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。     

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.     

The possible involvement of micro-organisms other than Helicobacter pylori in the development of rectal MALT lymphoma in H. pylori-negative patients

It remains unclear whether lymphoma of the mucosa-associated lymphoid tissue (MALT) in the extragastric organs is related to Helicobacter pylori infection or not. This report describes three patients with rectal MALT lymphoma negative for H. pylori infection, all of whom showed disease regression after being treated with antibiotics. One patient had MALT lymphoma in both the descending colon and the rectum; the other two patients had rectal disease only. None of the patients had chronic gastritis which was detectable either endoscopically or histologically and H. pylori infection was completely ruled out by various methods, including a urease breath test. These patients received antibiotic therapy. In all the patients, regression of MALT lymphoma was observed endoscopically and histologically, and polymerase chain reaction revealed that a previously observed rearranged band of immunoglobulin heavy chain had also disappeared after antibiotic treatment. These cases therefore suggest involvement of micro-organisms other than H. pylori in the development of rectal MALT lymphoma.     

Helicobacter pylori strikes again: gastric mucosa-associated lymphoid tissue (MALT) lymphoma.

Infection with Helicobacter pylori is common. Over 50% of the world's population is estimated to be colonized with the bacteria. The association between Helicobacter pylori and gastric mucosa-associated lymphoid tissue (MALT) lymphoma is well documented. Anti-Helicobacter pylori treatment and the successful eradication of the bacteria can potentially cure patients who test positive for the bacteria and who are diagnosed with low-grade gastric MALT lymphoma. The purpose of this article is to review the evidence implicating Helicobacter pylori as a causal pathogen for the development of gastric MALT lymphoma and to determine that anti-Helicobacter pylori therapy is an effective first-line treatment. The clinical presentation, endoscopic findings, diagnosis, staging, treatment, and follow-up of patients with gastric MALT lymphoma who are treated with anti-Helicobacter pylori therapy are also discussed.     

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.     

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.     

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.     

VacA and HP-NAP, Ying and Yang of Helicobacter pylori-associated gastric inflammation

Helicobacter pylori is a Gram-negative bacterium which infects almost half of the population worldwide and represents the major cause of gastroduodenal pathologies, such as duodenal and gastric ulcer, gastric cancer, B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) and autoimmune gastritis. H. pylori colonization is followed by infiltration of the gastric mucosa by polymorphonuclear cells, macrophages and lymphocytes. Two of the major H. pylori virulence factors are the vacuolating cytotoxin (VacA) and the H. pylori neutrophil-activating protein (HP-NAP). VacA has been proposed as a modulator of immune cell function because of its capacity to interfere with antigen presentation and to inhibit T-cell activation. HP-NAP was designated as neutrophil-activating protein because it stimulates high production of oxygen radicals from neutrophils. We have recently demonstrated that HP-NAP is able to recruit leukocytes in vivo and to stimulate either neutrophils or monocytes to release IL-12, a key cytokine for the differentiation of naive Th cells into the Th1 phenotype. Altogether these evidences indicate that both VacA and HP-NAP play a major role in generating and maintaining the gastric inflammatory response associated with the H. pylori infection.     

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.     

MALT淋巴瘤病因及发病机制研究进展

黏膜相关淋巴组织(MALT)淋巴瘤为起源于淋巴结外MALT的低度恶性B细胞淋巴瘤,是非霍奇金淋巴瘤中边缘区B细胞淋巴瘤最常见类型。MALT淋巴瘤常发生于胃、唾液腺、甲状腺及眼眶附属器等部位,其中发生于胃肠道的病例占全部MALT淋巴瘤的50%,胃肠道MALT淋巴瘤已证实与幽门螺杆菌(HP)感染有关,其主要机制为免疫反应,在部分染色体易位患者抗HP治疗无效,提示存在其他致病机制。在MALT淋巴瘤中发现的染色体易位包括t(11;18)(q21;q21)、t(1;14)(p22;q32)、t(14;18)(q32;q21)、t(3;14)(p14.1;q32)。最近研究发现了一些新的染色体异常如6q23.3等,它们对淋巴瘤的临床过程及预后等均有影响。MALT淋巴瘤的染色体异常通常激活共同的分子通路核因子(NF)-κB,持续活化的NF-κB使肿瘤细胞增殖或活化,最终导致MALT淋巴瘤的发生。本文就近年来MALT淋巴瘤病因及发病机制的研究进展做一综述。     

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.     

Gastric malignant lymphoma

Primary gastric lymphoma is a rare tumor and the frequency is less than 5% of gastric neoplasms. Although the histological diagnosis is diverse, the majority is MALT lymphoma and diffuses large B-cell lymphoma. MALT lymphoma is derived from marginal B-cell of lymphoid follicle, which is induced by Helicobacter pylori infection. The 60-80% of them is regressed by the eradication treatment. A part of MALT lymphoma is characterized by chromosomal translocations, t(11;18), t(1;14) or t(14;18) that is poor response factors to the eradication. Interestingly, all chimeric proteins produced by the translocations have activated NF-kappaB in the cells. The phenotype of diffuse large B-cell lymphoma is heterogeneous. However, the combination treatment of rituximab plus CHOP is effective and it is capable to preserve the stomach. A non-surgical treatment is recommended to gastric lymphoma.     

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.     

Gastric Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue and Signet Ring Cell Carcinoma,Synchronous Collision Tumour of the Stomach: A Case Report

Objective

To report a rare case of synchronous marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) signet ring cell carcinoma occurring as a collision tumour in the stomach.

Clinical Presentation and Intervention

A 53-year-old man was diagnosed initially with signet ring cell carcinoma of the stomach. The microscopy of the subsequent total gastrectomy revealed a collision tumour of MALT lymphoma and signet ring cell carcinoma associated with Helicobacter pylori gastritis.

Conclusion

This case highlighted the importance of a careful evaluation of the accompanying lymphoid population in the biopsy samples of gastric adenocarcinoma and underlined the need for multiple endoscopic biopsies to detect these rare synchronous tumours.Key Words: Mucosa-associated lymphoid tissue lymphoma, Adenocarcinoma, Collision, Stomach     

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.     

BCA-1 is highly expressed in Helicobacter pylori-induced mucosa-associated lymphoid tissue and gastric lymphoma

Infection with Helicobacter pylori (Hp) induces the formation of lymphoid tissue in the stomach and the occasional development of primary gastric B-cell lymphomas. We have studied the expression of 2 chemokines that attract B lymphocytes, BCA-1 and SLC, in gastric tissue samples obtained from patients with chronic gastritis induced by Hp infection or nonsteroidal anti-inflammatory drugs, as well as from patients with Hp-associated low-grade and high-grade gastric lymphomas. High-level expression of BCA-1 and its receptor, CXCR5, was observed in all mucosal lymphoid aggregates and in the mantle zone of all secondary lymphoid follicles in Hp-induced gastric mucosa-associated lymphoid tissue (MALT). Follicular dendritic cells and B lymphocytes are possible sources of BCA-1, which is not expressed by T lymphocytes, macrophages, or CD1a(+) dendritic cells. Strong expression of BCA-1 and CXCR5 was also detected in the transformed B cells of gastric MALT lymphomas. By contrast, SLC was confined almost exclusively to endothelial cells in and outside the lymphoid tissue. Only scant, occasional SLC expression was observed in the marginal zone of MALT follicles. Our findings indicate that BCA-1, which functions as a homing chemokine in normal lymphoid tissue, is induced in chronic Hp gastritis and is involved in the formation of lymphoid follicles and gastric lymphomas of the MALT type.     

Collision tumor: invasive ductal carcinoma in association with mucosa-associated lymphoid tissue (MALT) lymphoma in the same breast

Synchronous occurrence of multiple neoplastic processes is uncommon and the relationship between breast cancer with lymphoproliferative diseases is unusual as well. Furthermore, breast involvement by malignant lymphoma is a rare event and primary breast mucosa-associated lymphoid tissue (MALT) lymphoma is even rarer. We report a patient with synchronous occurrence of malignant lymphoma of MALT type and ductal carcinoma of the breast, presenting as "collision tumor," invading each other and occurring as a single mass in the breast. Involvement of the sentinel lymph node by MALT lymphoma was demonstrated with no evidence of metastatic carcinoma. Staging bone marrow biopsy did not show involvement by malignant lymphoma or carcinoma. Our patient was treated with chemotherapy for the lymphoma. She also received radiotherapy and aromatase inhibitor as adjuvant therapy for the breast carcinoma.     

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。     

Sonographic appearances of mucosa-associated lymphoid tissue lymphoma of the submandibular gland confirmed with sonographically guided core needle biopsy

A 71-year-old man presented with mucosa-associated lymphoid tissue (MALT) lymphoma of the submandibular gland 52 months after initial diagnosis of MALT lymphoma of the lung. Ultrasonography showed a well-demarcated, markedly hypoechoic, heterogeneous solid mass with linear echogenic strands and hypervascularity. Ultrasound-guided core-needle biopsy demonstrated histological findings of MALT lymphoma. Sonographic features of MALT lymphoma of the submandibular gland are characteristic and ultrasound-guided core-needle biopsy may be a suitable replacement for surgical biopsy.     

A case of Helicobacter pylori infection complicated with gastric cancer, gastric mucosa-associated lymphoid tissue lymphoma, and idiopathic thrombocytopenic purpura successfully treated with laparoscopy-assisted total gastrectomy and splenectomy

Helicobacter pylori infection plays a key role in the pathogenesis of H. pylori-associated diseases, including gastroduodenal and non-gastroduodenal diseases. A 71-year-old man was evaluated for a positive fecal occult blood test by upper gastrointestinal endoscopy, which revealed H. pylori infection, two adenocarcinomas and two gastric mucosa-associated lymphoid tissue lymphomas. Hematological examination revealed low platelet-count, elevated platelet-associated immunoglobulin G and anti-H. pylori immunoglobulin G antibodies. We diagnosed H. pylori infection complicated by simultaneous occurrence of gastric cancer, gastric mucosa-associated lymphoid tissue lymphoma, and idiopathic thrombocytopenic purpura. These diseases were successfully treated with laparoscopy-assisted total gastrectomy and splenectomy, and there was no evidence of recurrence for about 2 years. This is the first reported case of H. pylori infection complicated by these three diseases and cured with laparoscopic surgery.