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Logo of gutliverThis ArticleAims and ScopeInstructions to AuthorsE-SubmissionGut and Liver
 
Gut Liver. 2009 September; 3(3): 235–236.
Published online 2009 September 30. doi:  10.5009/gnl.2009.3.3.235
PMCID: PMC2852709

Concerns about the Predictive Factors for Tumor Regression, Definition, and Management of Nonresponders, and Relapse of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma Related to Helicobacter pylori

I read with interest the recent review article by Suzuki et al.1 This paper helps gastroenterologists to understand the link between gastric mucosa-associated lymphoid tissue (MALT) lymphoma and Helicobacter pylori (H. pylori), but several questions remain unanswered: (i) the predictive factors for regression of gastric MALT lymphoma after H. pylori eradication, (ii) the characteristic endoscopic findings, (iii) how to optimize the definition and managemnet of nonresponders, and (iv) how to manage the relapse and recurrence of these tumors.

The first report in 19932 has been followed by numerous reports of regression of MALT lymphoma after H. pylori eradication. However, not all gastric MALT lymphomas regress after H. pylori eradication, and thus three factors related to the prediction of tumor regression need to be considered: (i) the characteristics of gastric MALT lymphoma itself, (ii) the presence of H. pylori infection, and (iii) factors related to the host, such as the score on the international prognostic index and blood-test results. For example, even the location of the tumor has been mentioned as a predictive factor, with gastric MALT lymphomas on the proximal side being linked to autoimmunity.3 These proximal-side tumors progress very slowly and often fail to regress because they are linked to autoantigen responsive T cells.3,4 In addition, histological features of MALT lymphoma are known to be unresponsive to eradication therapy.5

An endoscopic apperance mimiking submucosal tumors and cobblestone like elevated lesions have been classified as polypoid gastric MALT lymphoma, and characterized as H. pylori-negative gastric MALT lymphoma.6,7 Although Suzuki et al. described this briefly in their review,1 H. pylori negativity needs to be defined. Since there is no single gold-standard methods for diagnosing H. pylori infection, the combination of several diagnostic methods including H. pylori IgG antibody, histology, culture, immunohistochemistry, PCR, and the urease breath test is considered to be suitable for confirming H. pylori negativity.8 In addition, the characteristics of H. pylori-negative gastric MALT lymphoma should be managed based on previous reports.9 Put simply, the treatment should differ from H. pylori eradication in these H. pylori-negative gastric MALT lymphoma due to the absence of H. pylori. However, these lymphomas also respond to antibiotic treatment in both the stomach and other parts of the gastrointestinal tracts.10 What mechanism underlies this phenomenon? Does this represent a clue for a false-negative diagnosis of H. pylori infection? What would be the possible hypothesis based on previous reports?

On the other hand, non-H. pylori helicobacters related to MALT lymphoma should also be considered, such as H. helimannii and H. felis.11 Interestingly, some of these regress merely after the application of first-line H. pylori eradication therapy.12 In addition, these organisms are detected in both gastric and rectal lymphomas.13

Optimizing the definition and management of nonresponders requires consideration of three issues: (i) the minimum observation period needed to define regression, (ii) interpretating discrepancies between the histologic and endoscopic regression, and (iii) choosing between a "wait and see strategy" and a second-line treatment such as gastrectomy, chemotherapy, and radiotherapy. Although a Japanese study adressed the last issue,14 the optimal strategy remains unclear. In addition to the definition and management, the relapse and recurrence of gastric MALT lymphoma after successful regression on H. pylori eradication also need to be clarified. There are some reports of the development of high-grade tumor (diffuse large B-cell lymphoma) or gastric adenocarcinoma after successful regression of gastric MALT lymphoma. What would be the mechanisms and prognostic factors in such tumors?

In summary, answers to the above questions that arose when I read the review by professor Suzuki and colleagues would be of considerable interest to readers of Gut and Liver. There are already several interesting published papers written by Japanese authors that strengthen our knowledge in this field, and I strongly believe that addressing the above issues would greatly increase the interest in their review article.

References

1. Suzuki H, Saito Y, Hibi T. Helicobacter pylori and gastric MALT lymphoma: updated systemic review of clinical outcomes and molecular pathogenesis. Gut Liver. 2009;3:81–87. [PMC free article] [PubMed]
2. Wotherspoon AC, Doglioni C, Diss TC, et al. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet. 1993;342:575–577. [PubMed]
3. Steinbach G, Ford R, Glober G, et al. Antibiotic treatment of gastric lymphoma of mucosa-associated lymphoid tissue. Ann Intern Med. 1999;131:88–95. [PubMed]
4. Greiner A, Marx A, Heesemann J, Leebmann J, Schmausser B, Müller-Hermelink HK. Idiotype identity in a MALT-type lymphoma and B cells in Helicobacter pylori associated chronic gastritis. Lab Invest. 1994;70:572–578. [PubMed]
5. Yokoi T, Nakamura T, Nakamura S. Histological features of gastric mucosa-associated lymphoid tissue (MALT) lymphoma irresponsive to eradication therapy. Stomach Intest. 2002;37:531–536.
6. Yokoi T, Nakamura T, Kasugai K, et al. Primary low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma with polypoid appearance. Polypoid gastric MALT lymphoma: a clinicopathologic study of eight cases. Pathol Int. 1999;49:702–709. [PubMed]
7. Nakamura T, Nakamura S, Yonezumi M, Seto M, Yokoi T. The t(11;18)(q21;q21) translocation in Helicobacter pylori-negative low-grade gastric mucosa-associated lymphoid tissue lymphoma. Am J Gastroenterol. 2000;95:3314–3315. [PubMed]
8. Eck M, Greiner A, Schmausser B, et al. Evaluation of Helicobacter pylori in gastric MALT-type lymphoma: differences between histologic and serologic diagnosis. Mod Pathol. 1999;12:1148–1151. [PubMed]
9. Ye H, Liu H, Raderer M, et al. High incidence of t(11;18) (q21;q21) in Helicobacter pylori-negative gastric MALT lymphoma. Blood. 2003;101:2547–2550. [PubMed]
10. Inoue F, Chiba T. Regression of MALT lymphoma of the rectum after anti-H. pylori therapy in a patient negative for H. pylori. Gastroenterology. 1999;117:514–515. [PubMed]
11. Fox JG. The non-H. pylori helicobacters: their expanding role in gastrointestinal and systemic diseases. Gut. 2002;50:273–283. [PMC free article] [PubMed]
12. Morgner A, Lehn N, Andersen LP, et al. Helicobacter heilmannii-associated primary gastric low-grade MALT lymphoma: complete remission after curing the infection. Gastroenterology. 2000;118:821–828. [PubMed]
13. Nakase H, Okazaki K, Ohana M, et al. The possible involvement of micro-organisms other than Helicobacter pylori in the development of rectal MALT lymphoma in H. pylori-negative patients. Endoscopy. 2002;34:343–346. [PubMed]
14. Ono H, Oda I, Inui T, et al. Clinical management for nonresponders with low-grade gastric mucosa-associated lymphoid tissue lymphoma after Helicobacter pylori eradication therapy. Stomach Intest. 2002;37:521–529.

Articles from Gut and Liver are provided here courtesy of The Korean Society of Gastroenterology, the Korean Society of Gastrointestinal Endoscopy, the Korean Society of Neurogastroenterology and Motility, Korean College of Helicobacter and Upper Gastrointestinal Research, Korean Association for the Study of Intestinal Diseases, the Korean Association for the Study of the Liver, the Korean Society of Pancreatobiliary Disease, and the Korean Society of Gastrointestinal Cancer