of anti‐H. pylori antibodies (67.6, 2.5–1800), and titers of anti‐rHSP60 antibody (6.4, 1.2–36) were identified as significantly associated factors with the outcome of MALT lymphoma. Conclusions. Measurement of serum antibodies to H. pylori and HSP60 might be useful for predicting the response of gastric MALT lymphoma to eradication of H. pylori.     

Early B-cell precursors in scid mice: normal numbers of cells transformable with Abelson murine leukemia virus (A-MuLV)

scid mice lack detectable B and T lymphocytes; there are no typical pre-B cells as defined by c mu and surface markers in their bone marrow and their thymus contains only 1% of the normal number of cells. In these characters scid mice seem to lack lymphoid stem cells. However, some mice have detectable serum immunoglobulin and others develop thymomas; both observations indicate that the block in lymphoid development is not absolute. To determine whether scid mice have any B-cell precursors, we looked for pre-B cells by their ability to be transformed by Abelson murine leukemia virus (A-MuLV). Surprisingly, scid mice contain as many B-cell precursors transformable with A-MuLV as normal control mice. Cell-surface markers specific for pre-B and B cells were detected on the A-MuLV-transformed bone marrow cells of both scid and normal mice, indicating that the A-MuLV-transformed cells belong to the B lineage. Interestingly, the same surface markers were undetectable on nontransformed scid bone marrow cells. We conclude from these results that scid mice have normal numbers of early B-cell precursors but that their differentiation into functional B cells is severely impaired.     

Immunohistochemical comparison of CD5, lambda,and kappa expression in primary and recurrent buccal Mucosa-associated lymphoid tissue (MALT) lymphomas

Mucosa-associated lymphoid tissue (MALT) lymphoma is a type of extranodal marginal zone B-cell lymphoma and is a distinct subtype of non-Hodgkin's lymphoma.Primary MALT lymphomas can also occur in the oral cavity, although their appearance in this location is rare. The neoplastic cells of which MALT lymphomas are composed express B-cell antigens and show monotypic immunoglobulin expression with light-chain restriction.Although neoplastic MALT lymphoma cells do not express CD5, previous studies have shown that CD5 positive MALT lymphomas are more prone to dissemination than those that do not express CD5. Moreover, there are some reports that describe kappa- and lambda- dual light chain expression in B cell malignant neoplasms.A 66-year-old Japanese woman with swelling of the right buccal mucosa was referred to our hospital. The lesion was excised and was pathologically diagnosed as a MALT lymphoma tumor with a t(11;18)(q21;q21) chromosome translocation.Swelling of the right buccal mucosa recurred 2 years later. The recurrent tumor was then excised and pathologically diagnosed as MALT lymphoma.Immunohistochemical examination of CD5, lambda, and kappa expressions revealed that the primary tumor was positive for CD5, kappa, and lambda, but the recurrent tumor was weakly positive for CD5 and kappa.With respect to lambda positivity, the recurrent tumor showed negativity.Our study suggests that immunohistochemical expression of CD5, kappa, and lambda in oral MALT lymphoma have the risk of recurrence.We first described the recurrence of CD5 positive MALT lymphoma in the oral cavity and compared the immunohistochemical expressions of CD5, lambda, and kappa between the primary and recurrent tumors.     

Helicobacter pylori. One bacterium and a broad spectrum of human disease! An overview.

Since the historical rediscovery of gastric spiral Helicobacter pylori in the gastric mucosa of patients with chronic gastritis by Warren and Marshall in 1983, peptic ulcer disease has been largely viewed as being of infectious aetiology. Indeed, there is a strong association between the presence of H. pylori and chronic active gastritis in histology. The bacterium can be isolated in not less than 70% of gastric and in over 90% of duodenal ulcer patients. Eradication of the organism has been associated with histologic improvement of gastritis, lower relapse rate and less risk of bleeding from duodenal ulcer. The bacterium possesses several virulence factors enabling it to survive the strong acid milieu inside the stomach and possibly damaging host tissues. The sequence of events by which the bacterium might cause gastric or duodenal ulcer is still not fully elucidated and Koch's postulates have never been fulfilled. In the majority of individuals, H. pylori infection is largely or entirely asymptomatic and there is no convincing data to suggest an increase in the prevalence of peptic ulcer disease among these subjects. An increasingly growing body of literature suggests an association between colonization by H. pylori in the stomach and a risk for developing gastric mucosa-associated lymphoid tissue (MALT), MALT lymphoma, gastric adenocarcinoma and even pancreatic adenocarcinoma. The bacterium has been implicated also in a number of extra-gastrointestinal disorders such as ischaemic heart disease, ischaemic cerebrovascular disease, atherosclerosis, and skin diseases such as rosacea, but a causal role for the bacterium is missing. Eradication of H. pylori thus seems to be a beneficial impact on human health. Various drug regimens are in use to eradicate H. pylori involving the administration of three or four drugs including bismuth compounds, metronidazole, clarithromycin, tetracyclines, amoxycillin, ranitidine, omeprazole for 1-2 weeks. The financial burden, side effects and emergence of drug resistant strains due to an increase in the use in antibiotics for H. pylori eradication therapy need further reconsideration.