Malignant lymphoma and Helicobacter pylori infection

Lymphoid tissue is acquired in the stomach in response to antigenic stimulation, so called mucosa-associated lymphoid tissue(MALT). In 1983, Isaacson had named a type of malignant B-cell lymphoma "MALT lymphoma" which grow in the marginal zone of lymphoid foliclies in the gastric mucosa. MALT lymphoma has lately attracted attention because of the relation of Helicobacter pylori(H. pylori). There are several studies that H. pylori can be detected in more than 90% of patients with MALT lymphoma and cure of H. pylori infection is followed by a complete regression of these tumors in most patient. This paper reviews the current knowledge about MALT lymphoma, and immunological and molecular aspects in the pathogenesis of the disease.     

Helicobacter pylori: why it still matters in 2005

Despite falling prevalence rates in the developed world, H pylori is still present in the United States and is particularly prevalent among racial minorities and recent immigrants. H pylori infection is clearly associated with an increased risk of peptic ulcer disease, gastric cancer, and MALT lymphoma, and it is associated with some cases of uninvestigated dyspepsia. Identification and eradication of H pylori improves outcomes in patients with peptic ulcer disease and causes tumor regression in patients with MALT lymphoma. It is uncertain whether H pylori eradication will improve outcomes in patients with gastric cancer. Decision analytic models suggest that a test-and-treat strategy for H pylori is rational and cost-effective for patients with uninvestigated dyspepsia.     

Primary mucosa-associated lymphoid tissue (MALT) lymphoma occurring in the rectum: a case report and review of the literature

The primary extranodal B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is a distinct clinical pathologic entity that develops in diverse anatomic locations such as the stomach, salivary gland, thyroid, lung, and breast; however, colorectal involvement is rare. To the best of our knowledge, only 30 cases of primary rectal MALT lymphoma have been published in the English language literature, mostly from Japan. A single case has been reported from the US before this report. The most common symptoms ranged from asymptomatic to occult or gross gastrointestinal bleeding. Simultaneous involvement of the cecum or colon was seen in 20% of the patients. Ninety percent of the patients were classified as low grade, Stage 1 at the time of diagnosis. Polypoid lesions were 10-fold more common than ulcerative lesions. Seven patients were reported to have H pylori in the stomach. The majority of the patients underwent surgical or endoscopic resection as a cure; however, controversy exists with regards to antibiotic treatment or observation alone because of unknown etiopathogenesis. Infection with microorganisms other than H pylori has been postulated in the development of rectal MALT lymphoma; however, this hypothesis remains unproven. The overall prognosis of rectal MALT lymphoma appears favorable; however, long-term follow-up data is lacking. Therefore, periodic clinical monitoring should be done in these patients.     

Treatment of gastric MALT lymphoma by H. pylori eradication

Strong evidence exists for the efficacy of H. pylori eradication in achieving gastric low-grade MALT lymphoma (L-MALT) regression when the bacteria present. Besides histological evaluation, the appearance of endoscopic finding such as 'discolored mucosa-like atrophy' after treatment may be useful for the prediction of its outcome (endoscopic evaluation). However, a reliable marker for molecular evaluation is not obtained so far. On the other hand, long-term control of L-MALT with H. pylori eradication therapy is uncertain and there still remains a subset of patients with no evidence of H. pylori or who fail H. pylori eradication therapy. Therefore, the optimal non antibiotic therapy for these patients has been studied. According to the recent report, radiation therapy appears to be well tolerated and effective for patients with gastric L-MALT.     

Long-term outcomes of gastric mucosa-associated lymphoid tissue lymphomas after Helicobacter pylori eradication therapy

Mucosa-associated lymphoid tissue (MALT) lymphomas are localized primarily in the gastrointestinal tract and are characterized by an indolent nature and favorable outcome with specific therapy. Gastric MALT lymphomas are closely linked to Helicobacter pylori (H. pylori) infection, for which eradication therapy is recognized as an effective primary treatment for the disease. However, there is little information about long-term outcomes after the therapy. In the present study, we elucidated the long-term outcomes of 74 patients (70 H. pylori-positive and 4 negative cases) followed up by endoscopy at least 12 months after exclusive eradication therapy alone. The median follow-up period was 46 months. When the remission status was estimated at the time point of 12 months post-eradication, the numbers of patients with complete remission (CR), histologically residual disease with macroscopic normalization (hRD), partial remission with more than 50% tumor reduction (PR) or no response (NR) were 56, 12, 2 and 4, respectively. During follow-ups of over 12 months post-eradication, 11 of the 12 hRD cases were belatedly induced to CR but one CR case histologically relapsed into hRD. One of the 2 PR cases eventually turned into hRD 20 months later. Therefore, 66 CR, 3 hRD, 1 PR, and 4 NR cases (including 3 H. pylori-negative) were identified at the last follow-up of the present study. All 74 patients were followed up without any second-line therapies, but none exhibited disease progression. Thus, the long-term outcome of localized gastric MALT lymphoma after H. pylori eradication therapy was favorable. A watch and wait strategy may be a reasonable approach for hRD since the majority might be in the process of turning into delayed CR.     

Gastric MALT lymphoma in the absence of Helicobacter pylori infection presenting as an upper gastrointestinal hemorrhage

Gastric MALT lymphoma is almost exclusively a sequelae of Helicobacter pylori infection and rarely presents with profuse bleeding. Gastric mucosa is not normally thought to contain lymphoid tissue, yet in the presence of H pylori reactive lymphoid follicles form which are possibly throught to predispose the patient to developing lymphoma. GI bleeding from these tumors is common during treatment as a consequence of tumor regression or necrosis. We present the case of a MALT Lymphoma in a 59 year-old woman manifesting as a brisk upper GI bleed without serologic or microbiologic evidence of an H pylori infection.     

Causal relationship between Helicobacter pylori infection and upper gastroduodenal diseases

Helicobacter pylori infection causes chronic gastritis (nonatrophic gastritis), which progresses to atrophic gastritis and intestinal metaplasia over a period of decades. Atrophy may result from inflammation and apoptosis caused by H. pylori infection. H. pylori is an important risk factor for peptic ulcer disease. Duodenitis in the gastric metaplasia of the duodenum, hypergastrinemia, and impaired proximal duodenal mucosal bicarbonate secretion are considered causal factors for duodenal ulcer disease. Low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue (MALT) develops in response to H. pylori infection. Studies of Mongolian gerbil model demonstrated that H. pylori had an initiator or promoter effect on gastric carcinogenesis.     

胃黏膜相关淋巴组织淋巴瘤幽门螺杆菌分离株与胃炎分离株的转录组比较

目的本研究对胃黏膜相关淋巴组织淋巴瘤（MALT淋巴瘤）幽门螺杆菌分离株与胃炎分离株的转录组进行比较，以阐述胃MALT淋巴瘤幽门螺杆菌分离株的转录组特征。方法对2株分离自胃MALT淋巴瘤的菌株与胃炎菌株26695的转录组进行比较。结果胃MALT淋巴瘤幽门螺杆菌分离株之间转录组非常相似，而与胃炎菌株26695之间差异较大。 对差异表达基因进行GO功能富集分析，结果显示富集基因数前5位的为催化活性、代谢进程、细胞进程、结合、单组织进程。 Pathway显著性富集分析表明差异基因的功能主要参与氨基酸和核苷酸糖代谢、卟啉和叶绿素代谢以及乙醛和二羧酸代谢。结论胃MALT淋巴瘤幽门螺杆菌相关菌株可能通过代谢调控菌体生长和侵染宿主，从而在胃MALT淋巴瘤形成过程中发挥着重要作用。     

Helicobacter pylori infection and eradication

H. pylori infection is associated with various gastroduodenal diseases such as gastritis, peptic ulcer, gastric cancer, gastric MALT lymphoma. H. pylori infection is suggested that it plays a role as protective factor not promoting factor for reflux esophagitis and GERD. Epidemiological studies showed lower prevalence of H. pylori infection in reflux esophagitis and Barrett's esophagus comparing the control. Increased occurrence of reflux esophagitis after curing of H. pylori infection was reported. However, the relationship between H. pylori infection and reflux esophagitis has not been actually made clear. Also the mechanism of reflux esophagitis occurrence after H. pylori eradication is not obscure.     

Mucosa-associated lymphoid tissue (MALT) lymphoma

OBJECTIVES: To review the pathogenesis of MALT lymphoma, and the associations with antigenic stimulation, presentation, and unique treatment. DATA SOURCES: Research and review articles and textbooks. CONCLUSION: MALT lymphoma is a heterogeneous but unique pathologic form of extranodal B-cell non-Hodgkin's lymphoma. The gastrointestinal tract is the most common site of disease, but involvement of multiple other organ systems has been reported. In the case of gastric MALT lymphomas, H. pylori has been highly implicated as the stimulating agent. Treatment strategies for early disease involve eradication of H. pylori when it is involved and/or radiotherapy, which alone may result in cure of this lymphoma. Chemotherapy is used in more advanced or resistant disease. IMPLICATIONS FOR NURSING PRACTICE: Nurses play a significant role in the education of patients about this unique malignancy and follow-up regarding compliance with therapy. Attention to social needs of the patients is critical.     

Gastric mucosal immunity induced by H. pylori infection

H. pylori infection induces various humoral and cellular immunities in gastric mucosa. Some reports indicate predominant CD4+ cells infiltrate in H. pylori infected gastric mucosa, and these cells express the T helper 1 phenotype. Local humoral immunity is also induced. Gastric plasma cells produce anti-H. pylori antibodies, however, their protective immunity is not enough to eradicate bacteria in human. We found heat shock protein 60 kDa (hsp60) may be closely associated with pathogenesis in MALT lymphoma. IgG1 antibodies to hsp60 were significantly correlated with the antibodies to H. pylori whole cell in patients with MALT lymphoma. CD40-CD40L dependent B cell proliferation was induced by cytokine and/or hsp60 stimulations in those patients. Cytotoxicity of gastric epithelial cells which is associated with host immunity induced by H. pylori infection is still unclear. We found that lymphocytes from patients with peptic ulcer showed cytotoxicity to gastric cell line HGC-27 in vitro. Cytotoxicity was enhanced by cytokine stimulus to T-lymphocytes and by heat stress and/or patients' antibodies treatment of HGC-27 cells. The pathogenicity of H. pylori may involve not only bacterial virulence factor but also host immunity. Studies of mucosal local immunity will help explain the mechanisms of H. pylori induced gastrodoudenal diseases.     

The role of H pylori in gastrointestinal disease. A guide to identification and eradication

Helicobacter pylori, which is responsible for the most common infection worldwide, has been implicated in several gastrointestinal diseases, such as peptic ulcer disease, gastric adenocarcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma. In this article, Dr Knigge discusses the unique adaptation of H pylori to the acidic gastric environment and describes diagnostic tests to identify the organism, treatment recommendations, and tools to confirm eradication of infection.     

黏膜相关淋巴组织淋巴瘤的发病机制及治疗策略

黏膜相关淋巴组织(MALT)淋巴瘤是B细胞来源的非霍奇金淋巴瘤,其发生主要与感染、基因突变等相关,常见发病部位为胃肠道.MALT诊断及其分期主要依赖于针对各病变组织的辅助检查,尤其是病理活组织检查及免疫组织化学检查.MALT治疗主要以抗感染治疗及观察等待治疗策略为主,辅以放、化疗及靶向免疫治疗等.MALT淋巴瘤患者的总体预后较好,如何提高复发/难治性MALT患者的预后为进一步研究的主要方向.这主要依赖于对MALT发病机制的深入了解,以及基于MALT发病机制的新药研发.笔者拟就MALT淋巴瘤的发病机制及治疗策略的研究进展进行综述.     

The perspectives of upper GI tract diseases

Recently, most of the upper GI tract diseases, peptic ulcer, chronic gastritis, gastric cancer as well as MALT lymphoma, have been explained by the infection of Helicobacter pylori (H. pylori). However, it is not evident whether or not gastric cancer is induced solely by the bacterial infection at this stage. On the other hand, it is reported that the eradication of H. pylori might evoke the reflux esophagitis as well as esophageal and fundic cancer. These important issues remain to be elucidated for the investigation of upper GI tract in the 21st century. The development of new endoscopic technology may be another promising field of upper GI tract.     

Treatment of Helicobacter pylori infection

Helicobacter pylori infection has been shown to be the principal cause of peptic ulcer disease and has been associated with MALT lymphoma and gastric cancer. Eradication of H. pylori has been shown to change the natural history of peptic ulcer disease by preventing relapse and to reduce health care expenditures when compared with traditional therapy. Two-drug regimens have been superceded by three-drug regimens because they are more effective in eradication. Therapies with the highest efficacy are cost-effective because failed eradication is associated with high costs.     

49例MALT淋巴瘤临床资料分析

本研究旨在探讨黏膜相关淋巴组织淋巴瘤（mucosa-associated lymphoid tissue lymphoma，MALTlymphoma）临床特点、APl2．MALTl基因的表达与预后的关系。通过回顾临床资料，研究我院49例MALT淋巴瘤患者的临床特点，并通过RT．PCR法检测部分石蜡标本APl2．MALTl基因重排。结果表明：MALT淋巴瘤患者的发病平均年龄为52，4岁，50岁以上的患者占67．4％，肿瘤多发生在胃肠道，其次在甲状腺；49例中I、Ⅱ期患者占776．％，Ⅲ、IV期患者占22．4％；APl2-MALTl基因重排在低度恶性组、转化组的阳性率分别为38．1％和12、5％；3年生存率为93．8％。结论：MALT淋巴瘤患者的临床进展缓慢，对化疗敏感，预后较好，可根据有无APl2-MALTl基因重排选择不同的治疗方法，对I期HP阳性患者可采用抗HP治疗。     

Regression of high-grade gastric B-cell lymphoma after eradication of Helicobacter pylori

Regression of high-grade gastric B-cell lymphoma after eradication of Helicobacter pylori with antibiotic therapy has recently been shown in a very small number of patients. We describe here a patient with a 5-cm polypoid gastric lymphoma, who received a 7-day course of triple therapy when the histopathology was unknown. A second endoscopic examination 4 weeks later showed partial tumor regression without biopsy evidence of malignancy. Endoscopic mucosectomy was performed 8 weeks after the initial diagnosis. Again, in the histological analysis of the specimen, no evidence of B-cell lymphoma could be found. To confirm that the original biopsies were from the same patient, DNA analyses were carried out which gave identical results. This case suggests that a subgroup of primary gastric B-cell lymphomas responds to eradication of H. pylori with antibiotic therapy.     

An observational study of upper gastrointestinal bleeding in intensive care units: is Helicobacter pylori the culprit?

OBJECTIVE: Upper gastrointestinal bleeding (UGIB) related to stress ulcers was formerly a fearsome complication of intensive care. The incidence of this event has decreased over the years. However, the morbidity, mortality, and causes of UGIB, particularly the etiologic role of Helicobacter pylori infection, are still controversial. Therefore, we prospectively assessed the incidence of UGIB in the intensive care unit (ICU) and evaluated the role of H. pylori infection. DESIGN: A prospective observational study followed by a case-control study. SETTING: Seven ICUs in the Paris area, five of them located in teaching hospitals. PATIENTS: All patients admitted consecutively to seven ICUs during a 1-year period were monitored for signs of clinically relevant UGIB. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Only cases of endoscopically confirmed UGIB were analyzed. Patients whose hemorrhage originated from the stomach and/or duodenum were tested for H. pylori infection, by means of serology, histologic examination, and stool antigen detection. The possible association between H. pylori and UGIB was examined in a case-control study. Twenty-nine of the 4,341 patients admitted to the seven ICUs during the study period had clinically relevant, endoscopically confirmed UGIB (incidence, 0.67%; 95% confidence interval, 0.56%-0.77%). Ulcers were most frequently observed endoscopically. Patients who bled had a higher Simplified Acute Physiology Score (SAPS II) at admission (mean +/- sd, 47 +/- 14 vs. 36 +/- 28; p < .001). Despite a higher in-ICU mortality rate among patients who bled (73% vs. 16%; p < .001), death was never due to bleeding. H. pylori infection was more frequent in patients who bled than in matched controls (36% vs. 16%; p = .04). CONCLUSIONS: Clinically relevant, endoscopically confirmed UGIB is a rare event in the ICU setting and tends to occur in severely ill patients. H. pylori infection is more frequent in patients with gastroduodenal hemorrhage than in nonbleeding patients.     

Primary hepatic mucosa-associated lymphoid tissue lymphoma with HP and previous HBV infection: A case report and literature review

Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively rare disease with low malignancy, and its aetiology is unclear. A 65-year-old man presented with abdominal pain. Hepatitis virus examination revealed a previous hepatitis B virus (HBV) infection, and a carbon-13 urea breath test result was positive for the patient. Abdominal contrast-enhanced computed tomography revealed a patch of abnormal density in the right posterior lobe of the liver. The patient underwent VI segment hepatectomy and was pathologically diagnosed with hepatic MALT lymphoma. After the operation, he received quadruple anti-Helicobacter pylori (HP) therapy and refused other treatments. He has been followed up by telephone for 20 months after discharge and is now in a stable condition. In this study, we counted 105 cases of hepatic MALT lymphomas reported in English or Chinese since 1995 and summarised the clinical characteristics and concomitant diseases in this condition. Based on the literature review, we speculated that chronic infectious diseases, especially viral infections (including hepatitis C virus (HCV) and HBV) and HP infection, are associated with the pathogenesis of primary hepatic MALT lymphoma. In addition, autoimmune diseases might also play a role in this condition.     

Laterally spreading tumor-like primary rectal mucosa-associated lymphoid tissue lymphoma: A case report

BACKGROUNDColorectal mucosa-associated lymphoid tissue (MALT) lymphoma is a rare disease, and only a few cases have been reported to date. It has no specific clinical presentations and shows various endoscopic appearances. There is no uniform consensus on its treatment. With the advancement of endoscopic technology, endoscopic treatment has achieved better results in individual case reports of early-stage patients.CASE SUMMARYWe report a case of rectal MALT in a 57-year-old Chinese man with no symptoms who received endoscopy as part of a routine physical examination, which incidentally found a 25 mm × 20 mm, laterally spreading tumor (LST)-like elevated lesion in the rectum. Therefore, he was referred to our hospital for further endoscopic treatment. Complete and curable removal of the tumor was performed by endoscopic submucosal dissection. We observed enlarged and dilated branch-like vessels similar to those of gastric MALT lymphoma on magnifying endoscopy with narrow-band imaging. And immunopathological staining showed hyperplastic capillaries in the mucosa. Histopathological findings revealed diffusely hyperplastic lymphoid tissue in the lamina propria, with a visible lymphoid follicle structure surrounded by a large number of diffusely infiltrated lymphoid cells that had a relatively simple morphology and clear cytoplasm. In addition, immunohistochemical analysis suggested strongly positive expression for CD20 and Bcl-2. Gene rearrangement results showed positivity for IGH-A, IGH-C, IGK-B, and IGL. Taking all the above findings together, we arrived at a diagnosis of extranodal marginal zone B-cell lymphoma of MALT lymphoma. Positron emission tomography-computed tomography examination showed no other lesions involved. The patient will be followed by periodic endoscopic observation.CONCLUSIONIn conclusion, we report a case of rectal MALT with an LST-like appearance treated by endoscopic submucosal dissection. Further studies will be needed to explore the clinical behavior, endoscopic appearance, and treatment of rectal MALT.