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Inoo S, Iwamuro M, Tanaka T, Kawahara Y, Ootuka M. Gastric Mucosa-associated Lymphoid Tissue Lymphoma That Relapsed after 11 Years Subsequent to Achieving Complete Remission. Intern Med 2024; 63:1697-1702. [PMID: 37926540 PMCID: PMC11239265 DOI: 10.2169/internalmedicine.2642-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 08/22/2023] [Indexed: 11/07/2023] Open
Abstract
A 38-year-old Japanese man was diagnosed with extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue in the stomach (gastric MALT lymphoma). Fluorescence in situ hybridization analysis revealed the absence of t (11;18) (q21;q21) translocation but the presence of extra copies of MALT1, indicating tetrasomy 18. Helicobacter pylori eradication led to complete remission (CR). However, the gastric MALT lymphoma relapsed after 11 years old. This case underscores the need for long-term observation (>10 years) of patients with gastric MALT lymphoma. Further investigation is warranted to elucidate the correlation between trisomy/tetrasomy 18 and the recurrence propensity.
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Affiliation(s)
- Shoko Inoo
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Japan
| | - Masaya Iwamuro
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Japan
| | | | - Yoshiro Kawahara
- Department of Practical Gastrointestinal Endoscopy, Okayama University Hospital, Japan
| | - Motoyuki Ootuka
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Japan
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Waldum H, Mjønes P. The central role of gastrin in gastric cancer. Front Oncol 2023; 13:1176673. [PMID: 37941554 PMCID: PMC10628637 DOI: 10.3389/fonc.2023.1176673] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 09/19/2023] [Indexed: 11/10/2023] Open
Abstract
The prevalence of gastric cancer has markedly declined, but due to the high mortality rates associated with gastric cancer, it is still a serious disease. The preferred classification of gastric cancer is according to Lauren into either the intestinal type, which has a glandular growth pattern, or the diffuse type, which does not have glandular structures. Both types have been classified as adenocarcinomas, with the latter type based on periodic acid-Schiff (PAS) positivity presumed to reflect mucin. However, the presence of mucin in the diffuse type, in contrast to neuroendocrine/enterochromaffin-like (ECL) cell markers, has not been confirmed by immunohistochemistry and in situ hybridization. The ECL cells are probably prone to becoming cancerous because they do not express E-cadherin. Gastric cancer is unique in that a bacterium, Helicobacter pylori, is thought to be its main cause. H. pylori predisposes infected individuals to cancer only after having caused oxyntic atrophy leading to gastric hypoacidity and hypergastrinemia. No single H. pylori factor has been convincingly proved to be carcinogenic. It is probable that gastrin is the pathogenetic factor for gastric cancer due to H. pylori, autoimmune gastritis, and long-term prolonged inhibition of gastric acid secretion. Hypergastrinemia induces ECL cell hyperplasia, which develops into neuroendocrine tumors (NETs) and then into neuroendocrine carcinomas in rodents, a sequence that has also been described in humans. During carcinogenesis, the tumor cells lose specific traits, requiring that sensitive methods be used to recognize their origin. Gastric cancer occurrence may hopefully be prevented by H. pylori eradication at a young age, and by the reduced use of inhibitors of acid secretion and use of a gastrin antagonist in those with previous long-term H. pylori infection and those with autoimmune gastritis.
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Affiliation(s)
- Helge Waldum
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
| | - Patricia Mjønes
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Pathology, St. Olav’s Hospital – Trondheim University Hospital, Trondheim, Norway
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Lemos FFB, Castro CTD, Calmon MS, Silva Luz M, Pinheiro SLR, Faria Souza Mendes dos Santos C, Correa Santos GL, Marques HS, Delgado HA, Teixeira KN, Souza CL, Oliveira MV, Freire de Melo F. Effectiveness of Helicobacter pylori eradication in the treatment of early-stage gastric mucosa-associated lymphoid tissue lymphoma: An up-to-date meta-analysis. World J Gastroenterol 2023; 29:2202-2221. [PMID: 37122607 PMCID: PMC10130965 DOI: 10.3748/wjg.v29.i14.2202] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 12/10/2022] [Accepted: 03/14/2023] [Indexed: 04/13/2023] Open
Abstract
BACKGROUND Gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML) is usually a low-grade B-cell neoplasia strongly associated with Helicobacter pylori (H. pylori)-induced chronic gastritis. Clinical practice guidelines currently recommend H. pylori eradication as the preferred initial treatment for early-stage GML. To determine the practical effect of bacterial eradication as the sole initial therapy for early-stage GML, an updated analysis and review of available evidence is imperative. AIM To perform a meta-analysis to assess the rate of complete remission (CR) of H. pylori-positive early-stage GML following bacterial eradication. METHODS We performed independent, computer-assisted literature searches using the PubMed/MEDLINE, Embase, and Cochrane Central databases through September 2022. Prospective and retrospective observational studies evaluating the CR of early-stage GML following bacterial eradication in H. pylori-positive patients. The risk of bias was assessed using Joanna Briggs Institute (JBI) Critical Appraisal Tools. The pooled estimate of the complete histopathological remission rate and respective confidence intervals (95%CI) were calculated following the random-effects model. Heterogeneity and inconsistency were assessed using Cochran's Q test and I2 statistic, and heterogeneity was defined as P < 0.01 and I² > 50%, respectively. Subgroup and meta-regression analyses were conducted to explore potential sources of heterogeneity. RESULTS The titles and abstracts of 1576 studies were screened; 96 articles were retrieved and selected for full-text reading. Finally, 61 studies were included in the proportional meta-analysis (P-MA). Forty-six were prospective and fifteen were retrospective uncontrolled, single-arm, observational studies. The overall risk of bias was low to moderate in all but a single report, with an average critical appraisal score across all studies of 79.02%. A total of 2936 H. pylori-positive early-stage GML patients, in whom H. pylori was successfully eradicated, were included in the analysis. The pooled CR of H. pylori-positive early-stage GML after bacterial eradication was 75.18% (95%CI: 70.45%-79.91%). P-MA indicated the substantial heterogeneity in CR reported across studies (I 2 = 92%; P < 0.01). Meta-regression analysis identified statistically significant effect modifiers, including the proportion of patients with t(11;18)(q21;q21)-positive GML and the risk of bias in each study. CONCLUSION Comprehensive synthesis of available evidence suggests that H. pylori eradication is effective as the sole initial therapy for early-stage GML. Although the substantial heterogeneity observed across studies limits the interpretation of the pooled overall CR, the present study is a relevant to informing clinical practice.
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Affiliation(s)
- Fabian Fellipe Bueno Lemos
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Bahia, Brazil
| | | | - Mariana Santos Calmon
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Bahia, Brazil
| | - Marcel Silva Luz
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Bahia, Brazil
| | - Samuel Luca Rocha Pinheiro
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Bahia, Brazil
| | | | - Gabriel Lima Correa Santos
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Bahia, Brazil
| | - Hanna Santos Marques
- Campus Vitória da Conquista, Universidade Estadual do Sudoeste da Bahia, Vitória da Conquista 45029094, Bahia, Brazil
| | - Henrique Affonso Delgado
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Bahia, Brazil
| | | | - Cláudio Lima Souza
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Bahia, Brazil
| | - Márcio Vasconcelos Oliveira
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Bahia, Brazil
| | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Bahia, Brazil
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Choi KH, Lee HH, Jung SE, Park KS, O JH, Jeon YW, Choi BO, Cho SG. Analysis of the response time to involved-field radiotherapy in primary gastrointestinal low-grade B-cell lymphoma. Radiat Oncol 2020; 15:210. [PMID: 32867796 PMCID: PMC7457476 DOI: 10.1186/s13014-020-01649-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 08/19/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Early-stage primary gastrointestinal (GI) low-grade B-cell lymphoma shows good therapeutic response to primary radiotherapy. However, there is no clear guideline for the evaluation of response to radiation therapy currently. The aim of this study was to analyze the relationship between the best response time and the clinical course after radiotherapy. METHODS Patients who underwent radiotherapy for treatment of primary GI low-grade B-cell lymphoma from September 2007 to December 2018 at Seoul St. Mary's Hospital were included. Early responders were defined by best response within 6 months after radiotherapy, and delayed responders after 6 months. Clinical and pathological factors associated with delayed response and survival analyses were performed to investigate the recurrence and survival during follow-up. RESULTS A total of 43 patients were evaluated and the number of gastric mucosa-associated lymphoid tissue and duodenal follicular lymphoma was 36 and 7, respectively. All of 43 patients showed complete remission to radiotherapy and the best response time after radiotherapy was a median of 3 months. There were 8 delayed responders with a median duration of 8.9 months. Early and delayed responders were characterized by a significant difference in depth of invasion beyond the mucosal layer. CONCLUSIONS Delayed responders did not show differences in oncological outcomes compared with early responders. They were allowed to watch and wait for an additional 6 to 12 months without further treatment.
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Affiliation(s)
- Kyu Hye Choi
- Department of Radiation Oncology, Catholic University Lymphoma Group, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Han Hee Lee
- Department of Gastroenterology, Catholic University Lymphoma Group, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Seung-Eun Jung
- Department of Radiology, Catholic University Lymphoma Group, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Kyung-Sin Park
- Department of Pathology, Catholic University Lymphoma Group, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Joo-Hyun O
- Department of Nuclear Medicine, Catholic University Lymphoma Group, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Young-Woo Jeon
- Department of Hematology, Catholic University Lymphoma Group, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Byung-Ock Choi
- Department of Radiation Oncology, Catholic University Lymphoma Group, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Seok-Goo Cho
- Department of Hematology, Catholic University Lymphoma Group, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
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Heterogeneity of clinical management of low-grade gastric lymphoma of mucosa-associated lymphoid tissue. An audit of 198 patients in Spain. GASTROENTEROLOGIA Y HEPATOLOGIA 2019; 43:79-86. [PMID: 31787375 DOI: 10.1016/j.gastrohep.2019.08.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 08/14/2019] [Accepted: 08/29/2019] [Indexed: 10/25/2022]
Abstract
INTRODUCTION Cure of Helicobacter pylori infection in patients with gastric lymphoma of mucosa-associated lymphoid tissue (MALT) leads to long-term clinical remission in the initial stages. As it is a rare disease, its management in clinical practice remains largely unknown and heterogeneity of care remains a concern. The aim was to audit the management and evolution of a large series of low-grade gastric MALT lymphomas from thirteen Spanish hospitals. MATERIALS AND METHODS Multicentre retrospective study including data on the diagnosis and follow-up of patients with gastric low-grade MALT lymphoma from January 1998 to December 2013. Clinical, biological and pathological data were analyzed and survival curves were drawn. RESULTS One-hundred and ninety-eight patients were included. Helicobacter pylori was present in 132 (69%) patients and 103 (82%) in tumors confined to the stomach (stage EI) and was eradicated in 92% of patients. Chemotherapy was given in 90 (45%) patients and 43 (33%) with stage EI. Marked heterogeneity in the use of diagnostic methods and chemotherapy was observed. Five-year overall survival was 86% (89% in EI). Survival was similar in EI patients receiving aggressive treatment and in those receiving only antibiotics (p=0.577). DISCUSSION Gastric MALT lymphoma has an excellent prognosis. We observed, however, a marked heterogeneity in the use of diagnostic methods or chemotherapy in early-stage patients.
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Sugizaki K, Tari A, Kitadai Y, Oda I, Nakamura S, Yoshino T, Sugiyama T. Anti-Helicobacter pylori therapy in localized gastric mucosa-associated lymphoid tissue lymphoma: A prospective, nationwide, multicenter study in Japan. Helicobacter 2018; 23:e12474. [PMID: 29504247 PMCID: PMC5900897 DOI: 10.1111/hel.12474] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND Helicobacter pylori eradication therapy was approved in Japan for the first-line, standard treatment of H. pylori-positive gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Although several retrospective studies or small-scale single-center studies have been reported, a prospective, large-scale, nationwide, multicenter study has not been reported from Japan. MATERIALS AND METHODS We conducted a prospective, nationwide, multicenter study to evaluate the clinical efficacy of rabeprazole-based triple H. pylori eradication therapy for patients with localized gastric MALT lymphoma in practice-based clinical trial. A total of 108 H. pylori-positive patients with stage I/II1 gastric MALT lymphoma underwent H. pylori eradication therapy. The primary endpoints were complete remission (CR) rate and the rate of transfer to secondary treatment. The secondary endpoints were CR maintenance duration and overall survival (OS). RESULTS CR of lymphoma was achieved in 84 of 97 patients (86.6%), during the period 2.0-44.7 months (median, 5.3 months) after starting H. pylori eradication treatment. CR was maintained in 77 of 81 patients (95.1%) for 0.4-53.2 months (median, 33.1 months). Secondary treatments (radiotherapy, rituximab, or gastrectomy) for gastric MALT lymphoma were needed in 10 of the 97 patients (10.31%). During follow-up, OS rate was 96.9% (94/97) and the causes of 3 deaths were not related to lymphoma. CONCLUSIONS Rabeprazole-based H. pylori eradication therapy demonstrated a high CR rate, long CR maintenance, and a good OS for patients with localized gastric MALT lymphoma in this prospective, practice-based, multicenter study.
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Affiliation(s)
| | - Akira Tari
- Division of GastroenterologyDepartment of Internal MedicineHiroshima Red Cross Hospital & Atomic‐bomb Survivors HospitalHiroshimaJapan
| | - Yasuhiko Kitadai
- Department of Health SciencesFaculty of Human Culture and SciencePrefectural University of HiroshimaHiroshimaJapan
| | - Ichiro Oda
- Endoscopy DivisionNational Cancer Center HospitalTokyoJapan
| | - Shotaro Nakamura
- Division of GastroenterologyDepartment of Internal MedicineSchool of MedicineIwate Medical UniversityMoriokaJapan
| | - Tadashi Yoshino
- Department of PathologyOkayama University Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayamaJapan
| | - Toshiro Sugiyama
- Department of Gastroenterology and HematologyGraduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
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Ramos CA. Marginal Zone Lymphomas (Extranodal/Malt, Splenic, and Nodal). Hematology 2018. [DOI: 10.1016/b978-0-323-35762-3.00079-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
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Tanaka H, Hayashi S, Ohtakara K, Hoshi H. Hepatic dysfunction after radiotherapy for primary gastric lymphoma. JOURNAL OF RADIATION RESEARCH 2013; 54:92-7. [PMID: 23283868 PMCID: PMC3534266 DOI: 10.1093/jrr/rrs062] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/08/2023]
Abstract
Patients with primary gastric lymphoma (PGL) are often treated with three-dimensional conformal radiotherapy (3D-CRT) in three to four fields to reduce the dose to the left kidney. However, the liver dose is higher than conventional parallel-opposed fields. This study was designed to evaluate hepatic dysfunction after 3D-CRT in patients with PGL. The data of 20 PGL patients treated with 3D-CRT were analyzed. Of the 20 patients, 3 had mucosa-associated lymphoid tissue (MALT) lymphoma and 17 had diffuse large B-cell lymphoma (DLBCL). The median dose used to treat MALT lymphoma was 30 Gy and 40 Gy for DLBCL. Pretreatment and post-treatment transaminase and alkaline phosphatase (ALP) values were compared. Radiation-induced hepatic dysfunction (RIHD) was defined as a more than 2-fold increase in transaminase or ALP levels, exceeding the upper limit within 4 months of the completion of radiotherapy. Increased transaminase or ALP levels were observed in 19 patients (95%). RIHD was observed in 14 patients (70%). The transaminase and ALP values were significantly different between pretreatment and post-treatment. There were significant differences in liver volumes receiving ≥5, ≥10, ≥15 and ≥20 Gy (V5, V10, V15 and V20) and in the mean liver doses between patients with and without RIHD. For patients with V10 > 60%, V15 > 50% or V20 > 30% in particular, the incidence rates of RIHD were significantly high. After radiotherapy for PGL, hepatic dysfunction occurred at a high rate. Thus, radiotherapy treatment should be planned in order to reduce liver doses.
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Affiliation(s)
- Hidekazu Tanaka
- Department of Radiology, Gifu University Hospital, Yanagido 1-1, Gifu 501-1194, Japan.
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Gisbert JP, Calvet X. Review article: common misconceptions in the management of Helicobacter pylori-associated gastric MALT-lymphoma. Aliment Pharmacol Ther 2011; 34:1047-62. [PMID: 21919927 DOI: 10.1111/j.1365-2036.2011.04839.x] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Helicobacter pylori infection is the main cause of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. AIM To review several common misconceptions in the management of H. pylori-associated gastric MALT-lymphoma. METHODS Bibliographical searches were performed in MEDLINE up to June 2011. RESULTS If adequate diagnostic methods are used, and if only low-grade lymphomas are considered, the prevalence of H. pylori infection is very high (almost 90%). H. pylori eradication is effective in treating approximately 80% of patients with early stage lymphoma. In H. pylori-positive gastric high-grade lymphomas, antibiotic therapy should always be prescribed, as approximately 50% of them regress after H. pylori eradication. Patients with early stage MALT lymphoma negative for H. pylori might still benefit from antibiotic treatment as the sole treatment. Complete remission of gastric MALT lymphoma after H. pylori eradication can take even >12 months. PCR assay for the detection of monoclonal B cells remains positive in many cases after complete remission has been reached. Patients with a persistent clonal band should not be treated unless the lymphoma can be histologically demonstrated. Synchronous occurrence of gastric adenocarcinoma and MALT lymphoma has been repeatedly reported. In some patients in complete remission, eradication of H. pylori does not prevent later development of early gastric cancer. Gastric lymphoma recurrence occurs in some patients after both bacterial and lymphoma regression. H. pylori reinfection does not constitute a prerequisite for lymphoma recurrence. CONCLUSIONS The present article states several misconceptions in the management of H. pylori-associated gastric MALT-lymphoma in clinical practice, reviews the related scientific evidence and proposes the adequate attitude in each case.
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Affiliation(s)
- J P Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain.
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Kim SJ, Yang S, Min BH, Lee JH, Rhee PL, Rhee JC, Kim JJ. [Helicobacter pylori eradication for stage I(E₁) gastric mucosa-associated lymphoid tissue lymphoma: predictive factors of complete remission]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2011; 55:94-9. [PMID: 20168055 DOI: 10.4166/kjg.2010.55.2.94] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND/AIMS Eradication of Helicobacter pylori (H. pylori) is accepted as initial treatment of stage I(E₁) gastric mucosa associated lymphoid tissue (MALT) lymphoma. However, 10-20% of gastric low grade MALT lymphomas are unresponsive to H. pylori eradication treatment. The aim of this study was to find out the predictive factors of complete remission of gastric MALT lymphoma after H. pylori eradication. METHODS From 1995 to 2006, consecutive 95 patients with modified Ann Arbor stage I(E₁) gastric MALT lymphoma were enrolled, and their medical records were reviewed. The patients were initially treated by H. pylori eradication. The complete remission was determined by endoscopic and histologic finding. RESULTS Eighty eight patients (92.6%) achieved complete remission after H. pylori eradication therapy. Mean follow up time for these patients was 40+/-25 months. Seven patients (7.4%) failed to achieve complete remission. There was no significant difference in the age, sex, endoscopic appearance, and large cell component between the remission group and failure group. Among 66 patients with distal tumor, 65 patients (98.5%) achieved complete remission. On the other hand, among 13 patient with proximal tumor, 9 patients (69.2%) achieved complete remission (p=0.001). The odds ratio of proximal tumor for H. pylori eradication failure was 28.9 (95% CI=2.9-288.0). CONCLUSIONS The proximally location of MALT lymphoma is a risk factor of the H. pylori eradication treatment failure. Therefore, the proximally located gastric MALT lymphoma should be carefully treated and followed.
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Affiliation(s)
- Su Jin Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Abstract
The diagnosis of gastric MALT lymphoma is frequently difficult for the general histopathologist. During recent years there have been relevant changes in the therapeutic approach to gastric MALT lymphoma and our knowledge about its pathogenesis has greatly improved. The management of this disease actually requires a close cooperation between the histopathologist and the clinicians. The histology report of biopsies of a newly diagnosed or of an already treated case implies information of clinical and therapeutical relevance. This paper aims at giving the histopathologist a general knowledge about the state of art of this disease and its management. The diagnostic process leading to a complete and competent report is then described step by step.
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MESH Headings
- Anti-Bacterial Agents/therapeutic use
- Biopsy
- Diagnosis, Differential
- Gastric Mucosa/pathology
- Gastroscopy
- Helicobacter pylori
- Humans
- Lymphoma, B-Cell/pathology
- Lymphoma, B-Cell, Marginal Zone/drug therapy
- Lymphoma, B-Cell, Marginal Zone/epidemiology
- Lymphoma, B-Cell, Marginal Zone/microbiology
- Lymphoma, B-Cell, Marginal Zone/pathology
- Neoplasm Staging
- Pathology/methods
- Pathology/standards
- Recurrence
- Remission Induction
- Stomach Neoplasms/drug therapy
- Stomach Neoplasms/epidemiology
- Stomach Neoplasms/microbiology
- Stomach Neoplasms/pathology
- Treatment Outcome
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Affiliation(s)
- Claudio Doglioni
- Department of Pathology, Scientific Institute San Raffaele, Milan, Italy.
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Park SH, Chi HS, Park SJ, Jang S, Park CJ, Huh JR. Prognostic Impact of Helicobacter pylori Infection and Eradication Therapy in Gastric Mucosa-associated Lymphoid Tissue Lymphoma. Ann Lab Med 2010; 30:547-53. [DOI: 10.3343/kjlm.2010.30.6.547] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Affiliation(s)
- Sang Hyuk Park
- Departments of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | - Hyun-Sook Chi
- Departments of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | - Seo-Jin Park
- Departments of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | - Seongsoo Jang
- Departments of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | - Chan-Jeoung Park
- Departments of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | - Joo Ryung Huh
- Departments of Pathology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
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Yamamoto S, Nakase H, Yamashita K, Matsuura M, Takada M, Kawanami C, Chiba T. Gastrointestinal follicular lymphoma: review of the literature. J Gastroenterol 2010; 45:370-88. [PMID: 20084529 DOI: 10.1007/s00535-009-0182-z] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2009] [Accepted: 11/23/2009] [Indexed: 02/04/2023]
Abstract
Gastrointestinal follicular lymphoma (GI-FL) is a relatively rare disease, accounting for only 1%-3.6% of gastrointestinal non-Hodgkin's lymphoma. Although the duodenum and terminal ileum are considered to be the most common sites of origin, the development of wireless capsule endoscopy and double-balloon enteroscopy has increased the detection of GI-FL in every part of the small intestine. Approximately 70% of patients with GI-FL are estimated to have multiple lesions throughout the entire gastrointestinal tract. FL is a low-grade lymphoma that usually develops very slowly. If the lymphoma causes no symptoms, immediate treatment may not be necessary. Standard therapy has not yet been established for GI-FL, but chemotherapy, radiotherapy, monoclonal antibody therapy, or a combination of these therapies, is sometimes performed based on the therapeutic regimens for nodal FL. Regimens including conventional chemotherapy with rituximab, which achieve high response rates in nodal FL, are commonly used for GI-FL. The long-term clinical outcome of GI-FL is unclear. The results of a few series on the long-term outcomes of patients with GI-FL treated with conventional therapy indicate a median relapse-free time ranging from 31 to 45 months. On the other hand, in patients with GI-FL who were followed without treatment, the median time to disease progression was 37.5 months. Thus, whether to initiate aggressive therapy or whether to continue watchful waiting in patients with GI-FL is a critically important decision. Ongoing research on biomarkers to guide individualized GI-FL therapy may provide invaluable information that will lead to the establishment of a standard therapeutic regimen.
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Affiliation(s)
- Shuji Yamamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
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Zullo A, Hassan C, Cristofari F, Andriani A, De Francesco V, Ierardi E, Tomao S, Stolte M, Morini S, Vaira D. Effects of Helicobacter pylori eradication on early stage gastric mucosa-associated lymphoid tissue lymphoma. Clin Gastroenterol Hepatol 2010; 8:105-10. [PMID: 19631287 DOI: 10.1016/j.cgh.2009.07.017] [Citation(s) in RCA: 188] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2009] [Revised: 07/08/2009] [Accepted: 07/11/2009] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Different remission rates of gastric low-grade, B-cell, mucosa-associated lymphoid tissue (MALT) lymphoma have been reported after Helicobacter pylori eradication. We assessed the long-term remission and relapse rates of early stage MALT lymphoma in patients treated only by H pylori eradication and identified factors that might predict outcome. METHODS This systematic review analyzed data from 32 studies, including 1408 patients. RESULTS The MALT lymphoma remission rate was 77.5% (95% confidence interval, 75.3-79.7), and was significantly higher in patients with stage I than stage II(1) lymphoma (78.4% vs 55.6%; P = .0003) and in Asian than in Western groups (84.1% vs 73.8%; P = .0001). Neoplasia confined to the submucosa regressed more frequently than that with deeper invasion (82.2% vs 54.5%; P = .0001); patients with lymphoma localized to the distal stomach experienced regression more frequently than those with lymphoma of the proximal stomach (91.8% vs 75.7%; P = .0037). The remission rate was higher among patients without the API2-MALT1 translocation than in those with this translocation (78% vs 22.2%; P = .0001). In an analysis of data from 994 patients, 7.2% experienced lymphoma relapse during 3253 patient-years of follow-up evaluation, with a yearly recurrence rate of 2.2%. Infection and lymphoma were cured by additional eradication therapy in all patients with H pylori recurrence (16.7%). Five (0.05%) of the patients initially cured of lymphoma developed high-grade lymphoma within 6 to 25 months of therapy. CONCLUSIONS H pylori eradication is effective in treating approximately 75% of patients with early stage gastric lymphoma. Long-term follow-up evaluation of these patients is needed to detect early lymphoma relapse or progression.
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Affiliation(s)
- Angelo Zullo
- Gastroenterology and Digestive Endoscopy, Nuovo Regina Margherita Hospital, Rome, Italy.
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15
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Chihara D, Kagami Y, Oki Y, Kato H, Onoda H, Ine S, Taji H, Yamamoto K, Morishima Y. R-CHOP therapy for MALT lymphoma of the rectum. Eur J Haematol 2009; 84:84-6. [PMID: 19737307 DOI: 10.1111/j.1600-0609.2009.01346.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
MESH Headings
- Aged
- Aged, 80 and over
- Antibodies, Monoclonal/administration & dosage
- Antibodies, Monoclonal, Murine-Derived
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Cyclophosphamide/administration & dosage
- Doxorubicin/administration & dosage
- Female
- Gastrointestinal Hemorrhage/etiology
- Humans
- Lymphoma, B-Cell, Marginal Zone/complications
- Lymphoma, B-Cell, Marginal Zone/diagnosis
- Lymphoma, B-Cell, Marginal Zone/drug therapy
- Middle Aged
- Prednisone/administration & dosage
- Rectal Neoplasms/complications
- Rectal Neoplasms/diagnosis
- Rectal Neoplasms/drug therapy
- Remission Induction
- Rituximab
- Vincristine/administration & dosage
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16
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Andriani A, Miedico A, Tedeschi L, Patti C, Di Raimondo F, Leone M, Schinocca L, Romanelli A, Bonanno G, Linea C, Giustini M, Hassan C, Cottone M, Zullo A. Management and long-term follow-up of early stage H. pylori-associated gastric MALT-lymphoma in clinical practice: an Italian, multicentre study. Dig Liver Dis 2009; 41:467-73. [PMID: 18945654 DOI: 10.1016/j.dld.2008.09.009] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2008] [Revised: 09/05/2008] [Accepted: 09/08/2008] [Indexed: 12/11/2022]
Abstract
BACKGROUND/AIM Data on management and long-term follow-up of Helicobacter pylori-associated MALT-lymphoma in clinical practice are scanty. We evaluate the long-term efficacy of H. pylori eradication on low-grade MALT-lymphoma, and the efficacy of further therapies in refractory patients. METHODS This study enrolled patients with stages I-II(1) MALT-lymphoma and H. pylori infection. H. pylori eradication was attempted in all patients. Patients with lymphoma persistence or progression following H. pylori treatments received further lymphoma treatments. Both 5-year and disease-free survivals were calculated. RESULTS Sixty patients (stage I/II(1): 50/10) were followed up for a median time of 65 months (range 7-156). H. pylori infection was successfully eradicated in 53 (88.3%) patients following three consecutive therapeutic attempts, and lymphoma regressed in 42 (79.2%) of these patients. Sixteen patients received anti-neoplastic treatments due to either lymphoma persistence or progression, and lymphoma was cured in 14 (87.5%) cases. At follow-up, lymphoma relapsed in 13/42 (30.9%) patients within a median time of 19 months (range 3-41), and all but 1 patient were cured with further therapies. Overall, lymphoma regression was achieved in 56 patients (93.3%). The 5-year and disease-free survivals were 94.7% and 74.6%, respectively. CONCLUSIONS In clinical practice, a conservative approach with antibiotic eradication seems to be appropriate management for early-stage MALT-lymphoma, with oncologic therapy being reserved for those patients who fail to respond to H. pylori therapy.
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Affiliation(s)
- A Andriani
- Haematology and Gastroenterology Department, San Giacomo Hospital, Rome, Italy.
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17
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Zullo A, Hassan C, Andriani A, Cristofari F, Bassanelli C, Spinelli GP, Tomao S, Morini S. Treatment of low-grade gastric MALT-lymphoma unresponsive to Helicobacter pylori therapy: a pooled-data analysis. Med Oncol 2009; 27:291-5. [PMID: 19308737 DOI: 10.1007/s12032-009-9207-y] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2009] [Accepted: 03/12/2009] [Indexed: 12/29/2022]
Abstract
The most favourable therapeutic strategy for gastric MALT-lymphoma not responding to Helicobacter pylori eradication still remains unclear, neither official guidelines nor randomised studies being available. We therefore performed a systematic review of the literature to evaluate the efficacy of different therapeutic approaches in these patients. Data regarding 315 patients were valuable, and lymphoma remission following the first therapeutic attempt was achieved in 90.1% cases. The most used therapy was radiotherapy (112 patients), followed by surgery (80 patients) and chemotherapy (68 patients), whilst a combination therapy was less frequent. Radiotherapy achieved a higher remission rate as compared to chemotherapy (97.3 vs. 85.3%; P = 0.007), being similar to surgery (97.3 vs. 92.5%; P = 0.2). No difference emerged when comparing lymphoma remission rate achieved by a single therapy with that of combined treatments (89.6 vs. 96.4%; P = 0.6). This is the first pooled-data analysis assessing the efficacy of different oncologic therapeutic approaches to treat gastric MALT-lymphoma unresponsive to H. pylori eradication. Radiotherapy seems to be the most suitable treatment in these patients.
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Affiliation(s)
- Angelo Zullo
- Gastroenterology and Digestive Endoscopy, Nuovo Regina Margherita Hospital, Via E Morosini 30, 00153 Rome, Italy.
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18
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Abstract
PURPOSE OF REVIEW The role of endoscopy, including endoscopic ultrasound, in the diagnosis and management of mucosa-associated lymphoid tissue lymphomas of the stomach has evolved steadily in the last two decades. The present review summarizes recent findings and puts them in context with studies on the diagnosis and management of mucosa-associated lymphoid tissue lymphoma published earlier. RECENT FINDINGS Several recent studies have emphasized the crucial role of endoscopic ultrasound in treatment planning in patients with gastric mucosa-associated lymphoid tissue lymphoma. This is important as early-stage gastric mucosa-associated lymphoid tissue lymphomas can be managed just by the eradication of Helicobacter pylori by appropriate antibiotic regimens. However, the more advanced lesions are treated with much more invasive treatment regimens involving radical gastrectomy, chemotherapy or radiation, or all. SUMMARY Endoscopic ultrasound staging is highly accurate in predicting response to Helicobacter pylori eradication in patients with gastric mucosa-associated lymphoid tissue lymphoma. Normalization of gastric wall thickness and architecture can be used to monitor tumor regression following treatment. Endoscopic ultrasound findings can also be used to identify treatment failures and relapses and can help identify patients who need more aggressive therapy.
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19
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Yamashita H, Nakagawa K, Asari T, Murakami N, Igaki H, Ohtomo K. Radiotherapy for 41 patients with stages I and II MALT lymphoma: a retrospective study. Radiother Oncol 2008; 87:412-7. [PMID: 18423914 DOI: 10.1016/j.radonc.2008.03.012] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2008] [Revised: 03/14/2008] [Accepted: 03/14/2008] [Indexed: 12/14/2022]
Abstract
PURPOSE Mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct disease with specific clinical and pathologic features that may affect diverse organs. We analyzed our recent experience with Stage I/II MALT lymphoma presenting in the stomach and other organs to assess the outcome following radiation therapy (RT) alone. PATIENTS AND METHODS Forty-one patients with Stages I (37) and II (4) disease were treated between 2000 and 2006. Patients with transformed MALT were excluded. The median age was 60 years (range, 25-86 years), male: female ratio 1:1. Presenting sites included stomach, 11; orbital adnexa, 21; thyroid, 1; other head and neck, 3; small bowel, 3; skin, 1; and rectum, 1. Thirty-five patients (85%) received RT-alone and 6 (15%) received antibiotics followed by RT. RT dose was 30Gy in 20 fractions (fr) in all 41 patients. Mean follow-up time was 32.0 months (range, 2.1-162 months). RESULTS A first complete response was achieved in all 41 patients. Only one patient died from bile duct carcinoma at 22 months from the start of irradiation for conjunctiva MALT lymphoma without recurrence of lymphoma. The other 40 patients were alive. Thirty-eight patients out of them were alive without recurrence. One patient with a duodenal lymphoma had a recurrence in non-irradiated distant sites at 1 month. Another patient with a bilateral eye lid lymphoma had a recurrence within radiation field at 41 months. The absolute local control rate with radiation was 98% (40/41 patients). CONCLUSION Localized MALT lymphomas have excellent prognosis following moderate-dose RT (30Gy/20fr).
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Affiliation(s)
- Hideomi Yamashita
- Department of Radiology, University of Tokyo Hospital, Hongo, Bunkyo-ku, Tokyo, Japan
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20
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Nakamura T, Seto M, Tajika M, Kawai H, Yokoi T, Yatabe Y, Nakamura S. Clinical features and prognosis of gastric MALT lymphoma with special reference to responsiveness to H. pylori eradication and API2-MALT1 status. Am J Gastroenterol 2008; 103:62-70. [PMID: 17894851 DOI: 10.1111/j.1572-0241.2007.01521.x] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Clinicopathologic characteristics and prognosis of Helicobacter pylori eradication-resistant gastric MALT lymphoma have not been well clarified. We analyzed a consecutive series of gastric MALT lymphomas at our institution regarding treatment, clinical course, and prognosis, with special reference to responsiveness to H. pylori eradication and presence of API2-MALT1. METHODS Subjects were 92 consecutive patients with gastric MALT lymphoma. Seventy were H. pylori positive, and 87 received H. pylori eradication therapy. The remaining five cases were API2-MALT1 positive and did not receive eradication treatment. Second-line treatments were radiation therapy, total gastrectomy, and chemotherapy (rituximab, rituximab plus CHOP, or rituximab plus 2-chlorodeoxyadenosine). RESULTS Gastric MALT lymphoma was classified into three groups, except one case with API2-MALT1 who responded to H. pylori eradication therapy: responders without API2-MALT1 (group A, N = 56, 65%), nonresponders without API2-MALT1 (group B, N = 16, 19%), and nonresponders with API2-MALT1 (group C, N = 14, 16%). Most cases in group A attained complete remission (CR) in 2 or 3 months and CR persisted for an average of 51.1 months (3-134 months). Recurrence was only seen in one case. In groups B and C, radiation therapy, chemotherapy, and total gastrectomy resulted in CR in 13, 5, and 2 cases, respectively. In 5 group B patients and 6 group C patients who did not undergo second-line therapy, disease did not progress for an average of 10.4 and 40.1 months, respectively. In 1 group C case who did not receive second-line treatment, lymphoma metastasized to the lung 12 yr after eradication. All group B patients and all but 2 group C patients remain alive; one of these deaths was from gastric carcinoma developing 7 yr after eradication. CONCLUSION Gastric MALT lymphoma responding to H. pylori eradication demonstrated good prognosis, and for nonresponsive cases, second-line treatments resulted in CR. However, careful observation for development of gastric carcinoma and disease progression is essential during follow-up of API2-MALT1-positive MALT lymphoma when patients decline second-line treatment.
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MESH Headings
- Adult
- Aged
- Aged, 80 and over
- Anti-Bacterial Agents/therapeutic use
- Biomarkers, Tumor/metabolism
- Biopsy
- Combined Modality Therapy/methods
- DNA, Neoplasm/genetics
- Endoscopy, Gastrointestinal
- Female
- Follow-Up Studies
- Helicobacter Infections/drug therapy
- Helicobacter Infections/metabolism
- Helicobacter Infections/pathology
- Helicobacter pylori/drug effects
- Helicobacter pylori/isolation & purification
- Humans
- Lymphoma, B-Cell, Marginal Zone/metabolism
- Lymphoma, B-Cell, Marginal Zone/pathology
- Lymphoma, B-Cell, Marginal Zone/therapy
- Male
- Middle Aged
- Oncogene Proteins, Fusion/genetics
- Oncogene Proteins, Fusion/metabolism
- Prognosis
- Proton Pump Inhibitors/therapeutic use
- Retrospective Studies
- Reverse Transcriptase Polymerase Chain Reaction
- Stomach Neoplasms/metabolism
- Stomach Neoplasms/pathology
- Stomach Neoplasms/therapy
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Affiliation(s)
- Tsuneya Nakamura
- Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan
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21
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Abstract
Mucosal associated lymphoid tissue (MALT) lymphoma may have specific clinical associations and molecular aberrations depending on its site of origin. We present a case of oral mucosal MALT lymphoma with clinical features simulating oral-facial granulomatosis. Dermatologists are frequently called upon for the diagnosis and treatment of mucosal lesions. Increased awareness and familiarity with oral mucosal MALT lymphoma and its clinical associations are of significant importance for optimal management of this condition.
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Affiliation(s)
- Pedram Gerami
- Department of Dermatology, Northwest University, Chicago, IL 60611, USA.
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22
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Morgner A, Schmelz R, Thiede C, Stolte M, Miehlke S. Therapy of gastric mucosa associated lymphoid tissue lymphoma. World J Gastroenterol 2007; 13:3554-66. [PMID: 17659705 PMCID: PMC4146794 DOI: 10.3748/wjg.v13.i26.3554] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2007] [Revised: 04/03/2007] [Accepted: 04/26/2007] [Indexed: 02/06/2023] Open
Abstract
Gastric mucosa associated lymphoid tissue (MALT) lymphoma has recently been incorporated into the World Health Organization (WHO) lymphoma classification, termed as extranodal marginal zone B-cell lymphoma of MALT-type. In about 90% of cases this lymphoma is associated with H pylori infection which has been clearly shown to play a causative role in lymphomagenesis. Although much knowledge has been gained in defining the clinical features, natural history, pathology, and molecular genetics of the disease in the last decade, the optimal treatment approach for gastric MALT lymphomas, especially locally advanced cases, is still evolving. In this review we focus on data for the therapeutic, stage dependent management of gastric MALT lymphoma. Hence, the role of eradication therapy, surgery, chemotherapy and radiotherapy is critically analyzed. Based on these data, we suggest a therapeutic algorithm that might help to better stratify patients for optimal treatment success.
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Affiliation(s)
- Andrea Morgner
- Medical Department I, University Hospital, Technical University Dresden, Germany.
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23
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Küpeli S, Varan A, Demir H, Aydin B, Yüce A, Büyükpamukçu M. Association of Helicobacter pylori and childhood lymphoma. J Pediatr Hematol Oncol 2007; 29:301-4. [PMID: 17483706 DOI: 10.1097/mph.0b013e3180587e8b] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
We aimed to estimate the frequency of association between non-Hodgkin lymphoma (NHL) with abdominal, gastric, or intestinal involvement and Helicobacter pylori in childhood. Between February 2003 and June 2006, we evaluated 15 children with newly diagnosed NHL who were diagnosed and treated at the Pediatric Oncology Department of Hacettepe University. Patients who were given chemotherapy previously or who received H. pylori eradication therapy were excluded from the study. Routine procedures were done for staging. Pathologic diagnosis was made by examining the biopsy samples. The presence of H. pylori was confirmed by H. pylori IgG serology with urea breath test (UBT) in cooperated children. Endoscopic examination was also planned for patients with positive test results. Twelve male and 3 female patients, with a median age of 7 (range: 3 to 16), were evaluated. They had extensive abdominal, gastric, and/or intestinal involvement. Six had stage IV characteristics, whereas another 9 patients had stage III disease. Ten had high-grade B-cell lymphoma. Only 3 patients had H. pylori IgG and UBT positivity (20%). First patient had T-cell lymphoma and stage IV disease with involvement in stomach, mediastinum, peripheral lymph nodes, and bone marrow. The second one had anaplastic large cell lymphoma exclusively in abdominal lymph nodes. Last patient had Burkitt lymphoma and stage IV disease, with primary tumor localization in abdominal lymph nodes, liver, and kidneys. The H. pylori IgG and UBT were both positive in 3 patients on admission. We did not find any positive test results in the other 12 patients with intestinal, stomach, or abdominal disease. Preliminary results of our study suggest that H. pylori may not be the responsible agent for NHL involved the abdomen in childhood.
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Affiliation(s)
- Serhan Küpeli
- Department of Pediatric Oncology, Institute of Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
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24
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Kim JS, Chung SJ, Choi YS, Cheon JH, Kim CW, Kim SG, Jung HC, Song IS. Helicobacter pylori eradication for low-grade gastric mucosa-associated lymphoid tissue lymphoma is more successful in inducing remission in distal compared to proximal disease. Br J Cancer 2007; 96:1324-8. [PMID: 17406363 PMCID: PMC2360178 DOI: 10.1038/sj.bjc.6603708] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
A series of studies has shown that Helicobacter pylori eradication induces remission in most patients with low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, there have been few reports about the effect of bacterial treatment on the gastric MALT lymphoma in Korea, a well-known H. pylori endemic area. A total of 111 H. pylori-infected patients were prospectively enrolled in Seoul National University Hospital and 99 among them were completely followed up according to our protocol. After H. pylori eradication, tumoural response was evaluated by endoscopy and histopathology every 2–3 months till complete remission (CR) and every 6 months after achieving CR. Median follow-up period was 41 months (range, 11–125 months). Helicobacter pylori was successfully eradicated in all 99 patients and CR was obtained in 84 (84.8%) of 99 patients. The median time to reach CR was 3 months and 94% of CR is in continuous complete remission. Five patients with CR relapsed after 10–22 months without the evidence of H. pylori reinfection. Cumulative recurrence rate was 2.3, 7.7 and 9.3% at 1, 2 and 3 years, respectively. Tumours were mainly located in distal stomach (67.7%) and tumours in distal stomach were associated with more favourable response than those in proximal stomach (P=0.001). Majority of patients with low-grade gastric MALT lymphoma treated by exclusive H. pylori eradication have a favourable long-term outcome, offering a real chance of cure. Tumour location could be a predictive factor for remission following H. pylori eradication.
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Affiliation(s)
- J S Kim
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - S J Chung
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Y S Choi
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - J H Cheon
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - C W Kim
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - S G Kim
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - H C Jung
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - I S Song
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-744, South Korea. E-mail:
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25
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Wang N, Fu Q, Wang YJ. Advances on the treatment of gastric mucosa-associated lymphoid tissue lymphoma. Shijie Huaren Xiaohua Zazhi 2007; 15:860-868. [DOI: 10.11569/wcjd.v15.i8.860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Gastric mucosa-associated lymphoid tissue (MALT) lymphomas are rare in the gut, and its occurrence rate was 1% to 5% of the malignant tumors. In histological type, most of them are non-Hodgin's lymphomas, while Hodgin's lymphomas are seldom seen. There have been a lot of controversies on the optimal treatments of gastric MALT lymphomas for a long time. Surgery was traditionally considered as the most important approach to cure the disease. However, anti-H. pylori therapy has been regarded as an alternative method since H. pylori infection was found to be relevant with the pathogenesis of gastric MALT lymphomas. In this article, we reviewed the current status and recent advances on the treatment of this disease.
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26
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Hong SS, Jung HY, Choi KD, Song HJ, Lee GH, Oh TH, Jo JY, Kim KJ, Byeon JS, Myung SJ, Yang SK, Hong WS, Kim JH, Min YI. A prospective analysis of low-grade gastric malt lymphoma after Helicobacter pylori eradication. Helicobacter 2006; 11:569-73. [PMID: 17083379 DOI: 10.1111/j.1523-5378.2006.00460.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
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.
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Affiliation(s)
- Seong Soo Hong
- Division of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Songpa-Gu, Seoul, Korea
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27
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Guidoboni M, Ferreri AJM, Ponzoni M, Doglioni C, Dolcetti R. Infectious agents in mucosa-associated lymphoid tissue-type lymphomas: pathogenic role and therapeutic perspectives. ACTA ACUST UNITED AC 2006; 6:289-300. [PMID: 16507206 DOI: 10.3816/clm.2006.n.003] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Mucosa-associated lymphoid tissue (MALT) lymphoma probably constitutes the best in vivo model showing how complex interplay between B lymphocytes and the surrounding microenvironment may lead to a neoplastic disorder. After the seminal discovery of the pathogenic association between Helicobacter pylori and gastric MALT lymphomas, evidence suggests the possible involvement of other infectious agents in the development of MALT lymphomas arising at different body sites. Although several other bacteria (Borrelia burgdorferi, Campylobacter jejuni, and Chlamydia psittaci) and viruses (Hepatitis C virus) seem to play a role in lymphomas presenting at different locations, a possible common pathogenic mechanism is emerging. Several lines of evidence suggest that different infectious agents might provide a chronic antigenic stimulation that elicits host immune responses able to promote clonal B-cell expansion. This model is also substantiated by the increasing number of patients with MALT lymphomas who exhibit objective clinical responses after antimicrobial therapy. A multidisciplinary approach is critical to better understand the complex etiopathogenesis of MALT lymphomas with the final goal to dissect the clinicopathologic heterogeneity of these disorders and design more tailored preventive and therapeutic approaches.
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Affiliation(s)
- Massimo Guidoboni
- Immunovirology and Biotherapy Unit, Department of Pre-Clinical and Epidemiological Research, Centro di Riferimento Oncologico, IRCCS National Cancer Institute, Aviano, Italy
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28
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Tsang RW, Gospodarowicz MK. Radiation therapy for localized low-grade non-Hodgkin's lymphomas. Hematol Oncol 2006; 23:10-7. [PMID: 16158458 DOI: 10.1002/hon.743] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
The most common low grade B-cell non-Hodgkin's lymphomas are follicular lymphomas, and extranodal marginal zone lymphomas, also known as mucosa-associated lymphoid tissue (MALT) lymphomas. Localized presentations of follicular lymphoma occur in 20-30% of cases, while for MALT lymphomas, stage I-II disease presentations occur in 70-90%. These are radiation-sensitive lymphomas. Following moderate dose local radiation treatment (30-35 Gy) for these stage I and II low grade lymphomas, the clinical results indicate long-term local control and possible cure. While local control is achieved with minimal morbidity with involved-field radiation therapy, a significant proportion of patients relapse with systemic disease outside of radiation fields. For follicular lymphoma, this occurs in approximately 50% of patients after 15 years, and for non-gastric MALT lymphoma, 30-40% after 10 years. Although patients with relapsed systemic disease are not curable with chemotherapy, the disease often behaves in an indolent fashion and prolonged survival is observed. For gastric MALT lymphomas, radiation therapy is indicated in patients whose lymphoma did not respond to Helicobacter pylori eradication therapy, or in gastric lymphoma not related to this microorganism. The subject of causative agents responsible for non-gastric MALT lymphomas is under active study and the identification of putative microorganisms will lead to improved treatment strategies for these unusual lymphomas, similar to the success in gastric lymphomas over the last decade.
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Affiliation(s)
- Richard W Tsang
- Department of Radiation Oncology, University of Toronto, Princess Margaret Hospital, Ontario, Canada.
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Reddy RP, Levy MJ, Wiersema MJ. Endoscopic ultrasound for luminal malignancies. Gastrointest Endosc Clin N Am 2005; 15:399-429, vii. [PMID: 15990049 DOI: 10.1016/j.giec.2005.03.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Luminal gastrointestinal (GI) tract cancers are responsible for substantial morbidity and mortality. Since the first pairing of ultrasonography with endoscopy in 1980, technologic advances and the increased availability of trained endosonographers have propelled endoscopic ultrasonography (EUS) to the forefront of luminal GI cancer staging. In this article we discuss the role of EUS for evaluating luminal GI cancers.
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Affiliation(s)
- Raghuram P Reddy
- Developmental Endoscopy Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
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30
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Isaacson PG, Du MQ. Gastrointestinal lymphoma: where morphology meets molecular biology. J Pathol 2005; 205:255-74. [PMID: 15643667 DOI: 10.1002/path.1703] [Citation(s) in RCA: 128] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Primary gastrointestinal lymphomas are best exemplified by mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach and enteropathy-type T-cell lymphoma (ETL). Both lymphomas were initially recognized on morphological grounds and their identification as distinct clinicopathological entities has subsequently been vindicated following integrated immunophenotypic, molecular, and cellular biological investigations. Delineation of the phenotypic, molecular, and biological properties of these lymphomas at various clinicopathological stages of their development has also provided critical information for the clinical management of patients with these diseases. Here, the histopathology and recent advances in phenotypic and molecular characterization of gastric MALT lymphoma and ETL and their applications in diagnosis and clinical management are reviewed.
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Affiliation(s)
- Peter G Isaacson
- Department of Histopathology, University College London, London WC1E 6JJ, UK.
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de Mascarel A, Ruskone-Fourmestraux A, Lavergne-Slove A, Megraud F, Dubus P, Merlio JP. Clinical, histological and molecular follow-up of 60 patients with gastric marginal zone lymphoma of mucosa-associated lymphoid tissue. Virchows Arch 2005; 446:219-24. [PMID: 15742170 DOI: 10.1007/s00428-005-1217-3] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2004] [Accepted: 01/11/2005] [Indexed: 01/14/2023]
Abstract
The persistence of gastric lymphoma after Helicobacter pylori eradication may be difficult to evidence on endoscopic and histological examination. The aims of the study were to evaluate the detection of monoclonal immunoglobulin H (IgH) gene rearrangement in endoscopically infiltrated and normal mucosa at diagnosis and during follow-up in order to determine its clinical and prognostic impact. We studied 60 gastric marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT), and IgH monoclonality was detected at diagnosis in 52 patients (87%). The endoscopically normal mucosa contained clonal lymphomatous cells in 69% of cases before remission. A complete histological remission (HR) was observed in 28 patients (47%). Among them, 23 were followed for molecular remission (MR). The median delay was 10 months to achieve HR and 18 months to achieve MR. Interestingly, patients with HR but not MR had a longer delay to achieve HR (21 months) (P=0.0006) and a more frequent clonal normal mucosa at diagnosis (88%) than patients with both HR and MR (10 months and 39%, respectively). The presence of monoclonal B cells at both infiltrated and normal sites may therefore identify patients with a longer delay to achieve complete response, suggesting that molecular dissemination may require therapeutic intensification.
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Affiliation(s)
- Antoine de Mascarel
- Department of Pathology, University Victor Segalen Bordeaux 2, Hôpital Haut-Lévêque, 33604 Pessac cedex, France.
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Hung PD, Schubert ML, Mihas AA. Marginal Zone B-cell Lymphoma (MALT Lymphoma). CURRENT TREATMENT OPTIONS IN GASTROENTEROLOGY 2004; 7:133-138. [PMID: 15010027 DOI: 10.1007/s11938-004-0034-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
The preferred terminology for mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach (variously referred to as MALT lymphoma, MALToma, low-grade MALToma, or pseudolymphoma) is marginal zone B-cell lymphoma (MZBL). MZBL, the hallmark of which is the lymphoepithelial lesion, develops as a consequence of Helicobacter pylori infection in susceptible individuals. In general, MZBL is slow growing, can remain localized for years, and has an excellent prognosis. Staging involves endoscopy with biopsy, computed tomography scanning, and endoscopic ultrasound. In patients with limited disease, eradication of H. pylori leads to remission. In patients who fail eradication therapy or have more extensive disease, surgery, chemotherapy, and radiation alone and in various combinations have been used successfully.
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Affiliation(s)
- Patrick D. Hung
- Division of Gastroenterology; 111N, McGuire VAMC, 1201 Broad Rock Boulevard, Richmond, VA 23249, USA.
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33
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Tsang RW, Gospodarowicz MK, Pintilie M, Wells W, Hodgson DC, Sun A, Crump M, Patterson BJ. Localized mucosa-associated lymphoid tissue lymphoma treated with radiation therapy has excellent clinical outcome. J Clin Oncol 2003; 21:4157-64. [PMID: 14615444 DOI: 10.1200/jco.2003.06.085] [Citation(s) in RCA: 262] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
PURPOSE Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a distinct lymphoma with unique clinicopathologic features. We report the clinical outcome of stage I and II MALT lymphoma treated with involved field radiation therapy (RT). PATIENTS AND METHODS From 1989 to 2000, 103 patients with stage IE and IIE disease were referred. Their median age was 60 years, with a 2:1 female predominance. Presenting sites were stomach (17 patients), orbital adnexa (31 patients), salivary glands (24 patients), thyroid gland (13 patients), and other sites (18 patients). Ninety-three patients received RT--85 received RT alone, and eight received chemotherapy and RT--with a median dose of 30 Gy. The median follow-up time was 5.1 years. RESULTS A complete response (CR) to RT alone was achieved in 84 of 85 patients. Among CR patients, 14 experienced relapse. Relapse sites were mostly contralateral paired-organ or distant MALT locations and, infrequently, lymph nodes. The crude local control rate with RT was 95.3% (81 of 85 patients). No relapses were observed in patients with stomach or thyroid lymphoma, whereas 14 of 63 patients (22%) experienced relapse in the other sites. The overall 5-year survival rate was 98%, and the disease-free survival rate was 77%. Transformed lymphoma was observed in 14% of patients (two of 14) experiencing relapse. CONCLUSION Moderate-dose RT achieved excellent local control in localized MALT lymphomas and had curative potential for three fourths of the patients. Gastric and thyroid MALT lymphomas had better outcome, whereas distant failures were common for other sites. Despite relapse, the disease often maintained an indolent course.
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MESH Headings
- Adult
- Aged
- Aged, 80 and over
- Anti-Bacterial Agents/therapeutic use
- Antineoplastic Combined Chemotherapy Protocols/administration & dosage
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Combined Modality Therapy
- Disease-Free Survival
- Female
- Follow-Up Studies
- Helicobacter Infections/complications
- Helicobacter Infections/drug therapy
- Helicobacter pylori
- Humans
- Lymphoma, B-Cell, Marginal Zone/drug therapy
- Lymphoma, B-Cell, Marginal Zone/radiotherapy
- Lymphoma, B-Cell, Marginal Zone/surgery
- Male
- Middle Aged
- Neoplasm Recurrence, Local/drug therapy
- Neoplasm Recurrence, Local/radiotherapy
- Neoplasm Recurrence, Local/surgery
- Neoplasm Staging
- Neoplasms, Second Primary/epidemiology
- Prognosis
- Remission Induction
- Survival Rate
- Treatment Outcome
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Affiliation(s)
- Richard W Tsang
- Department of Radiation Oncology and Biostatistics, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Canada.
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Abstract
The connection between Helicobacter pylori and gastric mucosa-associated lymphoid tissue (MALT) lymphoma is well established. H. pylori infection causes an immunological response, leading to chronic gastritis with formation of lymphoid follicles within the stomach. These lymphoid follicles resemble nodal tissues found throughout the body and are composed of reactive T cells and activated plasmal cells and B cells. The B cells are responsible for initiating a clonal expansion of centrocyte-like cells that form the basic histology of MALT lymphoma. Early diagnosis of MALT lymphoma is difficult but essential for adequate treatment. Clinical symptoms are vague and varied, with abdominal pain being a common presenting complaint. The endoscopic appearance of this tumor is varied and can be infiltrative, exophytic, or ulcerative. In addition, the tumor can have a multifocal distribution, and therefore aggressive tissue sampling is crucial for diagnosis. Endoscopic ultrasound is essential to document the extent of disease and is more accurate than CT scan in detection of spread to perigastric lymph nodes. Lesions that are confined to the mucosa or submucosa of the gastric wall are believed to be dependent on H. pylori stimulation and therefore can be successfully treated with H. pylori eradication. Those MALT lymphomas that present at more advanced stages require more aggressive management and can be treated with surgical resection, radiation, or chemotherapy. Follow-up is critical in all patients who have been treated with H. pylori eradication and consists of multiple endoscopic biopsies for histological and molecular studies as well as endoscopic ultrasound at 3, 6, and 12 months after treatment. The reappearance of MALT lymphomas has been seen years after treatment, and therefore follow-up of these patients should be indefinite.
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Affiliation(s)
- Asyia Ahmad
- Division of Gastroenterology and Hepatology, Drexel University, Philadelphia, Pennsylvania 19107, USA
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Vilella A, Ginés A, Dolz C. [MALT gastric lymphoma]. Med Clin (Barc) 2003; 120:349-52. [PMID: 12646113 DOI: 10.1016/s0025-7753(03)73698-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Angels Vilella
- Servicio Digestivo, Fundación Hospital Son Llàtzer, Palma de Mallorca, España.
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Abstract
The development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma depends critically on Helicobacter pylori infection. The bacterial infection stimulates the lymphoma B-cells through both direct (auto-antigen) and indirect (H. pylori specific intra-tumour T-cells) immunological stimulation. It also promotes the acquisition of genetic abnormality through activated neutrophils, which release oxygen reactive species. Malignant clones bearing t(11;18)(q21;q21) form lymphomas that are H. pylori growth independent. Those without t(11;18)(q21;q21) but with other genetic abnormality such as trisomy 3 depend critically on H. pylori mediated immune response at early stages and are therefore responsive to H. pylori eradication. However, at late stages when additional genetic defects such as t(1;14)(p22;q32) accumulate, the tumour may escape its growth dependence on H. pylori mediated immune response. Detection of these chromosomal translocations has significant implication in clinical management of patients with gastric MALT lymphoma.
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Affiliation(s)
- Ming-Qing Du
- Department of Histopathology, Royal Free and University College Medical School, University of College London, London, UK.
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Levy M, Copie-Bergman C, Traulle C, Lavergne-Slove A, Brousse N, Flejou JF, de Mascarel A, Hemery F, Gaulard P, Delchier JC. Conservative treatment of primary gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue: predictive factors of response and outcome. Am J Gastroenterol 2002; 97:292-7. [PMID: 11866264 DOI: 10.1111/j.1572-0241.2002.05460.x] [Citation(s) in RCA: 87] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Primary gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue may regress with conservative treatment such as anti-Helicobacterpylori therapy or monochemotherapy. The aims of the present study were to analyze the predictive factors of response to anti-H. pylori treatment, to assess the effects of an adjuvant therapy in responding patients, and to evaluate an alternative therapy in nonresponding patients. METHODS From 1995 to 2000, 48 H. pylori-infected patients with localized primary gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue were treated with anti-H. pylori therapy. Endoscopic and endoscopic ultrasonography features and histological grading of large cells' proportion were analyzed. Eradication of H. pylori and tumoral response were assessed at 2 and 6 months, respectively. From 1996, patients in remission at 6 months were randomized to receive either chlorambucil p.o. for 6 months or no treatment. Patients who did not respond to H. pylori eradication received chlorambucil p.o. for 1 yr. RESULTS Among the 48 treated patients, 33 (69%) were in complete (n = 28) or in partial (n = 5) remission, and 15 (31%) were in treatment failure at 6 months. H. pylori was eradicated in 47 patients. The response was not correlated with the endoscopic features or with the histological grade. In contrast, it was related to ultrasonographic features: remission was achieved in 76% of patients when no perigastric lymph node was detected versus only 33% when endoscopic ultrasonography showed presence of lymph nodes (p = 0.025). All responding patients remained in remission (median 34 months) whatever the treatment they received (no treatment or chlorambucil). Remission could be achieved with chlorambucil in 58% of the nonresponding patients to anti-H. pylori treatment. CONCLUSIONS The major negative predictive factor of the tumoral response to anti-H. pylori treatment in patients with primary gastric low-grade B-cell lymphoma of mucosaassociated lymphoid tissue was the presence of perigastric lymph nodes on endoscopic ultrasonography. In responding patients, remission remained stable, suggesting that adjuvant chemotherapy was not useful. In patients who failed to respond to H. pylori eradication, monochemotherapy with chlorambucil proved to be efficient, but new therapeutic modalities should be evaluated to improve the control of the tumoral process.
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Affiliation(s)
- Michaël Levy
- Service d'Hépatologie et de Gastroentérologie, Département de Pathologie et EA 2348, and Service de Biostatistiques et d'Informatique, Hĵpital Henri Mondor, Créteil, France
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Abstract
The development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is dependent on Helicobacter pylori infection. Bacterial colonisation of the gastric mucosa triggers lymphoid infiltration and the formation of acquired MALT. The bacterial infection induces and sustains an actively proliferating B-cell population through direct (autoantigen) and indirect (intratumoral T cells specific for H. pylori) immunological stimulation. Moreover, the bacterial infection provokes a neutrophilic response, which causes the release of oxygen free radicals. These reactive species may promote the acquisition of genetic abnormalities and malignant transformation of reactive B cells. A transformed clone carrying the translocation t(1;18)(q21;q21) forms a MALT lymphoma, the growth of which is independent of H. pylori and will not respond to bacterial eradication. Malignant clones without t(11;18)(q21;q21), but with other genetic abnormalities, such as trisomy 3 or microsatellite instability, depend critically on immune stimulation mediated by H. pylori for their clonal expansion. In the early stages, the tumour can be successfully treated by eradication of the bacterium, whereas at later stages the tumour may escape its growth dependency through acquisition of additional genetic abnormalities such as t(1;14)(p22;q32) and t(1;2)(p22,p12) involving the BCL-10 gene. Finally, further genetic abnormalities, such as inactivation of the tumour suppressor genes, p53 and p16, can lead to high-grade transformation. Detection of these abnormalities may help with the clinical management of patients with gastric MALT lymphoma.
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Affiliation(s)
- Ming-Qing Du
- Department of Histopathology, Royal Free and University College Medical School, University College London, UK.
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Morgner A, Thiede C, Bayerdörffer E, Alpen B, Wündisch T, Neubauer A, Stolte M. Long-term follow-up of gastric MALT lymphoma after H. pylori eradication. Curr Gastroenterol Rep 2001; 3:516-22. [PMID: 11696290 DOI: 10.1007/s11894-001-0073-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
For almost 10 years, we have been familiar with the concept of mucosa-associated lymphoid tissue (MALT)-type lymphoma of the stomach caused by chronic Helicobacter pylori infection. Many epidemiologic, biologic, and molecular genetic studies have implicated H. pylori for its role in lymphoma genesis. Since the first reports on complete remission of gastric MALT lymphomas after cure of bacterial infection, many clinical studies have investigated the effect of eradicating H. pylori on the course of MALT lymphoma, and indeed were able to confirm remission of the lymphoma. To date, more than 650 patients worldwide have been treated for gastric MALT lymphoma with antibiotics, and we have gained many new insights concerning the biologic behavior of this disease, especially from the deepened knowledge of cytogenetics. Furthermore, factors relevant for the prediction of treatment outcome have been identified, which has helped to stratify patients into risk groups.
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Affiliation(s)
- A Morgner
- Institute for Pathology, Klinikum Bayreuth, Preuschwitzer Str. 101, 95455 Bayreuth, Germany.
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40
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Alpen B, Thiede C, Wündisch T, Bayerdörffer E, Stolte M, Neubauer A. Molecular diagnostics in low-grade gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type after Helicobacter pylori eradication therapy. CLINICAL LYMPHOMA 2001; 2:103-8. [PMID: 11707850 DOI: 10.3816/clm.2001.n.015] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The primary gastric lymphomas are extranodal non-Hodgkin's lymphomas that likely originate from the mucosa-associated lymphoid tissue (MALT). Data suggest that chronic infection with Helicobacter pylori (H pylori) is significantly associated with the pathogenesis of low-grade gastric MALT lymphomas. This is in keeping with the observation that many patients with early low-grade MALT lymphomas have complete remissions after H pylori eradication therapy. However, the stability of these remissions remains unclear and relapses have been reported. It can be difficult to distinguish between early malignant and benign disorders of the gastric mucosa. A polymerase chain reaction (PCR) assay can detect rearrangements of the variable region of immunoglobulin heavy chains. This assay can be used to distinguish the clonality of B lymphocytes and has been investigated as a test for differential diagnosis of MALT lymphomas. Monoclonality is observed in the majority of MALT-lymphoma samples at diagnosis but has been found in gastritis samples as well. Whether the presence of monoclonal B cells is associated with the risk of lymphoma progression remains unclear. As many as 50% of patients who have complete histologic remissions of MALT lymphoma after H pylori eradication therapy have persisting monoclonal bands in follow-up PCR monitoring. Although it is unclear as to whether monoclonality indicates the presence of minimal residual disease, patients who have persistent monoclonal bands during follow-up should be considered at risk for relapse. The PCR assay for rearrangements of the variable region of the immunoglobulin heavy-chain gene appears to be of low value in the diagnosis of B-cell malignancies but could provide a useful tool in the follow-up of patients who achieve remissions after H pylori eradication.
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Affiliation(s)
- B Alpen
- Abteilung Hämatologie/Onkologie/Immunologie, Philipps-Universität, Marburg, Germany
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41
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Tsang RW, Gospodarowicz MK, Pintilie M, Bezjak A, Wells W, Hodgson DC, Crump M. Stage I and II MALT lymphoma: results of treatment with radiotherapy. Int J Radiat Oncol Biol Phys 2001; 50:1258-64. [PMID: 11483337 DOI: 10.1016/s0360-3016(01)01549-8] [Citation(s) in RCA: 122] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
PURPOSE Mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct disease with specific clinical and pathologic features that may affect diverse organs. We analyzed our recent experience with Stage I/II MALT lymphoma presenting in the stomach and other organs to assess the outcome following involved field radiation therapy (RT). PATIENTS AND METHODS Seventy patients with Stage IE (62) and IIE (8) disease were treated between 1989 and 1998. Patients with transformed MALT were excluded. The median age was 62 years (range, 24--83 years), M:F ratio 1:2.2. Presenting sites included stomach, 15; orbital adnexa, 19; salivary glands, 15; thyroid, 8; lung, 5; upper airways, 3 (nasopharynx, 2; larynx, 1); urinary bladder, 3; breast, 1; and rectum, 1. Staging included site-specific imaging, CT abdomen in 66 patients (94%) and bone marrow biopsy in 54 (77%). Sixty-two patients received radiation therapy: 52 received RT alone, 7 received chemotherapy and RT, and 3 received antibiotics followed by RT. Median RT dose was 30 Gy (range, 17.5--35 Gy). Most frequently used RT prescriptions were 25 Gy (26 patients-18 orbit, 6 stomach, and 2 salivary glands), 30 Gy (23 patients), and 35 Gy (8 patients). Five patients had complete surgical excision of lymphoma and no other treatment (stomach 1, salivary 2, lung 2), whereas 2 patients with gastric lymphoma received antibiotics only. One patient refused treatment and was excluded from the analysis of treatment outcome, leaving 69 patients with a median follow-up of 4.2 years (range, 0.3-11.4 years). RESULTS A complete response was achieved in 66/69 patients, and 3 patients had partial response (2 lung, 1 orbit). The 5-year disease-free survival (DFS) was 76%, and the overall survival was 96%. No relapses were observed in patients with stomach and thyroid lymphoma. The 5-year DFS for these patients was 93%, in contrast to 69% for patients presenting in other sites (p = 0.006). Among the 5 patients treated with surgery only, 2 relapsed locally (lung, and minor salivary gland). Among 62 patients who received RT, 8 relapsed (2 salivary, 3 orbit, 1 nasopharynx, 1 larynx, 1 breast). Three patients relapsed in the nonirradiated contralateral paired organ, 4 in distant sites, and 1 in both local and distant sites. The overall local control rate with radiation was 97% (60/62 patients). CONCLUSION Localized MALT lymphomas have excellent prognosis following moderate-dose RT. Gastric and thyroid MALT lymphomas have better early outcome, as compared to the other sites where distant failure is more common. Relapses were observed in nonirradiated paired organs or distant sites. Further follow-up is required to assess the impact of failure on survival.
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Affiliation(s)
- R W Tsang
- Department of Radiation Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Canada.
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42
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Wündisch T, Thiede C, Alpen B, Stolte M, Neubauer A. Are lymphocytic monoclonality and immunoglobulin heavy chain (IgH) rearrangement premalignant conditions in chronic gastritis? Microsc Res Tech 2001; 53:414-8. [PMID: 11525259 DOI: 10.1002/jemt.1110] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Normal gastric mucosa is devoid of lymphoid cells. Any increase of lymphocytes suggests chronic inflammation. Infection with Helicobacter pylori (Hp) is the major cause for nonautoimmune chronic gastritis and induces a mixed cellular response resulting in an acquired lymphoid tissue, or MALT (mucosa-associated lymphoid tissue). Hp has also been implicated in the genesis of gastric MALT-lymphoma. Polymerase chain reaction-based assays to detect the expansion of monoclonal B-cells have also been used to corroborate the diagnosis. In a considerable number of cases monoclonal B-cells remain detectable in follow-up biopsies, with the lymphoma being in complete histological remission. The clinical relevance of this finding is not clear yet. However, there also exist different reports that monoclonal B-cells can be found in gastric biopsies of patients with neither a histological sign nor a present or past history of lymphoma. In the light of these findings we address the question whether B-cell monoclonality can be seen as a premalignant condition in chronic gastritis and conclude that as of now the relevance of the finding of B-cell monoclonality remains unclear. As of now the only and gold standard for the diagnosis of gastric MALT-lymphoma is histopathology.
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Affiliation(s)
- T Wündisch
- Abteilung für Hämatologie, Onkologie und Immunologie, Philipps Universität, Marburg, Germany
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43
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Wotherspoon AC. A critical review of the effect of Helicobacter pylori eradication on gastric MALT lymphoma. Curr Gastroenterol Rep 2000; 2:494-8. [PMID: 11079052 DOI: 10.1007/s11894-000-0014-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/15/2023]
Abstract
Low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) are thought to arise within organized lymphoid tissue in the gastric mucosa that is most frequently acquired in response to Helicobacter pylori infection. This close association between the organism and the lymphoma is further reflected by the demonstration that the proliferation of the lymphoma cells can be driven by the presence of H. pylori organisms through a complex path of cellular interactions involving specific T cells. From these observations it was suggested that removal of one of the proliferative drives to the neoplastic cells in the form of eradication of the organism might induce a remission in the tumor. Several large multicenter studies are now underway to consider this question, and interim reports suggest that long-term remissions can be induced in low-grade MALT lymphomas in 70% to 80% of cases. The lymphomas that are most likely to respond to H. pylori eradication are those that are located superficially within the gastric mucosa. It has been suggested that certain genetic abnormalities, such as t(11;18) and the Bcl-10 mutation, may be associated with lack of response to this therapy. Recurrences of low-grade lymphoma are encountered in patients treated by H. pylori eradication, but these appear to be infrequent and may be self-limiting and spontaneously regress without further therapy.
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Affiliation(s)
- A C Wotherspoon
- Department of Histopathology, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK.
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