MALT Lymphoma, Stress Ulcer and Cholinergic Nerves from the Viewpoint of Bilateral and Unilateral Truncal Vagotomy and Substance P

Background: Vagal nerve plays an important role in the stomach function. The cholinergic nerves are the most abundantly distributed nerves in the gastric tissue. It has recently been reported that the vagal nerve is significantly related to both gastric cancer development and progression. However, its relation to the mesenchymal tumor, including MALT lymphoma, is not known. In this study, we investigated the effect of unilateral truncal vagotomy on gastric MALT lymphoma development by using Helicobacter heilmannii-infected mouse model as well as that of bilateral truncal vagotomy on stress-induced ulcer formation. Methods: In the first part of this study, the distribution of the cholinergic nerves in the rat gastric mucosa and the effect of bilateral truncal vagotomy, as well as various kinds of agents acting on autonomic nerves in rats, were investigated by the histochemical and macroscopic method. In the second part, we employed MALT lymphoma formation in C57BL/6NCrl mice that were infected with Helicobacter heilmannii. A total of 38 infected mice underwent unilateral vagotomy under microscopy. The mice were randomized into 4 groups from which samples were collected; 2, 3, 4 and 6 months after infection. Both the anterior and posterior sides of the stomachs were sampled from each mouse for pathological and immunohistochemical analyses. Results: The bilateral truncal vagotomy significantly suppressed the restraint-induced gastric ulcer formation in rats, while bethanechol, and 6-hydroxydopamine led to an increase of the gastric ulcer formation. In the unilateral truncal vagotomy study using MALT lymphoma, the thickness of the gastric mucosa was reduced in the vagotomized side compared to the non-vagotomized side. Furthermore, the gastric MALT lymphoma was more prominently found in the vagotomized anterior side of stomach compared with that in the non-vagotomized posterior side of stomach. Substance P-immunoreactive nerves markedly increased surrounding the MALT lymphoma and the neurokinin-1 receptor immunoreactive lymphocytes increased within the MALT lymphoma in the vagotomized side. In conclusion, vagotomy enhanced gastric MALT lymphoma development possibly through the substance P-neurokinin-1 receptor pathway.

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Role of substance P and CGRP in gastric MALT lymphoma induced by Helicobacter heilmannii infection (1052.5)

The FASEB Journal ◽

10.1096/fasebj.28.1_supplement.1052.5 ◽

2014 ◽

Vol 28 (S1) ◽

Author(s):

Masahiko Nakamura ◽

Hidenori Matsui ◽

Tetsufumi Takahashi ◽

Kanji Tsuchimoto

Keyword(s):

Substance P ◽

Malt Lymphoma ◽

Gastric Malt Lymphoma ◽

Helicobacter Heilmannii

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Genetic Characterization and Clinical Features of Helicobacter pylori Negative Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

Cancers ◽

10.3390/cancers13122993 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2993

Author(s):

Barbara Kiesewetter ◽

Christiane Copie-Bergman ◽

Michael Levy ◽

Fangtian Wu ◽

Jehan Dupuis ◽

...

Keyword(s):

Gastric Mucosa ◽

Signaling Pathways ◽

Clinical Features ◽

Malt Lymphoma ◽

Lymphoid Tissue ◽

Targeted Sequencing ◽

Clinicopathological Parameters ◽

Gastric Malt Lymphoma ◽

Genetic Changes ◽

H Pylori

Background: In Western countries, the prevalence of gastric mucosa-associated lymphoid tissue (MALT) lymphoma has declined over the last three decades. Contemporaneously, H. pylori negative gastric MALT lymphoma is increasingly encountered, and their genetic basis and clinical features remain elusive. Methods: A total of 57 cases of H. pylori negative gastric MALT lymphoma were reviewed and investigated for chromosome translocation by fluorescence in-situ hybridization and for somatic mutations by the targeted sequencing of 93 genes. Results: MALT1 translocation, most likely t(11;18)(q21;q21)/BIRC3-MALT1, was detected in 39% (22/57) cases, and IGH translocation was further seen in 12 MALT1-negative cases, together accounting for 60% of the cohort. Targeted sequencing was successful in 35 cases, and showed frequent mutations in NF-κB signaling pathways (TNFAIP3 = 23%, CARD11 = 9%, MAP3K14 = 9%), together affecting 14 cases (40%). The NF-κB pathway mutations were mutually exclusive from MALT1, albeit not IGH translocation, altogether occurring in 86% of cases. There was no significant correlation between the genetic changes and clinicopathological parameters. The patients showed a median of progression-free survival (PFS) of 66.3 months, and a significant superior PFS when treated with systemic versus antibiotic therapy (p = 0.004). Conclusion: H. pylori negative gastric MALT lymphoma is characterized by highly frequent genetic changes in the NF-κB signaling pathways.

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Clone-specific PCR reveals wide dissemination of gastric MALT lymphoma to the gastric mucosa

The Journal of Pathology ◽

10.1002/1096-9896(2000)9999:9999<::aid-path727>3.0.co;2-j ◽

2000 ◽

Vol 192 (4) ◽

pp. 488-493 ◽

Cited By ~ 29

Author(s):

Ming-Qing Du ◽

Tim C. Diss ◽

Ahmet Dogan ◽

Hong-Tao Ye ◽

Antonella Aiello ◽

...

Keyword(s):

Gastric Mucosa ◽

Malt Lymphoma ◽

Gastric Malt Lymphoma ◽

Specific Pcr ◽

Wide Dissemination

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Preferential Dissemination of B-Cell Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma to the Splenic Marginal Zone

Blood ◽

10.1182/blood.v90.10.4071 ◽

1997 ◽

Vol 90 (10) ◽

pp. 4071-4077 ◽

Cited By ~ 51

Author(s):

Ming-Qing Du ◽

Huai-Zheng Peng ◽

Ahmet Dogan ◽

Tim C. Diss ◽

Haiqun Liu ◽

...

Keyword(s):

Gastric Mucosa ◽

B Cell ◽

Malt Lymphoma ◽

Lymphoid Tissue ◽

Marginal Zone ◽

Gastric Lymphoma ◽

Gastric Malt Lymphoma ◽

Lymphoma Cells ◽

Marginal Zone B Cells ◽

Clonal Identity

Abstract The tendency for gastric mucosa-associated lymphoid tissue (MALT) lymphoma cells preferentially to localize around reactive B-cell follicles, both in the mucosa and regional lymph nodes, coupled with their immunophenotype, has led to the proposal that the normal cell counterpart of this lymphoma is the marginal zone B cell. In keeping with this proposition, lymphocytes expressing the lymphoma idiotype have been detected in the splenic marginal zone in a single case of gastric MALT lymphoma. To confirm that this truly represented preferential homing of MALT lymphoma to the splenic marginal zone, we have now re-examined this case, together with 17 other cases, using both immunohistochemical and molecular methods in an attempt to establish clonal identity between the gastric lymphoma and cells in the splenic marginal zone. In three cases, the spleen was characterized by marked expansion of marginal zones by cells showing the same pattern of Ig light chain restriction as the gastric lymphoma. None of the remaining 15 cases showed histologic evidence of lymphomatous infiltration. Analysis of the Ig genes by polymerase chain reaction (PCR), cloning, and sequencing confirmed clonal identity between the splenic marginal zone infiltrates and the gastric lymphoma in the histologically involved cases. Amplifiable DNA could be extracted from only 5 of the remaining 15 cases. In 3 of these cases, including the case previously studied using an anti-idiotype, involvement of the splenic marginal zone could be confirmed using microdissection and clone-specific PCR. No involvement could be detected in the remaining 2 cases. In addition, we have shown that mucosal addressin cell adhesion molecule-1 (MAdCAM-1), the primary homing receptor of gut-mucosa for lymphocytes, was strongly expressed by the sinus lining cells of the splenic marginal zone. These results provide strong evidence for preferential involvement of the marginal zone when gastric MALT lymphomas disseminate to the spleen, which is in keeping with the notion that the marginal zone B cells are the normal counterparts of MALT lymphoma cells.

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Helicobacter pylori–Negative MALT Lymphoma Presenting as a Massive Recurrent Gastrointestinal Hemorrhage

Journal of Investigative Medicine High Impact Case Reports ◽

10.1177/2324709620937166 ◽

2020 ◽

Vol 8 ◽

pp. 232470962093716

Author(s):

Prateek S. Harne ◽

Samiran Mukherjee ◽

Ted Achufusi ◽

Dhruv Lowe ◽

Divey Manocha

Keyword(s):

Helicobacter Pylori ◽

Gastric Mucosa ◽

Malt Lymphoma ◽

Lymphoid Tissue ◽

Gastric Lymphoma ◽

Hypovolemic Shock ◽

Gastric Neoplasms ◽

Gastric Malt Lymphoma ◽

Primary Gastric Lymphoma ◽

Life Threatening

Primary gastric lymphoma is rare, representing 5% of all primary gastric neoplasms. The presenting complaints of gastric mucosa-associated lymphoid tissue (MALT) lymphoma are usually nonspecific. However, life-threatening gastrointestinal bleeding from the stomach is unusual and sparsely reported. While studies reveal an indolent course, we present a case that presented with massive and recurrent hematemesis leading to hypovolemic shock secondary to endoscopically confirmed MALT lymphoma, which was treated with radiotherapy to achieve remission. She had no autoimmune diseases and tested negative for Helicobacter pylori. Our case emphasizes the importance of early diagnosis and timely intensive radiotherapy of a localized but aggressive gastric MALT lymphoma.

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Radiotherapy for localized gastric mucosa–associated lymphoid tissue lymphoma: long-term outcomes over 10 years

Journal of Radiation Research ◽

10.1093/jrr/rrw044 ◽

2017 ◽

Vol 58 (4) ◽

pp. 537-542 ◽

Cited By ~ 10

Author(s):

Yu Ohkubo ◽

Yoshihiro Saito ◽

Hiroki Ushijima ◽

Masahiro Onishi ◽

Tomoko Kazumoto ◽

...

Keyword(s):

Gastric Mucosa ◽

Malt Lymphoma ◽

Lymphoid Tissue ◽

Residual Disease ◽

Distant Metastases ◽

Gastric Malt Lymphoma ◽

Long Term Outcomes ◽

Abdominal Lymph Node

Abstract This study aimed to assess the long-term outcomes of radiotherapy in patients with localized gastric mucosa–associated lymphoid tissue (MALT) lymphoma. Twenty-seven patients with Stage I gastric MALT lymphoma were treated with radiotherapy from 1999 to 2010. The median age was 65 years (range: 31–84). Fifteen patients were Helicobacter pylori–negative. Thirteen patients were treated with definitive radiotherapy alone. The other 14 patients who had refractory or residual disease following a prior treatment received salvage radiotherapy. The median dose of the radiotherapy was 30 Gy in 20 fractions (range: 30–39.5 Gy). The median follow-up period was 121 months (range: 8–176 months). The 5- and 10-year overall survival rates for all patients were 92% and 87%, respectively. No patients died from MALT lymphoma. Three patients died of other diseases at 8, 33 and 74 months after radiotherapy (myocardial infarction, pneumonia and hepatocellular carcinoma, respectively). No cases of local recurrence were observed during the follow-up period. There were no serious late gastric, liver or kidney complications during a median follow-up period of over 10 years. Two patients remain alive with distant metastases: a lung metastasis and an abdominal lymph node metastasis at 104 months and 21 months after radiotherapy, respectively. Excellent long-term local control was observed in patients with localized gastric MALT lymphoma after radiotherapy. However, lifelong follow-up should be conducted to detect cases of late recurrence, especially distant metastases.

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Association of T-Cell Regulatory Gene Polymorphisms With Susceptibility to Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2005.05.5434 ◽

2006 ◽

Vol 24 (21) ◽

pp. 3483-3489 ◽

Cited By ~ 54

Author(s):

Tsu-Yao Cheng ◽

Jaw-Town Lin ◽

Li-Tzong Chen ◽

Chia-Tung Shun ◽

Hsiu-Po Wang ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Gastric Mucosa ◽

Malt Lymphoma ◽

Crucial Role ◽

Lymphoid Tissue ◽

Gene Polymorphisms ◽

Gastric Malt Lymphoma ◽

H Pylori

Purpose Helicobacter pylori infection and host susceptibility interact to develop gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and activation of specific T cells might play a crucial role in this process. Recent investigations show that the CTLA4, CD28, and ICOS genes are located on chromosome 2q33 and their polymorphisms confer susceptibility to infectious and immune diseases through deregulation of T-cell stimulation. We aimed to determine the role of CTLA4, CD28, and ICOS polymorphisms in gastric MALT lymphoma. Patients and Methods Genotyping for CTLA4 (49 A/G, −318 C/T, and CT60 A/G), CD28 (IVS3+ 17T/C), and ICOS (c.602 A/C and c.1624C/T) was performed for 62 patients with gastric MALT lymphoma and compared with 250 unrelated healthy controls. Results H pylori infection was significantly higher in patients with gastric MALT lymphoma (90.3%) compared with controls (66.4%; P < .001). The CTLA4 −318 C/T genotype was associated with a lower risk of developing gastric MALT lymphoma (odds ratio [OR] = 0.3; P = .022), whereas CTLA4 49 G/G genotype was linked to a higher risk (OR = 4.1; P = .044). In patients with H pylori infection, CTLA4 49 G/G genotype was associated with an even higher risk (OR = 6.4; P = .047). Carriage of the tightly linked −318C –49G haplotype conferred a four-fold higher susceptibility to MALT lymphoma (OR = 4.2; P = .042). Complete remission after H pylori eradication was related to tumor stage but not to genotypes or haplotypes. Conclusion These results indicate a genetic link of CTLA4 gene polymorphisms to development of gastric MALT lymphoma and indirectly support the crucial role of host activated T cells in the MALT lymphomagenesis.

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